Aging of clean foams

NASA Astrophysics Data System (ADS)

Weon, Byung Mook; Stewart, Peter S.

2014-11-01

Aging is an inevitable process in living systems. Here we show how clean foams age with time through sequential coalescence events: in particular, foam aging resembles biological aging. We measure population dynamics of bubbles in clean foams through numerical simulations with a bubble network model. We demonstrate that death rates of individual bubbles increase exponentially with time, independent on initial conditions, which is consistent with the Gompertz mortality law as usually found in biological aging. This consistency suggests that clean foams as far-from-equilibrium dissipative systems are useful to explore biological aging. This work (NRF-2013R1A22A04008115) was supported by Mid-career Researcher Program through NRF grant funded by the MEST.

Biological age and tempos of aging in women over 60 in connection with their morphofunctional characteristics

PubMed Central

2014-01-01

Background The study of aging processes and the changes in morphological, physiological, and functional characteristics that are associated with aging is of great interest not only for researchers, but also for the general public. The aim of the present paper is to study the biological age and tempos of aging in women older than 60 years, including long-lived females (over 90-years-old), and their associations with morphofunctional characteristics. Results Somatic traits, body mass components, and functional characteristics were investigated in 119 elderly (between 60 and 74-years-old) and long-lived (over 90-years-old) women in Tiraspol. With the special PC software ‘Diagnostics of Aging: BioAge’ (National Gerontological Center, Moscow, Russia) the biological age and tempos of aging were evaluated in the study participants. The results show close connections between morphofunctional changes, particularly in body mass components, and biological age. The software demonstrated its validity in the estimation of biological age in the group of elderly women. In the homogenous (according to their chronological age) group of women, three subgroups were separated with different tempos of aging: those with lower rates of aging (biological age less than chronological age by two years or more); those consistent with their chronological age, and those with accelerated tempos of aging (biological age higher than chronological age by two years or more). Conclusions Morphofunctional characteristics in the studied groups of women demonstrate the trends of age-involutive changes which can be traced through all groups, from those with slow rates of aging, to those with average rates, to those with accelerated tempos of aging, and finally in long-lived women. The results of comparative analysis show that women with accelerated aging are characterized with such traits as lower skeletal muscle mass, lower hand grip strength, and higher metabolic rate. Canonical discriminant analysis revealed a number of morphofunctional characteristics which differentiate the early-aging women from women with average rates of aging: higher BMI values, excessive fat mass, lower skeletal muscle mass and low values of hand grip strength. Thus the presence of such characteristics in elderly women can be considered as additional risk factor towards the early onset of the aging process. PMID:24887211

The role of low-grade inflammation and metabolic flexibility in aging and nutritional modulation thereof: a systems biology approach.

PubMed

Calçada, Dulce; Vianello, Dario; Giampieri, Enrico; Sala, Claudia; Castellani, Gastone; de Graaf, Albert; Kremer, Bas; van Ommen, Ben; Feskens, Edith; Santoro, Aurelia; Franceschi, Claudio; Bouwman, Jildau

2014-01-01

Aging is a biological process characterized by the progressive functional decline of many interrelated physiological systems. In particular, aging is associated with the development of a systemic state of low-grade chronic inflammation (inflammaging), and with progressive deterioration of metabolic function. Systems biology has helped in identifying the mediators and pathways involved in these phenomena, mainly through the application of high-throughput screening methods, valued for their molecular comprehensiveness. Nevertheless, inflammation and metabolic regulation are dynamical processes whose behavior must be understood at multiple levels of biological organization (molecular, cellular, organ, and system levels) and on multiple time scales. Mathematical modeling of such behavior, with incorporation of mechanistic knowledge on interactions between inflammatory and metabolic mediators, may help in devising nutritional interventions capable of preventing, or ameliorating, the age-associated functional decline of the corresponding systems. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

The short-lived African turquoise killifish: an emerging experimental model for ageing.

PubMed

Kim, Yumi; Nam, Hong Gil; Valenzano, Dario Riccardo

2016-02-01

Human ageing is a fundamental biological process that leads to functional decay, increased risk for various diseases and, ultimately, death. Some of the basic biological mechanisms underlying human ageing are shared with other organisms; thus, animal models have been invaluable in providing key mechanistic and molecular insights into the common bases of biological ageing. In this Review, we briefly summarise the major applications of the most commonly used model organisms adopted in ageing research and highlight their relevance in understanding human ageing. We compare the strengths and limitations of different model organisms and discuss in detail an emerging ageing model, the short-lived African turquoise killifish. We review the recent progress made in using the turquoise killifish to study the biology of ageing and discuss potential future applications of this promising animal model. © 2016. Published by The Company of Biologists Ltd.

A Cluster Randomized Controlled Trial on the Effects of Technology-aided Testing and Feedback on Physical Activity and Biological Age Among Employees in a Medium-sized Enterprise.

PubMed

Liukkonen, Mika; Nygård, Clas-Håkan; Laukkanen, Raija

2017-12-01

It has been suggested that engaging technology can empower individuals to be more proactive about their health and reduce their health risks. The aim of the present intervention was to study the effects of technology-aided testing and feedback on physical activity and biological age of employees in a middle-sized enterprise. In all, 121 employees (mean age 42 ± 10 years) participated in the 12-month three-arm cluster randomized trial. The fitness measurement process (Body Age) determined the participants' biological age in years. Physical activity was measured with the International Physical Activity Questionnaire Short Form. Physical activity did not change during the intervention. Biological age (better fitness) improved in all groups statistically significantly ( p  < 0.001), but with no interaction effects. The mean changes (years) in the groups were -2.20 for the controls, -2.83 for the group receiving their biological age and feedback, and -2.31 for the group receiving their biological age, feedback, and a training computer. Technology-aided testing with feedback does not seem to change the amount of physical activity but may enhance physical fitness measured by biological age.

[Fundamental aspects of extreme aging].

PubMed

Tréton, J

2002-07-01

Major developments in molecular biology in invertebrates have recently shown the determining effect of genetics on aging. The first finding was that artificial selection can highlight the genetic aspect of the aging process, demonstrating the polygenetic property of longevity. Another finding showed that certain gene transfers can modulate the lifespan of an organism. Recent progress has been made in three fields: genetic markers of aging, biological basis of cell maintenance, and hereditary factors contributing to late onset genetic disease. These new developments open new avenues of research in clinical biology. In regard to genetic markers of aging, it has been demonstrated that the ends of the chromosomes, telomeres, play a role in cell senescence. Telomeres can be viewed as markers of aging. Shortened telomeres are associated with replicative senescence and antitumor action. DNA anomalies are also more frequent: simple or double breaks, additions and base substitutions. Data on the biological basis of cell maintenance obtained in invertebrates show the polygenetic property of aging involving four significant mechanisms, control of metabolism, resistance to stress, chromatin-dependent gene regulation of genetic homeostasis. Finally, recent studies have shown that late onset hereditary diseases would be linked with particular genes, some of which have been identified. Two non-exclusive mechanisms could be involved: an adaptive mechanism involving gene selection during the evolutionary process, for example in obesity; and non-adaptive accumulation of gene expression during the post-reproductive phase, for example in Alzheimer's disease. These findings open a new era for the biology of aging.

Aging, Rejuvenation, and Epigenetic Reprogramming: Resetting the Aging Clock

PubMed Central

Rando, Thomas A.; Chang, Howard Y.

2012-01-01

The underlying cause of aging remains one of the central mysteries of biology. Recent studies in several different systems suggest that not only may the rate of aging be modified by environmental and genetic factors, but also that the aging clock can be reversed, restoring characteristics of youthfulness to aged cells and tissues. This Review focuses on the emerging biology of rejuvenation through the lens of epigenetic reprogramming. By defining youthfulness and senescence as epigenetic states, a framework for asking new questions about the aging process emerges. PMID:22265401

Early-Life Intelligence Predicts Midlife Biological Age

PubMed Central

Caspi, Avshalom; Belsky, Daniel W.; Harrington, Honalee; Houts, Renate; Israel, Salomon; Levine, Morgan E.; Sugden, Karen; Williams, Benjamin; Poulton, Richie; Moffitt, Terrie E.

2016-01-01

Objectives: Early-life intelligence has been shown to predict multiple causes of death in populations around the world. This finding suggests that intelligence might influence mortality through its effects on a general process of physiological deterioration (i.e., individual variation in “biological age”). We examined whether intelligence could predict measures of aging at midlife before the onset of most age-related disease. Methods: We tested whether intelligence assessed in early childhood, middle childhood, and midlife predicted midlife biological age in members of the Dunedin Study, a population-representative birth cohort. Results: Lower intelligence predicted more advanced biological age at midlife as captured by perceived facial age, a 10-biomarker algorithm based on data from the National Health and Nutrition Examination Survey (NHANES), and Framingham heart age (r = 0.1–0.2). Correlations between intelligence and telomere length were less consistent. The associations between intelligence and biological age were not explained by differences in childhood health or parental socioeconomic status, and intelligence remained a significant predictor of biological age even when intelligence was assessed before Study members began their formal schooling. Discussion: These results suggest that accelerated aging may serve as one of the factors linking low early-life intelligence to increased rates of morbidity and mortality. PMID:26014827

Early-Life Intelligence Predicts Midlife Biological Age.

PubMed

Schaefer, Jonathan D; Caspi, Avshalom; Belsky, Daniel W; Harrington, Honalee; Houts, Renate; Israel, Salomon; Levine, Morgan E; Sugden, Karen; Williams, Benjamin; Poulton, Richie; Moffitt, Terrie E

2016-11-01

Early-life intelligence has been shown to predict multiple causes of death in populations around the world. This finding suggests that intelligence might influence mortality through its effects on a general process of physiological deterioration (i.e., individual variation in "biological age"). We examined whether intelligence could predict measures of aging at midlife before the onset of most age-related disease. We tested whether intelligence assessed in early childhood, middle childhood, and midlife predicted midlife biological age in members of the Dunedin Study, a population-representative birth cohort. Lower intelligence predicted more advanced biological age at midlife as captured by perceived facial age, a 10-biomarker algorithm based on data from the National Health and Nutrition Examination Survey (NHANES), and Framingham heart age (r = 0.1-0.2). Correlations between intelligence and telomere length were less consistent. The associations between intelligence and biological age were not explained by differences in childhood health or parental socioeconomic status, and intelligence remained a significant predictor of biological age even when intelligence was assessed before Study members began their formal schooling. These results suggest that accelerated aging may serve as one of the factors linking low early-life intelligence to increased rates of morbidity and mortality. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Aging Biology and Novel Targets for Drug Discovery

PubMed Central

McLachlan, Andrew J.; Quinn, Ronald J.; Simpson, Stephen J.; de Cabo, Rafael

2012-01-01

Despite remarkable technological advances in genetics and drug screening, the discovery of new pharmacotherapies has slowed and new approaches to drug development are needed. Research into the biology of aging is generating many novel targets for drug development that may delay all age-related diseases and be used long term by the entire population. Drugs that successfully delay the aging process will clearly become “blockbusters.” To date, the most promising leads have come from studies of the cellular pathways mediating the longevity effects of caloric restriction (CR), particularly target of rapamycin and the sirtuins. Similar research into pathways governing other hormetic responses that influence aging is likely to yield even more targets. As aging becomes a more attractive target for drug development, there will be increasing demand to develop biomarkers of aging as surrogate outcomes for the testing of the effects of new agents on the aging process. PMID:21693687

Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies

PubMed Central

Salvioli, S.; Sikora, E.; Cooper, E. L.

2007-01-01

Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells. PMID:17549234

[Products of bee-keeping and prophylaxis of premature aging].

PubMed

Dubtsova, E A; Kas'ianenko, V I; Komissarenko, I A; Lazebnik, L B

2008-01-01

Natural bee honey is one of compound natural products in which structure more than four hundred various components are revealed, including enzymes, organic acids, vitamins and microelements. One of the basic biological properties of honey is the ability to slow down processes of aging, because there are vitamins E, C, enzymes with antioxidative properties and a succinic acid in its structure. Examination of 193 beekeepers daily using honey in quantity of 57.2 +/- 8.6 gram with definition of their biological age was carried out. The received results have been compared to results of examination of 35 workers who are doing manual labour in the same degree, as the beekeepers, but do not use products of beekeeping. The research has shown that the biological age of 70% of beekeepers is lower than that of the average in population, 15% of beekeepers are of the same and 15% are of higher biological age than that of the average in population. The biological age of people in the group of comparison is lower than the average in population only in 28.6% of cases, corresponds in 31.4% and is higher than the average in population in 40.0% of cases. The biological age of beekeepers appeared not only less, than of the persons who are not using products of beekeeping, but it also is less than biological age of the population as a whole.

Biology of Healthy Aging and Longevity.

PubMed

Carmona, Juan José; Michan, Shaday

2016-01-01

As human life expectancy is prolonged, age-related diseases are thriving. Aging is a complex multifactorial process of molecular and cellular decline that affects tissue function over time, rendering organisms frail and susceptible to disease and death. Over the last decades, a growing body of scientific literature across different biological models, ranging from yeast, worms, flies, and mice to primates, humans and other long-lived animals, has contributed greatly towards identifying conserved biological mechanisms that ward off structural and functional deterioration within living systems. Collectively, these data offer powerful insights into healthy aging and longevity. For example, molecular integrity of the genome, telomere length, epigenetic landscape stability, and protein homeostasis are all features linked to "youthful" states. These molecular hallmarks underlie cellular functions associated with aging like mitochondrial fitness, nutrient sensing, efficient intercellular communication, stem cell renewal, and regenerative capacity in tissues. At present, calorie restriction remains the most robust strategy for extending health and lifespan in most biological models tested. Thus, pathways that mediate the beneficial effects of calorie restriction by integrating metabolic signals to aging processes have received major attention, such as insulin/insulin growth factor-1, sirtuins, mammalian target of rapamycin, and 5' adenosine monophosphate-activated protein kinase. Consequently, small-molecule targets of these pathways have emerged in the impetuous search for calorie restriction mimetics, of which resveratrol, metformin, and rapamycin are the most extensively studied. A comprehensive understanding of the molecular and cellular mechanisms that underlie age-related deterioration and repair, and how these pathways interconnect, remains a major challenge for uncovering interventions to slow human aging while extending molecular and physiological youthfulness, vitality, and health. This review summarizes key molecular mechanisms underlying the biology of healthy aging and longevity.

Molecular and physiological manifestations and measurement of aging in humans.

PubMed

Khan, Sadiya S; Singer, Benjamin D; Vaughan, Douglas E

2017-08-01

Biological aging is associated with a reduction in the reparative and regenerative potential in tissues and organs. This reduction manifests as a decreased physiological reserve in response to stress (termed homeostenosis) and a time-dependent failure of complex molecular mechanisms that cumulatively create disorder. Aging inevitably occurs with time in all organisms and emerges on a molecular, cellular, organ, and organismal level with genetic, epigenetic, and environmental modulators. Individuals with the same chronological age exhibit differential trajectories of age-related decline, and it follows that we should assess biological age distinctly from chronological age. In this review, we outline mechanisms of aging with attention to well-described molecular and cellular hallmarks and discuss physiological changes of aging at the organ-system level. We suggest methods to measure aging with attention to both molecular biology (e.g., telomere length and epigenetic marks) and physiological function (e.g., lung function and echocardiographic measurements). Finally, we propose a framework to integrate these molecular and physiological data into a composite score that measures biological aging in humans. Understanding the molecular and physiological phenomena that drive the complex and multifactorial processes underlying the variable pace of biological aging in humans will inform how researchers assess and investigate health and disease over the life course. This composite biological age score could be of use to researchers seeking to characterize normal, accelerated, and exceptionally successful aging as well as to assess the effect of interventions aimed at modulating human aging. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

The role of epigenetics in cardiovascular health and ageing: A focus on physical activity and nutrition.

PubMed

Wallace, Robert G; Twomey, Laura C; Custaud, Marc-Antoine; Turner, Jonathan D; Moyna, Niall; Cummins, Philip M; Murphy, Ronan P

2017-11-16

The cardiovascular system is responsible for transport of blood and nutrients to tissues, and is pivotal to the physiological health and longevity. Epigenetic modification is a natural, age-associated process resulting in highly contextualised gene expression with clear implications for cell differentiation and disease onset. Biological/epigenetic age is independent of chronological age, constituting a highly reflective snapshot of an individual's overall health. Accelerated vascular ageing is of major concern, effectively lowering disease threshold. Age-related chronic illness involves a complex interplay between many biological processes and is modulated by non-modifiable and modifiable risk factors. These alter the static genome by a number of epigenetic mechanisms, which change gene expression in an age and lifestyle dependent manner. This 'epigenetic drift' impacts health and contributes to the etiology of chronic illness. Lifestyle factors may cause acceleration of this epigenetic "clock", pre-disposing individuals to cardiovascular disease. Nutrition and physical activity are modifiable lifestyle choices, synergistically contributing to cardiovascular health. They represent a powerful potential epigenetic intervention point for effective cardiovascular protective and management strategies. Thus, together with traditional risk factors, monitoring the epigenetic signature of ageing may prove beneficial for tailoring lifestyle to fit biology - supporting the increasingly popular concept of "ageing well". Copyright © 2017 Elsevier B.V. All rights reserved.

Oxidative stress and adipocyte biology: focus on the role of AGEs.

PubMed

Boyer, Florence; Vidot, Jennifer Baraka; Dubourg, Alexis Guerin; Rondeau, Philippe; Essop, M Faadiel; Bourdon, Emmanuel

2015-01-01

Diabetes is a major health problem that is usually associated with obesity, together with hyperglycemia and increased advanced glycation endproducts (AGEs) formation. Elevated AGEs elicit severe downstream consequences via their binding to receptors of AGEs (RAGE). This includes oxidative stress and oxidative modifications of biological compounds together with heightened inflammation. For example, albumin (major circulating protein) undergoes increased glycoxidation with diabetes and may represent an important biomarker for monitoring diabetic pathophysiology. Despite the central role of adipose tissue in many physiologic/pathologic processes, recognition of the effects of greater AGEs formation in this tissue is quite recent within the obesity/diabetes context. This review provides a brief background of AGEs formation and adipose tissue biology and thereafter discusses the impact of AGEs-adipocyte interactions in pathology progression. Novel data are included showing how AGEs (especially glycated albumin) may be involved in hyperglycemia-induced oxidative damage in adipocytes and its potential links to diabetes progression.

Reproductive Benefit of Oxidative Damage: An Oxidative Stress “Malevolence”?

PubMed Central

Poljsak, B.; Milisav, I.; Lampe, T.; Ostan, I.

2011-01-01

High levels of reactive oxygen species (ROS) compared to antioxidant defenses are considered to play a major role in diverse chronic age-related diseases and aging. Here we present an attempt to synthesize information about proximate oxidative processes in aging (relevant to free radical or oxidative damage hypotheses of aging) with an evolutionary scenario (credited here to Dawkins hypotheses) involving tradeoffs between the costs and benefits of oxidative stress to reproducing organisms. Oxidative stress may be considered a biological imperfection; therefore, the Dawkins' theory of imperfect adaptation of beings to environment was applied to the role of oxidative stress in processes like famine and infectious diseases and their consequences at the molecular level such as mutations and cell signaling. Arguments are presented that oxidative damage is not necessarily an evolutionary mistake but may be beneficial for reproduction; this may prevail over its harmfulness to health and longevity in evolution. Thus, Dawkins' principle of biological “malevolence” may be an additional biological paradigm for explaining the consequences of oxidative stress. PMID:21969876

Biomarkers of Aging: From Function to Molecular Biology

PubMed Central

Wagner, Karl-Heinz; Cameron-Smith, David; Wessner, Barbara; Franzke, Bernhard

2016-01-01

Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products. PMID:27271660

The biological age linked to oxidative stress modifies breast cancer aggressiveness.

PubMed

Sáez-Freire, María Del Mar; Blanco-Gómez, Adrián; Castillo-Lluva, Sonia; Gómez-Vecino, Aurora; Galvis-Jiménez, Julie Milena; Martín-Seisdedos, Carmen; Isidoro-García, María; Hontecillas-Prieto, Lourdes; García-Cenador, María Begoña; García-Criado, Francisco Javier; Patino-Alonso, María Carmen; Galindo-Villardón, Purificación; Mao, Jian-Hua; Prieto, Carlos; Castellanos-Martín, Andrés; Kaderali, Lars; Pérez-Losada, Jesús

2018-05-20

The incidence of breast cancer increases with age until menopause, and breast cancer is more aggressive in younger women. The existence of epidemiological links between breast cancer and aging indicates that both processes share some common mechanisms of development. Oxidative stress is associated with both cancer susceptibility and aging. Here we observed that ERBB2-positive breast cancer, which developed in genetically heterogeneous ERBB2-positive transgenic mice generated by a backcross, is more aggressive in chronologically younger than in older mice (differentiated by the median survival of the cohort that was 79 weeks), similar to what occurs in humans. In this cohort, we estimated the oxidative biological age using a mathematical model that integrated several subphenotypes directly or indirectly related to oxidative stress. The model selected the serum levels of HDL-cholesterol and magnesium and total AKT1 and glutathione concentrations in the liver. The grade of aging was calculated as the difference between the predicted biological age and the chronological age. This comparison permitted the identification of biologically younger and older mice compared with their chronological age. Interestingly, biologically older mice developed more aggressive breast cancer than the biologically younger mice. Genomic regions on chromosomes 2 and 15 linked to the grade of oxidative aging were identified. The levels of expression of Zbp1 located on chromosome 2, a gene related to necroptosis and inflammation, positively correlated with the grade of aging and tumour aggressiveness. Moreover, the pattern of gene expression of genes linked to the inflammation and the response to infection pathways was enriched in the livers of biologically old mice. This study shows part of the complex interactions between breast cancer and aging. Copyright © 2018 Elsevier Inc. All rights reserved.

Anatomy of ageing face.

PubMed

Ilankovan, V

2014-03-01

Ageing is a biological process that results from changes at a cellular level, particularly modification of mRNA. The face is affected by the same physiological process and results in skeletal, muscular, and cutaneous ageing; ligamentous attenuation, descent of fat, and ageing of the appendages. I describe these changes on a structural and clinical basis and summarise possible solutions for a rejuvenation surgeon. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

A Twin Protection Effect? Explaining Twin Survival Advantages with a Two-Process Mortality Model

PubMed Central

2016-01-01

Twin studies that focus on the correlation in age-at-death between twin pairs have yielded important insights into the heritability and role of genetic factors in determining lifespan, but less attention is paid to the biological and social role of zygosity itself in determining survival across the entire life course. Using data from the Danish Twin Registry and the Human Mortality Database, we show that monozygotic twins have greater cumulative survival proportions at nearly every age compared to dizygotic twins and the Danish general population. We examine this survival advantage by fitting these data with a two-process mortality model that partitions survivorship patterns into extrinsic and intrinsic mortality processes roughly corresponding to acute, environmental and chronic, biological origins. We find intrinsic processes confer a survival advantage at older ages for males, while at younger ages, all monozygotic twins show a health protection effect against extrinsic death akin to a marriage protection effect. While existing research suggests an increasingly important role for genetic factors at very advanced ages, we conclude that the social closeness of monozygotic twins is a plausible driver of the survival advantage at ages <65. PMID:27192433

Driving records of persons 65 years of age and older : are insurance rate reductions warranted?.

DOT National Transportation Integrated Search

1971-01-01

There are many elements that constitute the makeup of the automobile insurance premium, the major ones being age, sex, marital, status, and the utilization of the automobile. While the biological aging process places health limitations on drivers age...

The effect of sanitary landfill leachate aging on the biological treatment and assessment of photoelectrooxidation as a pre-treatment process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Müller, Gabriel Timm; Giacobbo, Alexandre; Santos Chiaramonte, Edson Abel dos

Highlights: • Photoelectrooxidation (PEO) emerges as a new technology for leachate treatment. • Aging of sanitary landfills acts on leachate composition and biodegradability. • PEO is applied as leachate pretreatment before the biological processes. • PEO produced significant changes in the leachate matrix, easing biological process. - Abstract: The sanitary landfill leachate is a dark liquid, of highly variable composition, with recalcitrant features that hamper conventional biological treatment. The physical–chemical characteristics of the leachate along the landfill aging, as well as their effects on the efficiency of the conventional treatment, were evaluated at this paper. The feasibility of photoelectrooxidation processmore » as an alternative technique for treatment of landfill leachates was also determined. Photoelectrooxidation experiments were conducted in a bench-scale reactor. Analysis of the raw leachate revealed many critical parameters demonstrating that the recalcitrance of leachate tends to increase with time, directly influencing the decline in efficiency of the conventional treatment currently employed. The effects of current density and lamp power were investigated. Using a 400 W power lamp and a current density of 31.5 mA cm{sup −2}, 53% and 61% efficiency for the removal of ammoniacal nitrogen and chemical oxygen demand were respectively achieved by applying photoelectrooxidation process. With the removal of these pollutants, downstream biological treatment should be improved. These results demonstrate that photoelectrooxidation is a feasible technique for the treatment of sanitary landfill leachate, even considering this effluent’s high resistance to treatment.« less

BioAge: Toward A Multi-Determined, Mechanistic Account of Cognitive Aging

PubMed Central

DeCarlo, Correne A.; Tuokko, Holly A.; Williams, Dorothy; Dixon, Roger A.; MacDonald, Stuart W.S.

2014-01-01

The search for reliable early indicators of age-related cognitive decline represents a critical avenue for progress in aging research. Chronological age is a commonly used developmental index; however, it offers little insight into the mechanisms underlying cognitive decline. In contrast, biological age (BioAge), reflecting the vitality of essential biological systems, represents a promising operationalization of developmental time. Current BioAge models have successfully predicted age-related cognitive deficits. Research on aging-related cognitive function indicates that the interaction of multiple risk and protective factors across the human lifespan confers individual risk for late-life cognitive decline, implicating a multi-causal explanation. In this review, we explore current BioAge models, describe three broad yet pathologically relevant biological processes linked to cognitive decline, and propose a novel operationalization of BioAge accounting for both moderating and causal mechanisms of cognitive decline and dementia. We argue that a multivariate and mechanistic BioAge approach will lead to a greater understanding of disease pathology as well as more accurate prediction and early identification of late-life cognitive decline. PMID:25278166

BioAge: toward a multi-determined, mechanistic account of cognitive aging.

PubMed

DeCarlo, Correne A; Tuokko, Holly A; Williams, Dorothy; Dixon, Roger A; MacDonald, Stuart W S

2014-11-01

The search for reliable early indicators of age-related cognitive decline represents a critical avenue for progress in aging research. Chronological age is a commonly used developmental index; however, it offers little insight into the mechanisms underlying cognitive decline. In contrast, biological age (BioAge), reflecting the vitality of essential biological systems, represents a promising operationalization of developmental time. Current BioAge models have successfully predicted age-related cognitive deficits. Research on aging-related cognitive function indicates that the interaction of multiple risk and protective factors across the human lifespan confers individual risk for late-life cognitive decline, implicating a multi-causal explanation. In this review, we explore current BioAge models, describe three broad yet pathologically relevant biological processes linked to cognitive decline, and propose a novel operationalization of BioAge accounting for both moderating and causal mechanisms of cognitive decline and dementia. We argue that a multivariate and mechanistic BioAge approach will lead to a greater understanding of disease pathology as well as more accurate prediction and early identification of late-life cognitive decline. Copyright © 2014 Elsevier B.V. All rights reserved.

Diffusion Tensor Tractography Reveals Disrupted Structural Connectivity during Brain Aging

NASA Astrophysics Data System (ADS)

Lin, Lan; Tian, Miao; Wang, Qi; Wu, Shuicai

2017-10-01

Brain aging is one of the most crucial biological processes that entail many physical, biological, chemical, and psychological changes, and also a major risk factor for most common neurodegenerative diseases. To improve the quality of life for the elderly, it is important to understand how the brain is changed during the normal aging process. We compared diffusion tensor imaging (DTI)-based brain networks in a cohort of 75 healthy old subjects by using graph theory metrics to describe the anatomical networks and connectivity patterns, and network-based statistic (NBS) analysis was used to identify pairs of regions with altered structural connectivity. The NBS analysis revealed a significant network comprising nine distinct fiber bundles linking 10 different brain regions showed altered white matter structures in young-old group compare with middle-aged group (p < .05, family-wise error-corrected). Our results might guide future studies and help to gain a better understanding of brain aging.

Learning through the Ages: How We Grow Old.

ERIC Educational Resources Information Center

Blystone, Robert V.; And Others

1988-01-01

Provides suggestions for a unit on the biological process of aging. Includes three activity sheets on the comparison of jaws and dentition from differently aged people, a denture survey, and eating and living without teeth. Includes a framework for organizing a course on the physiology of aging. (RT)

Investigating cholesterol metabolism and ageing using a systems biology approach.

PubMed

Morgan, A E; Mooney, K M; Wilkinson, S J; Pickles, N A; Mc Auley, M T

2017-08-01

CVD accounted for 27 % of all deaths in the UK in 2014, and was responsible for 1·7 million hospital admissions in 2013/2014. This condition becomes increasingly prevalent with age, affecting 34·1 and 29·8 % of males and females over 75 years of age respectively in 2011. The dysregulation of cholesterol metabolism with age, often observed as a rise in LDL-cholesterol, has been associated with the pathogenesis of CVD. To compound this problem, it is estimated by 2050, 22 % of the world's population will be over 60 years of age, in culmination with a growing resistance and intolerance to pre-existing cholesterol regulating drugs such as statins. Therefore, it is apparent research into additional therapies for hypercholesterolaemia and CVD prevention is a growing necessity. However, it is also imperative to recognise this complex biological system cannot be studied using a reductionist approach; rather its biological uniqueness necessitates a more integrated methodology, such as that offered by systems biology. In this review, we firstly discuss cholesterol metabolism and how it is affected by diet and the ageing process. Next, we describe therapeutic strategies for hypercholesterolaemia, and finally how the systems biology paradigm can be utilised to investigate how ageing interacts with complex systems such as cholesterol metabolism. We conclude by emphasising the need for nutritionists to work in parallel with the systems biology community, to develop novel approaches to studying cholesterol metabolism and its interaction with ageing.

[Time and temporality in gerontology and the ontologic privation theory of biological aging].

PubMed

Kment, A

1989-01-01

We have seen how our conception of time has changed in the course of the years. Up to the beginning of this century people believed in absolute time. According to today's views, time and temporality do not consist of a continuous flow of time successions, as generally assumed, the essence lies in the inner character of events. Therefore, in order to comprehend the true nature of time and temporality in gerontology, we must pay particular attention to the constitutional structures of events or happenings. Here we must comprehend the implication of an ontological change and the constitutions of time as metaphysical structure. Time and temporality are measured in happenings and processes, and not vice versa. Whitehead, showed that we are concerned with an ontological interpretation of time and temporality. The biodynamics of an individual reveal the largely autonomous structure and bionomy of the processes of life, as well as the continuous interaction and shifts of the biological cycles of formation, change, and decline. The ontological privation of biological aging and death are just as much a part of life as conception and birth. Only what lives can mature, age, and die. The imminent "purpose" of the biological aging of the individual is dying and death, i.e., the return home into "absolute being".

Proteomics and metabolomics in ageing research: from biomarkers to systems biology.

PubMed

Hoffman, Jessica M; Lyu, Yang; Pletcher, Scott D; Promislow, Daniel E L

2017-07-15

Age is the single greatest risk factor for a wide range of diseases, and as the mean age of human populations grows steadily older, the impact of this risk factor grows as well. Laboratory studies on the basic biology of ageing have shed light on numerous genetic pathways that have strong effects on lifespan. However, we still do not know the degree to which the pathways that affect ageing in the lab also influence variation in rates of ageing and age-related disease in human populations. Similarly, despite considerable effort, we have yet to identify reliable and reproducible 'biomarkers', which are predictors of one's biological as opposed to chronological age. One challenge lies in the enormous mechanistic distance between genotype and downstream ageing phenotypes. Here, we consider the power of studying 'endophenotypes' in the context of ageing. Endophenotypes are the various molecular domains that exist at intermediate levels of organization between the genotype and phenotype. We focus our attention specifically on proteins and metabolites. Proteomic and metabolomic profiling has the potential to help identify the underlying causal mechanisms that link genotype to phenotype. We present a brief review of proteomics and metabolomics in ageing research with a focus on the potential of a systems biology and network-centric perspective in geroscience. While network analyses to study ageing utilizing proteomics and metabolomics are in their infancy, they may be the powerful model needed to discover underlying biological processes that influence natural variation in ageing, age-related disease, and longevity. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Proteomics and metabolomics in ageing research: from biomarkers to systems biology

PubMed Central

Hoffman, Jessica M.; Lyu, Yang; Pletcher, Scott D.; Promislow, Daniel E.L.

2017-01-01

Age is the single greatest risk factor for a wide range of diseases, and as the mean age of human populations grows steadily older, the impact of this risk factor grows as well. Laboratory studies on the basic biology of ageing have shed light on numerous genetic pathways that have strong effects on lifespan. However, we still do not know the degree to which the pathways that affect ageing in the lab also influence variation in rates of ageing and age-related disease in human populations. Similarly, despite considerable effort, we have yet to identify reliable and reproducible ‘biomarkers’, which are predictors of one’s biological as opposed to chronological age. One challenge lies in the enormous mechanistic distance between genotype and downstream ageing phenotypes. Here, we consider the power of studying ‘endophenotypes’ in the context of ageing. Endophenotypes are the various molecular domains that exist at intermediate levels of organization between the genotype and phenotype. We focus our attention specifically on proteins and metabolites. Proteomic and metabolomic profiling has the potential to help identify the underlying causal mechanisms that link genotype to phenotype. We present a brief review of proteomics and metabolomics in ageing research with a focus on the potential of a systems biology and network-centric perspective in geroscience. While network analyses to study ageing utilizing proteomics and metabolomics are in their infancy, they may be the powerful model needed to discover underlying biological processes that influence natural variation in ageing, age-related disease, and longevity. PMID:28698311

The aging-disease false dichotomy: understanding senescence as pathology

PubMed Central

Gems, David

2015-01-01

From a biological perspective aging (senescence) appears to be a form of complex disease syndrome, though this is not the traditional view. This essay aims to foster a realistic understanding of aging by scrutinizing ideas old and new. The conceptual division between aging-related diseases and an underlying, non-pathological aging process underpins various erroneous traditional ideas about aging. Among biogerontologists, another likely error involves the aspiration to treat the entire aging process, which recent advances suggest is somewhat utopian. It also risks neglecting a more modest but realizable goal: to develop preventative treatments that partially protect against aging. PMID:26136770

Musculoskeletal system in the old age and the demand for healthy ageing biomarkers.

PubMed

Collino, Sebastiano; Martin, François-Pierre; Karagounis, Leonidas G; Horcajada, Marie Noelle; Moco, Sofia; Franceschi, Claudio; Kussmann, Martin; Offord, Elizabeth

2013-01-01

Population ageing has emerged as a major demographic trend worldwide due to improved health and longevity. This global ageing phenomenon will have a major impact on health-care systems worldwide due to increased morbidity and greater needs for hospitalization/institutionalization. As the ageing population increases worldwide, there is an increasing awareness not only of increased longevity but also of the importance of "healthy ageing" and "quality of life". Yet, the age related chronic inflammation is believed to be pathogenic with regards to its contribution to frailty and degenerative disorders. In particular, the frailty syndrome is increasingly being considered as a key risk indicator of adverse health outcomes. In addition, elderly may be also prone to be resistant to anabolic stimuli which is likely a key factor in the loss of skeletal muscle mass with ageing. Vital to understand these key biological processes is the development of biological markers, through system biology approaches, aiding at strategies for tailored therapeutic and personalized nutritional program. Overall aim is to prevent or attenuate decline of key physiological functions required to live an active, independent life. This review focus on core indicators of health and functions in older adults, where nutrition and tailored personalized programs could exhibit preventive roles, and where the aid of metabolomics technologies are increasingly displaying potential in revealing key molecular mechanisms/targets linked to specific ageing and/or healthy ageing processes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Reprint of: Musculoskeletal system in the old age and the demand for healthy ageing biomarkers.

PubMed

Collino, Sebastiano; Martin, François-Pierre; Karagounis, Leonidas G; Horcajada, Marie Noelle; Moco, Sofia; Franceschi, Claudio; Kussmann, Martin; Offord, Elizabeth

2014-01-01

Population ageing has emerged as a major demographic trend worldwide due to improved health and longevity. This global ageing phenomenon will have a major impact on health-care systems worldwide due to increased morbidity and greater needs for hospitalization/institutionalization. As the ageing population increases worldwide, there is an increasing awareness not only of increased longevity but also of the importance of "healthy ageing" and "quality of life". Yet, the age related chronic inflammation is believed to be pathogenic with regards to its contribution to frailty and degenerative disorders. In particular, the frailty syndrome is increasingly being considered as a key risk indicator of adverse health outcomes. In addition, elderly may be also prone to be resistant to anabolic stimuli which is likely a key factor in the loss of skeletal muscle mass with ageing. Vital to understand these key biological processes is the development of biological markers, through system biology approaches, aiding at strategies for tailored therapeutic and personalized nutritional program. Overall aim is to prevent or attenuate decline of key physiological functions required to live an active, independent life. This review focus on core indicators of health and functions in older adults, where nutrition and tailored personalized programs could exhibit preventive roles, and where the aid of metabolomics technologies are increasingly displaying potential in revealing key molecular mechanisms/targets linked to specific ageing and/or healthy ageing processes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Understanding the immune response to seasonal influenza vaccination in older adults: a systems biology approach.

PubMed

Lambert, Nathaniel D; Ovsyannikova, Inna G; Pankratz, V Shane; Jacobson, Robert M; Poland, Gregory A

2012-08-01

Annual vaccination against seasonal influenza is recommended to decrease disease-related mortality and morbidity. However, one population that responds suboptimally to influenza vaccine is adults over the age of 65 years. The natural aging process is associated with a complex deterioration of multiple components of the host immune system. Research into this phenomenon, known as immunosenescence, has shown that aging alters both the innate and adaptive branches of the immune system. The intricate mechanisms involved in immune response to influenza vaccine, and how these responses are altered with age, have led us to adopt a more encompassing systems biology approach to understand exactly why the response to vaccination diminishes with age. Here, the authors review what changes occur with immunosenescence, and some immunogenetic factors that influence response, and outline the systems biology approach to understand the immune response to seasonal influenza vaccination in older adults.

Evaluating the physiological reserves of older patients with cancer: the value of potential biomarkers of aging?

PubMed

Pallis, Athanasios G; Hatse, Sigrid; Brouwers, Barbara; Pawelec, Graham; Falandry, Claire; Wedding, Ulrich; Lago, Lissandra Dal; Repetto, Lazzaro; Ring, Alistair; Wildiers, Hans

2014-04-01

Aging of an individual entails a progressive decline of functional reserves and loss of homeostasis that eventually lead to mortality. This process is highly individualized and is influenced by multiple genetic, epigenetic and environmental factors. This individualization and the diversity of factors influencing aging result in a significant heterogeneity among people with the same chronological age, representing a major challenge in daily oncology practice. Thus, many factors other than mere chronological age will contribute to treatment tolerance and outcome in the older patients with cancer. Clinical/comprehensive geriatric assessment can provide information on the general health status of individuals, but is far from perfect as a prognostic/predictive tool for individual patients. On the other hand, aging can also be assessed in terms of biological changes in certain tissues like the blood compartment which result from adaptive alterations due to past history of exposures, as well as intrinsic aging processes. There are major signs of 'aging' in lymphocytes (e.g. lymphocyte subset distribution, telomere length, p16INK4A expression), and also in (inflammatory) cytokine expression and gene expression patterns. These result from a combination of the above two processes, overlaying genetic predispositions which contribute significantly to the aging phenotype. These potential "aging biomarkers" might provide additional prognostic/predictive information supplementing clinical evaluation. The purpose of the current paper is to describe the most relevant potential "aging biomarkers" (markers that indicate the biological functional age of patients) which focus on the biological background, the (limited) available clinical data, and technical challenges. Despite their great potential interest, there is a need for much more (validated) clinical data before these biomarkers could be used in a routine clinical setting. This manuscript tries to provide a guideline on how these markers can be integrated in future research aimed at providing such data. © 2013.

Optical Sensing of Polarization States Changes in Meat due to the Ageing

NASA Astrophysics Data System (ADS)

Tománek, Pavel; Mikláš, Jan; Abubaker, Hamed Mohamed; Grmela, Lubomír

2010-11-01

Food materials or biological materials display large compositional variations, inhomogeneities, and anisotropic structures. The biological tissues consist of cells which dimensions are bigger than a wavelength of visible light, therefore Mie scattering of transmitted and reflected light occurs and different polarization states arise. The meat industry needs reliable meat quality information throughout the production process in order to guarantee high-quality meat products for consumers. The minor importance is still given to the food quality control and inspection during processing operations or storing conditions. The paper presents a quite simple optical method allowing measure the freshness or ageing of products. The principle is to study temporal characteristics of polarization states of forward or backward scattered laser light in the samples in function of meat ageing.

Cultural and biological factors modulate spatial biases over development.

PubMed

Girelli, Luisa; Marinelli, Chiara Valeria; Grossi, Giuseppe; Arduino, Lisa S

2017-11-01

Increasing evidence supports the contribution of both biological and cultural factors to visuospatial processing. The present study adds to the literature by exploring the interplay of perceptual and linguistic mechanisms in determining visuospatial asymmetries in adults (Experiment 1) and children (Experiment 2). In particular, pre-schoolers (3 and 5 year-olds), school-aged children (8 year-old), and adult participants were required to bisect different types of stimuli, that is, lines, words, and figure strings. In accordance with the literature, results yielded a leftward bias for lines and words and a rightward bias for figure strings, in adult participants. More critically, different biases were found for lines, words, and figure strings in children as a function of age, reflecting the impact of both cultural and biological factors on the processing of different visuospatial materials. Specifically, an adult-like pattern of results emerged only in the older group of children (8 year-old), but not in pre-schoolers. Results are discussed in terms of literacy, reading habits exposure, and biological maturation.

Age gene expression and coexpression progressive signatures in peripheral blood leukocytes.

PubMed

Irizar, Haritz; Goñi, Joaquín; Alzualde, Ainhoa; Castillo-Triviño, Tamara; Olascoaga, Javier; Lopez de Munain, Adolfo; Otaegui, David

2015-12-01

Both cellular senescence and organismic aging are known to be dynamic processes that start early in life and progress constantly during the whole life of the individual. In this work, with the objective of identifying signatures of age-related progressive change at the transcriptomic level, we have performed a whole-genome gene expression analysis of peripheral blood leukocytes in a group of healthy individuals with ages ranging from 14 to 93 years. A set of genes with progressively changing gene expression (either increase or decrease with age) has been identified and contextualized in a coexpression network. A modularity analysis has been performed on this network and biological-term and pathway enrichment analyses have been used for biological interpretation of each module. In summary, the results of the present work reveal the existence of a transcriptomic component that shows progressive expression changes associated to age in peripheral blood leukocytes, highlighting both the dynamic nature of the process and the need to complement young vs. elder studies with longitudinal studies that include middle aged individuals. From the transcriptional point of view, immunosenescence seems to be occurring from a relatively early age, at least from the late 20s/early 30s, and the 49-56 year old age-range appears to be critical. In general, the genes that, according to our results, show progressive expression changes with aging are involved in pathogenic/cellular processes that have classically been linked to aging in humans: cancer, immune processes and cellular growth vs. maintenance. Copyright © 2015 Elsevier Inc. All rights reserved.

Multi-tissue DNA methylation age predictor in mouse.

PubMed

Stubbs, Thomas M; Bonder, Marc Jan; Stark, Anne-Katrien; Krueger, Felix; von Meyenn, Ferdinand; Stegle, Oliver; Reik, Wolf

2017-04-11

DNA methylation changes at a discrete set of sites in the human genome are predictive of chronological and biological age. However, it is not known whether these changes are causative or a consequence of an underlying ageing process. It has also not been shown whether this epigenetic clock is unique to humans or conserved in the more experimentally tractable mouse. We have generated a comprehensive set of genome-scale base-resolution methylation maps from multiple mouse tissues spanning a wide range of ages. Many CpG sites show significant tissue-independent correlations with age which allowed us to develop a multi-tissue predictor of age in the mouse. Our model, which estimates age based on DNA methylation at 329 unique CpG sites, has a median absolute error of 3.33 weeks and has similar properties to the recently described human epigenetic clock. Using publicly available datasets, we find that the mouse clock is accurate enough to measure effects on biological age, including in the context of interventions. While females and males show no significant differences in predicted DNA methylation age, ovariectomy results in significant age acceleration in females. Furthermore, we identify significant differences in age-acceleration dependent on the lipid content of the diet. Here we identify and characterise an epigenetic predictor of age in mice, the mouse epigenetic clock. This clock will be instrumental for understanding the biology of ageing and will allow modulation of its ticking rate and resetting the clock in vivo to study the impact on biological age.

Long noncoding RNAs(lncRNAs) and the molecular hallmarks of aging.

PubMed

Grammatikakis, Ioannis; Panda, Amaresh C; Abdelmohsen, Kotb; Gorospe, Myriam

2014-12-01

During aging, progressive deleterious changes increase the risk of disease and death. Prominent molecular hallmarks of aging are genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, cellular senescence, stem cell exhaustion, and altered intercellular communication. Long noncoding RNAs (lncRNAs) play important roles in a wide range of biological processes, including age-related diseases like cancer, cardiovascular pathologies, and neurodegenerative disorders. Evidence is emerging that lncRNAs influence the molecular processes that underlie age-associated phenotypes. Here, we review our current understanding of lncRNAs that control the development of aging traits.

Long noncoding RNAs (lncRNAs) and the molecular hallmarks of aging

PubMed Central

Abdelmohsen, Kotb; Gorospe, Myriam

2014-01-01

During aging, progressive deleterious changes increase the risk of disease and death. Prominent molecular hallmarks of aging are genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, cellular senescence, stem cell exhaustion, and altered intercellular communication. Long noncoding RNAs (lncRNAs) play important roles in a wide range of biological processes, including age-related diseases like cancer, cardiovascular pathologies, and neurodegenerative disorders. Evidence is emerging that lncRNAs influence the molecular processes that underlie age-associated phenotypes. Here, we review our current understanding of lncRNAs that control the development of aging traits. PMID:25543668

Age-related DNA methylation changes for forensic age-prediction.

PubMed

Yi, Shao Hua; Jia, Yun Shu; Mei, Kun; Yang, Rong Zhi; Huang, Dai Xin

2015-03-01

There is no available method of age-prediction for biological samples. The accumulating evidences indicate that DNA methylation patterns change with age. Aging resembles a developmentally regulated process that is tightly controlled by specific epigenetic modifications and age-associated methylation changes exist in human genome. In this study, three age-related methylation fragments were isolated and identified in blood of 40 donors. Age-related methylation changes with each fragment was validated and replicated in a general population sample of 65 donors over a wide age range (11-72 years). Methylation of these fragments is linearly correlated with age over a range of six decades (r = 0.80-0.88). Using average methylation of CpG sites of three fragments, a regression model that explained 95 % of the variance in age was built and is able to predict an individual's age with great accuracy (R (2 )= 0.93). The predicted value is highly correlated with the observed age in the sample (r = 0.96) and has great accuracy of average 4 years difference between predicted age and true age. This study implicates that DNA methylation can be an available biological marker of age-prediction. Further measurement of relevant markers in the genome could be a tool in routine screening to predict age of forensic biological samples.

Molecular insights into the pathogenesis of Alzheimer's disease and its relationship to normal aging.

PubMed

Podtelezhnikov, Alexei A; Tanis, Keith Q; Nebozhyn, Michael; Ray, William J; Stone, David J; Loboda, Andrey P

2011-01-01

Alzheimer's disease (AD) is a complex neurodegenerative disorder that diverges from the process of normal brain aging by unknown mechanisms. We analyzed the global structure of age- and disease-dependent gene expression patterns in three regions from more than 600 brains. Gene expression variation could be almost completely explained by four transcriptional biomarkers that we named BioAge (biological age), Alz (Alzheimer), Inflame (inflammation), and NdStress (neurodegenerative stress). BioAge captures the first principal component of variation and includes genes statistically associated with neuronal loss, glial activation, and lipid metabolism. Normally BioAge increases with chronological age, but in AD it is prematurely expressed as if some of the subjects were 140 years old. A component of BioAge, Lipa, contains the AD risk factor APOE and reflects an apparent early disturbance in lipid metabolism. The rate of biological aging in AD patients, which cannot be explained by BioAge, is associated instead with NdStress, which includes genes related to protein folding and metabolism. Inflame, comprised of inflammatory cytokines and microglial genes, is broadly activated and appears early in the disease process. In contrast, the disease-specific biomarker Alz was selectively present only in the affected areas of the AD brain, appears later in pathogenesis, and is enriched in genes associated with the signaling and cell adhesion changes during the epithelial to mesenchymal (EMT) transition. Together these biomarkers provide detailed description of the aging process and its contribution to Alzheimer's disease progression. © 2011 Podtelezhnikov et al.

Molecular Insights into the Pathogenesis of Alzheimer's Disease and Its Relationship to Normal Aging

PubMed Central

Podtelezhnikov, Alexei A.; Tanis, Keith Q.; Nebozhyn, Michael; Ray, William J.

2011-01-01

Alzheimer's disease (AD) is a complex neurodegenerative disorder that diverges from the process of normal brain aging by unknown mechanisms. We analyzed the global structure of age- and disease-dependent gene expression patterns in three regions from more than 600 brains. Gene expression variation could be almost completely explained by four transcriptional biomarkers that we named BioAge (biological age), Alz (Alzheimer), Inflame (inflammation), and NdStress (neurodegenerative stress). BioAge captures the first principal component of variation and includes genes statistically associated with neuronal loss, glial activation, and lipid metabolism. Normally BioAge increases with chronological age, but in AD it is prematurely expressed as if some of the subjects were 140 years old. A component of BioAge, Lipa, contains the AD risk factor APOE and reflects an apparent early disturbance in lipid metabolism. The rate of biological aging in AD patients, which cannot be explained by BioAge, is associated instead with NdStress, which includes genes related to protein folding and metabolism. Inflame, comprised of inflammatory cytokines and microglial genes, is broadly activated and appears early in the disease process. In contrast, the disease-specific biomarker Alz was selectively present only in the affected areas of the AD brain, appears later in pathogenesis, and is enriched in genes associated with the signaling and cell adhesion changes during the epithelial to mesenchymal (EMT) transition. Together these biomarkers provide detailed description of the aging process and its contribution to Alzheimer's disease progression. PMID:22216330

An observational assessment method for aging laboratory rats

EPA Science Inventory

The growth of the aging population highlights the need for laboratory animal models to study the basic biological processes ofaging and susceptibility to toxic chemicals and disease. Methods to evaluate health ofaging animals over time are needed, especially efficient methods for...

In Silico Approaches and the Role of Ontologies in Aging Research

PubMed Central

Boerries, Melanie; Busch, Hauke; de Grey, Aubrey; Hahn, Udo; Hiller, Thomas; Hoeflich, Andreas; Jansen, Ludger; Janssens, Georges E.; Kaleta, Christoph; Meinema, Anne C.; Schäuble, Sascha; Simm, Andreas; Schofield, Paul N.; Smith, Barry; Sühnel, Juergen; Vera, Julio; Wagner, Wolfgang; Wönne, Eva C.; Wuttke, Daniel

2013-01-01

Abstract The 2013 Rostock Symposium on Systems Biology and Bioinformatics in Aging Research was again dedicated to dissecting the aging process using in silico means. A particular focus was on ontologies, because these are a key technology to systematically integrate heterogeneous information about the aging process. Related topics were databases and data integration. Other talks tackled modeling issues and applications, the latter including talks focused on marker development and cellular stress as well as on diseases, in particular on diseases of kidney and skin. PMID:24188080

A synopsis on aging—Theories, mechanisms and future prospects

PubMed Central

da Costa, João Pinto; Vitorino, Rui; Silva, Gustavo M.; Vogel, Christine; Duarte, Armando C.; Rocha-Santos, Teresa

2018-01-01

Answering the question as to why we age is tantamount to answering the question of what is life itself. There are countless theories as to why and how we age, but, until recently, the very definition of aging – senescence – was still uncertain. Here, we summarize the main views of the different models of senescence, with a special emphasis on the biochemical processes that accompany aging. Though inherently complex, aging is characterized by numerous changes that take place at different levels of the biological hierarchy. We therefore explore some of the most relevant changes that take place during aging and, finally, we overview the current status of emergent aging therapies and what the future holds for this field of research. From this multi-dimensional approach, it becomes clear that an integrative approach that couples aging research with systems biology, capable of providing novel insights into how and why we age, is necessary. PMID:27353257

Investigation of temperature dependence of development and aging

NASA Technical Reports Server (NTRS)

Sacher, G. A.

1969-01-01

Temperature dependence of maturation and metabolic rates in insects, and the failure of vital processes during development were investigated. The paper presented advances the general hypothesis that aging in biological systems is a consequence of the production of entropy concomitant with metabolic activity.

Effect of sex, age, and breed on genetic recombination features in cattle

USDA-ARS?s Scientific Manuscript database

Meiotic recombination is a fundamental biological process which generates genetic diversity, affects fertility, and influences evolvability. Here we investigate the roles of sex, age, and breed in cattle recombination features, including recombination rate, location and crossover interference. Usin...

The first Seriatum study of growth by R. E. Scammon.

PubMed

Miller, Elizabeth M

2018-03-01

Richard E. Scammon's article, "The First Seriatim Study of Human Growth," provided one of the best-known visuals in the field of human biology. Scammon resurrected longitudinal height data of one child from Buffon's Histoire Naturelle, converted them to metric, and plotted these measurements as a function of age. The result was the first graph of one individual's growth curve from birth to 18 years of age. This image was subsequently reproduced in numerous texts on human growth and biology. Published in 1927, Scammon's article provides a snapshot of the state of growth research at the time and gives a (literal) picture of the future of human biology. The graph of the growth of one child symbolizes the importance of process and variation in biological anthropology. © 2018 Wiley Periodicals, Inc.

Rationale and methods of discovering hormetins as drugs for healthy ageing.

PubMed

Rattan, Suresh I S

2012-05-01

Mild stress-induced hormesis is becoming increasingly attractive as an ageing interventional strategy and is leading to the discovery of hormesis-inducing compounds called hormetins. Almost 50 years of modern biogerontolgical research has established a clear framework regarding the biological basis of ageing and longevity, and it is now generally accepted that ageing occurs in spite of the presence of complex pathways of maintenance, repair and defense, and there is no 'enemy within.' This viewpoint makes modulation of ageing different from the treatment of one or more age-related diseases. A promising strategy to slow down ageing and prevent or delay the onset of age-related diseases is that of mild stress-induced hormesis by using hormetins. The article presents the rationale and a strategy for discovering novel hormetins as potential drugs for ageing intervention by elucidating multiple stress responses of normal human cells. Furthermore, it discusses the first steps in identifying prospective hormetin drugs and provides a recent example of successful product development, based on the ideas of hormesis and by following the strategy described here. As a biomedical issue, the biological process of ageing underlies several major diseases, and although the optimal treatment of every disease, irrespective of age, is a social and moral necessity, preventing the onset of age-related diseases by intervening in the basic process of ageing is the best approach for achieving healthy ageing and for extending the healthspan.

Molecular genetics of aging in the fly: is this the end of the beginning?

PubMed

Helfand, Stephen L; Rogina, Blanka

2003-02-01

How we age and what we can do about it have been uppermost in human thought since antiquity. The many false starts have frustrated experimentalists and theoretical arguments pronouncing the inevitability of the process have created a nihilistic climate among scientists and the public. The identification of single gene alterations that substantially extend life span in nematodes and flies however, have begun to reinvigorate the field. Drosophila's long history of contributions to aging research, rich storehouse of genetic information, and powerful molecular techniques make it an excellent system for studying the molecular mechanisms underlying the process of aging. In recent years, Drosophila has been used to test current theories on aging and explore new directions of potential importance to the biology of aging. One such example is the surprising finding that, as opposed to the commonly held assumption that adult life is a period of random passive decline in which all things are thought to fall apart, the molecular life of the adult fly appears to be a state of dynamic well-regulated change. In the fly, the level of expression of many different genes changes in an invariant, often age-dependent, manner. These as well as other molecular genetic studies and demographic analyses using the fly have begun to challenge widely held ideas about aging providing evidence that aging may be a much more dynamic and malleable process than anticipated. With the enormous success that Drosophila molecular genetics has demonstrated in helping understand complex biological phenomena such as development there is much optimism that similar approaches can be adapted to assist in understanding the process of aging. Copyright 2003 Wiley Periodicals, Inc.

Increases in Cognitive and Linguistic Processing Primarily Account for Increases in Speaking Rate with Age

ERIC Educational Resources Information Center

Nip, Ignatius S. B.; Green, Jordan R.

2013-01-01

Age-related increases of speaking rate are not fully understood, but have been attributed to gains in biologic factors and learned skills that support speech production. This study investigated developmental changes in speaking rate and articulatory kinematics of participants aged 4 ("N" = 7), 7 ("N" = 10), 10…

Identification of common coexpression modules based on quantitative network comparison.

PubMed

Jo, Yousang; Kim, Sanghyeon; Lee, Doheon

2018-06-13

Finding common molecular interactions from different samples is essential work to understanding diseases and other biological processes. Coexpression networks and their modules directly reflect sample-specific interactions among genes. Therefore, identification of common coexpression network or modules may reveal the molecular mechanism of complex disease or the relationship between biological processes. However, there has been no quantitative network comparison method for coexpression networks and we examined previous methods for other networks that cannot be applied to coexpression network. Therefore, we aimed to propose quantitative comparison methods for coexpression networks and to find common biological mechanisms between Huntington's disease and brain aging by the new method. We proposed two similarity measures for quantitative comparison of coexpression networks. Then, we performed experiments using known coexpression networks. We showed the validity of two measures and evaluated threshold values for similar coexpression network pairs from experiments. Using these similarity measures and thresholds, we quantitatively measured the similarity between disease-specific and aging-related coexpression modules and found similar Huntington's disease-aging coexpression module pairs. We identified similar Huntington's disease-aging coexpression module pairs and found that these modules are related to brain development, cell death, and immune response. It suggests that up-regulated cell signalling related cell death and immune/ inflammation response may be the common molecular mechanisms in the pathophysiology of HD and normal brain aging in the frontal cortex.

Risk factors for wasting and stunting among children in Metro Cebu, Philippines.

PubMed

Ricci, J A; Becker, S

1996-06-01

Risk factors for wasting and stunting were examined in a longitudinal study of 18 544 children younger than 30 mo in Metro Cebu, Philippines. Measures of household demographic and socioeconomic characteristics, maternal characteristics and behavior, and child biological variables were analyzed cross-sectionally in six child age-residence strata by using logistic regression. Our results support biological and epidemiologic evidence that wasting and stunting represent different processes of malnutrition. They also indicate that the principal risk factors for stunting and wasting in infants < 6 mo of age were either maternal behaviors or child biological characteristics under maternal control, eg, breast-feeding status and birth weight. After 6 mo of age, household socioeconomic characteristics emerged with behavioral and biological variables as important determinants of malnutrition, eg, father's education and presence of a television and/or radio. Household socioeconomic status influenced the risk of stunting earlier in rural than in urban barangays. Implications of the results for interventions are discussed.

From Hayflick to Walford: the role of T cell replicative senescence in human aging.

PubMed

Effros, Rita B

2004-06-01

The immunologic theory of aging, proposed more than 40 years ago by Roy Walford, suggests that the normal process of aging in man and in animals is pathogenetically related to faulty immunological processes. Since that time, research on immunological aging has undergone extraordinary expansion, leading to new information in areas spanning from molecular biology and cell signaling to large-scale clinical studies. Investigation in this area has also provided unexpected insights into HIV disease, many aspects of which represent accelerated immunological aging. This article describes the initial insights and vision of Roy Walford into one particular facet of human immunological aging, namely, the potential relevance of the well-studied human fibroblast replicative senescence model, initially developed by Leonard Hayflick, to cells of the immune system. Extensive research on T cell senescence in cell culture has now documented changes in vitro that closely mirror alterations occurring during in vivo aging in humans, underscoring the biological significance of T cell replicative senescence. Moreover, the inclusion of high proportions of putatively senescent T cells in the 'immune risk phenotype' that is associated with early mortality in octogenarians provides initial clinical confirmation of both the immunologic theory of aging and the role of the T cell Hayflick Limit in human aging, two areas of gerontological research pioneered by Roy Walford.

Associations of genetic risk scores based on adult adiposity pathways with childhood growth and adiposity measures.

PubMed

Monnereau, Claire; Vogelezang, Suzanne; Kruithof, Claudia J; Jaddoe, Vincent W V; Felix, Janine F

2016-08-18

Results from genome-wide association studies (GWAS) identified many loci and biological pathways that influence adult body mass index (BMI). We aimed to identify if biological pathways related to adult BMI also affect infant growth and childhood adiposity measures. We used data from a population-based prospective cohort study among 3,975 children with a mean age of 6 years. Genetic risk scores were constructed based on the 97 SNPs associated with adult BMI previously identified with GWAS and on 28 BMI related biological pathways based on subsets of these 97 SNPs. Outcomes were infant peak weight velocity, BMI at adiposity peak and age at adiposity peak, and childhood BMI, total fat mass percentage, android/gynoid fat ratio, and preperitoneal fat area. Analyses were performed using linear regression models. A higher overall adult BMI risk score was associated with infant BMI at adiposity peak and childhood BMI, total fat mass, android/gynoid fat ratio, and preperitoneal fat area (all p-values < 0.05). Analyses focused on specific biological pathways showed that the membrane proteins genetic risk score was associated with infant peak weight velocity, and the genetic risk scores related to neuronal developmental processes, hypothalamic processes, cyclicAMP, WNT-signaling, membrane proteins, monogenic obesity and/or energy homeostasis, glucose homeostasis, cell cycle, and muscle biology pathways were associated with childhood adiposity measures (all p-values <0.05). None of the pathways were associated with childhood preperitoneal fat area. A genetic risk score based on 97 SNPs related to adult BMI was associated with peak weight velocity during infancy and general and abdominal fat measurements at the age of 6 years. Risk scores based on genetic variants linked to specific biological pathways, including central nervous system and hypothalamic processes, influence body fat development from early life onwards.

Impact of biology knowledge on the conservation and management of large pelagic sharks.

PubMed

Yokoi, Hiroki; Ijima, Hirotaka; Ohshimo, Seiji; Yokawa, Kotaro

2017-09-06

Population growth rate, which depends on several biological parameters, is valuable information for the conservation and management of pelagic sharks, such as blue and shortfin mako sharks. However, reported biological parameters for estimating the population growth rates of these sharks differ by sex and display large variability. To estimate the appropriate population growth rate and clarify relationships between growth rate and relevant biological parameters, we developed a two-sex age-structured matrix population model and estimated the population growth rate using combinations of biological parameters. We addressed elasticity analysis and clarified the population growth rate sensitivity. For the blue shark, the estimated median population growth rate was 0.384 with a range of minimum and maximum values of 0.195-0.533, whereas those values of the shortfin mako shark were 0.102 and 0.007-0.318, respectively. The maturity age of male sharks had the largest impact for blue sharks, whereas that of female sharks had the largest impact for shortfin mako sharks. Hypotheses for the survival process of sharks also had a large impact on the population growth rate estimation. Both shark maturity age and survival rate were based on ageing validation data, indicating the importance of validating the quality of these data for the conservation and management of large pelagic sharks.

Landauer in the Age of Synthetic Biology: Energy Consumption and Information Processing in Biochemical Networks

NASA Astrophysics Data System (ADS)

Mehta, Pankaj; Lang, Alex H.; Schwab, David J.

2016-03-01

A central goal of synthetic biology is to design sophisticated synthetic cellular circuits that can perform complex computations and information processing tasks in response to specific inputs. The tremendous advances in our ability to understand and manipulate cellular information processing networks raises several fundamental physics questions: How do the molecular components of cellular circuits exploit energy consumption to improve information processing? Can one utilize ideas from thermodynamics to improve the design of synthetic cellular circuits and modules? Here, we summarize recent theoretical work addressing these questions. Energy consumption in cellular circuits serves five basic purposes: (1) increasing specificity, (2) manipulating dynamics, (3) reducing variability, (4) amplifying signal, and (5) erasing memory. We demonstrate these ideas using several simple examples and discuss the implications of these theoretical ideas for the emerging field of synthetic biology. We conclude by discussing how it may be possible to overcome these limitations using "post-translational" synthetic biology that exploits reversible protein modification.

Epigenetic Mechanisms Impacting Aging: A Focus on Histone Levels and Telomeres

PubMed Central

Song, Shufei

2018-01-01

Aging and age-related diseases pose some of the most significant and difficult challenges to modern society as well as to the scientific and medical communities. Biological aging is a complex, and, under normal circumstances, seemingly irreversible collection of processes that involves numerous underlying mechanisms. Among these, chromatin-based processes have emerged as major regulators of cellular and organismal aging. These include DNA methylation, histone modifications, nucleosome positioning, and telomere regulation, including how these are influenced by environmental factors such as diet. Here we focus on two interconnected categories of chromatin-based mechanisms impacting aging: those involving changes in the levels of histones or in the functions of telomeres. PMID:29642537

Reciprocal interactions between circadian clocks and aging.

PubMed

Banks, Gareth; Nolan, Patrick M; Peirson, Stuart N

2016-08-01

Virtually, all biological processes in the body are modulated by an internal circadian clock which optimizes physiological and behavioral performance according to the changing demands of the external 24-h world. This circadian clock undergoes a number of age-related changes, at both the physiological and molecular levels. While these changes have been considered to be part of the normal aging process, there is increasing evidence that disruptions to the circadian system can substantially impact upon aging and these impacts will have clear health implications. Here we review the current data of how both the physiological and core molecular clocks change with age and how feedback from external cues may modulate the aging of the circadian system.

Protein Tyrosine Nitration: Role in Aging.

PubMed

Chakravarti, Bulbul; Chakravarti, Deb N

2017-01-01

Aging is the inevitable fate of all living organisms, but the molecular basis of physiological aging is poorly understood. Oxidative stress is believed to play a key role in the aging process. In addition to Reactive Oxygen Species (ROS), Reactive Nitrogen Species (RNS) are generated during aerobic metabolism in living organisms. Although protein damage and functional modification by ROS have been demonstrated in details, fewer studies have been reported on protein damage by RNS and its implication in the aging process. Proteins undergoing tyrosine nitration are associated with pathophysiology of several diseases, as well as physiological aging. The purpose of the current review article is to provide a brief summary of the biochemical mechanisms of tyrosine nitration, methodologies used for the detection of these modified proteins, effect of RNS induced post translational modification on biological functions and the putative role of tyrosine nitrated proteins in the aging process. Published studies on the role of RNS in age related functional alteration of various organs/ tissues were critically reviewed and evaluated. Covalent modification of various proteins by tyrosine nitration is associated with modification of biological functions of various organs/tissues such as skeletal muscle, heart, brain and liver due to aging. This information will be helpful to further investigate the interplay of different biochemical pathways and networks involved in the tyrosine nitration of various proteins due to aging with the ultimate goal to prevent the detrimental effects of RNS on the functional activities of these proteins. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A synopsis on aging-Theories, mechanisms and future prospects.

PubMed

da Costa, João Pinto; Vitorino, Rui; Silva, Gustavo M; Vogel, Christine; Duarte, Armando C; Rocha-Santos, Teresa

2016-08-01

Answering the question as to why we age is tantamount to answering the question of what is life itself. There are countless theories as to why and how we age, but, until recently, the very definition of aging - senescence - was still uncertain. Here, we summarize the main views of the different models of senescence, with a special emphasis on the biochemical processes that accompany aging. Though inherently complex, aging is characterized by numerous changes that take place at different levels of the biological hierarchy. We therefore explore some of the most relevant changes that take place during aging and, finally, we overview the current status of emergent aging therapies and what the future holds for this field of research. From this multi-dimensional approach, it becomes clear that an integrative approach that couples aging research with systems biology, capable of providing novel insights into how and why we age, is necessary. Copyright © 2016 Elsevier B.V. All rights reserved.

Injuries and illnesses in a cohort of elite youth alpine ski racers and the influence of biological maturity and relative age: a two-season prospective study

PubMed Central

Müller, Lisa; Hildebrandt, Carolin; Müller, Erich; Oberhoffer, Renate; Raschner, Christian

2017-01-01

Background Studies on injuries and illnesses involving youth ski racers younger than 15 years are lacking in the literature. The aim of this study was prospectively to assess the incidence, prevalence, and severity of traumatic and overuse injuries, as well as illnesses of elite youth ski racers with regard to sex, biological maturity status, and relative age. Subjects and methods A prospective, longitudinal cohort design was used to monitor the anthropometrics, training characteristics, traumatic and overuse injuries, and illnesses of 82 elite youth ski racers (51 males, 31 females, age 9–14 years) over 2 consecutive years. The exact training exposure (skiing and athletic) was recorded. Relative age and estimated biological maturity status were assessed. Results Relatively low injury incidence or prevalence (traumatic, 0.86/1,000 hours of training; overuse, 0.28/1,000 hours) and comparably high illness prevalence (2.4/athlete) were reported. The knee was the most commonly affected body part (traumatic injuries 36.5%, overuse injuries 82%). A high number of bone fractures were revealed (46%), while no stress fractures occurred; 66% of the illnesses were respiratory tract infections. No differences were found between males and females, the differing maturity groups, or relative age quartiles. Early-maturing athletes had comparably low traumatic and overuse-injury rates. Relatively younger athletes had low traumatic injury rates. Conclusion The injury-prevention measures implemented in the training process of youth ski racers seem to contribute to a low incidence of injury. Biological maturity status should be considered in the training process to prevent injuries in late-maturing athletes. PMID:28546774

Radiation-Related Treatment Effects across the Age Spectrum: Differences and Similarities or What The Old and Young Can Learn From Each Other

PubMed Central

Krasin, Matthew J.; Constine, Louis S.; Friedman, Debra; Marks, Lawrence B.

2010-01-01

Radiation related effects in children and adults limit the delivery of effective radiation doses and result in long-term morbidity affecting function and quality of life. Improvements in our understanding of the etiology and biology of these effects, including the influence of clinical variables, dosimetric factors, and the underlying biologic processes has made treatment safer and more efficacious. However, the approach to studying and understanding these effects differs between children and adults. By using the pulmonary and skeletal organ systems as examples, comparisons are made across the age spectrum for radiation related effects including pneumonitis, pulmonary fibrosis, osteonecrosis and fracture. Methods for dosimetric analysis, incorporation of imaging and biology as well a length of follow-up are compared, contrasted and discussed for both organ systems in children and adults. Better understanding of each age specific approach and how it differs may improve our ability to study late effects of radiation across the ages PMID:19959028

Effects of species biological traits and environmental heterogeneity on simulated tree species distribution shifts under climate change.

PubMed

Wang, Wen J; He, Hong S; Thompson, Frank R; Spetich, Martin A; Fraser, Jacob S

2018-09-01

Demographic processes (fecundity, dispersal, colonization, growth, and mortality) and their interactions with environmental changes are not well represented in current climate-distribution models (e.g., niche and biophysical process models) and constitute a large uncertainty in projections of future tree species distribution shifts. We investigate how species biological traits and environmental heterogeneity affect species distribution shifts. We used a species-specific, spatially explicit forest dynamic model LANDIS PRO, which incorporates site-scale tree species demography and competition, landscape-scale dispersal and disturbances, and regional-scale abiotic controls, to simulate the distribution shifts of four representative tree species with distinct biological traits in the central hardwood forest region of United States. Our results suggested that biological traits (e.g., dispersal capacity, maturation age) were important for determining tree species distribution shifts. Environmental heterogeneity, on average, reduced shift rates by 8% compared to perfect environmental conditions. The average distribution shift rates ranged from 24 to 200myear -1 under climate change scenarios, implying that many tree species may not able to keep up with climate change because of limited dispersal capacity, long generation time, and environmental heterogeneity. We suggest that climate-distribution models should include species demographic processes (e.g., fecundity, dispersal, colonization), biological traits (e.g., dispersal capacity, maturation age), and environmental heterogeneity (e.g., habitat fragmentation) to improve future predictions of species distribution shifts in response to changing climates. Copyright © 2018 Elsevier B.V. All rights reserved.

The impact of ageing on natural killer cell function and potential consequences for health in older adults.

PubMed

Hazeldine, Jon; Lord, Janet M

2013-09-01

Forming the first line of defence against virally infected and malignant cells, natural killer (NK) cells are critical effector cells of the innate immune system. With age, significant impairments have been reported in the two main mechanisms by which NK cells confer host protection: direct cytotoxicity and the secretion of immunoregulatory cytokines and chemokines. In elderly subjects, decreased NK cell activity has been shown to be associated with an increased incidence and severity of viral infection, highlighting the clinical implications that age-associated changes in NK cell biology have on the health of older adults. However, is an increased susceptibility to viral infection the only consequence of these age-related changes in NK cell function? Recently, evidence has emerged that has shown that in addition to eliminating transformed cells, NK cells are involved in many other biological processes such as immune regulation, anti-microbial immune responses and the recognition and elimination of senescent cells, novel functions that involve NK-mediated cytotoxicity and/or cytokine production. Thus, the decrease in NK cell function that accompanies physiological ageing is likely to have wider implications for the health of older adults than originally thought. Here, we give a detailed description of the changes in NK cell biology that accompany human ageing and propose that certain features of the ageing process such as: (i) the increased reactivation rates of latent Mycobacterium tuberculosis, (ii) the slower resolution of inflammatory responses and (iii) the increased incidence of bacterial and fungal infection are attributable in part to an age-associated decline in NK cell function. Copyright © 2013 Elsevier B.V. All rights reserved.

Not All Smokers Die Young: A Model for Hidden Heterogeneity within the Human Population

PubMed Central

Levine, Morgan; Crimmins, Eileen

2014-01-01

The ability of some individuals to reach extreme old age in the presence of clearly high exposure to damaging factors may signal an innate biological advantage. For this study we used data on 4,655 current and never smokers, ages 50 and above, from NHANES III to examine whether long-lived smokers represent a biologically resilient phenotype that could facilitate our understanding of heterogeneity in the aging process. Using a proportional hazards model, our results showed that while smoking significantly increased mortality in most age groups, it did not increase the mortality risk for those who were age 80 and over at baseline. Additionally when comparing the adjusted means of biomarkers between never and current smokers, we found that long-lived smokers (80+) had similar inflammation, HDL, and lung function levels to never smokers. Given that factors which allow some individuals to withstand smoking may also enable others to cope with everyday biological stressors, the investigation of long-lived smokers may eventually allow us to identify molecular and genetic mechanisms which enable longevity extension. PMID:24520332

Early vascular ageing in translation: from laboratory investigations to clinical applications in cardiovascular prevention.

PubMed

Nilsson, Peter M; Boutouyrie, Pierre; Cunha, Pedro; Kotsis, Vasilios; Narkiewicz, Krzysztof; Parati, Gianfranco; Rietzschel, Ernst; Scuteri, Angelo; Laurent, Stephane

2013-08-01

The ageing of the vascular tree is a fundamental reflection of biological ageing in general and a determinant of organ function. In the arterial wall this is characterized by a reduction in the elastin content, as well as by an increased content of collagen and its cross-linkages, leading to increased arterial stiffness and elevated central as well as brachial blood pressure, accompanied by increased SBP variability. In recent years a better understanding of these processes have led to the proposal of a condition named early vascular ageing (EVA) in patients with increased arterial stiffness for their age and sex. This is a condition that could increase cardiovascular risk and is associated with various degrees of cognitive dysfunction, as well as other features of biological ageing. This brief review aims to give an update on EVA and how the concept can be used in clinical practice.

Cell autonomous expression of inflammatory genes in biologically aged fibroblasts associated with elevated NF-kappaB activity.

PubMed

Kriete, Andres; Mayo, Kelli L; Yalamanchili, Nirupama; Beggs, William; Bender, Patrick; Kari, Csaba; Rodeck, Ulrich

2008-07-16

Chronic inflammation is a well-known corollary of the aging process and is believed to significantly contribute to morbidity and mortality of many age-associated chronic diseases. However, the mechanisms that cause age-associated inflammatory changes are not well understood. Particularly, the contribution of cell stress responses to age-associated inflammation in 'non-inflammatory' cells remains poorly defined. The present cross-sectional study focused on differences in molecular signatures indicative of inflammatory states associated with biological aging of human fibroblasts from donors aged 22 to 92 years. Gene expression profiling revealed elevated steady-state transcript levels consistent with a chronic inflammatory state in fibroblast cell-strains obtained from older donors. We also observed enhanced NF-kappaB DNA binding activity in a subset of strains, and the NF-kappaB profile correlated with mRNA expression levels characteristic of inflammatory processes, which include transcripts coding for cytokines, chemokines, components of the complement cascade and MHC molecules. This intrinsic low-grade inflammatory state, as it relates to aging, occurs in cultured cells irrespective of the presence of other cell types or the in vivo context. Our results are consistent with the view that constitutive activation of inflammatory pathways is a phenomenon prevalent in aged fibroblasts. It is possibly part of a cellular survival process in response to compromised mitochondrial function. Importantly, the inflammatory gene expression signature described here is cell autonomous, i.e. occurs in the absence of prototypical immune or pro-inflammatory cells, growth factors, or other inflammatory mediators.

Computer-aided discovery of biological activity spectra for anti-aging and anti-cancer olive oil oleuropeins.

PubMed

Corominas-Faja, Bruna; Santangelo, Elvira; Cuyàs, Elisabet; Micol, Vicente; Joven, Jorge; Ariza, Xavier; Segura-Carretero, Antonio; García, Jordi; Menendez, Javier A

2014-09-01

Aging is associated with common conditions, including cancer, diabetes, cardiovascular disease, and Alzheimer's disease. The type of multi-targeted pharmacological approach necessary to address a complex multifaceted disease such as aging might take advantage of pleiotropic natural polyphenols affecting a wide variety of biological processes. We have recently postulated that the secoiridoids oleuropein aglycone (OA) and decarboxymethyl oleuropein aglycone (DOA), two complex polyphenols present in health-promoting extra virgin olive oil (EVOO), might constitute a new family of plant-produced gerosuppressant agents. This paper describes an analysis of the biological activity spectra (BAS) of OA and DOA using PASS (Prediction of Activity Spectra for Substances) software. PASS can predict thousands of biological activities, as the BAS of a compound is an intrinsic property that is largely dependent on the compound's structure and reflects pharmacological effects, physiological and biochemical mechanisms of action, and specific toxicities. Using Pharmaexpert, a tool that analyzes the PASS-predicted BAS of substances based on thousands of "mechanism-effect" and "effect-mechanism" relationships, we illuminate hypothesis-generating pharmacological effects, mechanisms of action, and targets that might underlie the anti-aging/anti-cancer activities of the gerosuppressant EVOO oleuropeins.

Linking Biological and Cognitive Aging: Toward Improving Characterizations of Developmental Time

PubMed Central

DeCarlo, Correne A.; Dixon, Roger A.

2011-01-01

Objectives. Chronological age is the most frequently employed predictor in life-span developmental research, despite repeated assertions that it is best conceived as a proxy for true mechanistic changes that influence cognition across time. The present investigation explores the potential that selected functional biomarkers may contribute to the more effective conceptual and operational definitions of developmental time. Methods. We used data from the Victoria Longitudinal Study to explore both static and dynamic biological or physiological markers that arguably influence process-specific mechanisms underlying cognitive changes in late life. Multilevel models were fit to test the dynamic coupling between change in theoretically relevant biomarkers (e.g., grip strength, pulmonary function) and change in select cognitive measures (e.g., executive function, episodic and semantic memory). Results. Results showed that, independent of the passage of developmental time (indexed as years in study), significant time-varying covariation was observed linking corresponding declines for select cognitive outcomes and biological markers. Discussion. Our findings support the interpretation that cognitive decline is not due to chronological aging per se but rather reflects multiple causal factors from a broad range of biological and physical health domains that operate along the age continuum. PMID:21743053

A Test of Biological and Behavioral Explanations for Gender Differences in Telomere Length: The Multi-Ethnic Study of Atherosclerosis

PubMed Central

NEEDHAM, BELINDA L.; DIEZ ROUX, ANA V.; BIRD, CHLOE E.; BRADLEY, RYAN; FITZPATRICK, ANNETTE L.; JACOBS, DAVID R.; OUYANG, PAMELA; SEEMAN, TERESA E.; THURSTON, REBECCA C.; VAIDYA, DHANANJAY; WANG, STEVEN

2015-01-01

The purpose of this study was to examine biological and behavioral explanations for gender differences in leukocyte telomere length (LTL), a biomarker of cell aging that has been hypothesized to contribute to women’s greater longevity. Data are from a subsample (n = 851) of the Multi-Ethnic Study of Atherosclerosis, a population-based study of women and men aged 45 to 84. Mediation models were used to examine study hypotheses. We found that women had longer LTL than men, but the gender difference was smaller at older ages. Gender differences in smoking and processed meat consumption partially mediated gender differences in telomere length, whereas gender differences in estradiol, total testosterone, oxidative stress, and body mass index did not. Neither behavioral nor biological factors explained why the gender difference in LTL was smaller at older ages. Longitudinal studies are needed to assess gender differences in the rate of change in LTL over time; to identify the biological, behavioral, and psychosocial factors that contribute to these differences throughout the life course; and to determine whether gender differences in LTL explain the gender gap in longevity. PMID:25343364

A test of biological and behavioral explanations for gender differences in telomere length: the multi-ethnic study of atherosclerosis.

PubMed

Needham, Belinda L; Diez Roux, Ana V; Bird, Chloe E; Bradley, Ryan; Fitzpatrick, Annette L; Jacobs, David R; Ouyang, Pamela; Seeman, Teresa E; Thurston, Rebecca C; Vaidya, Dhananjay; Wang, Steven

2014-01-01

The purpose of this study was to examine biological and behavioral explanations for gender differences in leukocyte telomere length (LTL), a biomarker of cell aging that has been hypothesized to contribute to women's greater longevity. Data are from a subsample (n = 851) of the Multi-Ethnic Study of Atherosclerosis, a population-based study of women and men aged 45 to 84. Mediation models were used to examine study hypotheses. We found that women had longer LTL than men, but the gender difference was smaller at older ages. Gender differences in smoking and processed meat consumption partially mediated gender differences in telomere length, whereas gender differences in estradiol, total testosterone, oxidative stress, and body mass index did not. Neither behavioral nor biological factors explained why the gender difference in LTL was smaller at older ages. Longitudinal studies are needed to assess gender differences in the rate of change in LTL over time; to identify the biological, behavioral, and psychosocial factors that contribute to these differences throughout the life course; and to determine whether gender differences in LTL explain the gender gap in longevity.

Metabolic profiles of biological aging in American Indians: the Strong Heart Family Study.

PubMed

Zhao, Jinying; Zhu, Yun; Uppal, Karan; Tran, ViLinh T; Yu, Tianwei; Lin, Jue; Matsuguchi, Tet; Blackburn, Elizabeth; Jones, Dean; Lee, Elisa T; Howard, Barbara V

2014-03-01

Short telomere length, a marker of biological aging, has been associated with age-related metabolic disorders. Telomere attrition induces profound metabolic dysfunction in animal models, but no study has examined the metabolome of telomeric aging in human. Here we studied 423 apparently healthy American Indians participating in the Strong Family Heart Study. Leukocyte telomere length (LTL) was measured by qPCR. Metabolites in fasting plasma were detected by untargeted LC/MS. Associations of LTL with each metabolite and their combined effects were examined using generalized estimating equation adjusting for chronological age and other aging-related factors. Multiple testing was corrected using the q-value method (q<0.05). Of the 1,364 distinct m/z features detected, nineteen metabolites in the classes of glycerophosphoethanolamines, glycerophosphocholines, glycerolipids, bile acids, isoprenoids, fatty amides, or L-carnitine ester were significantly associated with LTL, independent of chronological age and other aging-related factors. Participants with longer (top tertile) and shorter (bottom tertile) LTL were clearly separated into distinct groups using a multi-marker score comprising of all these metabolites, suggesting that these newly detected metabolites could be novel metabolic markers of biological aging. This is the first study to interrogate the human metabolome of telomeric aging. Our results provide initial evidence for a metabolic control of LTL and may reveal previously undescribed new roles of various lipids in the aging process.

Evolutionary theory of ageing and the problem of correlated Gompertz parameters.

PubMed

Burger, Oskar; Missov, Trifon I

2016-11-07

The Gompertz mortality model is often used to evaluate evolutionary theories of ageing, such as the Medawar-Williams' hypothesis that high extrinsic mortality leads to faster ageing. However, fits of the Gompertz mortality model to data often find the opposite result that mortality is negatively correlated with the rate of ageing. This negative correlation has been independently discovered in several taxa and is known in actuarial studies of ageing as the Strehler-Mildvan correlation. We examine the role of mortality selection in determining late-life variation in susceptibility to death, which has been suggested to be the cause of this negative correlation. We demonstrate that fixed-frailty models that account for heterogeneity in frailty do not remove the correlation and that the correlation is an inherent statistical property of the Gompertz distribution. Linking actuarial and biological rates of ageing will continue to be a pressing challenge, but the Strehler-Mildvan correlation itself should not be used to diagnose any biological, physiological, or evolutionary process. These findings resolve some key tensions between theory and data that affect evolutionary and biological studies of ageing and mortality. Tests of evolutionary theories of ageing should include direct measures of physiological performance or condition. Copyright © 2016 Elsevier Ltd. All rights reserved.

Why and How We Age, and Is That Process Modifiable?

NASA Astrophysics Data System (ADS)

Arking, R.

Aging is an almost-universal biological process that is better understood in terms of an evolutionary explanation than in terms of a medical or adaptationist explanation. The major advances in human longevity which took place in developed countries during the past century arose from decreases in external (e.g., environmental) sources of mortality, and not from any effect on the aging process. Laboratory studies show that the aging process is under genetic control, can be manipulated, and can be expressed in three different phenotypes. The adult lifespan consists of the health span (ages 20-55 yrs) and the senescent span (ages 55+), with a relatively short but variable transition phase between the two. The most socially desirable phenotype would be that where the transition phase is delayed and the health span extended with little effect on the senescent span. The genetic, nutritional, cell-signaling and pharmecutical interventions inducing this phenotype are discussed. The genetic architecture of senescence is discussed and its stochastic nature made clear. The social and ethical consequences of pharmecutical intervention into the aging process are briefly discussed.

Free Radicals in Chemical Biology: from Chemical Behavior to Biomarker Development

PubMed Central

Chatgilialoglu, Chryssostomos; Ferreri, Carla; Masi, Annalisa; Melchiorre, Michele; Sansone, Anna; Terzidis, Michael A.; Torreggiani, Armida

2013-01-01

The involvement of free radicals in life sciences has constantly increased with time and has been connected to several physiological and pathological processes. This subject embraces diverse scientific areas, spanning from physical, biological and bioorganic chemistry to biology and medicine, with applications to the amelioration of quality of life, health and aging. Multidisciplinary skills are required for the full investigation of the many facets of radical processes in the biological environment and chemical knowledge plays a crucial role in unveiling basic processes and mechanisms. We developed a chemical biology approach able to connect free radical chemical reactivity with biological processes, providing information on the mechanistic pathways and products. The core of this approach is the design of biomimetic models to study biomolecule behavior (lipids, nucleic acids and proteins) in aqueous systems, obtaining insights of the reaction pathways as well as building up molecular libraries of the free radical reaction products. This context can be successfully used for biomarker discovery and examples are provided with two classes of compounds: mono-trans isomers of cholesteryl esters, which are synthesized and used as references for detection in human plasma, and purine 5',8-cyclo-2'-deoxyribonucleosides, prepared and used as reference in the protocol for detection of such lesions in DNA samples, after ionizing radiations or obtained from different health conditions. PMID:23629513

A Systematic Investigation into Aging Related Genes in Brain and Their Relationship with Alzheimer's Disease.

PubMed

Meng, Guofeng; Zhong, Xiaoyan; Mei, Hongkang

2016-01-01

Aging, as a complex biological process, is accompanied by the accumulation of functional loses at different levels, which makes age to be the biggest risk factor to many neurological diseases. Even following decades of investigation, the process of aging is still far from being fully understood, especially at a systematic level. In this study, we identified aging related genes in brain by collecting the ones with sustained and consistent gene expression or DNA methylation changes in the aging process. Functional analysis with Gene Ontology to these genes suggested transcriptional regulators to be the most affected genes in the aging process. Transcription regulation analysis found some transcription factors, especially Specificity Protein 1 (SP1), to play important roles in regulating aging related gene expression. Module-based functional analysis indicated these genes to be associated with many well-known aging related pathways, supporting the validity of our approach to select aging related genes. Finally, we investigated the roles of aging related genes on Alzheimer's Disease (AD). We found that aging and AD related genes both involved some common pathways, which provided a possible explanation why aging made the brain more vulnerable to Alzheimer's Disease.

Is biological aging accelerated in drug addiction?

PubMed

Bachi, Keren; Sierra, Salvador; Volkow, Nora D; Goldstein, Rita Z; Alia-Klein, Nelly

2017-02-01

Drug-addiction may trigger early onset of age-related disease, due to drug-induced multi-system toxicity and perilous lifestyle, which remains mostly undetected and untreated. We present the literature on pathophysiological processes that may hasten aging and its relevance to addiction, including: oxidative stress and cellular aging, inflammation in periphery and brain, decline in brain volume and function, and early onset of cardiac, cerebrovascular, kidney, and liver disease. Timely detection of accelerated aging in addiction is crucial for the prevention of premature morbidity and mortality.

Are microRNAs true sensors of ageing and cellular senescence?

PubMed

Williams, Justin; Smith, Flint; Kumar, Subodh; Vijayan, Murali; Reddy, P Hemachandra

2017-05-01

All living beings are programmed to death due to aging and age-related processes. Aging is a normal process of every living species. While all cells are inevitably progressing towards death, many disease processes accelerate the aging process, leading to senescence. Pathologies such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, cardiovascular disease, cancer, and skin diseases have been associated with deregulated aging. Healthy aging can delay onset of all age-related diseases. Genetics and epigenetics are reported to play large roles in accelerating and/or delaying the onset of age-related diseases. Cellular mechanisms of aging and age-related diseases are not completely understood. However, recent molecular biology discoveries have revealed that microRNAs (miRNAs) are potential sensors of aging and cellular senescence. Due to miRNAs capability to bind to the 3' untranslated region (UTR) of mRNA of specific genes, miRNAs can prevent the translation of specific genes. The purpose of our article is to highlight recent advancements in miRNAs and their involvement in cellular changes in aging and senescence. Our article discusses the current understanding of cellular senescence, its interplay with miRNAs regulation, and how they both contribute to disease processes. Copyright © 2016 Elsevier B.V. All rights reserved.

The application of biological motion research: biometrics, sport, and the military.

PubMed

Steel, Kylie; Ellem, Eathan; Baxter, David

2015-02-01

The body of research that examines the perception of biological motion is extensive and explores the factors that are perceived from biological motion and how this information is processed. This research demonstrates that individuals are able to use relative (temporal and spatial) information from a person's movement to recognize factors, including gender, age, deception, emotion, intention, and action. The research also demonstrates that movement presents idiosyncratic properties that allow individual discrimination, thus providing the basis for significant exploration in the domain of biometrics and social signal processing. Medical forensics, safety garments, and victim selection domains also have provided a history of research on the perception of biological motion applications; however, a number of additional domains present opportunities for application that have not been explored in depth. Therefore, the purpose of this paper is to present an overview of the current applications of biological motion-based research and to propose a number of areas where biological motion research, specific to recognition, could be applied in the future.

Aging on a different scale--chronological versus pathology-related aging.

PubMed

Melis, Joost P M; Jonker, Martijs J; Vijg, Jan; Hoeijmakers, Jan H J; Breit, Timo M; van Steeg, Harry

2013-10-01

In the next decades the elderly population will increase dramatically, demanding appropriate solutions in health care and aging research focusing on healthy aging to prevent high burdens and costs in health care. For this, research targeting tissue-specific and individual aging is paramount to make the necessary progression in aging research. In a recently published study we have attempted to make a step interpreting aging data on chronological as well as pathological scale. For this, we sampled five major tissues at regular time intervals during the entire C57BL/6J murine lifespan from a controlled in vivo aging study, measured the whole transcriptome and incorporated temporal as well as physical health aspects into the analyses. In total, we used 18 different age-related pathological parameters and transcriptomic profiles of liver, kidney, spleen, lung and brain and created a database that can now be used for a broad systems biology approach. In our study, we focused on the dynamics of biological processes during chronological aging and the comparison between chronological and pathology-related aging.

The Demographic and Biomedical Case for Late-Life Interventions in Aging

PubMed Central

Rae, Michael J.; Butler, Robert N.; Campisi, Judith; de Grey, Aubrey D. N. J.; Finch, Caleb E.; Gough, Michael; Martin, George M.; Vijg, Jan; Perrott, Kevin M.; Logan, Barbara J.

2013-01-01

The social and medical costs of the biological aging process are high and will rise rapidly in coming decades, creating an enormous challenge to societies worldwide. In recent decades, researchers have expanded their understanding of the underlying deleterious structural and physiological changes (aging damage) that underlie the progressive functional impairments, declining health, and rising mortality of aging humans and other organisms and have been able to intervene in the process in model organisms, even late in life. To preempt a global aging crisis, we advocate an ambitious global initiative to translate these findings into interventions for aging humans, using three complementary approaches to retard, arrest, and even reverse aging damage, extending and even restoring the period of youthful health and functionality of older people. PMID:20630854

Understanding the Writing Process through Brain Hemisphere Neurology.

ERIC Educational Resources Information Center

Hogge, Joan Ellet

Acknowledging that ordering, spatial orientation, and synthesis are important properties in achieving clarity in writing, a study investigated the biological influences on students' writing processes and ways to help writers produce more coherent written products. Subjects, two males and four females ranging in age from 19 to 40, were tested using…

Simultaneous measurement of NAD metabolome in aged mice tissue using liquid chromatography tandem-mass spectrometry.

PubMed

Yaku, Keisuke; Okabe, Keisuke; Nakagawa, Takashi

2018-06-01

Nicotinamide adenine dinucleotide (NAD) is a major co-factor that mediates multiple biological processes including redox reaction and gene expression. Recently, NAD metabolism has received considerable attention because administration of NAD precursors exhibited beneficial effects against aging-related metabolic disorders in animals. Although numerous studies have reported that NAD levels decline with aging in multiple animal tissues, the pathway and kinetics of NAD metabolism in aged organs are not completely understood. To determine the NAD metabolism upon aging, we developed targeted metabolomics based on an LC/MS/MS system. Our method is simple and applicable to crude biological samples, including culture cells and animal tissues. Unlike a conventional enzymatic cycling assay, our approach can determine NAD and NADH (reduced form of NAD) by performing a single sample preparation. Further, we validated our method using biological samples and investigated the alteration of the NAD metabolome during aging. Consistent with previous reports, the NAD levels in the liver and skeletal muscle decreased with aging. Further, we detected a significant increase in nicotinamide mononucleotide and nicotinamide riboside in the kidney upon aging. The LC/MS/MS-based NAD metabolomics that we have developed is extensively applicable to biomedical studies, and the results will present innovative ideas for the aging studies, especially for that of NAD metabolism. Copyright © 2018 John Wiley & Sons, Ltd.

Biological timing and the clock metaphor: oscillatory and hourglass mechanisms.

PubMed

Rensing, L; Meyer-Grahle, U; Ruoff, P

2001-05-01

Living organisms have developed a multitude of timing mechanisms--"biological clocks." Their mechanisms are based on either oscillations (oscillatory clocks) or unidirectional processes (hourglass clocks). Oscillatory clocks comprise circatidal, circalunidian, circadian, circalunar, and circannual oscillations--which keep time with environmental periodicities--as well as ultradian oscillations, ovarian cycles, and oscillations in development and in the brain, which keep time with biological timescales. These clocks mainly determine time points at specific phases of their oscillations. Hourglass clocks are predominantly found in development and aging and also in the brain. They determine time intervals (duration). More complex timing systems combine oscillatory and hourglass mechanisms, such as the case for cell cycle, sleep initiation, or brain clocks, whereas others combine external and internal periodicities (photoperiodism, seasonal reproduction). A definition of a biological clock may be derived from its control of functions external to its own processes and its use in determining temporal order (sequences of events) or durations. Biological and chemical oscillators are characterized by positive and negative feedback (or feedforward) mechanisms. During evolution, living organisms made use of the many existing oscillations for signal transmission, movement, and pump mechanisms, as well as for clocks. Some clocks, such as the circadian clock, that time with environmental periodicities are usually compensated (stabilized) against temperature, whereas other clocks, such as the cell cycle, that keep time with an organismic timescale are not compensated. This difference may be related to the predominance of negative feedback in the first class of clocks and a predominance of positive feedback (autocatalytic amplification) in the second class. The present knowledge of a compensated clock (the circadian oscillator) and an uncompensated clock (the cell cycle), as well as relevant models, are briefly re viewed. Hourglass clocks are based on linear or exponential unidirectional processes that trigger events mainly in the course of development and aging. An important hourglass mechanism within the aging process is the limitation of cell division capacity by the length of telomeres. The mechanism of this clock is briefly reviewed. In all clock mechanisms, thresholds at which "dependent variables" are triggered play an important role.

Molecular Age-Related Changes in the Anterior Segment of the Eye.

PubMed

Hernandez-Zimbron, Luis Fernando; Gulias-Cañizo, Rosario; Golzarri, María F; Martínez-Báez, Blanca Elizabeth; Quiroz-Mercado, Hugo; Gonzalez-Salinas, Roberto

2017-01-01

To examine the current knowledge about the age-related processes in the anterior segment of the eye at a biological, clinical, and molecular level. We reviewed the available published literature that addresses the aging process of the anterior segment of the eye and its associated molecular and physiological events. We performed a search on PubMed, CINAHL, and Embase using the MeSH terms "eye," "anterior segment," and "age." We generated searches to account for synonyms of these keywords and MESH headings as follows: (1) "Eye" AND "ageing process" OR "anterior segment ageing" and (2) "Anterior segment" AND "ageing process" OR "anterior segment" AND "molecular changes" AND "age." Results . Among the principal causes of age-dependent alterations in the anterior segment of the eye, we found the mutation of the TGF- β gene and loss of autophagy in addition to oxidative stress, which contributes to the pathogenesis of degenerative diseases. In this review, we summarize the current knowledge regarding some of the molecular mechanisms related to aging in the anterior segment of the eye. We also introduce and propose potential roles of autophagy, an important mechanism responsible for maintaining homeostasis and proteostasis under stress conditions in the anterior segment during aging.

Longevity and aging: role of genes and of the extracellular matrix.

PubMed

Robert, L; Labat-Robert, J

2015-02-01

Longevity is different for every animal species as well as their genome, suggesting a correlation between genes and life-span. Estimates put the genetic effect from 5 to 35% approximately, suggesting that even genetic effects are dependent on environmental conditions. This contention is largely confirmed by the study of identical twins raised apart. They do not die at the same age and also for different reasons. Aging is not "genetically programmed", it is outside evolutionary constraint. Evolution favors early and efficient reproduction, but does not care for longevity. A number of mechanisms were shown to be involved in the age-dependent decline of vital functions, among them the Maillard reaction (non-enzymatic glycosylation) and the age-dependent upregulation of proteolytic activity. Aging of ECM is a complex process, comprising progressive modification of its macromolecular components and of cell-matrix interactions. An important process is the uncoupling with age of the elastin-receptor from its "young" transmission pathway loosing all physiological effects, but enhancing free radical and elastase release. These processes contribute to age-related ECM degradation, production of matrikins (ECM degradation products with biological activity) aggravating functional loss with age. Both genetic and post-genetic mechanisms are susceptible to be influenced by medical, pharmacological and dietary interventions. Among the genetic mechanisms, those attributed to Sirtuins (7 orthologs identified in the human genome) are especially important. Among the environmental effects, nutrition, hygiene and weather conditions play a role. These data justify some predictions on the evolution of life expectancy taking in account also socio-economic factors. Biological constraints become evident by the comparison of centenarians and supercentenarians (less than 1% of the centenarians) putting an upper limit to the attainable human lifespan.

Humane Science Projects: Suggestions for Biology Studies That Are Scientifically Educational and Ethically Non-Controversial.

ERIC Educational Resources Information Center

Balcombe, Jonathan P., Comp.

This paper lists 35 studies in biology which can be tailored to suit the full range of student age groups and are designed to involve most or all of the key elements of the scientific process (study design, data collection and presentation, and experimental manipulation). Examples of some studies are: (1) study the growth of molds on food items…

Does the Body Survive Death? Cultural Variation in Beliefs About Life Everlasting.

PubMed

Watson-Jones, Rachel E; Busch, Justin T A; Harris, Paul L; Legare, Cristine H

2017-04-01

Mounting evidence suggests that endorsement of psychological continuity and the afterlife increases with age. This developmental change raises questions about the cognitive biases, social representations, and cultural input that may support afterlife beliefs. To what extent is there similarity versus diversity across cultures in how people reason about what happens after death? The objective of this study was to compare beliefs about the continuation of biological and psychological functions after death in Tanna, Vanuatu (a Melanesian archipelago), and the United States (Austin, Texas). Children, adolescents, and adults were primed with a story that contained either natural (non-theistic) or supernatural (theistic) cues. Participants were then asked whether or not different biological and psychological processes continue to function after death. We predicted that across cultures individuals would be more likely to endorse the continuation of psychological processes over biological processes (dualism) and that a theistic prime would increase continuation responses regarding both types of process. Results largely supported predictions; U.S. participants provided more continuation responses for psychological than biological processes following both the theistic and non-theistic primes. Participants in Vanuatu, however, provided more continuation responses for biological than psychological processes following the theistic prime. The data provide evidence for both cultural similarity and variability in afterlife beliefs and demonstrate that individuals use both natural and supernatural explanations to interpret the same events. Copyright © 2016 Cognitive Science Society, Inc.

Developmental Origins of Biological Explanations: The case of infants' internal property bias.

PubMed

Taborda-Osorio, Hernando; Cheries, Erik W

2017-10-01

People's explanations about the biological world are heavily biased toward internal, non-obvious properties. Adults and children as young as 5 years of age find internal properties more causally central than external features for explaining general biological processes and category membership. In this paper, we describe how this 'internal property bias' may be grounded in two different developmental precursors observed in studies with infants: (1) an early understanding of biological agency that is apparent in infants' reasoning about animals, and (2) the acquisition of kind-based representations that distinguish between essential and accidental properties, spanning from animals to artifacts. We argue that these precursors may support the progressive construction of the notion of biological kinds and explanations during childhood. Shortly after their first year of life, infants seem to represent the internal properties of animates as more central and identity-determining that external properties. Over time, this skeletal notion of biological kinds is integrated into diverse explanations about kind membership and biological processes, with an increasingly better understanding of the causal role of internal properties.

Biological age as a useful index to predict seventeen-year survival and mortality in Koreans.

PubMed

Yoo, Jinho; Kim, Yangseok; Cho, Eo Rin; Jee, Sun Ha

2017-01-05

Many studies have been conducted to quantitatively estimate biological age using measurable biomarkers. Biological age should function as a valid proxy for aging, which is closely related with future work ability, frailty, physical fitness, and/or mortality. A validation study using cohort data found biological age to be a superior index for disease-related mortality than chronological age. The purpose of this study is to demonstrate the validity of biological age as a useful index to predict a person's risk of death in the future. The data consists of 13,106 cases of death from 557,940 Koreans at 20-93 years old, surveyed from 1994 to 2011. Biological ages were computed using 15 biomarkers measured in general health check-ups using an algorithm based on principal component analysis. The influence of biological age on future mortality was analyzed using Cox proportional hazards regression considering gender, chronological age, and event type. In the living subjects, the average biological age was almost the same as the average chronological age. In the deceased, the biological age was larger than the chronological age: largest increment of biological age over chronological age was observed when their baseline chronological age was within 50-59 years. The death rate significantly increased as biological age became larger than chronological age (linear trend test, p value < 0.0001). The largest hazard ratio was observed in subjects whose baseline chronological age was within 50-59 years when the cause was death from non-cancerous diseases (HR = 1.30, 95% confidence intervals = 1.26 - 1.34). The survival probability, over the 17 year term of the study, was significantly decreased in the people whose biological age was larger than chronological age (log rank test, p value < 0.001). Biological age could be used to predict future risk of death, and its effect size varied according to gender, chronological age, and cause of death.

Impact of TiO2 on the chemical and biological transformation of formulated chiral-metalaxyl in agricultural soils.

PubMed

Huang, Junxing; Zhang, Xu; Liang, Chuanzhou; Hu, Jun

2018-04-15

The impacts of TiO 2 on the chemical and biological transformation of racemic metalaxyl wettable powder (rac-metalaxyl WP) in agricultural soils, and soil microorganisms were investigated. Under simulated solar irradiation, TiO 2 highly promoted the transformation of rac-metalaxyl WP without changing the enantiomer fraction, with the promotion amplitude (60-1280%) being dependent on TiO 2 characteristics. TiO 2 characteristics showed different influence on the transformation of rac-metalaxyl WP in soils and aqueous solutions because their characteristics changed differently in soils. The impact of the mancozeb and other co-constituents on the transformation of rac-metalaxyl WP was smaller in soil media than in aqueous solution. Autoclave sterilization changed soil properties and subsequently weakened the promotion effects of TiO 2 on the chemical transformations of rac-metalaxyl WP to 0-233%. Microorganism biomass and bacterial community were not statistically significant changed by TiO 2 exposure regardless of rac-metalaxyl WP, suggesting that the promotional effects occurred mainly through chemical processes. The results also showed TiO 2 -soil interactions may be strengthened with TiO 2 (Degussa P25) aging time in soils, which decreased its promotion amplitude from 1060% (without aging) to 880% (aging for 20 days). Intermediate formed in soil biological transformation process was different from that in TiO 2 photocatalysis process. Copyright © 2018 Elsevier B.V. All rights reserved.

Quantum biological channel modeling and capacity calculation.

PubMed

Djordjevic, Ivan B

2012-12-10

Quantum mechanics has an important role in photosynthesis, magnetoreception, and evolution. There were many attempts in an effort to explain the structure of genetic code and transfer of information from DNA to protein by using the concepts of quantum mechanics. The existing biological quantum channel models are not sufficiently general to incorporate all relevant contributions responsible for imperfect protein synthesis. Moreover, the problem of determination of quantum biological channel capacity is still an open problem. To solve these problems, we construct the operator-sum representation of biological channel based on codon basekets (basis vectors), and determine the quantum channel model suitable for study of the quantum biological channel capacity and beyond. The transcription process, DNA point mutations, insertions, deletions, and translation are interpreted as the quantum noise processes. The various types of quantum errors are classified into several broad categories: (i) storage errors that occur in DNA itself as it represents an imperfect storage of genetic information, (ii) replication errors introduced during DNA replication process, (iii) transcription errors introduced during DNA to mRNA transcription, and (iv) translation errors introduced during the translation process. By using this model, we determine the biological quantum channel capacity and compare it against corresponding classical biological channel capacity. We demonstrate that the quantum biological channel capacity is higher than the classical one, for a coherent quantum channel model, suggesting that quantum effects have an important role in biological systems. The proposed model is of crucial importance towards future study of quantum DNA error correction, developing quantum mechanical model of aging, developing the quantum mechanical models for tumors/cancer, and study of intracellular dynamics in general.

MicroRNA expression profiles from eggs of different qualities associated with post-ovulatory ageing in rainbow trout (Oncorhynchus mykiss)

USDA-ARS?s Scientific Manuscript database

Background: Egg quality is an important aspect in rainbow trout farming. Post-ovulatory aging is one of the most important factors affecting egg quality. MicroRNAs (miRNAs) are the major regulators in various biological processes and their expression profiles could serve as reliable biomarkers for v...

Human biological research since 2006 at the Christian-Albrechts-University in Kiel--aging, chronobiology, and high altitude adaptation.

PubMed

Dittmar, Manuela

2014-01-01

This article reviews the research at the Department of Human Biology at the Christian-Albrechts-University in Kiel since 2006. The research focuses on the investigation of recent human populations with respect to aging, chronobiology, and adaptation to high altitude. The research areas are outlined presenting findings, ongoing projects and future directions. Aging research examines biological changes in humans considering that aging is a multidimensional process. Changes in body composition, resting energy metabolism, oxidative stress, and sleep have been examined. The applicability of specific research methods to older people has been tested. Chronobiological research concentrates on investigating circadian rhythms of humans. The emphasis lies on the sleep-wake rhythm, body temperature rhythms, hormonal rhythms (cortisol and melatonin) and the circadian expression of so-called clock genes which are involved in the generation of circadian rhythms. Association studies examine the relationship between defined chronobiological phenotypes and clock gene polymorphisms. Genetic aspects are as well investigated within the third research area on the adaptation of native populations to life at high altitude in the South American Andes. Both candidate gene analysis and epigenetic parameters are investigated. Future research will concentrate on the aging of the circadian system.

Molecular Diagnostics of Ageing and Tackling Age-related Disease.

PubMed

Timmons, James A

2017-01-01

As average life expectancy increases there is a greater focus on health-span and, in particular, how to treat or prevent chronic age-associated diseases. Therapies which were able to control 'biological age' with the aim of postponing chronic and costly diseases of old age require an entirely new approach to drug development. Molecular technologies and machine-learning methods have already yielded diagnostics that help guide cancer treatment and cardiovascular procedures. Discovery of valid and clinically informative diagnostics of human biological age (combined with disease-specific biomarkers) has the potential to alter current drug-discovery strategies, aid clinical trial recruitment and maximize healthy ageing. I will review some basic principles that govern the development of 'ageing' diagnostics, how such assays could be used during the drug-discovery or development process. Important logistical and statistical considerations are illustrated by reviewing recent biomarker activity in the field of Alzheimer's disease, as dementia represents the most pressing of priorities for the pharmaceutical industry, as well as the chronic disease in humans most associated with age. Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular inflammation as an underlying mechanism of the aging process and age-related diseases.

PubMed

Chung, H Y; Lee, E K; Choi, Y J; Kim, J M; Kim, D H; Zou, Y; Kim, C H; Lee, J; Kim, H S; Kim, N D; Jung, J H; Yu, B P

2011-07-01

Aging is a biological process characterized by time-dependent functional declines that are influenced by changes in redox status and by oxidative stress-induced inflammatory reactions. An organism's pro-inflammatory status may underlie the aging process and age-related diseases. In this review, we explore the molecular basis of low-grade, unresolved, subclinical inflammation as a major risk factor for exacerbating the aging process and age-related diseases. We focus on the redox-sensitive transcription factors, NF-κB and FOXO, which play essential roles in the expression of pro-inflammatory mediators and anti-oxidant enzymes, respectively. Major players in molecular inflammation are discussed with respect to the age-related up-regulation of pro-inflammatory cytokines and adhesion molecules, cyclo-oxygenase-2, lipoxygenase, and inducible nitric oxide synthase. The molecular inflammation hypothesis proposed by our laboratory is briefly described to give further molecular insights into the intricate interplay among redox balance, pro-inflammatory gene activation, and chronic age-related inflammatory diseases. The final section discusses calorie restriction as an aging-retarding intervention that also exhibits extraordinarily effective anti-inflammatory activity by modulating GSH redox, NF-κB, SIRT1, PPARs, and FOXOs.

Computer Simulation of Biological Ageing-A Bird's-Eye View

NASA Astrophysics Data System (ADS)

Dasgupta, Subinay

For living organisms, the process of ageing consists of acquiring good and bad genetic mutations, which increase and decrease (respectively) the survival probability. When a child is born, the hereditary mutations of the parents are transmitted to the offspring. Such stochastic processes seem to be amenable to computer simulation. Over the last 10 years, simulation studies of this sort have been done in different parts of the globe to explain ageing. The objective of these studies have been to attempt an explanation of demographic data and of natural phenomena like preference of nature to the process of sexual reproduction (in comparison to the process of asexual reproduction). Here we shall attempt to discuss briefly the principles and the results of these works, with an emphasis on what is called Penna bit-string model.

Isolation and identification of age-related DNA methylation markers for forensic age-prediction.

PubMed

Yi, Shao Hua; Xu, Long Chang; Mei, Kun; Yang, Rong Zhi; Huang, Dai Xin

2014-07-01

Age-prediction is an important part of forensic science. There is no available method of individual age-prediction for general forensic biological samples at crime scenes. Accumulating evidence indicates that aging resembles a developmentally regulated process tightly controlled by specific age-associated methylation exists in human genome. This study isolated and identified eight gene fragments in which the degree of cytosine methylation is significantly correlated with age in blood of 40 donors. Furthermore, we validated two CpG sites of each gene fragment and replicated our results in a general population sample of 40 males and 25 females with a wide age-range (11-72 years). The methylation of these fragments is linear with age over a range of six decades (Fragment P1 (r=-0.64), P2 (r=-0.58), P3 (r=-0.79), R1 (r=0.82), R2 (r=0.63), R3 (r=0.59), R4 (r=0.63) and R5 (r=0.62)). Using average methylation of two CpG sites from each fragment, we built a regression model that explained 95% of the variance in age and is able to predict the age of an individual with great accuracy (R(2)=0.918). The predicted values are highly correlated with the observed age in the sample (r=0.91). This study implicates that DNA methylation will be an available biological marker of age-prediction. Furthermore, measurement of relevant sites in the genome could be a tool in routine forensic screening to predict age of biological samples. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Disease-aging network reveals significant roles of aging genes in connecting genetic diseases.

PubMed

Wang, Jiguang; Zhang, Shihua; Wang, Yong; Chen, Luonan; Zhang, Xiang-Sun

2009-09-01

One of the challenging problems in biology and medicine is exploring the underlying mechanisms of genetic diseases. Recent studies suggest that the relationship between genetic diseases and the aging process is important in understanding the molecular mechanisms of complex diseases. Although some intricate associations have been investigated for a long time, the studies are still in their early stages. In this paper, we construct a human disease-aging network to study the relationship among aging genes and genetic disease genes. Specifically, we integrate human protein-protein interactions (PPIs), disease-gene associations, aging-gene associations, and physiological system-based genetic disease classification information in a single graph-theoretic framework and find that (1) human disease genes are much closer to aging genes than expected by chance; and (2) diseases can be categorized into two types according to their relationships with aging. Type I diseases have their genes significantly close to aging genes, while type II diseases do not. Furthermore, we examine the topological characters of the disease-aging network from a systems perspective. Theoretical results reveal that the genes of type I diseases are in a central position of a PPI network while type II are not; (3) more importantly, we define an asymmetric closeness based on the PPI network to describe relationships between diseases, and find that aging genes make a significant contribution to associations among diseases, especially among type I diseases. In conclusion, the network-based study provides not only evidence for the intricate relationship between the aging process and genetic diseases, but also biological implications for prying into the nature of human diseases.

Mitochondrial pathways governing stress resistance, life, and death in the fungal aging model Podospora anserina.

PubMed

Osiewacz, Heinz D; Brust, Diana; Hamann, Andrea; Kunstmann, Birgit; Luce, Karin; Müller-Ohldach, Mathis; Scheckhuber, Christian Q; Servos, Jörg; Strobel, Ingmar

2010-06-01

Work from more than 50 years of research has unraveled a number of molecular pathways that are involved in controlling aging of the fungal model system Podospora anserina. Early research revealed that wild-type strain aging is linked to gross reorganization of the mitochondrial DNA. Later it was shown that aging of P. anserina does also take place, although at a slower pace, when the wild-type specific mitochondrial DNA rearrangements do not occur. Now it is clear that a network of different pathways is involved in the control of aging. Branches of these pathways appear to be connected and constitute a hierarchical system of responses. Although cross talk between the individual pathways seems to be fundamental in the coordination of the overall system, the precise underlying interactions remain to be unraveled. Such a systematic approach aims at a holistic understanding of the process of biological aging, the ultimate goal of modern systems biology.

Cognitive impairment, genomic instability and trace elements.

PubMed

Meramat, A; Rajab, N F; Shahar, S; Sharif, R

2015-01-01

Cognitive impairments are often related to aging and micronutrient deficiencies. Various essential micronutrients in the diet are involved in age-altered biological functions such as, zinc, copper, iron, and selenium that play pivotal roles either in maintaining and reinforcing the antioxidant performances or in affecting the complex network of genes (nutrigenomic approach) involved in encoding proteins for biological functions. Genomic stability is one of the leading causes of cognitive decline and deficiencies or excess in trace elements are two of the factors relating to it. In this review, we report and discuss the role of micronutrients in cognitive impairment in relation to genomic stability in an aging population. Telomere integrity will also be discussed in relation to aging and cognitive impairment, as well as, the micronutrients related to these events. This review will provide an understanding on how these three aspects can relate with each other and why it is important to keep a homeostasis of micronutrients in relation to healthy aging. Micronutrient deficiencies and aging process can lead to genomic instability.

[History and poetry in women's biological twilight: menopause and old age].

PubMed

Cruz y Hermida, Julio

2011-01-01

This is a poetical and historical approach to the last biological stages of the evolutive development of women, namely menopause and old age. It starts with the passages found in Egyptian Papirii such as Ebers or Smith, dated 1500-2000 BC, which describe, among other symptoms, the sweating and hig body temperatures caused by the diminishing hormon secretion of the ovaries. Other important works on the subject, some of them written in the 20th century and some others composed before that date, are also quoted, such as the Edad Crítica (Critical Age) by Dr. Marañon. The final stage of a woman's life, old age, is presented through the famous sonet "Alfa y Omega" (Alpha and Omega) by poet Manuel Machado. Using poetical strokes, the author conveys an image of the many phisiopatological consequences of old age in women: osteoporosis, genital prolapse, urine incontinence and "wrinkles" ("old age is neither shown by white hair nor by wrinkles but by the heart"). The work finishes with the famous statement uttered by Napoleon Bona-parte: "God wanted to be a writer: Man is His prose; His poetry, Women". The same poetry that Dr. Cruz y Hermida has found through the complexities of the evolutive process of feminine biology.

[Effect of pineal peptide on parameters of the biological age and life span in mice].

PubMed

Anisimov, V N; Khavinson, V Kh; Zavarzina, N Iu; Zabezhinskiĭ, M A; Zimina, O A; Popovich, I G; Shtylik, A V; Arutiunian, A V; Oparina, T I; Prokopenko, V M

2001-01-01

Female CBA mice were injected with s.c. synthetic tetrapeptide Epithalon from a 6-month age until death. The drug failed to affect the body weight or food consumption, physical activity or behavioural parameters. However, it slowed down the age-related switching off of the estrus function, decreased body temperature, decelerated free redical processes, prolonged the mice life span with an accompanying drop in spontaneous tumour incidence.

Physiological and comparative evidence fails to confirm an adaptive role for aging in evolution.

PubMed

Cohen, Alan A

2015-01-01

The longstanding debate about whether aging may have evolved for some adaptive reason is generally considered to pit evolutionary theory against empirical observations consistent with aging as a programmed aspect of organismal biology, in particular conserved aging genes. Here I argue that the empirical evidence on aging mechanisms does not support a view of aging as a programmed phenomenon, but rather supports a view of aging as the dysregulation of complex networks that maintain organismal homeostasis. The appearance of programming is due largely to the inadvertent activation of existing pathways during the process of dysregulation. It is argued that aging differs markedly from known programmed biological phenomena such as apoptosis in that it is (a) very heterogeneous in how it proceeds, and (b) much slower than it would need to be. Furthermore, the taxonomic distribution of aging across species does not support any proposed adaptive theories of aging, which would predict that aging rate would vary on a finer taxonomic scale depending on factors such as population density. Thus, while there are problems with the longstanding non-adaptive paradigm, current evidence does not support the notion that aging is programmed or that it may have evolved for adaptive reasons.

Caenorhabditis elegans - A model system for space biology studies

NASA Technical Reports Server (NTRS)

Johnson, Thomas E.; Nelson, Gregory A.

1991-01-01

The utility of the nematode Caenorhabditis elegans in studies spanning aspects of development, aging, and radiobiology is reviewed. These topics are interrelated via cellular and DNA repair processes especially in the context of oxidative stress and free-radical metabolism. The relevance of these research topics to problems in space biology is discussed and properties of the space environment are outlined. Exposure to the space-flight environment can induce rapid changes in living systems that are similar to changes occurring during aging; manipulation of these environmental parameters may represent an experimental strategy for studies of development and senescence. The current and future opportunities for such space-flight experimentation are presented.

Reduced orienting to audiovisual synchrony in infancy predicts autism diagnosis at 3 years of age.

PubMed

Falck-Ytter, Terje; Nyström, Pär; Gredebäck, Gustaf; Gliga, Teodora; Bölte, Sven

2018-01-23

Effective multisensory processing develops in infancy and is thought to be important for the perception of unified and multimodal objects and events. Previous research suggests impaired multisensory processing in autism, but its role in the early development of the disorder is yet uncertain. Here, using a prospective longitudinal design, we tested whether reduced visual attention to audiovisual synchrony is an infant marker of later-emerging autism diagnosis. We studied 10-month-old siblings of children with autism using an eye tracking task previously used in studies of preschoolers. The task assessed the effect of manipulations of audiovisual synchrony on viewing patterns while the infants were observing point light displays of biological motion. We analyzed the gaze data recorded in infancy according to diagnostic status at 3 years of age (DSM-5). Ten-month-old infants who later received an autism diagnosis did not orient to audiovisual synchrony expressed within biological motion. In contrast, both infants at low-risk and high-risk siblings without autism at follow-up had a strong preference for this type of information. No group differences were observed in terms of orienting to upright biological motion. This study suggests that reduced orienting to audiovisual synchrony within biological motion is an early sign of autism. The findings support the view that poor multisensory processing could be an important antecedent marker of this neurodevelopmental condition. © 2018 Association for Child and Adolescent Mental Health.

RNA sequencing reveals pronounced changes in the noncoding transcriptome of aging synaptosomes.

PubMed

Chen, Bei Jun; Ueberham, Uwe; Mills, James D; Kirazov, Ludmil; Kirazov, Evgeni; Knobloch, Mara; Bochmann, Jana; Jendrek, Renate; Takenaka, Konii; Bliim, Nicola; Arendt, Thomas; Janitz, Michael

2017-08-01

Normal aging is associated with impairments in cognitive functions. These alterations are caused by diminutive changes in the biology of synapses, and ineffective neurotransmission, rather than loss of neurons. Hitherto, only a few studies, exploring molecular mechanisms of healthy brain aging in higher vertebrates, utilized synaptosomal fractions to survey local changes in aging-related transcriptome dynamics. Here we present, for the first time, a comparative analysis of the synaptosomes transcriptome in the aging mouse brain using RNA sequencing. Our results show changes in the expression of genes contributing to biological pathways related to neurite guidance, synaptosomal physiology, and RNA splicing. More intriguingly, we also discovered alterations in the expression of thousands of novel, unannotated lincRNAs during aging. Further, detailed characterization of the cleavage and polyadenylation factor I subunit 1 (Clp1) mRNA and protein expression indicates its increased expression in neuronal processes of hippocampal stratum radiatum in aging mice. Together, our study uncovers a new layer of transcriptional regulation which is targeted by aging within the local environment of interconnecting neuronal cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Another stage of development: Biological degeneracy and the study of bodily ageing.

PubMed

Mason, Paul H; Maleszka, Ryszard; Dominguez D, Juan F

2017-04-01

Ageing is a poorly understood process of human development mired by a scientific approach that struggles to piece together distributed variable factors involved in ongoing transformations of living systems. Reconfiguring existing research paradigms, we review the concept of 'degeneracy', which has divergent popular and technical definitions. The technical meaning of degeneracy refers to the structural diversity underlying functional plasticity. Degeneracy is a distributed system property that can be observed within individual brains or across different brains. For example, dementias with similar behavioural anomalies can result from a diverse range of cellular "faults", which is an example of degeneracy because the symptoms are similar in spite of different underlying mechanisms. Degeneracy is a valuable epistemological tool that can transformatively enhance scientific models of bodily ageing. We propose that movement science is one of the first areas that can productively integrate degeneracy into models of bodily ageing. We also propose model organisms such as eusocial honey bees in which degeneracy can be studied at the molecular and cellular level. Developing a vocabulary for thinking about how distributed variable factors are interlinked is important if we are to understand bodily ageing not as a single entity, but as the heterogeneous construction of changing biological, social, and environmental processes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Social and Emotional Aging

PubMed Central

Charles, Susan; Carstensen, Laura L.

2014-01-01

The past several decades have witnessed unidimensional decline models of aging give way to life-span developmental models that consider how specific processes and strategies facilitate adaptive aging. In part, this shift was provoked by the stark contrast between findings that clearly demonstrate decreased biological, physiological, and cognitive capacity with those suggesting that people are generally satisfied in old age and experience relatively high levels of emotional well-being. In recent years, this supposed “paradox” of aging has been reconciled through careful theoretical analysis and empirical investigation. Viewing aging as adaptation sheds light on resilience, wellbeing, and emotional distress across adulthood. PMID:19575618

Aging and the Kidneys: Anatomy, Physiology and Consequences for Defining Chronic Kidney Disease.

PubMed

Glassock, Richard J; Rule, Andrew D

2016-01-01

The varied functions of the kidneys are influenced by the complex process of aging. The glomerular filtration rate (GFR) steadily declines with normal aging, and the progress of this process can be influenced by superimposed diseases. Microscopically, nephron numbers decrease as global glomerulosclerosis becomes more evident. The precise mechanisms underlying nephron loss with aging are not well understood, but derangements in podocyte biology appear to be involved. Classifications of chronic kidney disease (CKD) incorporate GFR values and attendant risk of adverse events. Arbitrary and fixed thresholds of GFR for defining CKD have led to an overdiagnosis of CKD in the elderly. An age-sensitive definition of CKD could offer a solution to this problem and more meaningfully capture the prognostic implications of CKD. © 2016 S. Karger AG, Basel.

The fetal programming of telomere biology hypothesis: an update.

PubMed

Entringer, Sonja; de Punder, Karin; Buss, Claudia; Wadhwa, Pathik D

2018-03-05

Research on mechanisms underlying fetal programming of health and disease risk has focused primarily on processes that are specific to cell types, organs or phenotypes of interest. However, the observation that developmental conditions concomitantly influence a diverse set of phenotypes, the majority of which are implicated in age-related disorders, raises the possibility that such developmental conditions may additionally exert effects via a common underlying mechanism that involves cellular/molecular ageing-related processes. In this context, we submit that telomere biology represents a process of particular interest in humans because, firstly, this system represents among the most salient antecedent cellular phenotypes for common age-related disorders; secondly, its initial (newborn) setting appears to be particularly important for its long-term effects; and thirdly, its initial setting appears to be plastic and under developmental regulation. We propose that the effects of suboptimal intrauterine conditions on the initial setting of telomere length and telomerase expression/activity capacity may be mediated by the programming actions of stress-related maternal-placental-fetal oxidative, immune, endocrine and metabolic pathways in a manner that may ultimately accelerate cellular dysfunction, ageing and disease susceptibility over the lifespan. This perspectives paper provides an overview of each of the elements underlying this hypothesis, with an emphasis on recent developments, findings and future directions.This article is part of the theme issue 'Understanding diversity in telomere dynamics'. © 2018 The Author(s).

The change in aggressiveness of neoplasms with age.

PubMed

Ershler, W B

1987-01-01

With aging, tumors occur more frequently. The "malignant" characteristics of tumors (ie, rapid growth and metastases), however, appear to be less prominent in the elderly. In experimental tumor models, similar observations have been recorded. The reason for this phenomenon could be that tumors (ie, malignant cells) are different in different-aged hosts. Alternatively, host features such as the fibrotic, angiogenic, or immune response may be altered by the aging process and may render the host "soil" less fertile for "malignant" tumor growth. Indeed, experimental evidence has supported the importance of each of these host features. The significance of the exploration and eventual understanding of the age-related change in tumor behavior extends beyond clinical geriatric medicine; it may, in fact, involve the very unraveling of some of the basic biology of both tumor control and the aging process itself.

Brain age predicts mortality

PubMed Central

Cole, J H; Ritchie, S J; Bastin, M E; Valdés Hernández, M C; Muñoz Maniega, S; Royle, N; Corley, J; Pattie, A; Harris, S E; Zhang, Q; Wray, N R; Redmond, P; Marioni, R E; Starr, J M; Cox, S R; Wardlaw, J M; Sharp, D J; Deary, I J

2018-01-01

Age-associated disease and disability are placing a growing burden on society. However, ageing does not affect people uniformly. Hence, markers of the underlying biological ageing process are needed to help identify people at increased risk of age-associated physical and cognitive impairments and ultimately, death. Here, we present such a biomarker, ‘brain-predicted age’, derived using structural neuroimaging. Brain-predicted age was calculated using machine-learning analysis, trained on neuroimaging data from a large healthy reference sample (N=2001), then tested in the Lothian Birth Cohort 1936 (N=669), to determine relationships with age-associated functional measures and mortality. Having a brain-predicted age indicative of an older-appearing brain was associated with: weaker grip strength, poorer lung function, slower walking speed, lower fluid intelligence, higher allostatic load and increased mortality risk. Furthermore, while combining brain-predicted age with grey matter and cerebrospinal fluid volumes (themselves strong predictors) not did improve mortality risk prediction, the combination of brain-predicted age and DNA-methylation-predicted age did. This indicates that neuroimaging and epigenetics measures of ageing can provide complementary data regarding health outcomes. Our study introduces a clinically-relevant neuroimaging ageing biomarker and demonstrates that combining distinct measurements of biological ageing further helps to determine risk of age-related deterioration and death. PMID:28439103

TiO2 micro-nano-hybrid surface to alleviate biological aging of UV-photofunctionalized titanium

PubMed Central

Iwasa, Fuminori; Tsukimura, Naoki; Sugita, Yoshihiko; Kanuru, Rajita Kodali; Kubo, Katsutoshi; Hasnain, Hafiz; Att, Wael; Ogawa, Takahiro

2011-01-01

Bioactivity and osteoconductivity of titanium degrade over time after surface processing. This time-dependent degradation is substantial and defined as the biological aging of titanium. UV treatment has shown to reactivate the aged surfaces, a process known as photofunctionalization. This study determined whether there is a difference in the behavior of biological aging for titanium with micro-nano-hybrid topography and titanium with microtopography alone, following functionalization. Titanium disks were acid etched to create micropits on the surface. Micro-nano-hybrid surfaces were created by depositioning 300-nm diameter TiO2 nodules onto the micropits using a previously established self-assembly protocol. These disks were stored for 8 weeks in the dark to allow sufficient aging, then treated with UV light for 48 hours. Rat bone marrow–derived osteoblasts were cultured on fresh disks (immediately after UV treatment), 3-day-old disks (disks stored for 3 days after UV treatment), and 7-day- old disks. The rates of cell attachment, spread, proliferation, and levels of alkaline phosphatase activity, and calcium deposition were reduced by 30%–50% on micropit surfaces, depending on the age of the titanium. In contrast, 7-day-old hybrid surfaces maintained equivalent levels of bioactivity compared with the fresh surfaces. Both micropit and micro-nano-hybrid surfaces were superhydrophilic immediately after UV treatment. However, after 7 days, the micro-nano- hybrid surfaces became hydrorepellent, while the micropit surfaces remained hydrophilic. The sustained bioactivity levels of the micro-nano-hybrid surfaces were nullified by treating these surfaces with Cl−anions. A thin TiO2 coating on the micropit surface without the formation of nanonodules did not result in the prevention or alleviation of the time-dependent decrease in biological activity. In conclusion, the micro-nano-hybrid titanium surfaces may slow the rate of time-dependent degradation of titanium bioactivity after UV photofunctionalization compared with titanium surfaces with microtopography alone. This antibiological aging effect was largely regulated by its sustained electropositivity uniquely conferred in TiO2 nanonodules, and was independent of the degree of hydrophilicity. These results demonstrate the potential usefulness of these hybrid surfaces to effectively utilize the benefits of UV photofunctionalization and provide a model to explore the mechanisms underlying antibiological aging properties. PMID:21760728

TiO2 micro-nano-hybrid surface to alleviate biological aging of UV-photofunctionalized titanium.

PubMed

Iwasa, Fuminori; Tsukimura, Naoki; Sugita, Yoshihiko; Kanuru, Rajita Kodali; Kubo, Katsutoshi; Hasnain, Hafiz; Att, Wael; Ogawa, Takahiro

2011-01-01

Bioactivity and osteoconductivity of titanium degrade over time after surface processing. This time-dependent degradation is substantial and defined as the biological aging of titanium. UV treatment has shown to reactivate the aged surfaces, a process known as photofunctionalization. This study determined whether there is a difference in the behavior of biological aging for titanium with micro-nano-hybrid topography and titanium with microtopography alone, following functionalization. Titanium disks were acid etched to create micropits on the surface. Micro-nano-hybrid surfaces were created by depositioning 300-nm diameter TiO(2) nodules onto the micropits using a previously established self-assembly protocol. These disks were stored for 8 weeks in the dark to allow sufficient aging, then treated with UV light for 48 hours. Rat bone marrow-derived osteoblasts were cultured on fresh disks (immediately after UV treatment), 3-day-old disks (disks stored for 3 days after UV treatment), and 7-day- old disks. The rates of cell attachment, spread, proliferation, and levels of alkaline phosphatase activity, and calcium deposition were reduced by 30%-50% on micropit surfaces, depending on the age of the titanium. In contrast, 7-day-old hybrid surfaces maintained equivalent levels of bioactivity compared with the fresh surfaces. Both micropit and micro-nano-hybrid surfaces were superhydrophilic immediately after UV treatment. However, after 7 days, the micro-nano- hybrid surfaces became hydrorepellent, while the micropit surfaces remained hydrophilic. The sustained bioactivity levels of the micro-nano-hybrid surfaces were nullified by treating these surfaces with Cl(-)anions. A thin TiO(2) coating on the micropit surface without the formation of nanonodules did not result in the prevention or alleviation of the time-dependent decrease in biological activity. In conclusion, the micro-nano-hybrid titanium surfaces may slow the rate of time-dependent degradation of titanium bioactivity after UV photofunctionalization compared with titanium surfaces with microtopography alone. This antibiological aging effect was largely regulated by its sustained electropositivity uniquely conferred in TiO(2) nanonodules, and was independent of the degree of hydrophilicity. These results demonstrate the potential usefulness of these hybrid surfaces to effectively utilize the benefits of UV photofunctionalization and provide a model to explore the mechanisms underlying antibiological aging properties.

Deep sequencing identifies circulating mouse miRNAs that are functionally implicated in manifestations of aging and responsive to calorie restriction.

PubMed

Dhahbi, Joseph M; Spindler, Stephen R; Atamna, Hani; Yamakawa, Amy; Guerrero, Noel; Boffelli, Dario; Mote, Patricia; Martin, David I K

2013-02-01

MicroRNAs (miRNAs) function to modulate gene expression, and through this property they regulate a broad spectrum of cellular processes. They can circulate in blood and thereby mediate cell-to-cell communication. Aging involves changes in many cellular processes that are potentially regulated by miRNAs, and some evidence has implicated circulating miRNAs in the aging process. In order to initiate a comprehensive assessment of the role of circulating miRNAs in aging, we have used deep sequencing to characterize circulating miRNAs in the serum of young mice, old mice, and old mice maintained on calorie restriction (CR). Deep sequencing identifies a set of novel miRNAs, and also accurately measures all known miRNAs present in serum. This analysis demonstrates that the levels of many miRNAs circulating in the mouse are increased with age, and that the increases can be antagonized by CR. The genes targeted by this set of age-modulated miRNAs are predicted to regulate biological processes directly relevant to the manifestations of aging including metabolic changes, and the miRNAs themselves have been linked to diseases associated with old age. This finding implicates circulating miRNAs in the aging process, raising questions about their tissues of origin, their cellular targets, and their functional role in metabolic changes that occur with aging.

Young adult survivors of childhood acute lymphoblastic leukemia show evidence of chronic inflammation and cellular aging.

PubMed

Ariffin, Hany; Azanan, Mohamad Shafiq; Abd Ghafar, Sayyidatul Syahirah; Oh, Lixian; Lau, Kee Hie; Thirunavakarasu, Tharshanadhevasheri; Sedan, Atiqah; Ibrahim, Kamariah; Chan, Adelyne; Chin, Tong Foh; Liew, Fong Fong; Jeyamogan, Shareni; Rosli, Erda Syerena; Baharudin, Rashidah; Yap, Tsiao Yi; Skinner, Roderick; Lum, Su Han; Hainaut, Pierre

2017-11-01

Large epidemiologic studies have reported the premature onset of age-related conditions, such as ischemic heart disease and diabetes mellitus, in childhood cancer survivors, decades earlier than in their peers. The authors investigated whether young adult survivors of childhood acute lymphoblastic leukemia (ALL) have a biologic phenotype of cellular ageing and chronic inflammation. Plasma inflammatory cytokines were measured using a cytometric bead array in 87 asymptomatic young adult survivors of childhood ALL (median age, 25 years; age range, 18-35 years) who attended annual follow-up clinic and compared with healthy, age-matched and sex-matched controls. Leukocyte telomere length (LTL) was measured using Southern blot analysis. Survivors had significant elevation of plasma interleukin-2 (IL-2), IL-10, IL-17a, and high-sensitivity C-reactive protein levels (all P < .05). A raised high-sensitivity C-reactive protein level (>0.8 mg/dL) was related to increased odds of having metabolic syndrome (odds ratio, 7.256; 95% confidence interval, 1.501-35.074). Survivors also had significantly shorter LTL compared with controls (median, 9866 vs 10,392 base pairs; P = .021). Compared with published data, LTL in survivors was similar to that in healthy individuals aged 20 years older. Survivors who received cranial irradiation had shorter LTL compared with those who had not (P = .013). Asymptomatic young adult survivors of childhood ALL demonstrate a biologic profile of chronic inflammation and telomere attrition, consistent with an early onset of cellular processes that drive accelerated aging. These processes may explain the premature development of age-related chronic conditions in childhood cancer survivors. Understanding their molecular basis may facilitate targeted interventions to disrupt the accelerated aging process and its long-term impact on overall health. Cancer 2017;123:4207-4214. © 2017 American Cancer Society. © 2017 American Cancer Society.

Epigenetic Age Acceleration Assessed with Human White-Matter Images.

PubMed

Hodgson, Karen; Carless, Melanie A; Kulkarni, Hemant; Curran, Joanne E; Sprooten, Emma; Knowles, Emma E; Mathias, Samuel; Göring, Harald H H; Yao, Nailin; Olvera, Rene L; Fox, Peter T; Almasy, Laura; Duggirala, Ravi; Blangero, John; Glahn, David C

2017-05-03

The accurate estimation of age using methylation data has proved a useful and heritable biomarker, with acceleration in epigenetic age predicting a number of age-related phenotypes. Measures of white matter integrity in the brain are also heritable and highly sensitive to both normal and pathological aging processes across adulthood. We consider the phenotypic and genetic interrelationships between epigenetic age acceleration and white matter integrity in humans. Our goal was to investigate processes that underlie interindividual variability in age-related changes in the brain. Using blood taken from a Mexican-American extended pedigree sample ( n = 628; age = 23.28-93.11 years), epigenetic age was estimated using the method developed by Horvath (2013). For n = 376 individuals, diffusion tensor imaging scans were also available. The interrelationship between epigenetic age acceleration and global white matter integrity was investigated with variance decomposition methods. To test for neuroanatomical specificity, 16 specific tracts were additionally considered. We observed negative phenotypic correlations between epigenetic age acceleration and global white matter tract integrity (ρ pheno = -0.119, p = 0.028), with evidence of shared genetic (ρ gene = -0.463, p = 0.013) but not environmental influences. Negative phenotypic and genetic correlations with age acceleration were also seen for a number of specific white matter tracts, along with additional negative phenotypic correlations between granulocyte abundance and white matter integrity. These findings (i.e., increased acceleration in epigenetic age in peripheral blood correlates with reduced white matter integrity in the brain and shares common genetic influences) provide a window into the neurobiology of aging processes within the brain and a potential biomarker of normal and pathological brain aging. SIGNIFICANCE STATEMENT Epigenetic measures can be used to predict age with a high degree of accuracy and so capture acceleration in biological age, relative to chronological age. The white matter tracts within the brain are also highly sensitive to aging processes. We show that increased biological aging (measured using epigenetic data from blood samples) is correlated with reduced integrity of white matter tracts within the human brain (measured using diffusion tensor imaging) with data from a large sample of Mexican-American families. Given the family design of the sample, we are also able to demonstrate that epigenetic aging and white matter tract integrity also share common genetic influences. Therefore, epigenetic age may be a potential, and accessible, biomarker of brain aging. Copyright © 2017 the authors 0270-6474/17/374735-09$15.00/0.

Skin anti-aging strategies

PubMed Central

Ganceviciene, Ruta; Liakou, Aikaterini I.; Theodoridis, Athanasios; Makrantonaki, Evgenia; Zouboulis, Christos C.

2012-01-01

Skin aging is a complex biological process influenced by a combination of endogenous or intrinsic and exogenous or extrinsic factors. Because of the fact that skin health and beauty is considered one of the principal factors representing overall “well-being” and the perception of “health” in humans, several anti-aging strategies have been developed during the last years. It is the intention of this article to review the most important anti-aging strategies that dermatologists have nowadays in hand, including including preventive measurements, cosmetological strategies, topical and systemic therapeutic agents and invasive procedures. PMID:23467476

Current research in aging: a report from the 2015 Ageing Summit.

PubMed

Moyse, Emmanuel; Lahousse, Lies; Krantic, Slavica

2015-01-01

Ageing Summit, London, UK, 10-12 February 2015 The Ageing Summit 2015 held on 10-12 February 2015 in London (UK) provided an extensive update to our knowledge of the 'Biology of Ageing' and a forum to discuss the participants' latest research progress. The meeting was subdivided into four thematic sessions: cellular level research including the aging brain; slowing down progression, rejuvenation and self-repair; genetic and epigenetic regulation; and expression and pathology of age-related diseases. Each session included multiple key presentations, three to five short research communications and ongoing poster presentations. The meeting provided an exciting multidisciplinary overview of the aging process from cellular and molecular mechanisms to medico-social aspects of human aging.

The free radical theory of aging revisited: the cell signaling disruption theory of aging.

PubMed

Viña, Jose; Borras, Consuelo; Abdelaziz, Kheira M; Garcia-Valles, Rebeca; Gomez-Cabrera, Mari Carmen

2013-09-10

The free radical theory of aging has provided a theoretical framework for an enormous amount of work leading to significant advances in our understanding of aging. Up to the turn of the century, the theory received abundant support from observations coming from fields as far apart as comparative physiology or molecular biology. Work from many laboratories supports the theory, for instance showing that overexpression of antioxidant enzymes results in increases in life-span. But other labs have shown that in some cases, there is an increased oxidative stress and increased longevity. The discovery that free radicals can not only cause molecular damage to cells, but also serve as signals; led to the proposal that they act as modulators of physiological processes. For instance, reactive oxygen species (ROS) stimulate physiological adaptations to physical exercise. A critical blow to the free radical theory of aging came from epidemiological studies showing that antioxidant supplementation did not lower the incidence of many age-associated diseases but, in some cases, increased the risk of death. Moreover, recent molecular evidence has shown that increasing generation of ROS, in some cases, increases longevity. Gerontologists interested in free radical biology are at a crossroads and clearly new insights are required to clarify the role of ROS in the process of aging. The hurdles are, no doubt, very high, but the intellectual and practical promise of these studies is of such magnitude that we feel that all efforts will be generously rewarding.

Frameworks for Proof-of-Concept Clinical Trials of Interventions That Target Fundamental Aging Processes

PubMed Central

Justice, Jamie; Miller, Jordan D.; Newman, John C.; Hashmi, Shahrukh K.; Halter, Jeffrey; Austad, Steve N.; Barzilai, Nir

2016-01-01

Therapies targeted at fundamental processes of aging may hold great promise for enhancing the health of a wide population by delaying or preventing a range of age-related diseases and conditions—a concept dubbed the “geroscience hypothesis.” Early, proof-of-concept clinical trials will be a key step in the translation of therapies emerging from model organism and preclinical studies into clinical practice. This article summarizes the outcomes of an international meeting partly funded through the NIH R24 Geroscience Network, whose purpose was to generate concepts and frameworks for early, proof-of-concept clinical trials for therapeutic interventions that target fundamental processes of aging. The goals of proof-of-concept trials include generating preliminary signals of efficacy in an aging-related disease or outcome that will reduce the risk of conducting larger trials, contributing data and biological samples to support larger-scale research by strategic networks, and furthering a dialogue with regulatory agencies on appropriate registration indications. We describe three frameworks for proof-of-concept trials that target age-related chronic diseases, geriatric syndromes, or resilience to stressors. We propose strategic infrastructure and shared resources that could accelerate development of therapies that target fundamental aging processes. PMID:27535966

Extracellular Vesicles: How the External and Internal Environment Can Shape Cell-To-Cell Communication.

PubMed

Neven, Kristof Y; Nawrot, Tim S; Bollati, Valentina

2017-03-01

To summarize the scientific evidence regarding the effects of environmental exposures on extracellular vesicle (EV) release and their contents. As environmental exposures might influence the aging phenotype in a very strict way, we will also report the role of EVs in the biological aging process. EV research is a new and quickly developing field. With many investigations conducted so far, only a limited number of studies have explored the potential role EVs play in the response and adaptation to environmental stimuli. The investigations available to date have identified several exposures or lifestyle factors able to modify EV trafficking including air pollutants, cigarette smoke, alcohol, obesity, nutrition, physical exercise, and oxidative stress. EVs are a very promising tool, as biological fluids are easily obtainable biological media that, if successful in identifying early alterations induced by the environment and predictive of disease, would be amenable to use for potential future preventive and diagnostic applications.

Potential Mars Exploration Rover Landing Sites West and South of Apollinaris Patera

NASA Technical Reports Server (NTRS)

Gulick, Virginia C.

2001-01-01

Apollinaris provides an exceptional site for astrobiological, geological, and climatalogical purposes. Fluvial (including ground water sapping) and associated processes were likely pervasive from the late Noachian, through the Hesperian, and into the Amazonian. Long-lived and large scale hydrothermal systems were certainly present throughout much if not all of this period. Thermal springs likely persisted for long periods. Water from the highlands via Ma'adim Valles and other smaller valley networks deposited highland-derived material in the area. In short, Apollinaris provides an excellent variety of rock types and ages and may preserve evidence of biologic or pre-biologic processes in associated thermal spring deposits.

Pattern identification in time-course gene expression data with the CoGAPS matrix factorization.

PubMed

Fertig, Elana J; Stein-O'Brien, Genevieve; Jaffe, Andrew; Colantuoni, Carlo

2014-01-01

Patterns in time-course gene expression data can represent the biological processes that are active over the measured time period. However, the orthogonality constraint in standard pattern-finding algorithms, including notably principal components analysis (PCA), confounds expression changes resulting from simultaneous, non-orthogonal biological processes. Previously, we have shown that Markov chain Monte Carlo nonnegative matrix factorization algorithms are particularly adept at distinguishing such concurrent patterns. One such matrix factorization is implemented in the software package CoGAPS. We describe the application of this software and several technical considerations for identification of age-related patterns in a public, prefrontal cortex gene expression dataset.

Effect of age on toxicokinetics among human volunteers exposed to propylene glycol methyl ether (PGME).

PubMed

Hopf, Nancy B; Vernez, David; Berthet, Aurelie; Charriere, Nicole; Arnoux, Christine; Tomicic, Catherine

2012-05-20

Aging adults represent the fastest growing population segment in many countries. Physiological and metabolic changes in the aging process may alter how aging adults biologically respond to pollutants. In a controlled human toxicokinetic study (exposure chamber; 12 m³), aging volunteers (n=10; >58 years) were exposed to propylene glycol monomethyl ether (PGME, CAS no. 107-98-2) at 50 ppm for 6 h. The dose-dependent renal excretion of oxidative metabolites, conjugated and free PGME could potentially be altered by age. (1) Compare PGME toxicokinetic profiles between aging and young volunteers (20-25 years) and gender; (2) test the predictive power of a compartmental toxicokinetic (TK) model developed for aging persons against urinary PGME concentrations found in this study. Urine samples were collected before, during, and after the exposure. Urinary PGME was quantified by capillary GC/FID. Differences in urinary PGME profiles were not noted between genders but between age groups. Metabolic parameters had to be changed to fit the age adjusted TK model to the experimental results, implying a slower enzymatic pathway in the aging volunteers. For an appropriate exposure assessment, urinary total PGME should be quantified. Age is a factor that should be considered when biological limit values are developed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Differential Proteome Analysis of a Flor Yeast Strain under Biofilm Formation.

PubMed

Moreno-García, Jaime; Mauricio, Juan Carlos; Moreno, Juan; García-Martínez, Teresa

2017-03-28

Several Saccharomyces cerevisiae strains (flor yeasts) form a biofilm (flor velum) on the surface of Sherry wines after fermentation, when glucose is depleted. This flor velum is fundamental to biological aging of these particular wines. In this study, we identify abundant proteins in the formation of the biofilm of an industrial flor yeast strain. A database search to enrich flor yeast "biological process" and "cellular component" according to Gene Ontology Terminology (GO Terms) and, "pathways" was carried out. The most abundant proteins detected were largely involved in respiration, translation, stress damage prevention and repair, amino acid metabolism (glycine, isoleucine, leucine and arginine), glycolysis/gluconeogenesis and biosynthesis of vitamin B9 (folate). These proteins were located in cellular components as in the peroxisome, mitochondria, vacuole, cell wall and extracellular region; being these two last directly related with the flor formation. Proteins like Bgl2p, Gcv3p, Hyp2p, Mdh1p, Suc2p and Ygp1p were quantified in very high levels. This study reveals some expected processes and provides new and important information for the design of conditions and genetic constructions of flor yeasts for improving the cellular survival and, thus, to optimize biological aging of Sherry wine production.

Klotho, stem cells, and aging.

PubMed

Bian, Ao; Neyra, Javier A; Zhan, Ming; Hu, Ming Chang

2015-01-01

Aging is an inevitable and progressive biological process involving dysfunction and eventually destruction of every tissue and organ. This process is driven by a tightly regulated and complex interplay between genetic and acquired factors. Klotho is an antiaging gene encoding a single-pass transmembrane protein, klotho, which serves as an aging suppressor through a wide variety of mechanisms, such as antioxidation, antisenescence, antiautophagy, and modulation of many signaling pathways, including insulin-like growth factor and Wnt. Klotho deficiency activates Wnt expression and activity contributing to senescence and depletion of stem cells, which consequently triggers tissue atrophy and fibrosis. In contrast, the klotho protein was shown to suppress Wnt-signaling transduction, and inhibit cell senescence and preserve stem cells. A better understanding of the potential effects of klotho on stem cells could offer novel insights into the cellular and molecular mechanisms of klotho deficiency-related aging and disease. The klotho protein may be a promising therapeutic agent for aging and aging-related disorders.

Redox proteomics and drug development.

PubMed

D'Alessandro, Angelo; Rinalducci, Sara; Zolla, Lello

2011-11-18

As alterations of the redox homeostasis lie at the root of many pathophysiological processes in human health, redox proteomics holds the promise to shed further light on fundamental biological processes. In this review, the mechanisms of reactive oxygen species (ROS) and reactive nitrogen species (RNS) production are reviewed, mainly addressing those chemical phenomena which have already been associated with pathological conditions (of the central nervous system, cardiovascular system, or simply related to aging and altered-cell cycle regulation). From Alzheimer's to Parkinson's and Hungtinton's disease, from ageing to cancer, oxidative stress (OS) appears to represent a common trait in so many relevant biological aspects of human health, that further investments in the field of redox proteomics ought to be mandatory. For the foreseeable future, redox proteomics will likely play a pivotal role in the quest for new therapeutical targets and their validation, in the process of determining OS-triggered cellular alteration upon drug treatments and thus in the very heart of the design and testing of new drugs and their metabolites against those pathologies relying on altered redox homeostasis. Copyright © 2011 Elsevier B.V. All rights reserved.

Metabolic Free Energy and Biological Codes: A 'Data Rate Theorem' Aging Model.

PubMed

Wallace, Rodrick

2015-06-01

A famous argument by Maturana and Varela (Autopoiesis and cognition. Reidel, Dordrecht, 1980) holds that the living state is cognitive at every scale and level of organization. Since it is possible to associate many cognitive processes with 'dual' information sources, pathologies can sometimes be addressed using statistical models based on the Shannon Coding, the Shannon-McMillan Source Coding, the Rate Distortion, and the Data Rate Theorems, which impose necessary conditions on information transmission and system control. Deterministic-but-for-error biological codes do not directly invoke cognition, but may be essential subcomponents within larger cognitive processes. A formal argument, however, places such codes within a similar framework, with metabolic free energy serving as a 'control signal' stabilizing biochemical code-and-translator dynamics in the presence of noise. Demand beyond available energy supply triggers punctuated destabilization of the coding channel, affecting essential biological functions. Aging, normal or prematurely driven by psychosocial or environmental stressors, must interfere with the routine operation of such mechanisms, initiating the chronic diseases associated with senescence. Amyloid fibril formation, intrinsically disordered protein logic gates, and cell surface glycan/lectin 'kelp bed' logic gates are reviewed from this perspective. The results generalize beyond coding machineries having easily recognizable symmetry modes, and strip a layer of mathematical complication from the study of phase transitions in nonequilibrium biological systems.

Early-life stress and reproductive cost: A two-hit developmental model of accelerated aging?

PubMed

Shalev, Idan; Belsky, Jay

2016-05-01

Two seemingly independent bodies of research suggest a two-hit model of accelerated aging, one highlighting early-life stress and the other reproduction. The first, informed by developmental models of early-life stress, highlights reduced longevity effects of early adversity on telomere erosion, whereas the second, informed by evolutionary theories of aging, highlights such effects with regard to reproductive cost (in females). The fact that both early-life adversity and reproductive effort are associated with shorter telomeres and increased oxidative stress raises the prospect, consistent with life-history theory, that these two theoretical frameworks currently informing much research are tapping into the same evolutionary-developmental process of increased senescence and reduced longevity. Here we propose a mechanistic view of a two-hit model of accelerated aging in human females through (a) early-life adversity and (b) early reproduction, via a process of telomere erosion, while highlighting mediating biological embedding mechanisms that might link these two developmental aging processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

The role of nutraceuticals in anti-aging medicine.

PubMed

Vranesić-Bender, Darija

2010-12-01

'Nutraceuticals' is a wide term including all kinds of food with health or medical effect. Regulations in the world on functional food and nutraceuticals are developed along with the development of new products. This nomenclature is not aligned across legal regulations in different countries. There are several theories trying to interpret the phenomenon of aging and the most interesting theory in terms of nutrition is free radical theory and the possible role of antioxidants in aging process. A large group of substances including vitamins, carotenoids, flavonoids and minerals have in vitro or in vivo clinically significant antioxidant characteristics. There is great interest in anti-aging substances derived from food, and the most popular ingredients are antioxidants, especially coenzyme Q10, phytoestrogens, probiotics and omega-3 fatty acids. These substances have beneficial effect on digestive and immune systems, and modulate inflammatory and degenerative processes in the body. The challenge in the future will be strategic combining of cosmeceuticals and nutraceuticals in order to intervene in biological aging processes and degenerative skin changes.

Evolution of the rate of biological aging using a phenotype based computational model.

PubMed

Kittas, Aristotelis

2010-10-07

In this work I introduce a simple model to study how natural selection acts upon aging, which focuses on the viability of each individual. It is able to reproduce the Gompertz law of mortality and can make predictions about the relation between the level of mutation rates (beneficial/deleterious/neutral), age at reproductive maturity and the degree of biological aging. With no mutations, a population with low age at reproductive maturity R stabilizes at higher density values, while with mutations it reaches its maximum density, because even for large pre-reproductive periods each individual evolves to survive to maturity. Species with very short pre-reproductive periods can only tolerate a small number of detrimental mutations. The probabilities of detrimental (P(d)) or beneficial (P(b)) mutations are demonstrated to greatly affect the process. High absolute values produce peaks in the viability of the population over time. Mutations combined with low selection pressure move the system towards weaker phenotypes. For low values in the ratio P(d)/P(b), the speed at which aging occurs is almost independent of R, while higher values favor significantly species with high R. The value of R is critical to whether the population survives or dies out. The aging rate is controlled by P(d) and P(b) and the amount of the viability of each individual is modified, with neutral mutations allowing the system more "room" to evolve. The process of aging in this simple model is revealed to be fairly complex, yielding a rich variety of results. 2010 Elsevier Ltd. All rights reserved.

A statistical approach to quasi-extinction forecasting.

PubMed

Holmes, Elizabeth Eli; Sabo, John L; Viscido, Steven Vincent; Fagan, William Fredric

2007-12-01

Forecasting population decline to a certain critical threshold (the quasi-extinction risk) is one of the central objectives of population viability analysis (PVA), and such predictions figure prominently in the decisions of major conservation organizations. In this paper, we argue that accurate forecasting of a population's quasi-extinction risk does not necessarily require knowledge of the underlying biological mechanisms. Because of the stochastic and multiplicative nature of population growth, the ensemble behaviour of population trajectories converges to common statistical forms across a wide variety of stochastic population processes. This paper provides a theoretical basis for this argument. We show that the quasi-extinction surfaces of a variety of complex stochastic population processes (including age-structured, density-dependent and spatially structured populations) can be modelled by a simple stochastic approximation: the stochastic exponential growth process overlaid with Gaussian errors. Using simulated and real data, we show that this model can be estimated with 20-30 years of data and can provide relatively unbiased quasi-extinction risk with confidence intervals considerably smaller than (0,1). This was found to be true even for simulated data derived from some of the noisiest population processes (density-dependent feedback, species interactions and strong age-structure cycling). A key advantage of statistical models is that their parameters and the uncertainty of those parameters can be estimated from time series data using standard statistical methods. In contrast for most species of conservation concern, biologically realistic models must often be specified rather than estimated because of the limited data available for all the various parameters. Biologically realistic models will always have a prominent place in PVA for evaluating specific management options which affect a single segment of a population, a single demographic rate, or different geographic areas. However, for forecasting quasi-extinction risk, statistical models that are based on the convergent statistical properties of population processes offer many advantages over biologically realistic models.

Aging scaled Brownian motion

NASA Astrophysics Data System (ADS)

Safdari, Hadiseh; Chechkin, Aleksei V.; Jafari, Gholamreza R.; Metzler, Ralf

2015-04-01

Scaled Brownian motion (SBM) is widely used to model anomalous diffusion of passive tracers in complex and biological systems. It is a highly nonstationary process governed by the Langevin equation for Brownian motion, however, with a power-law time dependence of the noise strength. Here we study the aging properties of SBM for both unconfined and confined motion. Specifically, we derive the ensemble and time averaged mean squared displacements and analyze their behavior in the regimes of weak, intermediate, and strong aging. A very rich behavior is revealed for confined aging SBM depending on different aging times and whether the process is sub- or superdiffusive. We demonstrate that the information on the aging factorizes with respect to the lag time and exhibits a functional form that is identical to the aging behavior of scale-free continuous time random walk processes. While SBM exhibits a disparity between ensemble and time averaged observables and is thus weakly nonergodic, strong aging is shown to effect a convergence of the ensemble and time averaged mean squared displacement. Finally, we derive the density of first passage times in the semi-infinite domain that features a crossover defined by the aging time.

Aging scaled Brownian motion.

PubMed

Safdari, Hadiseh; Chechkin, Aleksei V; Jafari, Gholamreza R; Metzler, Ralf

2015-04-01

Scaled Brownian motion (SBM) is widely used to model anomalous diffusion of passive tracers in complex and biological systems. It is a highly nonstationary process governed by the Langevin equation for Brownian motion, however, with a power-law time dependence of the noise strength. Here we study the aging properties of SBM for both unconfined and confined motion. Specifically, we derive the ensemble and time averaged mean squared displacements and analyze their behavior in the regimes of weak, intermediate, and strong aging. A very rich behavior is revealed for confined aging SBM depending on different aging times and whether the process is sub- or superdiffusive. We demonstrate that the information on the aging factorizes with respect to the lag time and exhibits a functional form that is identical to the aging behavior of scale-free continuous time random walk processes. While SBM exhibits a disparity between ensemble and time averaged observables and is thus weakly nonergodic, strong aging is shown to effect a convergence of the ensemble and time averaged mean squared displacement. Finally, we derive the density of first passage times in the semi-infinite domain that features a crossover defined by the aging time.

Using the brain's fight-or-flight response for predicting mental illness on the human space flight program

NASA Astrophysics Data System (ADS)

Losik, L.

A predictive medicine program allows disease and illness including mental illness to be predicted using tools created to identify the presence of accelerated aging (a.k.a. disease) in electrical and mechanical equipment. When illness and disease can be predicted, actions can be taken so that the illness and disease can be prevented and eliminated. A predictive medicine program uses the same tools and practices from a prognostic and health management program to process biological and engineering diagnostic data provided in analog telemetry during prelaunch readiness and space exploration missions. The biological and engineering diagnostic data necessary to predict illness and disease is collected from the pre-launch spaceflight readiness activities and during space flight for the ground crew to perform a prognostic analysis on the results from a diagnostic analysis. The diagnostic, biological data provided in telemetry is converted to prognostic (predictive) data using the predictive algorithms. Predictive algorithms demodulate telemetry behavior. They illustrate the presence of accelerated aging/disease in normal appearing systems that function normally. Mental illness can predicted using biological diagnostic measurements provided in CCSDS telemetry from a spacecraft such as the ISS or from a manned spacecraft in deep space. The measurements used to predict mental illness include biological and engineering data from an astronaut's circadian and ultranian rhythms. This data originates deep in the brain that is also damaged from the long-term exposure to cortisol and adrenaline anytime the body's fight or flight response is activated. This paper defines the brain's FOFR; the diagnostic, biological and engineering measurements needed to predict mental illness, identifies the predictive algorithms necessary to process the behavior in CCSDS analog telemetry to predict and thus prevent mental illness from occurring on human spaceflight missions.

Evolution of aging: individual life history trade-offs and population heterogeneity account for mortality patterns across species.

PubMed

Le Cunff, Y; Baudisch, A; Pakdaman, K

2014-08-01

A broad range of mortality patterns has been documented across species, some even including decreasing mortality over age. Whether there exist a common denominator to explain both similarities and differences in these mortality patterns remains an open question. The disposable soma theory, an evolutionary theory of aging, proposes that universal intracellular trade-offs between maintenance/lifespan and reproduction would drive aging across species. The disposable soma theory has provided numerous insights concerning aging processes in single individuals. Yet, which specific population mortality patterns it can lead to is still largely unexplored. In this article, we propose a model exploring the mortality patterns which emerge from an evolutionary process including only the disposable soma theory core principles. We adapt a well-known model of genomic evolution to show that mortality curves producing a kink or mid-life plateaus derive from a common minimal evolutionary framework. These mortality shapes qualitatively correspond to those of Drosophila melanogaster, Caenorhabditis elegans, medflies, yeasts and humans. Species evolved in silico especially differ in their population diversity of maintenance strategies, which itself emerges as an adaptation to the environment over generations. Based on this integrative framework, we also derive predictions and interpretations concerning the effects of diet changes and heat-shock treatments on mortality patterns. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Pubertal status associations with reward and threat sensitivities and subcortical brain volumes during adolescence.

PubMed

Urošević, Snežana; Collins, Paul; Muetzel, Ryan; Lim, Kelvin O; Luciana, Monica

2014-08-01

Adolescence is characterized by complex developmental processes that impact behavior, biology, and social functioning. Two such adolescence-specific processes are puberty and increases in reward sensitivity. Relations between these processes are poorly understood. The present study focused on examining unique effects of puberty, age, and sex on reward and threat sensitivities and volumes of subcortical brain structures relevant for reward/threat processing in a healthy sample of 9-18year-olds. Unlike age, pubertal status had a significant unique positive relationship with reward sensitivity. In addition, there was a trend for adolescent females to exhibit higher threat sensitivity with more advanced pubertal development and higher reward and threat sensitivity with older age. Similarly, there were significant puberty by sex interaction effects on striatal volumes, i.e., left nucleus accumbens and right pallidum. The present pattern of results suggests that pubertal development, independent of chronological age, is uniquely associated with reward hypersensitivity and with structural differences in striatal regions implicated in reward processing. Copyright © 2014 Elsevier Inc. All rights reserved.

Children's Sexual Thinking: A Comparative Study of Children Aged 5 to 15 Years in Australia, North America, Britain and Sweden.

ERIC Educational Resources Information Center

Goldman, Ronald; Goldman, Juliette

The purpose of this cross-national descriptive study is to measure the extent of children's sexual knowledge and sexual understanding at various ages and to identify what processes of thought children use in trying to explain biological functions and the phenomena of their own bodies as they grow and change. Sexual thinking is defined as thinking…

Biological and physical controls in the Southern Ocean on past millennial-scale atmospheric CO2 changes.

PubMed

Gottschalk, Julia; Skinner, Luke C; Lippold, Jörg; Vogel, Hendrik; Frank, Norbert; Jaccard, Samuel L; Waelbroeck, Claire

2016-05-17

Millennial-scale climate changes during the last glacial period and deglaciation were accompanied by rapid changes in atmospheric CO2 that remain unexplained. While the role of the Southern Ocean as a 'control valve' on ocean-atmosphere CO2 exchange has been emphasized, the exact nature of this role, in particular the relative contributions of physical (for example, ocean dynamics and air-sea gas exchange) versus biological processes (for example, export productivity), remains poorly constrained. Here we combine reconstructions of bottom-water [O2], export production and (14)C ventilation ages in the sub-Antarctic Atlantic, and show that atmospheric CO2 pulses during the last glacial- and deglacial periods were consistently accompanied by decreases in the biological export of carbon and increases in deep-ocean ventilation via southern-sourced water masses. These findings demonstrate how the Southern Ocean's 'organic carbon pump' has exerted a tight control on atmospheric CO2, and thus global climate, specifically via a synergy of both physical and biological processes.

Biological and physical controls in the Southern Ocean on past millennial-scale atmospheric CO2 changes

PubMed Central

Gottschalk, Julia; Skinner, Luke C.; Lippold, Jörg; Vogel, Hendrik; Frank, Norbert; Jaccard, Samuel L.; Waelbroeck, Claire

2016-01-01

Millennial-scale climate changes during the last glacial period and deglaciation were accompanied by rapid changes in atmospheric CO2 that remain unexplained. While the role of the Southern Ocean as a 'control valve' on ocean–atmosphere CO2 exchange has been emphasized, the exact nature of this role, in particular the relative contributions of physical (for example, ocean dynamics and air–sea gas exchange) versus biological processes (for example, export productivity), remains poorly constrained. Here we combine reconstructions of bottom-water [O2], export production and 14C ventilation ages in the sub-Antarctic Atlantic, and show that atmospheric CO2 pulses during the last glacial- and deglacial periods were consistently accompanied by decreases in the biological export of carbon and increases in deep-ocean ventilation via southern-sourced water masses. These findings demonstrate how the Southern Ocean's 'organic carbon pump' has exerted a tight control on atmospheric CO2, and thus global climate, specifically via a synergy of both physical and biological processes. PMID:27187527

Sirtuins, Melatonin and Circadian Rhythms: Building a Bridge between Aging and Cancer

PubMed Central

Jung-Hynes, Brittney; Reiter, Russel J.; Ahmad, Nihal

2010-01-01

Histone deacetylases (HDACs) have been under intense scientific investigation for a number of years. However, only recently the unique class III HDACs, sirtuins, have gained increasing investigational momentum. Originally linked to longevity in yeast, sirtuins and more specifically, SIRT1 have been implicated in numerous biological processes having both protective and/or detrimental effects. SIRT1 appears to play a critical role in the process of carcinogenesis, especially in age-related neoplasms. Similarly, alterations in circadian rhythms as well as production of the pineal hormone melatonin have been linked to aging and cancer risk. Melatonin has been found act as a differentiating agent in some cancer cells and to lower their invasive and metastatic status. In addition, melatonin synthesis and release occurs in a circadian rhythm fashion and it has been linked to the core circadian machinery genes (Clock, Bmal1, Periods, and Cryptochromes). Melatonin has also been associated with chronotherapy, the timely administration of chemotherapy agents to optimize trends in biological cycles. Interestingly, a recent set of studies have linked SIRT1 to the circadian rhythm machinery through direct deacetylation activity as well as through the NAD+ salvage pathway. In this review, we provide evidence for a possible connection between sirtuins, melatonin, and the circadian rhythm circuitry and their implications in aging, chronomodulation and cancer. PMID:20025641

Mitochondrial bioenergetics decay in aging: beneficial effect of melatonin.

PubMed

Paradies, Giuseppe; Paradies, Valeria; Ruggiero, Francesca M; Petrosillo, Giuseppe

2017-11-01

Aging is a biological process characterized by progressive decline in physiological functions, increased oxidative stress, reduced capacity to respond to stresses, and increased risk of contracting age-associated disorders. Mitochondria are referred to as the powerhouse of the cell through their role in the oxidative phosphorylation to generate ATP. These organelles contribute to the aging process, mainly through impairment of electron transport chain activity, opening of the mitochondrial permeability transition pore and increased oxidative stress. These events lead to damage to proteins, lipids and mitochondrial DNA. Cardiolipin, a phospholipid of the inner mitochondrial membrane, plays a pivotal role in several mitochondrial bioenergetic processes as well as in mitochondrial-dependent steps of apoptosis and in mitochondrial membrane stability and dynamics. Cardiolipin alterations are associated with mitochondrial bienergetics decline in multiple tissues in a variety of physiopathological conditions, as well as in the aging process. Melatonin, the major product of the pineal gland, is considered an effective protector of mitochondrial bioenergetic function. Melatonin preserves mitochondrial function by preventing cardiolipin oxidation and this may explain, at least in part, the protective role of this compound in mitochondrial physiopathology and aging. Here, mechanisms through which melatonin exerts its protective role against mitochondrial dysfunction associated with aging and age-associated disorders are discussed.

Balancing Between Aging and Cancer: Molecular Genetics Meets Traditional Chinese Medicine.

PubMed

Liu, Jing; Peng, Lei; Huang, Wenhui; Li, Zhiming; Pan, Jun; Sang, Lei; Lu, Siqian; Zhang, Jihong; Li, Wanyi; Luo, Ying

2017-09-01

The biological consequences of cellular senescence and immortalization in aging and cancer are in conflict. Organisms have developed common cellular signaling pathways and surveillance mechanisms to control the processing of aging against tumorigenesis. The imbalance of any signals involved in this process may result in either premature aging or tumorigenesis and reduce the life span of the organism. In contrast, the balance between aging and tumorigenesis at a higher level (homeostatic-balance) may benefit the organism with tumor-free longevity. The focus of this perspective is to review the literature on the balance between "Yin" and "Yang" in traditional Chinese medicine. Modern cellular and molecular techniques now permit a more robust system to screen herbs in traditional Chinese medicine for their activity in balancing aging and tumorigenesis. The understanding of the crosstalk between aging and tumorigenesis and new perspectives on the application of Chinese medicine might shed light on anti-aging and tumor-free strategies. J. Cell. Biochem. 118: 2581-2586, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Oxidative Stress and Epigenetic Regulation in Ageing and Age-Related Diseases

PubMed Central

Cencioni, Chiara; Spallotta, Francesco; Martelli, Fabio; Valente, Sergio; Mai, Antonello; Zeiher, Andreas M.; Gaetano, Carlo

2013-01-01

Recent statistics indicate that the human population is ageing rapidly. Healthy, but also diseased, elderly people are increasing. This trend is particularly evident in Western countries, where healthier living conditions and better cures are available. To understand the process leading to age-associated alterations is, therefore, of the highest relevance for the development of new treatments for age-associated diseases, such as cancer, diabetes, Alzheimer and cardiovascular accidents. Mechanistically, it is well accepted that the accumulation of intracellular damage determined by reactive oxygen species (ROS) might orchestrate the progressive loss of control over biological homeostasis and the functional impairment typical of aged tissues. Here, we review how epigenetics takes part in the control of stress stimuli and the mechanisms of ageing physiology and physiopathology. Alteration of epigenetic enzyme activity, histone modifications and DNA-methylation is, in fact, typically associated with the ageing process. Specifically, ageing presents peculiar epigenetic markers that, taken altogether, form the still ill-defined “ageing epigenome”. The comprehension of mechanisms and pathways leading to epigenetic modifications associated with ageing may help the development of anti-ageing therapies. PMID:23989608

[Outline on the phylogenetic history of Metazoa aging phenomenon (to the study of number of dominating pseudo-scientific concepts in biology of aging)].

PubMed

Boĭko, A G; Labas, Iu A; Gordeeva, A V

2009-01-01

Natural selection is just one of the factors determining genome evolution of Metazoa. But it's not a domineering one along with non-adaptive processes: horizontal gene transfer and input of egoistic genetic elements. That's why in phylogenesis (1) there are more genes of first Metazoa lost than new ones acquired; (2) the appearance of new genes among Metazoa branches is a very rare occasion; (3) genetically Metazoa is a homogeneous group of species with similar set of cellular mechanisms which was established in the course of evolution. The genome of first Metazoa turned to be so successful that evolution connected with organism amplification didn't demand radical changes in the genetic repertoire but it demanded changes in DNA sites regulating genes work. These facts along with the fact of existence of species of Metazoa with negligible aging overturn the core theories of aging biology which consider this or that cellular mechanism to be the initiating factor of organism's aging as sets of cellular mechanisms in aging and non-aging Metazoa forms are practically identical. That's why the basis of aging biology is in essence a collection of theories and dogmas that have never been proved but which are still in use and which have since long ago turned into a dangerous myth standing in the way of progress. If we are interested in progress of biogerontology a number of domineering pseudo scientific dogmas must be revisited. The matter of conservatism in this issue is inappropriate.

Biochemical marker reference values across pediatric, adult, and geriatric ages: establishment of robust pediatric and adult reference intervals on the basis of the Canadian Health Measures Survey.

PubMed

Adeli, Khosrow; Higgins, Victoria; Nieuwesteeg, Michelle; Raizman, Joshua E; Chen, Yunqi; Wong, Suzy L; Blais, David

2015-08-01

Biological covariates such as age and sex can markedly influence biochemical marker reference values, but no comprehensive study has examined such changes across pediatric, adult, and geriatric ages. The Canadian Health Measures Survey (CHMS) collected comprehensive nationwide health information and blood samples from children and adults in the household population and, in collaboration with the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER), examined biological changes in biochemical markers from pediatric to geriatric age, establishing a comprehensive reference interval database for routine disease biomarkers. The CHMS collected health information, physical measurements, and biosamples (blood and urine) from approximately 12 000 Canadians aged 3-79 years and measured 24 biochemical markers with the Ortho Vitros 5600 FS analyzer or a manual microplate. By use of CLSI C28-A3 guidelines, we determined age- and sex-specific reference intervals, including corresponding 90% CIs, on the basis of specific exclusion criteria. Biochemical marker reference values exhibited dynamic changes from pediatric to geriatric age. Most biochemical markers required some combination of age and/or sex partitioning. Two or more age partitions were required for all analytes except bicarbonate, which remained constant throughout life. Additional sex partitioning was required for most biomarkers, except bicarbonate, total cholesterol, total protein, urine iodine, and potassium. Understanding the fluctuations in biochemical markers over a wide age range provides important insight into biological processes and facilitates clinical application of biochemical markers to monitor manifestation of various disease states. The CHMS-CALIPER collaboration addresses this important evidence gap and allows the establishment of robust pediatric and adult reference intervals. © 2015 American Association for Clinical Chemistry.

Micromorphology of past urban soils: method and results (France, Iron Age - Middle Age)

NASA Astrophysics Data System (ADS)

Cammas, Cécilia

2014-05-01

Urban soils in French protohistoric and Roman towns and present-day towns of roman origin are several meters thick accumulations, with great spatial and vertical variability due to long duration of occupation. In order to improve our knowledge of both sedimentary and pedological characteristics as well as formation processes of urban soils, micromorphological analysis was carried out on buried towns. The studied sites include Iron Age towns (floodplain sites: Lattes or Lattara, Le Cailar; oppidum: Pech-Maho in the south of France), a roman buried town (Famars or Fanum Martis, North of France), and various towns occupied from the Roman period until now (urban and periurban sites in Paris, Strasbourg, Mâcon… North and East of France). Original method and sampling strategy were elaborated in order to try to encompass both spatial and vertical variability as well as the "mitage" of the present-day cities. In Lattes, representative elementary urban areas such as streets, courtyard, and houses were sampled for micromorphology during extensive excavation. These analyses revealed specific microscopic features related to complex anthropogenic processes (craft and domestic activities discarding, trampling, backfill, building), moisture and heat, and biological activity, which defined each kind of area. Comparison between well preserved buried town and current cities of roman origin, where the sequence of past urban soils is preserved in few place ("mitage") help to identify past activities, building rhythms as well as specific building materials. For example, in Paris, compacted sandy backfills alternate with watertight hardfloors during the Roman period (soils similar to Technosols). At the opposite, various kinds of loose bioturbated laminated dark earth resulting from activities such as craft refuses, backfills, compost or trampled layers were discriminated for Early Medieval Period (soils similar to Cumulic Anthroposol). Moreover, biological activity is usually considered destructive and an evidence of abandonment of the towns during Early Medieval Period by the archaeologists. These results show that in the studied sites the nature, location and intensity of biological activity (Lumbricidae, Enchytraeidae) is dependent on human activities (moisture, organic input) and is an evidence of human presence in town. Thus, the methodology allows identifying past activities and their location in the town, as well as their evolution with time. It highlights cultural and micro-local conditions specificities of each period, and it helps to elucidate urban site formation processes. It shows that soils and sub-soils of present-day cities are composed of a succession of different kinds of urban soils, and that micromorphology is a powerful tool to identify their characteristics such as their physical and biological properties and their discontinuities as well as their functioning. Key words: site formation processes, Iron Age towns, Roman towns, dark earth, biological activity, Enchytraeidae, Lumbricidae, Technosols, cumulic soils.

An application of characteristic function in order to predict reliability and lifetime of aeronautical hardware

NASA Astrophysics Data System (ADS)

Żurek, Józef; Kaleta, Ryszard; Zieja, Mariusz

2016-06-01

The forecasting of reliability and life of aeronautical hardware requires recognition of many and various destructive processes that deteriorate the health/maintenance status thereof. The aging of technical components of aircraft as an armament system proves of outstanding significance to reliability and safety of the whole system. The aging process is usually induced by many and various factors, just to mention mechanical, biological, climatic, or chemical ones. The aging is an irreversible process and considerably affects (i.e. reduces) reliability and lifetime of aeronautical equipment. Application of the characteristic function of the aging process is suggested to predict reliability and lifetime of aeronautical hardware. An increment in values of diagnostic parameters is introduced to formulate then, using the characteristic function and after some rearrangements, the partial differential equation. An analytical dependence for the characteristic function of the aging process is a solution to this equation. With the inverse transformation applied, the density function of the aging of aeronautical hardware is found. Having found the density function, one can determine the aeronautical equipment's reliability and lifetime. The in-service collected or the life tests delivered data are used to attain this goal. Coefficients in this relationship are found using the likelihood function.

An application of characteristic function in order to predict reliability and lifetime of aeronautical hardware

DOE Office of Scientific and Technical Information (OSTI.GOV)

Żurek, Józef; Kaleta, Ryszard; Zieja, Mariusz

2016-06-08

The forecasting of reliability and life of aeronautical hardware requires recognition of many and various destructive processes that deteriorate the health/maintenance status thereof. The aging of technical components of aircraft as an armament system proves of outstanding significance to reliability and safety of the whole system. The aging process is usually induced by many and various factors, just to mention mechanical, biological, climatic, or chemical ones. The aging is an irreversible process and considerably affects (i.e. reduces) reliability and lifetime of aeronautical equipment. Application of the characteristic function of the aging process is suggested to predict reliability and lifetime ofmore » aeronautical hardware. An increment in values of diagnostic parameters is introduced to formulate then, using the characteristic function and after some rearrangements, the partial differential equation. An analytical dependence for the characteristic function of the aging process is a solution to this equation. With the inverse transformation applied, the density function of the aging of aeronautical hardware is found. Having found the density function, one can determine the aeronautical equipment’s reliability and lifetime. The in-service collected or the life tests delivered data are used to attain this goal. Coefficients in this relationship are found using the likelihood function.« less

Modalities of gene action predicted by the classical evolutionary biological theory of aging.

PubMed

Martin, George M

2007-04-01

What might now be referred to as the "classical" evolutionary biological theory of why we age has had a number of serious challenges in recent years. While the theory might therefore have to be modified under certain circumstances, in the author's opinion, it still provides the soundest theoretical basis for thinking about how we age. Nine modalities of gene action that have the potential to modulate processes of aging are reviewed, including the two most widely reviewed and accepted concepts ("antagonistic pleiotropy" and "mutation accumulation"). While several of these nine mechanisms can be regarded as derivatives of the antagonistic pleiotropic concept, they frame more specific questions for future research. Such research should pursue what appears to be the dominant factor in the determination of intraspecific variations in longevity-stochastic mechanisms, most likely based upon epigenetics. This contrasts with the dominant factor in the determination of interspecific variations in longevity-the constitutional genome, most likely based upon variations in regulatory loci.

Biological age and sex-related declines in physical activity during adolescence.

PubMed

Cairney, John; Veldhuizen, Scott; Kwan, Matthew; Hay, John; Faught, Brent E

2014-04-01

Sex differences in the rate of decline in physical activity (PA) are most pronounced during adolescence. However, once boys and girls are aligned on biological age, sex differences in the patterns of PA become attenuated. The aim of this study was to test whether biological maturation can account for sex differences in participation in PA over time from late childhood to early adolescence. A prospective cohort of children (N = 2100; 1064 boys) was followed from ages 11 to 14 yr, with repeated assessments of PA and anthropometry. Self-reported participation in organized and free play activities was used to track participation in PA. Biological age was measured using an estimate of years to attainment of peak height velocity. Mixed-effects models were used to test whether controlling for biological age attenuates the effect of chronological age and sex on PA. As expected, the rate of decline in participation in PA was greater for girls than for boys (B = -1.18, P < 0.01). In multivariable analyses, adjusting for biological age completely attenuated the effect of sex and chronological age for participation in free play activities, but not for participation in organized play. Overall, biological age was a stronger predictor of participation than chronological age. The effect of biological age on sex by chronological age differences may be specific to certain types of PA participation. Given the importance of maturation to participation in activity, it is suggested that public health strategies target biological not chronological age to prevent declines in PA during adolescence particularly when promoting habitual or lifestyle activity.

Biological aging and physical fitness in men aged 20-70 years from Kraków, Poland.

PubMed

Gołąb, Stanisław; Woronkowicz, Agnieszka; Kryst, Łukasz

2016-07-01

The increasing problem of population aging requires appropriate economic and health-related measures to mitigate its negative effects. The aim was to categorize the biological age of men between 20 and 70 years of age and assess its relationship to their physical activity and fitness. Data included morphological variables, total body water, the results of five Eurofit motor tests and the percentage of maximum heart rate (HR%), during a cardiovascular test of more than 1,400 20-70 year-old men living in Kraków. Biological age was estimated with regression equations. There were significant and consistent differences in physical fitness profiles between the three established groups of relations between biological and chronological age (biologically younger, equal, and older). These three categories of biological age were generally consistent with the regression analysis of physical fitness results, although declared physical activity seemed to be an independent factor. The selected morphological variables represent a set of characteristics useful for the determination of the biological age. The existing relationship between physical activity and biological age indicates that physical activity may contribute to the inhibition of involutional changes, even if it had only been performed regularly in the past. Am. J. Hum. Biol. 28:503-509, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Nutrition and skin.

PubMed

Pappas, Apostolos; Liakou, Aikaterini; Zouboulis, Christos C

2016-09-01

Nutrition has long been associated with skin health, including all of its possible aspects from beauty to its integrity and even the aging process. Multiple pathways within skin biology are associated with the onset and clinical course of various common skin diseases, such as acne, atopic dermatitis, aging, or even photoprotection. These conditions have been shown to be critically affected by nutritional patterns and dietary interventions where well-documented studies have demonstrated beneficial effects of essential nutrients on impaired skin structural and functional integrity and have restored skin appearance and health. Although the subject could be vast, the intention of this review is to provide the most relevant and the most well-documented information on the role of nutrition in common skin conditions and its impact on skin biology.

Basic Biology for Beginners.

ERIC Educational Resources Information Center

Gustafson, Pamela Anderson; Sorenson, Juanita S.

This publication provides the elementary teacher with sequential and developmental objectives in the areas of plants, animals, ecology, and physiology. At least one motivating "hands-on" activity is included for each objective. Age level (5-8, 8-10, 10-12), process emphasized (classification, experimenting, etc.), and group size…

The Free Radical Theory of Aging Revisited: The Cell Signaling Disruption Theory of Aging

PubMed Central

Borras, Consuelo; Abdelaziz, Kheira M.; Garcia-Valles, Rebeca; Gomez-Cabrera, Mari Carmen

2013-01-01

Abstract Significance: The free radical theory of aging has provided a theoretical framework for an enormous amount of work leading to significant advances in our understanding of aging. Up to the turn of the century, the theory received abundant support from observations coming from fields as far apart as comparative physiology or molecular biology. Recent Advances: Work from many laboratories supports the theory, for instance showing that overexpression of antioxidant enzymes results in increases in life-span. But other labs have shown that in some cases, there is an increased oxidative stress and increased longevity. The discovery that free radicals can not only cause molecular damage to cells, but also serve as signals; led to the proposal that they act as modulators of physiological processes. For instance, reactive oxygen species (ROS) stimulate physiological adaptations to physical exercise. Critical Issues: A critical blow to the free radical theory of aging came from epidemiological studies showing that antioxidant supplementation did not lower the incidence of many age-associated diseases but, in some cases, increased the risk of death. Moreover, recent molecular evidence has shown that increasing generation of ROS, in some cases, increases longevity. Future Directions: Gerontologists interested in free radical biology are at a crossroads and clearly new insights are required to clarify the role of ROS in the process of aging. The hurdles are, no doubt, very high, but the intellectual and practical promise of these studies is of such magnitude that we feel that all efforts will be generously rewarding. Antioxid. Redox Signal. 19, 779–787. PMID:23841595

Nonenzymatic Reactions above Phospholipid Surfaces of Biological Membranes: Reactivity of Phospholipids and Their Oxidation Derivatives

PubMed Central

Solís-Calero, Christian; Ortega-Castro, Joaquín; Frau, Juan; Muñoz, Francisco

2015-01-01

Phospholipids play multiple and essential roles in cells, as components of biological membranes. Although phospholipid bilayers provide the supporting matrix and surface for many enzymatic reactions, their inherent reactivity and possible catalytic role have not been highlighted. As other biomolecules, phospholipids are frequent targets of nonenzymatic modifications by reactive substances including oxidants and glycating agents which conduct to the formation of advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs). There are some theoretical studies about the mechanisms of reactions related to these processes on phosphatidylethanolamine surfaces, which hypothesize that cell membrane phospholipids surface environment could enhance some reactions through a catalyst effect. On the other hand, the phospholipid bilayers are susceptible to oxidative damage by oxidant agents as reactive oxygen species (ROS). Molecular dynamics simulations performed on phospholipid bilayers models, which include modified phospholipids by these reactions and subsequent reactions that conduct to formation of ALEs and AGEs, have revealed changes in the molecular interactions and biophysical properties of these bilayers as consequence of these reactions. Then, more studies are desirable which could correlate the biophysics of modified phospholipids with metabolism in processes such as aging and diseases such as diabetes, atherosclerosis, and Alzheimer's disease. PMID:25977746

Chemical and Biological Properties of S-1-Propenyl-l-Cysteine in Aged Garlic Extract.

PubMed

Kodera, Yukihioro; Ushijima, Mitsuyasu; Amano, Hirotaka; Suzuki, Jun-Ichiro; Matsutomo, Toshiaki

2017-03-31

S-1-Propenyl-l-cysteine (S1PC) is a stereoisomer of S-1-Propenyl-l-cysteine (SAC), an important sulfur-containing amino acid that plays a role for the beneficial pharmacological effects of aged garlic extract (AGE). The existence of S1PC in garlic preparations has been known since the 1960's. However, there was no report regarding the biological and/or pharmacological activity of S1PC until 2016. Recently, we performed a series of studies to examine the chemical, biological, pharmacological and pharmacokinetic properties of S1PC, and obtained some interesting results. S1PC existed only in trace amounts in raw garlic, but its concentration increased almost up to the level similar of SAC through aging process of AGE. S1PC showed immunomodulatory effects in vitro and in vivo, and reduced blood pressure in a hypertensive animal model. A pharmacokinetic study revealed that S1PC was readily absorbed after oral administration in rats and dogs with bioavailability of 88-100%. Additionally, S1PC had little inhibitory influence on human cytochrome P450 activities, even at a concentration of 1 mM. Based on these findings, S1PC was suggested to be another important, pharmacologically active and safe component of AGE similar to SAC. In this review, we highlight some results from recent studies on S1PC and discuss the potential medicinal value of S1PC.

In vivo imaging of advanced glycation end products (AGEs) of albumin: first observations of significantly reduced clearance and liver deposition properties in mice.

PubMed

Tsutsui, Ayumi; Ogura, Akihiro; Tahara, Tsuyoshi; Nozaki, Satoshi; Urano, Sayaka; Hara, Mitsuko; Kojima, Soichi; Kurbangalieva, Almira; Onoe, Hirotaka; Watanabe, Yasuyoshi; Taniguchi, Naoyuki; Tanaka, Katsunori

2016-06-15

Advanced glycation end products (AGEs) are associated with various diseases, especially during aging and the development of diabetes and uremia. To better understand these biological processes, investigation of the in vivo kinetics of AGEs, i.e., analysis of trafficking and clearance properties, was carried out by molecular imaging. Following the preparation of Cy7.5-labeled AGE-albumin and intravenous injection in BALB/cA-nu/nu mice, noninvasive fluorescence kinetics analysis was performed. In vivo imaging and fluorescence microscopy analysis revealed that non-enzymatic AGEs were smoothly captured by scavenger cells in the liver, i.e., Kupffer and other sinusoidal cells, but were unable to be properly cleared from the body. Overall, these results highlight an important link between AGEs and various disorders associated with them, which may serve as a platform for future research to better understand the processes and mechanisms of these disorders.

New insight into hydration and aging mechanisms of paper by the line shape analysis of proton NMR spectra

NASA Astrophysics Data System (ADS)

Mallamace, D.; Vasi, S.; Missori, M.; Corsaro, C.

2016-05-01

The action of water within biological systems is strictly linked either with their physical chemical properties and with their functions. Cellulose is one of the most studied biopolymers due to its biological importance and its wide use in manufactured products. Among them, paper is mainly constituted by an almost equimolar ratio of cellulose and water. Therefore the study of the behavior of water within pristine and aged paper samples can help to shed light on the degradation mechanisms that irremediably act over time and spoil paper. In this work we present Nuclear Magnetic Resonance (NMR) experiments on modern paper samples made of pure cellulose not aged and artificially aged as well as on ancient paper samples made in 1413 in Perpignan (France). The line shape parameters of the proton NMR spectra were studied as a function of the hydration content. Results indicate that water in aged samples is progressively involved in the hydration of the byproducts of cellulose degradation. This enhances the degradation process itself through the progressive consumption of the cellulose amorphous regions.

Autism, Asthma, Inflammation, and the Hygiene Hypothesis

PubMed Central

Becker, Kevin G.

2007-01-01

Inflammation and the genes, molecules, and biological pathways that lead to inflammatory processes influence many important and disparate biological processes and disease states that are quite often not generally considered classical inflammatory or autoimmune disorders. These include development, reproduction, aging, tumor development and tumor rejection, cardiovascular pathologies, metabolic disorders, as well as neurological and psychiatric disorders. This paper compares parallel aspects of autism and inflammatory disorders with an emphasis on asthma. These comparisons include epidemiological, morphometric, molecular, and genetic aspects of both disease types, contributing to a hypothesis of autism in the context of the immune based hygiene hypothesis. This hypothesis is meant to address the apparent rise in the prevalence of autism in the population. PMID:17412520

Autism, asthma, inflammation, and the hygiene hypothesis.

PubMed

Becker, Kevin G

2007-01-01

Inflammation and the genes, molecules, and biological pathways that lead to inflammatory processes influence many important and disparate biological processes and disease states that are quite often not generally considered classical inflammatory or autoimmune disorders. These include development, reproduction, aging, tumor development and tumor rejection, cardiovascular pathologies, metabolic disorders, as well as neurological and psychiatric disorders. This paper compares parallel aspects of autism and inflammatory disorders with an emphasis on asthma. These comparisons include epidemiological, morphometric, molecular, and genetic aspects of both disease types, contributing to a hypothesis of autism in the context of the immune based hygiene hypothesis. This hypothesis is meant to address the apparent rise in the prevalence of autism in the population.

Age at menarche in urban Argentinian girls: association with biological and socioeconomic factors.

PubMed

Orden, Alicia B; Vericat, Agustina; Apezteguía, Maria C

2011-01-01

Age at menarche is regarded as a sensitive indicator of physical, biological, and psychosocial environment. The aim of this study was to determine the age at menarche and its association with biological and socioeconomic factors in girls from Santa Rosa (La Pampa, Argentina). An observational cross-sectional study was carried out on 1,221 schoolgirls aged 9-15 years. Menarche data were obtained by the status-quo method. Height, sitting height, weight, arm circumference, tricipital and subscapular skinfolds were measured. We also calculated body mass index, measures of body composition and proportions, and fat distribution. To assess socioeconomic factors, parents completed a self-administered questionnaire about their occupation and education, family size, household, and other family characteristics. The median age at menarche - estimated by the logit method--was 12.84 years (95% CI: 12.71, 12.97). Compared with their premenarcheal age peers, postmenarcheal girls had greater anthropometric dimensions through age 12. After this age, only height was higher in the latter group. Data were processed by fitting two logistic regressions, both including age. The first model included anthropometric variables and birth weight, while the second model included the socioeconomic variables. The significant variables derived from each model were incorporated into a new regression: height, sitting height ratio (first model), and maternal education (second model). These three variables remained significantly associated with menarche. The results suggest a relationship between linear growth and menarche and agree with those found in other populations where the advancement of menarche is associated with improved living conditions. In relatively uniform urban contexts, maternal education may be a good proxy for the standard of living.

Caloric restriction delays yeast chronological aging by remodeling carbohydrate and lipid metabolism, altering peroxisomal and mitochondrial functionalities, and postponing the onsets of apoptotic and liponecrotic modes of regulated cell death

PubMed Central

Arlia-Ciommo, Anthony; Leonov, Anna; Beach, Adam; Richard, Vincent R.; Bourque, Simon D.; Burstein, Michelle T.; Kyryakov, Pavlo; Gomez-Perez, Alejandra; Koupaki, Olivia; Feldman, Rachel; Titorenko, Vladimir I.

2018-01-01

A dietary regimen of caloric restriction delays aging in evolutionarily distant eukaryotes, including the budding yeast Saccharomyces cerevisiae. Here, we assessed how caloric restriction influences morphological, biochemical and cell biological properties of chronologically aging yeast advancing through different stages of the aging process. Our findings revealed that this low-calorie diet slows yeast chronological aging by mechanisms that coordinate the spatiotemporal dynamics of various cellular processes before entry into a non-proliferative state and after such entry. Caloric restriction causes a stepwise establishment of an aging-delaying cellular pattern by tuning a network that assimilates the following: 1) pathways of carbohydrate and lipid metabolism; 2) communications between the endoplasmic reticulum, lipid droplets, peroxisomes, mitochondria and the cytosol; and 3) a balance between the processes of mitochondrial fusion and fission. Through different phases of the aging process, the caloric restriction-dependent remodeling of this intricate network 1) postpones the age-related onsets of apoptotic and liponecrotic modes of regulated cell death; and 2) actively increases the chance of cell survival by supporting the maintenance of cellular proteostasis. Because caloric restriction decreases the risk of cell death and actively increases the chance of cell survival throughout chronological lifespan, this dietary intervention extends longevity of chronologically aging yeast. PMID:29662634

Mouse models of ageing and their relevance to disease.

PubMed

Kõks, Sulev; Dogan, Soner; Tuna, Bilge Guvenc; González-Navarro, Herminia; Potter, Paul; Vandenbroucke, Roosmarijn E

2016-12-01

Ageing is a process that gradually increases the organism's vulnerability to death. It affects different biological pathways, and the underlying cellular mechanisms are complex. In view of the growing disease burden of ageing populations, increasing efforts are being invested in understanding the pathways and mechanisms of ageing. We review some mouse models commonly used in studies on ageing, highlight the advantages and disadvantages of the different strategies, and discuss their relevance to disease susceptibility. In addition to addressing the genetics and phenotypic analysis of mice, we discuss examples of models of delayed or accelerated ageing and their modulation by caloric restriction. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Mitotic Dysfunction Associated with Aging Hallmarks.

PubMed

Macedo, Joana Catarina; Vaz, Sara; Logarinho, Elsa

2017-01-01

Aging is a biological process characterized by the progressive deterioration of physiological functions known to be the main risk factor for chronic diseases and declining health. There has been an emerging connection between aging and aneuploidy, an aberrant number of chromosomes, even though the molecular mechanisms behind age-associated aneuploidy remain largely unknown. In recent years, several genetic pathways and biochemical processes controlling the rate of aging have been identified and proposed as aging hallmarks. Primary hallmarks that cause the accumulation of cellular damage include genomic instability, telomere attrition, epigenetic alterations and loss of proteostasis (López-Otín et al., Cell 153:1194-1217, 2013). Here we review the provocative link between these aging hallmarks and the loss of chromosome segregation fidelity during cell division, which could support the correlation between aging and aneuploidy seen over the past decades. Secondly, we review the systemic impacts of aneuploidy in cell physiology and emphasize how these include some of the primary hallmarks of aging. Based on the evidence, we propose a mutual causality between aging and aneuploidy, and suggest modulation of mitotic fidelity as a potential means to ameliorate healthy lifespan.

Articular Cartilage Aging-Potential Regenerative Capacities of Cell Manipulation and Stem Cell Therapy

PubMed Central

Placek, Waldemar

2018-01-01

Changes in articular cartilage during the aging process are a stage of natural changes in the human body. Old age is the major risk factor for osteoarthritis but the disease does not have to be an inevitable consequence of aging. Chondrocytes are particularly prone to developing age-related changes. Changes in articular cartilage that take place in the course of aging include the acquisition of the senescence-associated secretory phenotype by chondrocytes, a decrease in the sensitivity of chondrocytes to growth factors, a destructive effect of chronic production of reactive oxygen species and the accumulation of the glycation end products. All of these factors affect the mechanical properties of articular cartilage. A better understanding of the underlying mechanisms in the process of articular cartilage aging may help to create new therapies aimed at slowing or inhibiting age-related modifications of articular cartilage. This paper presents the causes and consequences of cellular aging of chondrocytes and the biological therapeutic outlook for the regeneration of age-related changes of articular cartilage. PMID:29470431

Sex differences in the development of brain mechanisms for processing biological motion.

PubMed

Anderson, L C; Bolling, D Z; Schelinski, S; Coffman, M C; Pelphrey, K A; Kaiser, M D

2013-12-01

Disorders related to social functioning including autism and schizophrenia differ drastically in incidence and severity between males and females. Little is known about the neural systems underlying these sex-linked differences in risk and resiliency. Using functional magnetic resonance imaging and a task involving the visual perception of point-light displays of coherent and scrambled biological motion, we discovered sex differences in the development of neural systems for basic social perception. In adults, we identified enhanced activity during coherent biological motion perception in females relative to males in a network of brain regions previously implicated in social perception including amygdala, medial temporal gyrus, and temporal pole. These sex differences were less pronounced in our sample of school-age youth. We hypothesize that the robust neural circuitry supporting social perception in females, which diverges from males beginning in childhood, may underlie sex differences in disorders related to social processing. © 2013 Elsevier Inc. All rights reserved.

Sex Differences in the Development of Brain Mechanisms for Processing Biological Motion

PubMed Central

Anderson, L.C.; Bolling, D.Z.; Schelinski, S.; Coffman, M.C.; Pelphrey, K.A.; Kaiser, M.D.

2013-01-01

Disorders related to social functioning including autism and schizophrenia differ drastically in incidence and severity between males and females. Little is known about the neural systems underlying these sex-linked differences in risk and resiliency. Using functional magnetic resonance imaging and a task involving the visual perception of point-light displays of coherent and scrambled biological motion, we discovered sex differences in the development of neural systems for basic social perception. In adults, we identified enhanced activity during coherent biological motion perception in females relative to males in a network of brain regions previously implicated in social perception including amygdala, medial temporal gyrus, and temporal pole. These sex differences were less pronounced in our sample of school-age youth. We hypothesize that the robust neural circuitry supporting social perception in females, which diverges from males beginning in childhood, may underlie sex differences in disorders related to social processing. PMID:23876243

The fetal programming of telomere biology hypothesis: an update

PubMed Central

Entringer, Sonja; Buss, Claudia; Wadhwa, Pathik D.

2018-01-01

Research on mechanisms underlying fetal programming of health and disease risk has focused primarily on processes that are specific to cell types, organs or phenotypes of interest. However, the observation that developmental conditions concomitantly influence a diverse set of phenotypes, the majority of which are implicated in age-related disorders, raises the possibility that such developmental conditions may additionally exert effects via a common underlying mechanism that involves cellular/molecular ageing–related processes. In this context, we submit that telomere biology represents a process of particular interest in humans because, firstly, this system represents among the most salient antecedent cellular phenotypes for common age-related disorders; secondly, its initial (newborn) setting appears to be particularly important for its long-term effects; and thirdly, its initial setting appears to be plastic and under developmental regulation. We propose that the effects of suboptimal intrauterine conditions on the initial setting of telomere length and telomerase expression/activity capacity may be mediated by the programming actions of stress-related maternal–placental–fetal oxidative, immune, endocrine and metabolic pathways in a manner that may ultimately accelerate cellular dysfunction, ageing and disease susceptibility over the lifespan. This perspectives paper provides an overview of each of the elements underlying this hypothesis, with an emphasis on recent developments, findings and future directions. This article is part of the theme issue ‘Understanding diversity in telomere dynamics’. PMID:29335381

PTSD in the elderly: the interaction between trauma and aging.

PubMed

Lapp, Leann Kimberly; Agbokou, Catherine; Ferreri, Florian

2011-08-01

Because an increasingly large cohort of individuals is approaching their elderly years, there is concern about how the healthcare system will cope with the greater demands placed upon it. One area of concern is the impact of trauma and post traumatic stress disorder (PTSD) in the aged. Although several reviews have highlighted the lack of knowledge and research on the topic, there still remain gaps in the literature. Nevertheless, some recent behavioral, endocrinological and neuroimaging studies may provide new insights into the discussion. The central aims of this paper are to summarize the etiological, epidemiological and clinical aspects of PTSD, trauma, and the elderly, and to integrate this knowledge with (i) what is known about PTSD in adults, and (ii) the behavioral, hormonal and cerebral changes associated with healthy aging. A comprehensive search was performed with ISI Web of Science and PubMed for articles pertinent to the psychology and biology of PTSD, trauma, and the elderly. There exist both significant similarities and differences between adults and elderly with PTSD concerning cognitive and biological profile. Evidence suggests that PTSD in the elderly does not follow a simple clinical trajectory. PTSD in the elderly must be considered within the context of normal aging. Strong claims about an interaction between PTSD and aging are difficult to make due to sample heterogeneity, but it is clear that PTSD in this age group presents unique aspects not seen in younger cohorts. Further research must integrate their studies with the biological, psychological, and social changes already associated with the aging process.

Comparative Endocrinology of Aging and Longevity Regulation

PubMed Central

Allard, John B.; Duan, Cunming

2011-01-01

Hormones regulate growth, development, metabolism, and other complex processes in multicellular animals. For many years it has been suggested that hormones may also influence the rate of the aging process. Aging is a multifactorial process that causes biological systems to break down and cease to function in adult organisms as time passes, eventually leading to death. The exact underlying causes of the aging process remain a topic for debate, and clues that may shed light on these causes are eagerly sought after. In the last two decades, gene mutations that result in delayed aging and extended longevity have been discovered, and many of the affected genes have been components of endocrine signaling pathways. In this review we summarize the current knowledge on the roles of endocrine signaling in the regulation of aging and longevity in various animals. We begin by discussing the notion that conserved systems, including endocrine signaling pathways, “regulate” the aging process. Findings from the major model organisms: worms, flies, and rodents, are then outlined. Unique lessons from studies of non-traditional models: bees, salmon, and naked mole rats, are also discussed. Finally, we summarize the endocrinology of aging in humans, including changes in hormone levels with age, and the involvement of hormones in aging-related diseases. The most well studied and widely conserved endocrine pathway that affects aging is the insulin/insulin-like growth factor system. Mutations in genes of this pathway increase the lifespan of worms, flies, and mice. Population genetic evidence also suggests this pathway’s involvement in human aging. Other hormones including steroids have been linked to aging only in a subset of the models studied. Because of the value of comparative studies, it is suggested that the aging field could benefit from adoption of additional model organisms. PMID:22654825

Aging of cell membranes: facts and theories.

PubMed

Zs-Nagy, Imre

2014-01-01

This chapter is intended to outline the main results of a research trend realized by the author during the last 45 years, focused on the main role played by the cell membrane in the aging process. It is a very wide field; therefore, the reader cannot expect in this limited space a detailed description, but will be given a wide, interdisciplinary insight into the main facts and theories regarding cellular aging. The central idea described here is the concept called the membrane hypothesis of aging (MHA). The history, the chemical roots, physicochemical facts, biophysical processes, as well as the obligatory biochemical consequences are all touched in by indicating the most important sources of detailed knowledge for those who are more interested in the basic biology of the aging process. This chapter covers also the available anti-aging interventions on the cell membrane by means of the centrophenoxine treatment based on the MHA. It also briefly interprets the possibilities of a just developing anti-aging method by using the recombinant human growth hormone, essential basis of which is the species specificity, and the general presence of receptors of this hormone in the plasma membrane of all types of cells.

A systematic review of the neurobiological aspects of memory in the aging process

PubMed Central

de Oliveira, Eduardo Moreira; Kissaki, Priscilla Tiemi; Ordonez, Tiago Nascimento; Lima-Silva, Thaís Bento

2011-01-01

A systematic review of the neuroanatomical literature was performed to determine the neuropharmacological aspects most relevant to the study of memory processes. Articles were retrieved using the search terms "biology of memory", "memory and aging", "memory impairment", "elderly and memory," and their equivalents in Portuguese. Of the studies surveyed, five studies dealt with epidemiological and demographic issues, 12 were clinical trials i.e. were based on testing and implementation of instruments in human subjects, 33 studies were basic research involving studies of mice, rats and non-human primates, and biochemical and in vitro trials and finally, 52 studies were literature reviews or book chapters which in our view, fell into this category. Conclusions The work sought to highlight which neural networks are most involved in processing information, as well as their location within brain regions and the way in which neurotransmitters interact with each other for the formation of these memories. Moreover, it was shown how memory changes during the normal human aging process, both positively and negatively, by analyzing the morphological alterations that occur in the brain of aging individuals. PMID:29213758

[Ageing rate in workers of mechanic workshops of machinery construction industry in Armenia].

PubMed

Sarkisian, G T; Barkhudarov, M S; Kogan, V Iu

2004-01-01

Studies of biologic age formation and ageing rate in workers of mechanic workshops revealed that able-bodied population grew old demographically. That is proved by absent age group of 20-29 years and increased share of able-bodied workers older than 50. Young workers aged 30-39 appeared the most vulnerable for occupational hazards--they demonstrated increased ageing rate and maximal excess of biologic age over chronological age and due biologic age.

Evaluation of three aging techniques and back-calculated growth for introduced Blue Catfish from Lake Oconee, Georgia

USGS Publications Warehouse

Homer, Michael D.; Peterson, James T.; Jennings, Cecil A.

2015-01-01

Back-calculation of length-at-age from otoliths and spines is a common technique employed in fisheries biology, but few studies have compared the precision of data collected with this method for catfish populations. We compared precision of back-calculated lengths-at-age for an introducedIctalurus furcatus (Blue Catfish) population among 3 commonly used cross-sectioning techniques. We used gillnets to collect Blue Catfish (n = 153) from Lake Oconee, GA. We estimated ages from a basal recess, articulating process, and otolith cross-section from each fish. We employed the Frasier-Lee method to back-calculate length-at-age for each fish, and compared the precision of back-calculated lengths among techniques using hierarchical linear models. Precision in age assignments was highest for otoliths (83.5%) and lowest for basal recesses (71.4%). Back-calculated lengths were variable among fish ages 1–3 for the techniques compared; otoliths and basal recesses yielded variable lengths at age 8. We concluded that otoliths and articulating processes are adequate for age estimation of Blue Catfish.

The African Turquoise Killifish: A Model for Exploring Vertebrate Aging and Diseases in the Fast Lane.

PubMed

Harel, Itamar; Brunet, Anne

2015-01-01

Why and how organisms age remains a mystery, and it defines one of the biggest challenges in biology. Aging is also the primary risk factor for many human pathologies, such as cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases. Thus, manipulating the aging rate and potentially postponing the onset of these devastating diseases could have a tremendous impact on human health. Recent studies, relying primarily on nonvertebrate short-lived model systems, have shown the importance of both genetic and environmental factors in modulating the aging rate. However, relatively little is known about aging in vertebrates or what processes may be unique and specific to these complex organisms. Here we discuss how advances in genomics and genome editing have significantly expanded our ability to probe the aging process in a vertebrate system. We highlight recent findings from a naturally short-lived vertebrate, the African turquoise killifish, which provides an attractive platform for exploring mechanisms underlying vertebrate aging and age-related diseases. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Designing and testing a classroom curriculum to teach preschoolers about the biology of physical activity: The respiration system as an underlying biological causal mechanism

NASA Astrophysics Data System (ADS)

Ewing, Tracy S.

The present study examined young children's understanding of respiration and oxygen as a source of vital energy underlying physical activity. Specifically, the purpose of the study was to explore whether a coherent biological theory, characterized by an understanding that bodily parts (heart and lungs) and processes (oxygen in respiration) as part of a biological system, can be taught as a foundational concept to reason about physical activity. The effects of a biology-based intervention curriculum designed to teach preschool children about bodily functions as a part of the respiratory system, the role of oxygen as a vital substance and how physical activity acts an energy source were examined. Participants were recruited from three private preschool classrooms (two treatment; 1 control) in Southern California and included a total of 48 four-year-old children (30 treatment; 18 control). Findings from this study suggested that young children could be taught relevant biological concepts about the role of oxygen in respiratory processes. Children who received biology-based intervention curriculum made significant gains in their understanding of the biology of respiration, identification of physical and sedentary activities. In addition these children demonstrated that coherence of conceptual knowledge was correlated with improved accuracy at activity identification and reasoning about the inner workings of the body contributing to endurance. Findings from this study provided evidence to support the benefits of providing age appropriate but complex coherent biological instruction to children in early childhood settings.

Phospholipase A2 - nexus of aging, oxidative stress, neuronal excitability, and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment.

PubMed

Hermann, Petra M; Watson, Shawn N; Wildering, Willem C

2014-01-01

The aging brain undergoes a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative diseases is a core research goal in contemporary neuroscience. This review focuses on the idea that changes in intrinsic neuronal electrical excitability associated with (per)oxidation of membrane lipids and activation of phospholipase A2 (PLA2) enzymes are an important mechanism of learning and memory failure under normal aging conditions. Specifically, in the context of this special issue on the biology of cognitive aging we portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and recapitulate recent insights indicating a key role of lipid peroxidation-induced PLA2 as instruments of aging, oxidative stress and inflammation in age-associated neuronal and memory impairment in this model system. The findings are discussed in view of accumulating evidence suggesting involvement of analogous mechanisms in the etiology of age-associated dysfunction and disease of the human and mammalian brain.

Stimulus Sensitivity of a Spiking Neural Network Model

NASA Astrophysics Data System (ADS)

Chevallier, Julien

2018-02-01

Some recent papers relate the criticality of complex systems to their maximal capacity of information processing. In the present paper, we consider high dimensional point processes, known as age-dependent Hawkes processes, which have been used to model spiking neural networks. Using mean-field approximation, the response of the network to a stimulus is computed and we provide a notion of stimulus sensitivity. It appears that the maximal sensitivity is achieved in the sub-critical regime, yet almost critical for a range of biologically relevant parameters.

Aging effect in pattern, motion and cognitive visual evoked potentials.

PubMed

Kuba, Miroslav; Kremláček, Jan; Langrová, Jana; Kubová, Zuzana; Szanyi, Jana; Vít, František

2012-06-01

An electrophysiological study on the effect of aging on the visual pathway and various levels of visual information processing (primary cortex, associate visual motion processing cortex and cognitive cortical areas) was performed. We examined visual evoked potentials (VEPs) to pattern-reversal, motion-onset (translation and radial motion) and visual stimuli with a cognitive task (cognitive VEPs - P300 wave) at luminance of 17 cd/m(2). The most significant age-related change in a group of 150 healthy volunteers (15-85 years of age) was the increase in the P300 wave latency (2 ms per 1 year of age). Delays of the motion-onset VEPs (0.47 ms/year in translation and 0.46 ms/year in radial motion) and the pattern-reversal VEPs (0.26 ms/year) and the reductions of their amplitudes with increasing subject age (primarily in P300) were also found to be significant. The amplitude of the motion-onset VEPs to radial motion remained the most constant parameter with increasing age. Age-related changes were stronger in males. Our results indicate that cognitive VEPs, despite larger variability of their parameters, could be a useful criterion for an objective evaluation of the aging processes within the CNS. Possible differences in aging between the motion-processing system and the form-processing system within the visual pathway might be indicated by the more pronounced delay in the motion-onset VEPs and by their preserved size for radial motion (a biologically significant variant of motion) compared to the changes in pattern-reversal VEPs. Copyright © 2012 Elsevier Ltd. All rights reserved.

Disentangling Emotion Processes in Borderline Personality Disorder: Physiological and Self-reported Assessment of Biological Vulnerability, Baseline Intensity, and Reactivity to Emotionally-Evocative Stimuli

PubMed Central

Kuo, Janice R.; Linehan, Marsha M.

2014-01-01

This study investigated Linehan’s (1993) theory that individuals meeting criteria for borderline personality disorder (BPD) have high biological vulnerability to emotion dysregulation, including high baseline emotional intensity and high reactivity to emotionally-evocative stimuli. Twenty individuals with BPD, 20 age-matched individuals with generalized social anxiety disorder (SAD), and 20 age-matched normal controls (NC) participated in two separate emotion induction conditions, a standardized condition and a personally-relevant condition. Respiratory sinus arrhythmia (RSA), skin conductance response (SCR), and self-report measures were collected throughout the experiment. BPD participants displayed heightened biological vulnerability compared with NC as indicated by reduced basal RSA. BPD participants also exhibited high baseline emotional intensity, characterized by heightened SCR and heightened self-reported negative emotions at baseline. However, the BPD group did not display heightened reactivity as their physiological and self-reported changes from baseline to the emotion inductions tasks were not greater than the other two groups. PMID:19685950

[Identification of single nucleotide polymorphisms related to frailty].

PubMed

Inglés, Marta; Gimeno-Mallench, Lucia; Mas-Bargues, Cristina; Dromant, Mar; Cruz-Guerrero, Raquel; García-García, Francisco José; Rodríguez-Mañas, Leocadio; Gambini, Juan; Borrás, Consuelo; Viña, José

2018-04-07

The search for biomarkers that can lead to the early diagnosis and thus, early treatment of frailty, has become one of the main challenges facing the geriatric scientific community. The aim of the present study was to identify single nucleotide polymorphisms (SNPs) related to frailty. The study was conducted on 152 subjects from the Toledo Study for Healthy Aging (65 to 95 years of age), and classified as frail (n=78), and non-frail (n=74), according to Fried's criteria. After blood collection, DNA was isolated and amplified for the analysis of SNPs using Axiom TM Genotyping technology (Affymetrix). Statistical analyses were performed using the Plink program and library SNPassoc. The results of the study showed 15 SNPs with a P<.001. Those SNPs involved in processes related to frailty, such as energy metabolism, regulation of biological processes, cell motility and integrity, and cognition are highlighted. These results suggest that the genetic variations identified in frail individuals that are involved in biological processes related to frailty may be considered as biomarkers for the early detection of frailty. Copyright © 2018 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

Coparenting Conflict and Academic Readiness in Children of Teen Mothers: Effortful Control as a Mediator.

PubMed

Jahromi, Laudan B; Zeiders, Katharine H; Updegraff, Kimberly A; Umaña-Taylor, Adriana J; Bayless, Sara Douglass

2017-04-24

Children's exposure to coparenting conflict has important implications for their developmental functioning, yet limited work has focused on such processes in families with diverse structures or ethnically and culturally diverse backgrounds. This longitudinal study examined the processes by which Mexican-origin adolescent mothers' coparenting conflict with their 3-year-old children's grandmothers and biological fathers (N = 133 families) were linked to children's academic and social skills at 5 years of age, and whether children's effortful control at 4 years of age mediated the link between coparenting conflict and indices of children's academic readiness. Findings revealed that adolescent mothers' coparenting conflict with their child's biological father was linked to indices of children's academic and social school readiness through children's effortful control among girls, but not boys, whereas conflict with grandmothers was directly linked to boys' and girls' social functioning 2 years later. Findings offer information about different mechanisms by which multiple coparenting units in families of adolescent mothers are related to their children's outcomes, and this work has important implications for practitioners working with families of adolescent mothers. © 2017 Family Process Institute.

Individual heterogeneity in growth and age at sexual maturity: A gamma process analysis of capture–mark–recapture data

USGS Publications Warehouse

Link, William; Hesed, Kyle Miller

2015-01-01

Knowledge of organisms’ growth rates and ages at sexual maturity is important for conservation efforts and a wide variety of studies in ecology and evolutionary biology. However, these life history parameters may be difficult to obtain from natural populations: individuals encountered may be of unknown age, information on age at sexual maturity may be uncertain and interval-censored, and growth data may include both individual heterogeneity and measurement errors. We analyzed mark–recapture data for Red-backed Salamanders (Plethodon cinereus) to compare sex-specific growth rates and ages at sexual maturity. Aging of individuals was made possible by the use of a von Bertalanffy model of growth, complemented with models for interval-censored and imperfect observations at sexual maturation. Individual heterogeneity in growth was modeled through the use of Gamma processes. Our analysis indicates that female P. cinereus mature earlier and grow more quickly than males, growing to nearly identical asymptotic size distributions as males.

PerSubs: A Graph-Based Algorithm for the Identification of Perturbed Subpathways Caused by Complex Diseases.

PubMed

Vrahatis, Aristidis G; Rapti, Angeliki; Sioutas, Spyros; Tsakalidis, Athanasios

2017-01-01

In the era of Systems Biology and growing flow of omics experimental data from high throughput techniques, experimentalists are in need of more precise pathway-based tools to unravel the inherent complexity of diseases and biological processes. Subpathway-based approaches are the emerging generation of pathway-based analysis elucidating the biological mechanisms under the perspective of local topologies onto a complex pathway network. Towards this orientation, we developed PerSub, a graph-based algorithm which detects subpathways perturbed by a complex disease. The perturbations are imprinted through differentially expressed and co-expressed subpathways as recorded by RNA-seq experiments. Our novel algorithm is applied on data obtained from a real experimental study and the identified subpathways provide biological evidence for the brain aging.

Longevity factor klotho and chronic psychological stress

PubMed Central

Prather, A A; Epel, E S; Arenander, J; Broestl, L; Garay, B I; Wang, D; Dubal, D B

2015-01-01

Chronic psychological stress is associated with accelerated aging and premature morbidity and mortality; however, the biology linking chronic psychological stress and its maladaptive effects remains largely unknown. Klotho is a pleiotropic hormone that regulates the aging process and promotes better brain and body health. Whether klotho is linked to psychosocial stress or its negative impact in humans has not been investigated. To address this gap, we recruited 178 healthy women who were either chronically high-stress maternal caregivers for a child with autism spectrum disorder (n=90) or low-stress control mothers of a typically developing child (n=88). We found that women under high chronic stress displayed significantly lower levels of the longevity hormone klotho compared with low-stress controls (t(176)=2.92, P=0.004; d=0.44), and the decrease among those under high stress was age-dependent. In addition, high-stress caregivers who reported more depressive symptoms displayed even lower klotho levels compared with low-stress participants. These findings provide the first evidence that klotho levels are sensitive to psychosocial stressors and raise the possibility that klotho may serve as a novel biological link connecting stress, depression and risk for accelerated disease development. Furthermore, these findings have important implications for understanding the plasticity of the aging process and may represent a therapeutic target for mitigating the deleterious effects of chronic psychological stress on health and well-being. PMID:26080320

Secrets from immortal worms: What can we learn about biological ageing from the planarian model system?

PubMed

Sahu, Sounak; Dattani, Anish; Aboobaker, A Aziz

2017-10-01

Understanding how some animals are immortal and avoid the ageing process is important. We currently know very little about how they achieve this. Research with genetic model systems has revealed the existence of conserved genetic pathways and molecular processes that affect longevity. Most of these established model organisms have relatively short lifespans. Here we consider the use of planarians, with an immortal life-history that is able to entirely avoid the ageing process. These animals are capable of profound feats of regeneration fueled by a population of adult stem cells called neoblasts. These cells are capable of indefinite self-renewal that has underpinned the evolution of animals that reproduce only by fission, having disposed of the germline, and must therefore be somatically immortal and avoid the ageing process. How they do this is only now starting to be understood. Here we suggest that the evidence so far supports the hypothesis that the lack of ageing is an emergent property of both being highly regenerative and the evolution of highly effective mechanisms for ensuring genome stability in the neoblast stem cell population. The details of these mechanisms could prove to be very informative in understanding how the causes of ageing can be avoided, slowed or even reversed. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Protocol for Aging Anurans Using Skeletochronology

USGS Publications Warehouse

McCreary, Brome; Pearl, Christopher A.; Adams, Michael J.

2008-01-01

Age distribution information can be an important part of understanding the biology of any population. Age estimates collected from the annual growth rings found in tooth and bone cross sections, often referred to as Lines of Arrested Growth (LAGs), have been used in the study of various animals. In this manual, we describe in detail all necessary steps required to obtain estimates of age from anuran bone cross sections via skeletochronological assessment. We include comprehensive descriptions of how to fix and decalcify toe specimens (phalanges), process a phalange prior to embedding, embed the phalange in paraffin, section the phalange using a microtome, stain and mount the cross sections of the phalange and read the LAGs to obtain age estimates.

PubMed Central

Lambert, Yves; Paré, Lucie

1990-01-01

Various authors have suggested the possibility of a link between biological age and sexual activity. Zelnick (1981) described the relationship between sexual activity and age at menarche. To determine the relationship between biological age and age at first sexual intercourse, we presented a questionnaire to 450 students attending a comprehensive secondary school in Montreal. Age at menarche and age at first conscious ejaculation were used to measure biological age. A partial correlation was made between biological age and age at first sexual intercourse by controlling for chronological age. The results were r = 0.24 (p <0.029) for female students and r = 0.21 (p <0.08) for male students. The value of the correlation was weak but significant where the female students were concerned. For the male students, the value of the correlation could not be determined due to the insufficient number of respondents. Biological age would appear to be an indicator of the age at which sexual activity first occurs. This indicator could be used by clinicians directly, and to develop a more general model for determining the age at which sexual activity first occurs. PMID:21234038

Complex systems dynamics in aging: new evidence, continuing questions.

PubMed

Cohen, Alan A

2016-02-01

There have long been suggestions that aging is tightly linked to the complex dynamics of the physiological systems that maintain homeostasis, and in particular to dysregulation of regulatory networks of molecules. This review synthesizes recent work that is starting to provide evidence for the importance of such complex systems dynamics in aging. There is now clear evidence that physiological dysregulation--the gradual breakdown in the capacity of complex regulatory networks to maintain homeostasis--is an emergent property of these regulatory networks, and that it plays an important role in aging. It can be measured simply using small numbers of biomarkers. Additionally, there are indications of the importance during aging of emergent physiological processes, functional processes that cannot be easily understood through clear metabolic pathways, but can nonetheless be precisely quantified and studied. The overall role of such complex systems dynamics in aging remains an important open question, and to understand it future studies will need to distinguish and integrate related aspects of aging research, including multi-factorial theories of aging, systems biology, bioinformatics, network approaches, robustness, and loss of complexity.

Long-Term Alterations in Neural and Endocrine Processes Induced by Motherhood

PubMed Central

Bridges, Robert S.

2015-01-01

The reproductive experience of pregnancy, lactation and motherhood can significantly remodel the female’s biological state, affecting endocrine, neuroendocrine, neural, and immunological processes. The brain, pituitary gland, liver, thymus, and mammary tissue are among the structures that are modified by reproductive experience. The present review that focuses on rodent research, but also includes pertinent studies in sheep and other species, identifies specific changes in these processes brought about by the biological states of pregnancy, parturition, and lactation and how the components of reproductive experience contribute to the remodeling of the maternal brain and organ systems. Findings indicate that prior parity alters key circulating hormone levels and neural receptor gene expression. Moreover, reproductive experience results in modifications in neural processes and glial support. The possible role of pregnancy-induced neurogenesis is considered in the context of neuroplasticity and behavior, and the effects of reproductive experience on maternal memory, i.e. the retention of maternal behavior, together with anxiety and learning are presented. Together, these sets of findings support the concept that the neural and biological state of the adult female is significantly and dramatically altered on a long-term basis by the experiences of parity and motherhood. Remodeling of the maternal brain and other biological systems is posited to help facilitate adaptations to environmental/ecological challenges as the female raises young and ages. PMID:26388065

Biological Ageing, Inflammation and Nutrition: How Might They Impact on Systemic Sclerosis?

PubMed

Shiels, Paul G; Ritzau-Reid, Kaja

2015-01-01

The number of aged individuals within the global population is increasing, which foreshadows a major societal and global health challenge. By 2050 those over 65 years old will outnumber children under 15 years of age. This situation will bring with it multifarious variations in health and functional status, occurring with increasing age and which remain incompletely understood. Ageing, however, is not solely a passive degenerative process but one that is actively regulated by distinct molecular pathways. Understanding this molecular basis of ageing is an essential step for therapeutic manipulation to combat age-related disease. Diseases such as SSc, RA and SLE may share common age related pathways of early dysregulation with other diseases of ageing, such that the biomarkers and interventions applied to prevent late stage disease will also tackle common fundamental pathways of ageing processes. This chapter will seek to explore and discuss the possible influence of these factors and their impact on disease processes, with specific reference to SSc in the context of it being a disease of ageing. It will address the contribution of socioeconomic, psychosocial and nutritional confounders of health span through the life course. In particular, it will seek to contextualize the development of inflammatory burden and allostatic overload and their contribution to morbidity and mortality. Importantly, this chapter will provide a context for transgenerational and other epigenetic effects, which are emerging as contributory components in disease susceptibility and progression.

Treatment of waste metalworking fluid by a hybrid ozone-biological process.

PubMed

Jagadevan, Sheeja; Graham, Nigel J; Thompson, Ian P

2013-01-15

In metal machining processes, the regulation of heat generation and lubrication at the contact point are achieved by application of a fluid referred to as metalworking fluid (MWF). MWFs inevitably become operationally exhausted with age and intensive use, which leads to compromised properties, thereby necessitating their safe disposal. Disposal of this waste through a biological route is an increasingly attractive option, since it is effective with relatively low energy demands. However, successful biological treatment is challenging since MWFs are chemically complex, and include biocides specifically to retard microbial deterioration whilst the fluids are operational. In this study remediation of the recalcitrant component of a semi-synthetic MWF by a novel hybrid ozone-bacteriological treatment, was investigated. The hybrid treatment proved to be effective and reduced the chemical oxygen demand by 72% (26.9% and 44.9% reduction after ozonation and biological oxidation respectively). Furthermore, a near-complete degradation of three non-biodegradable compounds (viz. benzotriazole, monoethanolamine, triethanolamine), commonly added as biocides and corrosion inhibitors in MWF formulations, under ozonation was observed. Copyright © 2012 Elsevier B.V. All rights reserved.

Immune remodeling: lessons from repertoire alterations during chronological aging and in immune-mediated disease.

PubMed

Vallejo, Abbe N

2007-03-01

Immunological studies of aging and of patients with chronic immune-mediated diseases document overlap of immune phenotypes. Here, the term "immune remodeling" refers to these phenotypes that are indicative of biological processes of deterioration and repair. This concept is explored through lessons from studies about the changes in the T-cell repertoire and the functional diversity of otherwise oligoclonal, senescent T cells. Immune remodeling suggests a gradual process that occurs throughout life. However, similar but more drastic remodeling occurs disproportionately among young patients with chronic disease. In this article, I propose that immune remodeling is a beneficial adaptation of aging to promote healthy survival beyond reproductive performance, but acute remodeling poses risk of premature exhaustion of the immune repertoire and, thus, is detrimental in young individuals.

[Studies of the biological age in adult taiga ticks Ixodes persulcatus (Ixodinae)].

PubMed

Grigor'eva, L A

2013-01-01

The history of studies of the biological age in ixodid ticks is discussed. A method of estimation of the biological age in adult ticks of the genus Ixodes by the degree of fat inclusions in midgut cells and in the fat body is developed. An "age scale" for the determination of the calendar age was assumed.

High-speed atomic force microscopy coming of age

NASA Astrophysics Data System (ADS)

Ando, Toshio

2012-02-01

High-speed atomic force microscopy (HS-AFM) is now materialized. It allows direct visualization of dynamic structural changes and dynamic processes of functioning biological molecules in physiological solutions, at high spatiotemporal resolution. Dynamic molecular events unselectively appear in detail in an AFM movie, facilitating our understanding of how biological molecules operate to function. This review describes a historical overview of technical development towards HS-AFM, summarizes elementary devices and techniques used in the current HS-AFM, and then highlights recent imaging studies. Finally, future challenges of HS-AFM studies are briefly discussed.

High-resolution reflectometer for monitoring of biological samples

NASA Astrophysics Data System (ADS)

Men, Liqiu; Lu, Ping; Chen, Qiying

2008-06-01

High-resolution optical low-coherence reflectometry is applied to monitor biological samples. It has been found that the reflectivity of aged cow's milk is significantly lower than that of the fresh milk with a difference of 5.35dB. During the process of heating the fresh milk at a constant temperature of 80°C, the reflectivity of the milk gradually decreases with the increase of the heating duration. The technique is proved to be effective in monitoring the change in the refractive index of the sample.

Ageing and the telomere connection: An intimate relationship with inflammation.

PubMed

Zhang, Jingwen; Rane, Grishma; Dai, Xiaoyun; Shanmugam, Muthu K; Arfuso, Frank; Samy, Ramar Perumal; Lai, Mitchell Kim Peng; Kappei, Dennis; Kumar, Alan Prem; Sethi, Gautam

2016-01-01

Telomeres are the heterochromatic repeat regions at the ends of eukaryotic chromosomes, whose length is considered to be a determinant of biological ageing. Normal ageing itself is associated with telomere shortening. Here, critically short telomeres trigger senescence and eventually cell death. This shortening rate may be further increased by inflammation and oxidative stress and thus affect the ageing process. Apart from shortened or dysfunctional telomeres, cells undergoing senescence are also associated with hyperactivity of the transcription factor NF-κB and overexpression of inflammatory cytokines such as TNF-α, IL-6, and IFN-γ in circulating macrophages. Interestingly, telomerase, a reverse transcriptase that elongates telomeres, is involved in modulating NF-κB activity. Furthermore, inflammation and oxidative stress are implicated as pre-disease mechanisms for chronic diseases of ageing such as neurodegenerative diseases, cardiovascular disease, and cancer. To date, inflammation and telomere shortening have mostly been studied individually in terms of ageing and the associated disease phenotype. However, the interdependent nature of the two demands a more synergistic approach in understanding the ageing process itself and for developing new therapeutic approaches. In this review, we aim to summarize the intricate association between the various inflammatory molecules and telomeres that together contribute to the ageing process and related diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of paraquat-induced oxidative stress on gene expression and aging of the filamentous ascomycete Podospora anserina

PubMed Central

Wiemer, Matthias; Osiewacz, Heinz D.

2014-01-01

Aging of biological systems is influenced by various factors, conditions and processes. Among others, processes allowing organisms to deal with various types of stress are of key importance. In particular, oxidative stress as the result of the generation of reactive oxygen species (ROS) at the mitochondrial respiratory chain and the accumulation of ROS-induced molecular damage has been strongly linked to aging. Here we view the impact of ROS from a different angle: their role in the control of gene expression. We report a genome-wide transcriptome analysis of the fungal aging model Podospora anserina grown on medium containing paraquat (PQ). This treatment leads to an increased cellular generation and release of H2O2, a reduced growth rate, and a decrease in lifespan. The combined challenge by PQ and copper has a synergistic negative effect on growth and lifespan. The data from the transcriptome analysis of the wild type cultivated under PQ-stress and their comparison to those of a longitudinal aging study as well as of a copper-uptake longevity mutant of P. anserina revealed that PQ-stress leads to the up-regulation of transcripts coding for components involved in mitochondrial remodeling. PQ also affects the expression of copper-regulated genes suggesting an increase of cytoplasmic copper levels as it has been demonstrated earlier to occur during aging of P. anserina and during senescence of human fibroblasts. This effect may result from the induction of the mitochondrial permeability transition pore via PQ-induced ROS, leading to programmed cell death as part of an evolutionary conserved mechanism involved in biological aging and lifespan control. PMID:28357247

Translational Geroscience: Emphasizing function to achieve optimal longevity

PubMed Central

Seals, Douglas R.; Melov, Simon

2014-01-01

Among individuals, biological aging leads to cellular and organismal dysfunction and an increased risk of chronic degenerative diseases and disability. This sequence of events in combination with the projected increases in the number of older adults will result in a worldwide healthcare burden with dire consequences. Superimposed on this setting are the adults now reaching traditional retirement ages--the baby boomers--a group that wishes to remain active, productive and physically and cognitively fit as they grow older. Together, these conditions are producing an unprecedented demand for increased healthspan or what might be termed “optimal longevity”—to live long, but well. To meet this demand, investigators with interests in the biological aspects of aging from model organisms to human epidemiology (population aging) must work together within an interactive process that we describe as translational geroscience. An essential goal of this new investigational platform should be the optimization and preservation of physiological function throughout the lifespan, including integrative physical and cognitive function, which would serve to increase healthspan, compress morbidity and disability into a shorter period of late-life, and help achieve optimal longevity. To most effectively utilize this new approach, we must rethink how investigators and administrators working at different levels of the translational research continuum communicate and collaborate with each other, how best to train the next generation of scientists in this new field, and how contemporary biological-biomedical aging research should be organized and funded. PMID:25324468

Differences That Make A Difference: A Study in Collaborative Learning

NASA Astrophysics Data System (ADS)

Touchman, Stephanie

Collaborative learning is a common teaching strategy in classrooms across age groups and content areas. It is important to measure and understand the cognitive process involved during collaboration to improve teaching methods involving interactive activities. This research attempted to answer the question: why do students learn more in collaborative settings? Using three measurement tools, 142 participants from seven different biology courses at a community college and at a university were tested before and after collaborating about the biological process of natural selection. Three factors were analyzed to measure their effect on learning at the individual level and the group level. The three factors were: difference in prior knowledge, sex and religious beliefs. Gender and religious beliefs both had a significant effect on post-test scores.

Integrating Evolutionary and Molecular Genetics of Aging

PubMed Central

Flatt, Thomas; Schmidt, Paul S.

2010-01-01

Aging or senescence is an age-dependent decline in physiological function, demographically manifest as decreased survival and fecundity with increasing age. Since aging is disadvantageous it should not evolve by natural selection. So why do organisms age and die? In the 1940’s and 1950’s evolutionary geneticists resolved this paradox by positing that aging evolves because selection is inefficient at maintaining function late in life. By the 1980’s and 1990’s this evolutionary theory of aging had received firm empirical support, but little was known about the mechanisms of aging. Around the same time biologists began to apply the tools of molecular genetics to aging and successfully identified mutations that affect longevity. Today, the molecular genetics of aging is a burgeoning field, but progress in evolutionary genetics of aging has largely stalled. Here we argue that some of the most exciting and unresolved questions about aging require an integration of molecular and evolutionary approaches. Is aging a universal process? Why do species age at different rates? Are the mechanisms of aging conserved or lineage-specific? Are longevity genes identified in the laboratory under selection in natural populations? What is the genetic basis of plasticity in aging in response to environmental cues and is this plasticity adaptive? What are the mechanisms underlying trade-offs between early fitness traits and life span? To answer these questions evolutionary biologists must adopt the tools of molecular biology, while molecular biologists must put their experiments into an evolutionary framework. The time is ripe for a synthesis of molecular biogerontology and the evolutionary biology of aging. PMID:19619612

Integrating evolutionary and molecular genetics of aging.

PubMed

Flatt, Thomas; Schmidt, Paul S

2009-10-01

Aging or senescence is an age-dependent decline in physiological function, demographically manifest as decreased survival and fecundity with increasing age. Since aging is disadvantageous it should not evolve by natural selection. So why do organisms age and die? In the 1940s and 1950s evolutionary geneticists resolved this paradox by positing that aging evolves because selection is inefficient at maintaining function late in life. By the 1980s and 1990s this evolutionary theory of aging had received firm empirical support, but little was known about the mechanisms of aging. Around the same time biologists began to apply the tools of molecular genetics to aging and successfully identified mutations that affect longevity. Today, the molecular genetics of aging is a burgeoning field, but progress in evolutionary genetics of aging has largely stalled. Here we argue that some of the most exciting and unresolved questions about aging require an integration of molecular and evolutionary approaches. Is aging a universal process? Why do species age at different rates? Are the mechanisms of aging conserved or lineage-specific? Are longevity genes identified in the laboratory under selection in natural populations? What is the genetic basis of plasticity in aging in response to environmental cues and is this plasticity adaptive? What are the mechanisms underlying trade-offs between early fitness traits and life span? To answer these questions evolutionary biologists must adopt the tools of molecular biology, while molecular biologists must put their experiments into an evolutionary framework. The time is ripe for a synthesis of molecular biogerontology and the evolutionary biology of aging.

Measuring Biological Age via Metabonomics: The Metabolic Age Score.

PubMed

Hertel, Johannes; Friedrich, Nele; Wittfeld, Katharina; Pietzner, Maik; Budde, Kathrin; Van der Auwera, Sandra; Lohmann, Tobias; Teumer, Alexander; Völzke, Henry; Nauck, Matthias; Grabe, Hans Jörgen

2016-02-05

Chronological age is one of the most important risk factors for adverse clinical outcome. Still, two individuals at the same chronological age could have different biological aging states, leading to different individual risk profiles. Capturing this individual variance could constitute an even more powerful predictor enhancing prediction in age-related morbidity. Applying a nonlinear regression technique, we constructed a metabonomic measurement for biological age, the metabolic age score, based on urine data measured via (1)H NMR spectroscopy. We validated the score in two large independent population-based samples by revealing its significant associations with chronological age and age-related clinical phenotypes as well as its independent predictive value for survival over approximately 13 years of follow-up. Furthermore, the metabolic age score was prognostic for weight loss in a sample of individuals who underwent bariatric surgery. We conclude that the metabolic age score is an informative measurement of biological age with possible applications in personalized medicine.

Microarray gene-expression study in fibroblast and lymphoblastoid cell lines from antipsychotic-naïve first-episode schizophrenia patients.

PubMed

Gassó, Patricia; Mas, Sergi; Rodríguez, Natalia; Boloc, Daniel; García-Cerro, Susana; Bernardo, Miquel; Lafuente, Amalia; Parellada, Eduard

2017-12-01

Schizophrenia (SZ) is a chronic psychiatric disorder whose onset of symptoms occurs in late adolescence and early adulthood. The etiology is complex and involves important gene-environment interactions. Microarray gene-expression studies on SZ have identified alterations in several biological processes. The heterogeneity in the results can be attributed to the use of different sample types and other important confounding factors including age, illness chronicity and antipsychotic exposure. The aim of the present microarray study was to analyze, for the first time to our knowledge, differences in gene expression profiles in 18 fibroblast (FCLs) and 14 lymphoblastoid cell lines (LCLs) from antipsychotic-naïve first-episode schizophrenia (FES) patients and healthy controls. We used an analytical approach based on protein-protein interaction network construction and functional annotation analysis to identify the biological processes that are altered in SZ. Significant differences in the expression of 32 genes were found when LCLs were assessed. The network and gene set enrichment approach revealed the involvement of similar biological processes in FCLs and LCLs, including apoptosis and related biological terms such as cell cycle, autophagy, cytoskeleton organization and response to stress and stimulus. Metabolism and other processes, including signal transduction, kinase activity and phosphorylation, were also identified. These results were replicated in two independent cohorts using the same analytical approach. This provides more evidence for altered apoptotic processes in antipsychotic-naïve FES patients and other important biological functions such as cytoskeleton organization and metabolism. The convergent results obtained in both peripheral cell models support their usefulness for transcriptome studies on SZ. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Biology of Aging.

ERIC Educational Resources Information Center

Sprott, Richard L.; And Others

1992-01-01

Thirteen articles in this special issue discuss aging theories, biomarkers of aging, aging research, disease, cancer biology, Alzheimer's disease, stress, oxidation of proteins, gene therapy, service delivery, biogerontology, and ethics and aging research. (SK)

Animal models of aging research: implications for human aging and age-related diseases.

PubMed

Mitchell, Sarah J; Scheibye-Knudsen, Morten; Longo, Dan L; de Cabo, Rafael

2015-01-01

Aging is characterized by an increasing morbidity and functional decline that eventually results in the death of an organism. Aging is the largest risk factor for numerous human diseases, and understanding the aging process may thereby facilitate the development of new treatments for age-associated diseases. The use of humans in aging research is complicated by many factors, including ethical issues; environmental and social factors; and perhaps most importantly, their long natural life span. Although cellular models of human disease provide valuable mechanistic information, they are limited in that they may not replicate the in vivo biology. Almost all organisms age, and thus animal models can be useful for studying aging. Herein, we review some of the major models currently used in aging research and discuss their benefits and pitfalls, including interventions known to extend life span and health span. Finally, we conclude by discussing the future of animal models in aging research.

Vocal aging and adductor spasmodic dysphonia: response to botulinum toxin injection.

PubMed

Cannito, Michael P; Kahane, Joel C; Chorna, Lesya

2008-01-01

Aging of the larynx is characterized by involutional changes which alter its biomechanical and neural properties and create a biological environment that is different from younger counterparts. Illustrative anatomical examples are presented. This natural, non-disease process appears to set conditions which may influence the effectiveness of botulinum toxin injection and our expectations for its success. Adductor spasmodic dysphonia, a type of laryngeal dystonia, is typically treated using botulinum toxin injections of the vocal folds in order to suppress adductory muscle spasms which are disruptive to production of speech and voice. A few studies have suggested diminished response to treatment in older patients with adductor spasmodic dysphonia. This retrospective study provides a reanalysis of existing pre-to-post treatment data as function of age. Perceptual judgments of speech produced by 42 patients with ADSD were made by two panels of professional listeners with expertise in voice or fluency of speech. Results demonstrate a markedly reduced positive response to botulinum toxin treatment in the older patients. Perceptual findings are further elucidated by means of acoustic spectrography. Literature on vocal aging is reviewed to provide a specific set of biological mechanisms that best account for the observed interaction of botulinum toxin treatment with advancing age.

SENESCENCE (AGEING) @ 2011

PubMed Central

Nigam, Anjana

2011-01-01

Ageing, also called as senescence, is one of the most complex, intrinsic, biological processes of growing older and resulting into reduced functional ability of the organism. Telomerase, environment, low calorie diets, free radicals, etc., are all believed to affect this ageing process. A number of genetic components of ageing have been identified using model organisms. Genes, mainly the sirtuins, regulate the ageing speed by indirection and controlling organism resistance to damages by exogenous and endogenous stresses. In higher organisms, ageing is likely to be regulated, in part, through the insulin/insulin-like growth factor 1 pathway. Besides this, the induction of apoptosis in stem and progenitor cells, increased p53 activity, and autophagy is also thought to trigger premature organismal ageing. Ageing has also been shown to upregulate expression of inflammatory mediators in mouse adipose tissue. The understanding of pathophysiology of ageing over the past few years has posed tremendous challenges for the development of anti-ageing medicine for targeted therapy. Future research areas must include targeted role of systemic inflammatory markers such as C-reactive protein and interleukin 6 and other biochemical and genetic studies including gene signaling pathways, gene microarray analysis, gene modulation, gene therapy, and development of animal/human models for potential therapeutic measures and evaluations. PMID:22345758

Biological maturation of youth athletes: assessment and implications.

PubMed

Malina, Robert M; Rogol, Alan D; Cumming, Sean P; Coelho e Silva, Manuel J; Figueiredo, Antonio J

2015-07-01

The search for talent is pervasive in youth sports. Selection/exclusion in many sports follows a maturity-related gradient largely during the interval of puberty and growth spurt. As such, there is emphasis on methods for assessing maturation. Commonly used methods for assessing status (skeletal age, secondary sex characteristics) and estimating timing (ages at peak height velocity (PHV) and menarche) in youth athletes and two relatively recent anthropometric (non-invasive) methods (status-percentage of predicted near adult height attained at observation, timing-predicted maturity offset/age at PHV) are described and evaluated. The latter methods need further validation with athletes. Currently available data on the maturity status and timing of youth athletes are subsequently summarised. Selection for sport and potential maturity-related correlates are then discussed in the context of talent development and associated models. Talent development from novice to elite is superimposed on a constantly changing base-the processes of physical growth, biological maturation and behavioural development, which occur simultaneously and interact with each other. The processes which are highly individualised also interact with the demands of a sport per se and with involved adults (coaches, trainers, administrators, parents/guardians). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Childhood Maltreatment Predicts Allostatic Load in Adulthood

PubMed Central

Widom, Cathy Spatz; Horan, Jacqueline; Brzustowicz, Linda

2015-01-01

Childhood maltreatment has been linked to numerous negative health outcomes. However, few studies have examined mediating processes using longitudinal designs or objectively measured biological data. This study sought to determine whether child abuse and neglect predicts allostatic load (a composite indicator of accumulated stress-induced biological risk) and to examine potential mediators. Using a prospective cohort design, children (ages 0-11) with documented cases of abuse and neglect were matched with non-maltreated children and followed up into adulthood with in-person interviews and a medical status exam (mean age 41). Allostatic load was assessed with nine physical health indicators. Child abuse and neglect predicted allostatic load, controlling for age, sex, and race. The direct effect of child abuse and neglect persisted despite the introduction of potential mediators of internalizing and externalizing problems in adolescence and social support and risky lifestyle in middle adulthood. These findings reveal the long-term impact of childhood abuse and neglect on physical health over 30 years later. PMID:25700779

Insights into mortality patterns and causes of death through a process point of view model.

PubMed

Anderson, James J; Li, Ting; Sharrow, David J

2017-02-01

Process point of view (POV) models of mortality, such as the Strehler-Mildvan and stochastic vitality models, represent death in terms of the loss of survival capacity through challenges and dissipation. Drawing on hallmarks of aging, we link these concepts to candidate biological mechanisms through a framework that defines death as challenges to vitality where distal factors defined the age-evolution of vitality and proximal factors define the probability distribution of challenges. To illustrate the process POV, we hypothesize that the immune system is a mortality nexus, characterized by two vitality streams: increasing vitality representing immune system development and immunosenescence representing vitality dissipation. Proximal challenges define three mortality partitions: juvenile and adult extrinsic mortalities and intrinsic adult mortality. Model parameters, generated from Swedish mortality data (1751-2010), exhibit biologically meaningful correspondences to economic, health and cause-of-death patterns. The model characterizes the twentieth century epidemiological transition mainly as a reduction in extrinsic mortality resulting from a shift from high magnitude disease challenges on individuals at all vitality levels to low magnitude stress challenges on low vitality individuals. Of secondary importance, intrinsic mortality was described by a gradual reduction in the rate of loss of vitality presumably resulting from reduction in the rate of immunosenescence. Extensions and limitations of a distal/proximal framework for characterizing more explicit causes of death, e.g. the young adult mortality hump or cancer in old age are discussed.

Insights into mortality patterns and causes of death through a process point of view model

PubMed Central

Anderson, James J.; Li, Ting; Sharrow, David J.

2016-01-01

Process point of view models of mortality, such as the Strehler-Mildvan and stochastic vitality models, represent death in terms of the loss of survival capacity through challenges and dissipation. Drawing on hallmarks of aging, we link these concepts to candidate biological mechanisms through a framework that defines death as challenges to vitality where distal factors defined the age-evolution of vitality and proximal factors define the probability distribution of challenges. To illustrate the process point of view, we hypothesize that the immune system is a mortality nexus, characterized by two vitality streams: increasing vitality representing immune system development and immunosenescence representing vitality dissipation. Proximal challenges define three mortality partitions: juvenile and adult extrinsic mortalities and intrinsic adult mortality. Model parameters, generated from Swedish mortality data (1751-2010), exhibit biologically meaningful correspondences to economic, health and cause-of-death patterns. The model characterizes the 20th century epidemiological transition mainly as a reduction in extrinsic mortality resulting from a shift from high magnitude disease challenges on individuals at all vitality levels to low magnitude stress challenges on low vitality individuals. Of secondary importance, intrinsic mortality was described by a gradual reduction in the rate of loss of vitality presumably resulting from reduction in the rate of immunosenescence. Extensions and limitations of a distal/proximal framework for characterizing more explicit causes of death, e.g. the young adult mortality hump or cancer in old age are discussed. PMID:27885527

8-Oxoguanine DNA glycosylase1-driven DNA repair-A paradoxical role in lung aging.

PubMed

German, Peter; Saenz, David; Szaniszlo, Peter; Aguilera-Aguirre, Leopoldo; Pan, Lang; Hegde, Muralidhar L; Bacsi, Attila; Hajas, Gyorgy; Radak, Zsolt; Ba, Xueqing; Mitra, Sankar; Papaconstantinou, John; Boldogh, Istvan

2017-01-01

Age-associated changes in lung structure and function are some of the most important predictors of overall health, cognitive activities and longevity. Common to all aging cells is an increase in oxidatively modified DNA bases, primarily 8-oxo-7,8-dihydroguanine (8-oxoG). It is repaired via DNA base excision repair pathway driven by 8-oxoguanine DNA glycosylase-1 (OGG1-BER), whose role in aging has been the focus of many studies. This study hypothesizes that signaling and consequent gene expression during cellular response to OGG1-BER "wires" senescence/aging processes. To test OGG1-BER was mimicked by repeatedly exposing diploid lung fibroblasts cells and airways of mice to 8-oxoG base. Results showed that repeated exposures led to G1 cell cycle arrest and pre-matured senescence of cultured cells in which over 1000 genes were differentially expressed -86% of them been identical to those in naturally senesced cells. Gene ontology analysis of gene expression displayed biological processes driven by small GTPases, phosphoinositide 3-kinase and mitogen activated kinase cascades both in cultured cells and lungs. These results together, points to a new paradigm about the role of DNA damage and repair by OGG1 in aging and age-associated disease processes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Epigenomic maintenance through dietary intervention can facilitate DNA repair process to slow down the progress of premature aging.

PubMed

Ghosh, Shampa; Sinha, Jitendra Kumar; Raghunath, Manchala

2016-09-01

DNA damage caused by various sources remains one of the most researched topics in the area of aging and neurodegeneration. Increased DNA damage causes premature aging. Aging is plastic and is characterised by the decline in the ability of a cell/organism to maintain genomic stability. Lifespan can be modulated by various interventions like calorie restriction, a balanced diet of macro and micronutrients or supplementation with nutrients/nutrient formulations such as Amalaki rasayana, docosahexaenoic acid, resveratrol, curcumin, etc. Increased levels of DNA damage in the form of double stranded and single stranded breaks are associated with decreased longevity in animal models like WNIN/Ob obese rats. Erroneous DNA repair can result in accumulation of DNA damage products, which in turn result in premature aging disorders such as Hutchinson-Gilford progeria syndrome. Epigenomic studies of the aging process have opened a completely new arena for research and development of drugs and therapeutic agents. We propose here that agents or interventions that can maintain epigenomic stability and facilitate the DNA repair process can slow down the progress of premature aging, if not completely prevent it. © 2016 IUBMB Life, 68(9):717-721, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

Analytical approaches to the diagnosis and treatment of aging and aging-related disease: redox status and proteomics.

PubMed

Calabrese, V; Dattilo, S; Petralia, A; Parenti, R; Pennisi, M; Koverech, G; Calabrese, V; Graziano, A; Monte, I; Maiolino, L; Ferreri, T; Calabrese, E J

2015-05-01

Basal levels of oxidants are indispensible for redox signaling to produce adaptive cellular responses such as vitagenes linked to cell survival; however, at higher levels, they are detrimental to cells, contributing to aging and to the pathogenesis of numerous age-related diseases. Aging is a complex systemic process and the major gap in aging research reminds the insufficient knowledge about pathways shifting from normal "healthy" aging to disease-associated pathological aging. The major complication of normal "healthy" aging is in fact the increasing risk of age-related diseases such as cardiovascular diseases, diabetes mellitus, and neurodegenerative pathologies that can adversely affect the quality of life in general, with enhanced incidences of comorbidities and mortality. In this context, global "omics" approaches may help to dissect and fully study the cellular and molecular mechanisms of aging and age-associated processes. The proteome, being more close to the phenotype than the transcriptome and more stable than the metabolome, represents the most promising "omics" field in aging research. In the present study, we exploit recent advances in the redox biology of aging and discuss the potential of proteomics approaches as innovative tools for monitoring at the proteome level the extent of protein oxidative insult and related modifications with the identification of targeted proteins.

The Use of Informative Priors in Bayesian Modeling Age-at-death; a Quick Look at Chronological and Biological Age Changes in the Sacroiliac Joint in American Males.

PubMed

Godde, Kanya

2017-01-01

The aim of this study is to examine how well different informative priors model age-at-death in Bayesian statistics, which will shed light on how the skeleton ages, particularly at the sacroiliac joint. Data from four samples were compared for their performance as informative priors for auricular surface age-at-death estimation: (1) American population from US Census data; (2) county data from the US Census data; (3) a local cemetery; and (4) a skeletal collection. The skeletal collection and cemetery are located within the county that was sampled. A Gompertz model was applied to compare survivorship across the four samples. Transition analysis parameters, coupled with the generated Gompertz parameters, were input into Bayes' theorem to generate highest posterior density ranges from posterior density functions. Transition analysis describes the age at which an individual transitions from one age phase to another. The result is age ranges that should describe the chronological age of 90% of the individuals who fall in a particular phase. Cumulative binomial tests indicate the method performed lower than 90% at capturing chronological age as assigned to a biological phase, despite wide age ranges at older ages. The samples performed similarly overall, despite small differences in survivorship. Collectively, these results show that as we age, the senescence pattern becomes more variable. More local samples performed better at describing the aging process than more general samples, which implies practitioners need to consider sample selection when using the literature to diagnose and work with patients with sacroiliac joint pain.

Longevity and aging. Mechanisms and perspectives.

PubMed

Labat-Robert, J; Robert, L

2015-12-01

Longevity can mostly be determined with relative accuracy from birth and death registers when available. Aging is a multifactorial process, much more difficult to quantitate. Every measurable physiological function declines with specific speeds over a wide range. The mechanisms involved are also different, genetic factors are of importance for longevity determinations. The best-known genes involved are the Sirtuins, active at the genetic and epigenetic level. Aging is multifactorial, not "coded" in the genome. There are, however, a number of well-studied physical and biological parameters involved in aging, which can be determined and quantitated. We shall try to identify parameters affecting longevity as well as aging and suggest some reasonable predictions for the future. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Paternal Age Effect Mutations and Selfish Spermatogonial Selection: Causes and Consequences for Human Disease

PubMed Central

Goriely, Anne; Wilkie, Andrew O.M.

2012-01-01

Advanced paternal age has been associated with an increased risk for spontaneous congenital disorders and common complex diseases (such as some cancers, schizophrenia, and autism), but the mechanisms that mediate this effect have been poorly understood. A small group of disorders, including Apert syndrome (caused by FGFR2 mutations), achondroplasia, and thanatophoric dysplasia (FGFR3), and Costello syndrome (HRAS), which we collectively term “paternal age effect” (PAE) disorders, provides a good model to study the biological and molecular basis of this phenomenon. Recent evidence from direct quantification of PAE mutations in sperm and testes suggests that the common factor in the paternal age effect lies in the dysregulation of spermatogonial cell behavior, an effect mediated molecularly through the growth factor receptor-RAS signal transduction pathway. The data show that PAE mutations, although arising rarely, are positively selected and expand clonally in normal testes through a process akin to oncogenesis. This clonal expansion, which is likely to take place in the testes of all men, leads to the relative enrichment of mutant sperm over time—explaining the observed paternal age effect associated with these disorders—and in rare cases to the formation of testicular tumors. As regulation of RAS and other mediators of cellular proliferation and survival is important in many different biological contexts, for example during tumorigenesis, organ homeostasis and neurogenesis, the consequences of selfish mutations that hijack this process within the testis are likely to extend far beyond congenital skeletal disorders to include complex diseases, such as neurocognitive disorders and cancer predisposition. PMID:22325359

Alive and Well? Exploring Disease by Studying Lifespan

PubMed Central

Brett, Jamie O.; Rando, Thomas A.

2014-01-01

A common concept in aging research is that chronological age is the most important risk factor for the development of diverse diseases, including degenerative diseases and cancers. The mechanistic link between the aging process and disease pathogenesis, however, is still enigmatic. Nevertheless, measurement of lifespan, as a surrogate for biological aging, remains among the most frequently used assays in aging research. In this review, we examine the connection between “normal aging” and age-related disease from the point of view that they form a continuum of aging phenotypes. This notion of common mechanisms gives rise to the converse postulate that diseases may be risk factors for accelerated aging. We explore the advantages and caveats associated with using lifespan as a metric to understand cell and tissue aging, focusing on the elucidation of molecular mechanisms and potential therapies for age-related diseases. PMID:25005743

Sex differences in telomeres and lifespan in Soay sheep: From the beginning to the end.

PubMed

Dantzer, Ben; Garratt, Michael

2017-06-01

There is tremendous diversity in ageing rates and lifespan not only among taxa but within species, and particularly between the sexes. Women often live longer than men, and considerable research on this topic has revealed some of the potential biological, psychological and cultural causes of sex differences in human ageing and lifespan. However, sex differences in lifespan are widespread in nonhuman animals suggesting biology plays a prominent role in variation in ageing and lifespan. Recently, evolutionary biologists have borrowed techniques from biomedicine to identify whether similar mechanisms causing or contributing to variation in ageing and lifespan in humans and laboratory animals also operate in wild animals. Telomeres are repetitive noncoding DNA sequences capping the ends of chromosomes that are important for chromosomal stability but that can shorten during normal cell division and exposure to stress. Telomere shortening is hypothesized to directly contribute to the ageing process as once telomeres shorten to some length, the cells stop dividing and die. Men tend to have shorter telomeres and faster rates of telomere attrition with age than women, suggesting one possible biological cause of sex differences in lifespan. In this issue of Molecular Ecology, Watson et al. () show that telomere lengths in wild Soay sheep are similar between females and males near the beginning of life but quickly diverge with age because males but not females showed reduced telomere lengths at older ages. The authors further show that some of the observed sex difference in telomere lengths in old age may be due to male investment in horn growth earlier in life, suggesting that sexually dimorphic allocation to traits involved in sexual selection might underlie sex differences in telomere attrition. This study provides a rare example of how biological mechanisms potentially contributing to sex differences in lifespan in humans may also operate in free-living animals. However, future studies using a longitudinal approach are necessary to confirm these observations and identify the ultimate and proximate causes of any sex differences in telomere lengths. Collaborations between evolutionary biologists and gerontologists are especially needed to identify whether telomere lengths have a causal role in ageing, particularly in natural conditions, and whether this directly contributes to sex differences in lifespan. © 2017 John Wiley & Sons Ltd.

Distinguishing pathological from constitutional small for gestational age births in population-based studies.

PubMed

Ananth, Cande V; Vintzileos, Anthony M

2009-10-01

Small for gestational age (SGA) can occur following a pathological process or may represent constitutionally small fetuses. However, distinguishing these processes is often difficult, especially in large studies, where the term SGA is often used as a proxy for restricted fetal growth. Since biologic variation in fetal size is largely a third trimester phenomenon, we hypothesized that the definition of SGA at term may include a sizeable proportion of constitutionally small fetuses. In contrast, since biologic variation in fetal size is not fully expressed in (early) preterm gestations, it is plausible that SGA in early preterm gestations would comprise a large proportion of growth restricted fetuses. We compared mortality and morbidity rates between SGA and appropriate for gestational age (AGA) babies. A population-based study of over 19million non-malformed, singleton births (1995-04) in the United States was performed. Gestational age (24-44weeks) was based on a clinical estimate. SGA and AGA were defined as sex-specific birthweight <10th and 25-74th centiles, respectively, for gestational age. All analyses were adjusted for a variety of confounding factors. Excess mortality risk in SGA and AGA babies. On an additive scale, stillbirth and neonatal mortality rates were higher at every preterm gestation among SGA than AGA births, and similar at term gestations. An inverse relationship between gestational age and excess deaths between SGA and AGA babies delivered at <37weeks was evident. In early preterm gestations, the definition of SGA may well be justified as a proxy for IUGR. In contrast, SGA babies that are delivered at term are likely to be constitutionally small.

Nutritional strategies to optimise cognitive function in the aging brain.

PubMed

Wahl, Devin; Cogger, Victoria C; Solon-Biet, Samantha M; Waern, Rosilene V R; Gokarn, Rahul; Pulpitel, Tamara; Cabo, Rafael de; Mattson, Mark P; Raubenheimer, David; Simpson, Stephen J; Le Couteur, David G

2016-11-01

Old age is the greatest risk factor for most neurodegenerative diseases. During recent decades there have been major advances in understanding the biology of aging, and the development of nutritional interventions that delay aging including calorie restriction (CR) and intermittent fasting (IF), and chemicals that influence pathways linking nutrition and aging processes. CR influences brain aging in many animal models and recent findings suggest that dietary interventions can influence brain health and dementia in older humans. The role of individual macronutrients in brain aging also has been studied, with conflicting results about the effects of dietary protein and carbohydrates. A new approach known as the Geometric Framework (GF) has been used to unravel the complex interactions between macronutrients (protein, fat, and carbohydrate) and total energy on outcomes such as aging. These studies have shown that low-protein, high-carbohydrate (LPHC) diets are optimal for lifespan in ad libitum fed animals, while total calories have minimal effect once macronutrients are taken into account. One of the primary purposes of this review is to explore the notion that macronutrients may have a more translational potential than CR and IF in humans, and therefore there is a pressing need to use GF to study the impact of diet on brain aging. Furthermore, given the growing recognition of the role of aging biology in dementia, such studies might provide a new approach for dietary interventions for optimizing brain health and preventing dementia in older people. Copyright © 2016 Elsevier B.V. All rights reserved.

Indonesian kalkulator of oocytes (IKO): A smart application to determine our biological age

NASA Astrophysics Data System (ADS)

Wiweko, Budi; Narasati, Shabrina; Agung, Prince Gusti; Zesario, Aulia; Wibawa, Yohanes Satrya; Maidarti, Mila; Harzif, Achmad Kemal; Pratama, Gita; Sumapraja, Kanadi; Muharam, Raden; Hestiantoro, Andon

2018-02-01

Background: The use of smartphones and its associated application provides new opportunities for physicians. In current situations, there are still few applications are designed in the field of infertility and Assisted Reproductive Technologies (ART). A study conducted on 1616 subjects proved that AMH (Anti-Mullerian Hormone) could be used to predict a woman's biological age earlier than Follicle-Stimulating Hormone (FSH) and Antral Follicle Count (AFC). In this study, we describe the AMH nomogram that has been developed into a mobile application as "Indonesian Kalculator of Oocytes" (IKO). The software required to create IKO application was the Android 4.0.3 Ice Cream Sandwich and Java Application Development. The hardware specification that needed to develop the IKO apps were a 4.0-inch screen, 512 MB RAM (random-access memory), and CPU (central processing unit) with dual core 1.2 Ghz. The application is built using the Android SDK (Software Development Kit) and Java Application Development. In this application, we can predict the woman's biological age, some mature oocytes, and AMH level. This app is expected to help patients to plan effectively for pregnancy and help the doctor to choose the best intervention for patients who face infertility problems using Assisted Reproductive Technology (ART). IKO application can be downloaded for free on Google PlayStore and Apple Store.

Accelerated biological ageing in HIV-infected individuals in South Africa: a case–control study

PubMed Central

Pathai, Sophia; Lawn, Stephen D.; Gilbert, Clare E.; McGuinness, Dagmara; McGlynn, Liane; Weiss, Helen A.; Port, Jennifer; Christ, Theresa; Barclay, Karen; Wood, Robin; Bekker, Linda-Gail; Shiels, Paul G.

2013-01-01

Objectives: Little is known about the impact of HIV infection on biological ageing in sub-Saharan Africa. The study aimed to assess biological ageing in South African HIV-infected adults and HIV-seronegative individuals using two validated biomarkers, telomere length and CDKN2A expression (a mediator of cellular senescence). Design: A case–control study. Methods: Two hundred and thirty-six HIV-infected adults aged at least 30 years and 250 age and sex frequency matched HIV-seronegative individuals were recruited from clinics in township communities in Cape Town. Biological ageing was evaluated by measurement of telomere length and CDKN2A expression in peripheral blood leukocytes. Results: The median ages of the HIV-infected and HIV-seronegative participants were 39 and 40 years, respectively. Among HIV-infected participants, 87.1% were receiving antiretroviral therapy (ART), their median CD4+ cell count was 468 cells/μl and 84.3% had undetectable viral load. Both biomarkers were validated against chronological age in HIV-seronegative individuals. Telomere length was significantly shorter in HIV-infected individuals than in HIV-seronegative individuals (mean relative T/S ratio ±SE:0.91 ± 0.007 vs. 1.07 ± 0.008, P < 0.0001). CD2NKA expression was higher in HIV-infected participants than in HIV-seronegative individuals (mean expression: 0.45 ± 0.02 vs. 0.36 ± 0.03, P = 0.003). Socioeconomic factors were not associated with biological ageing in HIV-infected participants. However, in participants on ART with undetectable viral load, biomarker levels indicated greater biological ageing in those with lower current CD4+ cell counts. Conclusion: Telomere length and CDKN2A expression were both consistent with increased biological ageing in HIV-infected individuals. Prospective studies of the impact of HIV on biological ageing in sub-Saharan Africa are warranted. PMID:23751258

Heterochronic parabiosis for the study of the effects of aging on stem cells and their niches

PubMed Central

Conboy, Irina M.; Rando, Thomas A.

2012-01-01

Aging is unmistakable and undeniable in mammals. Interestingly, mice develop cataracts, muscle atrophy, osteoporosis, obesity, diabetes and cognitive deficits after just 2–3 postnatal years, while it takes seven or more decades for the same age-specific phenotypes to develop in humans. Thus, chronological age corresponds differently with biological age in metazoan species and although many theories exist, we do not understand what controls the rate of mammalian aging. One interesting idea is that species-specific rate of aging represents a ratio of tissue attrition to tissue regeneration. Furthermore, current findings suggest that the age-imposed biochemical changes in the niches of tissue stem cells inhibit performance of this regenerative pool, which leads to the decline of tissue maintenance and repair. If true, slowing down stem cell and niche aging, thereby promoting tissue regeneration, could slow down the process of tissue and organismal aging. In this regard, recent studies of heterochronic parabiosis provide important clues as to the mechanisms of stem cell aging and suggest novel strategies for enhancing tissue repair in the old. Here we review current literature on the relationship between the vigor of tissue stem cells and the process of aging, with an emphasis on the rejuvenation of old tissues by the extrinsic modifications of stem cell niches. PMID:22617385

Long-term alterations in neural and endocrine processes induced by motherhood in mammals.

PubMed

Bridges, Robert S

2016-01-01

This article is part of a Special Issue "Parental Care". The reproductive experience of pregnancy, lactation and motherhood can significantly remodel the female's biological state, affecting endocrine, neuroendocrine, neural, and immunological processes. The brain, pituitary gland, liver, thymus, and mammary tissue are among the structures that are modified by reproductive experience. The present review that focuses on rodent research, but also includes pertinent studies in sheep and other species, identifies specific changes in these processes brought about by the biological states of pregnancy, parturition, and lactation and how the components of reproductive experience contribute to the remodeling of the maternal brain and organ systems. Findings indicate that prior parity alters key circulating hormone levels and neural receptor gene expression. Moreover, reproductive experience results in modifications in neural processes and glial support. The possible role of pregnancy-induced neurogenesis is considered in the context of neuroplasticity and behavior, and the effects of reproductive experience on maternal memory, i.e. the retention of maternal behavior, together with anxiety and learning are presented. Together, these sets of findings support the concept that the neural and biological state of the adult female is significantly and dramatically altered on a long-term basis by the experiences of parity and motherhood. Remodeling of the maternal brain and other biological systems is posited to help facilitate adaptations to environmental/ecological challenges as the female raises young and ages. Copyright © 2015 Elsevier Inc. All rights reserved.

Hallmarks of progeroid syndromes: lessons from mice and reprogrammed cells

PubMed Central

López-Otín, Carlos

2016-01-01

ABSTRACT Ageing is a process that inevitably affects most living organisms and involves the accumulation of macromolecular damage, genomic instability and loss of heterochromatin. Together, these alterations lead to a decline in stem cell function and to a reduced capability to regenerate tissue. In recent years, several genetic pathways and biochemical mechanisms that contribute to physiological ageing have been described, but further research is needed to better characterize this complex biological process. Because premature ageing (progeroid) syndromes, including progeria, mimic many of the characteristics of human ageing, research into these conditions has proven to be very useful not only to identify the underlying causal mechanisms and identify treatments for these pathologies, but also for the study of physiological ageing. In this Review, we summarize the main cellular and animal models used in progeria research, with an emphasis on patient-derived induced pluripotent stem cell models, and define a series of molecular and cellular hallmarks that characterize progeroid syndromes and parallel physiological ageing. Finally, we describe the therapeutic strategies being investigated for the treatment of progeroid syndromes, and their main limitations. PMID:27482812

The interplay between immunity and aging in Drosophila.

PubMed

Garschall, Kathrin; Flatt, Thomas

2018-01-01

Here, we provide a brief review of the mechanistic connections between immunity and aging-a fundamental biological relationship that remains poorly understood-by considering two intertwined questions: how does aging affect immunity, and how does immunity affect aging? On the one hand, aging contributes to the deterioration of immune function and predisposes the organism to infections ("immuno-senescence"). On the other hand, excessive activation of the immune system can accelerate degenerative processes, cause inflammation and immunopathology, and thus promote aging ("inflammaging"). Interestingly, several recent lines of evidence support the hypothesis that restrained or curbed immune activity at old age (that is, optimized age-dependent immune homeostasis) might actually improve realized immune function and thereby promote longevity. We focus mainly on insights from Drosophila , a powerful genetic model system in which both immunity and aging have been extensively studied, and conclude by outlining several unresolved questions in the field.

Maturity status influences the relative age effect in national top level youth alpine ski racing and soccer

PubMed Central

Müller, Lisa; Gonaus, Christoph; Perner, Christoph; Müller, Erich; Raschner, Christian

2017-01-01

Since the relative age effect (RAE) characterizes a problem in all age categories of alpine ski racing and soccer and the fact that, yet, to date the underlying factors have not been well investigated, the aim of the present study was to assess the influence of the biological maturity status on the RAE among youth alpine ski racers (YSR) and soccer players (SP). In total, 183 male and female YSR selected for national final races and 423 male SP selected for Elite Youth Development Centres were investigated. Additionally, a comparison group of 413 non-athletes was evaluated. The birth months were split into four relative age quarters. The biological maturity status was assessed by the age at peak height velocity (APHV) method; according to the M±SD of the comparison group, the athletes were divided into normal, early and late maturing. Chi2-tests indicated a significant RAE among YSR (χ2(3,N = 183) = 18.0; p<0.001; ω = 0.31) and SP (χ2(3,N = 423) = 33.1; p<0.001; ω = 0.28). In total, only a small number of late maturing athletes were present (0.5–2.3%). Among relatively younger athletes, high percentages of early maturing athletes were found (43.1–43.3%). The findings indicate that relatively younger and less mature athletes are marginalized or totally excluded in alpine ski racing and soccer. Thus, selection criteria in both sports are effectively based on early biological development and relatively older age, both of which should be considered in future in the talent selection process. In this context, the easy feasible method of assessing the APHV can be used. PMID:28759890

Avoidance of accelerated aging in schizophrenia?: Clinical and biological characterization of an exceptionally high functioning individual.

PubMed

Palmer, Barton W; Moore, Raeanne C; Eyler, Lisa T; Pinto, Luz L; Saks, Elyn R; Jeste, Dilip V

2018-06-01

To determine the clinical and biological characteristics of an exceptionally high functioning index person (IP) with schizophrenia in her mid-50s, which may represent compensatory mechanisms, and potentially, avoidance of the accelerated aging typically associated with schizophrenia. IP, 11 other women with schizophrenia, and 11 non-psychiatric comparison (NC) women were assessed with standard ratings of psychopathology, neurocognitive function, decisional capacity, and functional brain imaging. IP was also compared to a sample of demographically similar NCs (N=45) and persons with schizophrenia (N=42) on a set of blood-based biomarkers of aging related to metabolic function, oxidative stress, and inflammation. IP's scores on working memory, and levels of brain activation during an affective face matching task in the left fusiform, right lingual, and left precentral gyri, exceeded NCs. IP was similar to NCs in severity of negative symptoms, most neurocognitive functions, decisional capacity, and brain activation in the left inferior occipital gyrus during a selective stopping task. IP's levels on 11 of 14 metabolic and inflammatory biomarkers of aging were better than NCs and the schizophrenia group. Although speculative, results suggest a possible model in which superior working memory permits a person to be aware of the potentially psychotic nature of a thought or perception, and adjust response accordingly. Compensatory overactivity of brain regions during affective processing may also reflect heightened meta-awareness in emotional situations. Biomarker levels raise the possibility that IP partially avoided the accelerated biological aging associated with schizophrenia. Published by Elsevier B.V.

Longevity and ageing: appraising the evolutionary consequences of growing old

PubMed Central

Bonsall, Michael B

2005-01-01

Senescence or ageing is an increase in mortality and/or decline in fertility with increasing age. Evolutionary theories predict that ageing or longevity evolves in response to patterns of extrinsic mortality or intrinsic damage. If ageing is viewed as the outcome of the processes of behaviour, growth and reproduction then it should be possible to predict mortality rate. Recent developments have shown that it is now possible to integrate these ecological and physiological processes and predict the shape of mortality trajectories. By drawing on the key exciting developments in the cellular, physiological and ecological process of longevity the evolutionary consequences of ageing are reviewed. In presenting these ideas an evolutionary demographic framework is used to argue how trade-offs in life-history strategies are important in the maintenance of variation in longevity within and between species. Evolutionary processes associated with longevity have an important role in explaining levels of biological diversity and speciation. In particular, the effects of life-history trait trade-offs in maintaining and promoting species diversity are explored. Such trade-offs can alleviate the effects of intense competition between species and promote species coexistence and diversification. These results have important implications for understanding a number of core ecological processes such as how species are divided among niches, how closely related species co-occur and the rules by which species assemble into food-webs. Theoretical work reveals that the proximate physiological processes are as important as the ecological factors in explaining the variation in the evolution of longevity. Possible future research challenges integrating work on the evolution and mechanisms of growing old are briefly discussed. PMID:16553312

[Effect of biologically active food additives on energy metabolism and human body weight].

PubMed

Gapparov, M M

1999-01-01

Review is devoted to analysis of human energy requirements depending on age, sex, occupational and living condition. Special attention was paid to importance of strict balance in organism between consumption and expense of energy. Modern views on mechanism of action food supplements as additional instrument of regulation of energy metabolism for correction of surplus body weight is given. Review is the first attempt of systematisation of biologically active food supplements according to their mechanism of action both on nutrition processes and on biochemical mechanisms of assimilation and utilisation of macronutrients, in particular of fats and carbohydrates.

A review of supervised machine learning applied to ageing research.

PubMed

Fabris, Fabio; Magalhães, João Pedro de; Freitas, Alex A

2017-04-01

Broadly speaking, supervised machine learning is the computational task of learning correlations between variables in annotated data (the training set), and using this information to create a predictive model capable of inferring annotations for new data, whose annotations are not known. Ageing is a complex process that affects nearly all animal species. This process can be studied at several levels of abstraction, in different organisms and with different objectives in mind. Not surprisingly, the diversity of the supervised machine learning algorithms applied to answer biological questions reflects the complexities of the underlying ageing processes being studied. Many works using supervised machine learning to study the ageing process have been recently published, so it is timely to review these works, to discuss their main findings and weaknesses. In summary, the main findings of the reviewed papers are: the link between specific types of DNA repair and ageing; ageing-related proteins tend to be highly connected and seem to play a central role in molecular pathways; ageing/longevity is linked with autophagy and apoptosis, nutrient receptor genes, and copper and iron ion transport. Additionally, several biomarkers of ageing were found by machine learning. Despite some interesting machine learning results, we also identified a weakness of current works on this topic: only one of the reviewed papers has corroborated the computational results of machine learning algorithms through wet-lab experiments. In conclusion, supervised machine learning has contributed to advance our knowledge and has provided novel insights on ageing, yet future work should have a greater emphasis in validating the predictions.

Investigating the specific core genetic-and-epigenetic networks of cellular mechanisms involved in human aging in peripheral blood mononuclear cells

PubMed Central

Li, Cheng-Wei; Wang, Wen-Hsin; Chen, Bor-Sen

2016-01-01

Aging is an inevitable part of life for humans, and slowing down the aging process has become a main focus of human endeavor. Here, we applied a systems biology approach to construct protein-protein interaction networks, gene regulatory networks, and epigenetic networks, i.e. genetic and epigenetic networks (GENs), of elderly individuals and young controls. We then compared these GENs to extract aging mechanisms using microarray data in peripheral blood mononuclear cells, microRNA (miRNA) data, and database mining. The core GENs of elderly individuals and young controls were obtained by applying principal network projection to GENs based on Principal Component Analysis. By comparing the core networks, we identified that to overcome the accumulated mutation of genes in the aging process the transcription factor JUN can be activated by stress signals, including the MAPK signaling, T-cell receptor signaling, and neurotrophin signaling pathways through DNA methylation of BTG3, G0S2, and AP2B1 and the regulations of mir-223 let-7d, and mir-130a. We also address the aging mechanisms in old men and women. Furthermore, we proposed that drugs designed to target these DNA methylated genes or miRNAs may delay aging. A multiple drug combination comprising phenylalanine, cholesterol, and palbociclib was finally designed for delaying the aging process. PMID:26895224

The yeast replicative aging model.

PubMed

He, Chong; Zhou, Chuankai; Kennedy, Brian K

2018-03-08

It has been nearly three decades since the budding yeast Saccharomyces cerevisiae became a significant model organism for aging research and it has emerged as both simple and powerful. The replicative aging assay, which interrogates the number of times a "mother" cell can divide and produce "daughters", has been a stalwart in these studies, and genetic approaches have led to the identification of hundreds of genes impacting lifespan. More recently, cell biological and biochemical approaches have been developed to determine how cellular processes become altered with age. Together, the tools are in place to develop a holistic view of aging in this single-celled organism. Here, we summarize the current state of understanding of yeast replicative aging with a focus on the recent studies that shed new light on how aging pathways interact to modulate lifespan in yeast. Copyright © 2018. Published by Elsevier B.V.

Molecular mechanisms of aging and immune system regulation in Drosophila.

PubMed

Eleftherianos, Ioannis; Castillo, Julio Cesar

2012-01-01

Aging is a complex process that involves the accumulation of deleterious changes resulting in overall decline in several vital functions, leading to the progressive deterioration in physiological condition of the organism and eventually causing disease and death. The immune system is the most important host-defense mechanism in humans and is also highly conserved in insects. Extensive research in vertebrates has concluded that aging of the immune function results in increased susceptibility to infectious disease and chronic inflammation. Over the years, interest has grown in studying the molecular interaction between aging and the immune response to pathogenic infections. The fruit fly Drosophila melanogaster is an excellent model system for dissecting the genetic and genomic basis of important biological processes, such as aging and the innate immune system, and deciphering parallel mechanisms in vertebrate animals. Here, we review the recent advances in the identification of key players modulating the relationship between molecular aging networks and immune signal transduction pathways in the fly. Understanding the details of the molecular events involved in aging and immune system regulation will potentially lead to the development of strategies for decreasing the impact of age-related diseases, thus improving human health and life span.

Molecular Mechanisms of Aging and Immune System Regulation in Drosophila

PubMed Central

Eleftherianos, Ioannis; Castillo, Julio Cesar

2012-01-01

Aging is a complex process that involves the accumulation of deleterious changes resulting in overall decline in several vital functions, leading to the progressive deterioration in physiological condition of the organism and eventually causing disease and death. The immune system is the most important host-defense mechanism in humans and is also highly conserved in insects. Extensive research in vertebrates has concluded that aging of the immune function results in increased susceptibility to infectious disease and chronic inflammation. Over the years, interest has grown in studying the molecular interaction between aging and the immune response to pathogenic infections. The fruit fly Drosophila melanogaster is an excellent model system for dissecting the genetic and genomic basis of important biological processes, such as aging and the innate immune system, and deciphering parallel mechanisms in vertebrate animals. Here, we review the recent advances in the identification of key players modulating the relationship between molecular aging networks and immune signal transduction pathways in the fly. Understanding the details of the molecular events involved in aging and immune system regulation will potentially lead to the development of strategies for decreasing the impact of age-related diseases, thus improving human health and life span. PMID:22949833

Hydrogeology, Ground-Water-Age Dating, Water Quality, and Vulnerability of Ground Water to Contamination in a Part of the Whitewater Valley Aquifer System near Richmond, Indiana, 2002-2003

USGS Publications Warehouse

Buszka, Paul M.; Watson, Lee R.; Greeman, Theodore K.

2007-01-01

Results of detailed water-quality analyses, ground-waterage dating, and dissolved-gas analyses indicated the vulnerability of ground water to specific types of contamination, the sequence of contaminant introduction to the aquifer relative to greenfield development, and processes that may mitigate the contamination. Concentrations of chloride and sodium and chloride/bromide weight ratios in sampled water from five wells indicated the vulnerability of the upper aquifer to roaddeicer contamination. Ground-water-age estimates from these wells indicated the onset of upgradient road-deicer use within the previous 25 years. Nitrate in the upper aquifer predates the post-1972 development, based on a ground-water-age date (30 years) and the nitrate concentration (5.12 milligrams per liter as nitrogen) in water from a deep well. Vulnerability of the aquifer to nitrate contamination is limited partially by denitrification. Detection of one to four atrazine transformation products in water samples from the upper aquifer indicated biological and hydrochemical processes that may limit the vulnerability of the ground water to atrazine contamination. Microbial processes also may limit the aquifer vulnerability to small inputs of halogenated aliphatic compounds, as indicated by microbial transformations of trichlorofluoromethane and trichlorotrifluoroethane relative to dichlorodifluoromethane. The vulnerability of ground water to contamination in other parts of the aquifer system also may be mitigated by hydrodynamic dispersion and biologically mediated transformations of nitrate, pesticides, and some organic compounds. Identification of the sequence of contamination and processes affecting the vulnerability of ground water to contamination would have been unlikely with conventional assessment methods.

[Reversal of aging and lifespan elongation. Current biomedical key publications and the implications for geriatrics].

PubMed

Bollheimer, L C; Volkert, D; Bertsch, T; Sieber, C C; Büttner, R

2013-08-01

Biological aging means a time-dependent accumulation of changes to which a living organism is being exposed during its lifetime. Biological aging normally concurs with chronological aging the time frame of which is set by an upper limit, the lifespan (in humans approximately 120 years). New findings in experimental biogerontology are challenging both the dogma of irreversibility of biological aging and the preset species-specific limitations of life. The present overview first explains the general principle of rejuvenation and reversal of biological aging with paradigms from stem cell research. Secondly, recent key publications on artificial telomerase elongation and (alleged) lifespan enhancement by sirtuins and resveratrol will be discussed with an emphasis on the implications for (future) geriatric medicine.

Comparing Computer-Supported Dynamic Modeling and "Paper & Pencil" Concept Mapping Technique in Students' Collaborative Activity

ERIC Educational Resources Information Center

Komis, Vassilis; Ergazaki, Marida; Zogza, Vassiliki

2007-01-01

This study aims at highlighting the collaborative activity of two high school students (age 14) in the cases of modeling the complex biological process of plant growth with two different tools: the "paper & pencil" concept mapping technique and the computer-supported educational environment "ModelsCreator". Students' shared activity in both cases…

Development of Motion Processing in Children with Autism

ERIC Educational Resources Information Center

Annaz, Dagmara; Remington, Anna; Milne, Elizabeth; Coleman, Mike; Campbell, Ruth; Thomas, Michael S. C.; Swettenham, John

2010-01-01

Recent findings suggest that children with autism may be impaired in the perception of biological motion from moving point-light displays. Some children with autism also have abnormally high motion coherence thresholds. In the current study we tested a group of children with autism and a group of typically developing children aged 5 to 12 years of…

Gender Role and Social Identifications: The Two Major Factors to Shape Turkish Women

ERIC Educational Resources Information Center

Erden-Imamoglu, Seval

2013-01-01

The process of being a woman starts with biological gender but it is shaped by learning the social gender roles. Besides social gender role; age, education, marriage, and motherhood supply social roles and attributions and they have an impact on women identification and their interpersonal relationships. The aim of the study is to investigate…

Biological embedding of perinatal social relationships in infant stress reactivity.

PubMed

Thomas, Jenna C; Letourneau, Nicole; Bryce, Crystal I; Campbell, Tavis S; Giesbrecht, Gerald F

2017-05-01

Whereas significant advances have been made in understanding how exposure to early adversity "gets under the skin" of children to result in long term changes in developmental outcomes, the processes by which positive social relationships become biologically embedded remain poorly understood. The aim of this study was to understand the pathways by which maternal and infant social environments become biologically embedded in infant cortisol reactivity. Two hundred seventy-two pregnant women and their infants were prospectively assessed during pregnancy and at 6 months postpartum. In serial mediation analyses, higher perceived social support from partners during pregnancy was associated with lower infant cortisol reactivity or larger decreases in cortisol in response to a stressor at 6 months of age via lower self-reported prenatal maternal depression and higher mother-infant interaction quality. The findings add to our understanding of how perinatal social relationships become biologically embedded in child development. © 2017 Wiley Periodicals, Inc.

American Federation for Aging Research

MedlinePlus

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Subcortical encoding of sound is enhanced in bilinguals and relates to executive function advantages

PubMed Central

Krizman, Jennifer; Marian, Viorica; Shook, Anthony; Skoe, Erika; Kraus, Nina

2012-01-01

Bilingualism profoundly affects the brain, yielding functional and structural changes in cortical regions dedicated to language processing and executive function [Crinion J, et al. (2006) Science 312:1537–1540; Kim KHS, et al. (1997) Nature 388:171–174]. Comparatively, musical training, another type of sensory enrichment, translates to expertise in cognitive processing and refined biological processing of sound in both cortical and subcortical structures. Therefore, we asked whether bilingualism can also promote experience-dependent plasticity in subcortical auditory processing. We found that adolescent bilinguals, listening to the speech syllable [da], encoded the stimulus more robustly than age-matched monolinguals. Specifically, bilinguals showed enhanced encoding of the fundamental frequency, a feature known to underlie pitch perception and grouping of auditory objects. This enhancement was associated with executive function advantages. Thus, through experience-related tuning of attention, the bilingual auditory system becomes highly efficient in automatically processing sound. This study provides biological evidence for system-wide neural plasticity in auditory experts that facilitates a tight coupling of sensory and cognitive functions. PMID:22547804

The concept of ageing in evolutionary algorithms: Discussion and inspirations for human ageing.

PubMed

Dimopoulos, Christos; Papageorgis, Panagiotis; Boustras, George; Efstathiades, Christodoulos

2017-04-01

This paper discusses the concept of ageing as this applies to the operation of Evolutionary Algorithms, and examines its relationship to the concept of ageing as this is understood for human beings. Evolutionary Algorithms constitute a family of search algorithms which base their operation on an analogy from the evolution of species in nature. The paper initially provides the necessary knowledge on the operation of Evolutionary Algorithms, focusing on the use of ageing strategies during the implementation of the evolutionary process. Background knowledge on the concept of ageing, as this is defined scientifically for biological systems, is subsequently presented. Based on this information, the paper provides a comparison between the two ageing concepts, and discusses the philosophical inspirations which can be drawn for human ageing based on the operation of Evolutionary Algorithms. Copyright © 2017 Elsevier B.V. All rights reserved.

Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue.

PubMed

Gautieri, Alfonso; Passini, Fabian S; Silván, Unai; Guizar-Sicairos, Manuel; Carimati, Giulia; Volpi, Piero; Moretti, Matteo; Schoenhuber, Herbert; Redaelli, Alberto; Berli, Martin; Snedeker, Jess G

2017-05-01

Concurrent with a progressive loss of regenerative capacity, connective tissue aging is characterized by a progressive accumulation of Advanced Glycation End-products (AGEs). Besides being part of the typical aging process, type II diabetics are particularly affected by AGE accumulation due to abnormally high levels of systemic glucose that increases the glycation rate of long-lived proteins such as collagen. Although AGEs are associated with a wide range of clinical disorders, the mechanisms by which AGEs contribute to connective tissue disease in aging and diabetes are still poorly understood. The present study harnesses advanced multiscale imaging techniques to characterize a widely employed in vitro model of ribose induced collagen aging and further benchmarks these data against experiments on native human tissues from donors of different age. These efforts yield unprecedented insight into the mechanical changes in collagen tissues across hierarchical scales from molecular, to fiber, to tissue-levels. We observed a linear increase in molecular spacing (from 1.45nm to 1.5nm) and a decrease in the D-period length (from 67.5nm to 67.1nm) in aged tissues, both using the ribose model of in vitro glycation and in native human probes. Multiscale mechanical analysis of in vitro glycated tendons strongly suggests that AGEs reduce tissue viscoelasticity by severely limiting fiber-fiber and fibril-fibril sliding. This study lays an important foundation for interpreting the functional and biological effects of AGEs in collagen connective tissues, by exploiting experimental models of AGEs crosslinking and benchmarking them for the first time against endogenous AGEs in native tissue. Copyright © 2016 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Evaluation of status of calcium, magnesium, potassium, and sodium levels in biological samples in children of different age groups with normal vision and night blindness.

PubMed

Afridi, Hassan Imran; Kazi, Tasneem Gul; Kazi, Naveed; Kandhro, Ghulam Abbas; Baig, Jameel Ahmed; Shah, Abdul Qadir; Khan, Sumaira; Kolachi, Nida Fatima; Wadhwa, Sham Kumar; Shah, Faheem

2011-01-01

The most common cause of blindness in developing countries is vitamin A deficiency. The World Health Organization (WHO) estimates 13.8 million children have some degree of visual loss related to vitamin A deficiency. The causes of night blindness in children are multifactorial and particular consideration has been given to childhood nutritional deficiency, which is the most common problem found in underdeveloped countries. Such deficiency can result in physiological and pathological processes that in turn influence biological sample composition. Vitamin and mineral deficiency prevents more than two billion people from achieving their full intellectual and physical potential. This study was designed to compare the levels of magnesium (Mg), calcium (Ca), potassium (K), and sodium (Na) in scalp hair, serum, blood, and urine of night blindness children in two age groups, (1-5) and (6-10) years, of both genders comparing them to sex- and age-matched controls. A microwave assisted wet acid digestion procedure was developed as a sample pretreatment for the determination of Mg, Ca, K, and Na in biological samples of children with night blindness. The proposed method was validated by using conventional wet digestion and certified reference samples of hair, serum, blood, and urine. The digests of all biological samples were analysed for Mg, Ca, K, and Na by flame atomic absorption spectrometry (FAAS) using an air/acetylene flame. The results indicated significantly lower levels of Mg, Ca, and K in the biological samples (blood, serum, and scalp hair) of male and female children with night blindness and higher values of Na compared with control subjects of both genders. These data present guidance to clinicians and other professionals investigating deficiency of essential mineral elements in biological samples (scalp hair, serum, and blood) of children with night blindness.

[Physical activity patterns of school adolescents: Validity, reliability and percentiles proposal for their evaluation].

PubMed

Cossío Bolaños, Marco; Méndez Cornejo, Jorge; Luarte Rocha, Cristian; Vargas Vitoria, Rodrigo; Canqui Flores, Bernabé; Gomez Campos, Rossana

2017-02-01

Regular physical activity (PA) during childhood and adolescence is important for the prevention of non-communicable diseases and their risk factors. To validate a questionnaire for measuring patterns of PA, verify the reliability, comparing the levels of PA aligned with chronological and biological age, and to develop percentile curves to assess PA levels depending on biological maturation. Descriptive cross-sectional study was performed on a sample non-probabilistic quota of 3,176 Chilean adolescents (1685 males and 1491 females), with a mean age range from 10.0 to 18.9 years. An analysis was performed on, weight, standing and sitting height. The biological age through the years of peak growth rate and chronological age in years was determined. Body Mass Index was calculated and a survey of PA was applied. The LMS method was used to develop percentiles. The values for the confirmatory analysis showed saturations between 0.517 and 0.653. The value of adequacy of Kaiser-Meyer-Olkin (KMO) was 0.879 and with 70.8% of the variance explained. The Cronbach alpha values ranged from 0.81 to 0.86. There were differences between the genders when aligned chronological age. There were no differences when aligned by biological age. Percentiles are proposed to classify the PA of adolescents of both genders according to biological age and sex. The questionnaire used was valid and reliable, plus the PA should be evaluated by biological age. These findings led to the development of percentiles to assess PA according to biological age and gender.

Genomic Approach to Understand the Association of DNA Repair with Longevity and Healthy Aging Using Genomic Databases of Oldest-Old Population

PubMed Central

Kim, Hyun Soo

2018-01-01

Aged population is increasing worldwide due to the aging process that is inevitable. Accordingly, longevity and healthy aging have been spotlighted to promote social contribution of aged population. Many studies in the past few decades have reported the process of aging and longevity, emphasizing the importance of maintaining genomic stability in exceptionally long-lived population. Underlying reason of longevity remains unclear due to its complexity involving multiple factors. With advances in sequencing technology and human genome-associated approaches, studies based on population-based genomic studies are increasing. In this review, we summarize recent longevity and healthy aging studies of human population focusing on DNA repair as a major factor in maintaining genome integrity. To keep pace with recent growth in genomic research, aging- and longevity-associated genomic databases are also briefly introduced. To suggest novel approaches to investigate longevity-associated genetic variants related to DNA repair using genomic databases, gene set analysis was conducted, focusing on DNA repair- and longevity-associated genes. Their biological networks were additionally analyzed to grasp major factors containing genetic variants of human longevity and healthy aging in DNA repair mechanisms. In summary, this review emphasizes DNA repair activity in human longevity and suggests approach to conduct DNA repair-associated genomic study on human healthy aging.

Ultralow contact angle hysteresis and no-aging effects in superhydrophobic tangled nanofiber structures generated by controlling the pore size of a 99.5% aluminum foil

NASA Astrophysics Data System (ADS)

Lee, Sangmin; Hwang, Woonbong

2009-03-01

Superhydrophobic surfaces designed to improve hydrophobicity have high advancing contact angles corresponding to the Cassie state, but these surfaces also exhibit high contact angle hysteresis. We report here a simple and inexpensive method for fabricating superhydrophobic tangled nanofiber structures with ultralow contact angle hysteresis and no-aging degradation, based on a widening process. The resulting nanostructures are suitable for diverse applications including microfluidic devices for biological studies and industrial self-cleaning products for automobiles, ships and houses.

NAMPT-Mediated NAD Biosynthesis as the Internal Timing Mechanism: In NAD+ World, Time Is Running in Its Own Way.

PubMed

Poljsak, Borut

2017-09-08

The biological age of organisms differs from the chronological age and is determined by internal aging clock(s). How cells estimate time on a scale of 24 hours is relatively well studied; however, how biological time is measured by cells, tissues, organs, or organisms in longer time periods (years and decades) is largely unknown. What is clear and widely agreed upon is that the link to age and age-related diseases is not chronological, as it does not depend on a fixed passage of time. Rather, this link depends on the biological age of an individual cell, tissue, organ, or organism and not on time in a strictly chronological sense. Biological evolution does not invent new methods as often as improving upon already existing ones. It should be easier to evolve and remodel the existing (circadian) time clock mechanism to use it for measurement or regulation of longer time periods than to invent a new time mechanism/clock. Specifically, it will be demonstrated that the circadian clock can also be used to regulate circannual or even longer time periods. Nicotinamide phosphoribosyltransferase (NAMPT)-mediated nicotinamide adenine dinucleotide (NAD+) levels, being regulated by the circadian clock, might be the missing link between aging, cell cycle control, DNA damage repair, cellular metabolism and the aging clock, which is responsible for the biological age of an organism. The hypothesis that NAMPT/NAD+/SIRT1 might represent the time regulator that determines the organismal biological age will be presented. The biological age of tissues and organs might be regulated and synchronized through eNAMPT blood secretion. The "NAD World 2.0" concept will be upgraded with detailed insights into mechanisms that regulate NAD + -mediated aging clock ticking, the duration and amplitude of which are responsible for the aging rate of humans.

[The assimilation of the books on animals of Aristotle in the medicine of Arnau de Vilanova (c. 1240-1311)].

PubMed

2015-01-01

The Latin translation of Aristotle's books on animals, which was carried out during the middle ages, lead to the dissemination of new theories in the field of biology and zoology in the western culture. From the second half of the 13th century, this group of books contributed to the development of a new medical practice based on the recovery of classical authorities and natural philosophy. On different occasions, Arnau de Vilanova (c. 1240-1311)--one of the most preeminent physicians of the Latin middle ages--used the books on animals to describe biological and physiological processes, and also to formulate a new medical discipline within the framework of discussions between natural philosophy and medicine in Montpellier; this took place at the end of the 13th century and early 14h century.

iPSCs-based anti-aging therapies: Recent discoveries and future challenges.

PubMed

Pareja-Galeano, Helios; Sanchis-Gomar, Fabián; Pérez, Laura M; Emanuele, Enzo; Lucia, Alejandro; Gálvez, Beatriz G; Gallardo, María Esther

2016-05-01

The main biological hallmarks of the aging process include stem cell exhaustion and cellular senescence. Consequently, research efforts to treat age-related diseases as well as anti-aging therapies in general have recently focused on potential 'reprogramming' regenerative therapies. These new approaches are based on induced pluripotent stem cells (iPSCs), including potential in vivo reprogramming for tissue repair. Another possibility is targeting pathways of cellular senescence, e.g., through modulation of p16INK4a signaling and especially inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Here, we reviewed and discussed these recent developments together with their possible usefulness for future treatments against sarcopenia, a major age-related condition. Copyright © 2016 Elsevier B.V. All rights reserved.

Fasting and Fast Food Diet Play an Opposite Role in Mice Brain Aging.

PubMed

Castrogiovanni, Paola; Li Volti, Giovanni; Sanfilippo, Cristina; Tibullo, Daniele; Galvano, Fabio; Vecchio, Michele; Avola, Roberto; Barbagallo, Ignazio; Malaguarnera, Lucia; Castorina, Sergio; Musumeci, Giuseppe; Imbesi, Rosa; Di Rosa, Michelino

2018-01-20

Fasting may be exploited as a possible strategy for prevention and treatment of several diseases such as diabetes, obesity, and aging. On the other hand, high-fat diet (HFD) represents a risk factor for several diseases and increased mortality. The aim of the present study was to evaluate the impact of fasting on mouse brain aging transcriptome and how HFD regulates such pathways. We used the NCBI Gene Expression Omnibus (GEO) database, in order to identify suitable microarray datasets comparing mouse brain transcriptome under fasting or HFD vs aged mouse brain transcriptome. Three microarray datasets were selected for this study, GSE24504, GSE6285, and GSE8150, and the principal molecular mechanisms involved in this process were evaluated. This analysis showed that, regardless of fasting duration, mouse brain significantly expressed 21 and 30 upregulated and downregulated genes, respectively. The involved biological processes were related to cell cycle arrest, cell death inhibition, and regulation of cellular metabolism. Comparing mouse brain transcriptome under fasting and aged conditions, we found out that the number of genes in common increased with the duration of fasting (222 genes), peaking at 72 h. In addition, mouse brain transcriptome under HFD resembles for the 30% the one of the aged mice. Furthermore, several molecular processes were found to be shared between HFD and aging. In conclusion, we suggest that fasting and HFD play an opposite role in brain transcriptome of aged mice. Therefore, an intermittent diet could represent a possible clinical strategy to counteract aging, loss of memory, and neuroinflammation. Furthermore, low-fat diet leads to the inactivation of brain degenerative processes triggered by aging.

The role of estrogen in cutaneous ageing and repair.

PubMed

Wilkinson, Holly N; Hardman, Matthew J

2017-09-01

Combined advances in modern medical practice and increased human longevity are driving an ever-expanding elderly population. Females are particularly at risk of age-associated pathology, spending more of their lives in a post-menopausal state. Menopause, denoted by a rapid decline in serum sex steroid levels, accelerates biological ageing across the body's tissues. Post-menopause physiological changes are particularly noticeable in the skin, which loses structural architecture and becomes prone to damage. The sex steroid most widely discussed as an intrinsic contributor to skin ageing and pathological healing is 17β-estradiol (or estrogen), although many others are involved. Estrogen deficiency is detrimental to many wound-healing processes, notably inflammation and re-granulation, while exogenous estrogen treatment widely reverses these effects. Over recent decades, many of the molecular and cellular correlates to estrogen's beneficial effect on normal skin homeostasis and wound healing have been reported. However, disparities still exist, particularly in the context of mechanistic studies investigating estrogen receptor signalling and its potential cellular effects. New molecular techniques, coupled with increased understanding of estrogen in skin biology, will provide further opportunities to develop estrogen receptor-targeted therapeutics. Copyright © 2017 Elsevier B.V. All rights reserved.

Redox signaling in skeletal muscle: role of aging and exercise.

PubMed

Ji, Li Li

2015-12-01

Skeletal muscle contraction is associated with the production of ROS due to altered O2 distribution and flux in the cell. Despite a highly efficient antioxidant defense, a small surplus of ROS, such as hydrogen peroxide and nitric oxide, may serve as signaling molecules to stimulate cellular adaptation to reach new homeostasis largely due to the activation of redox-sensitive signaling pathways. Recent research has highlighted the important role of NF-κB, MAPK, and peroxisome proliferator-activated receptor-γ coactivator-1α, along with other newly discovered signaling pathways, in some of the most vital biological functions, such as mitochondrial biogenesis, antioxidant defense, inflammation, protein turnover, apoptosis, and autophagy. There is evidence that the inability of the cell to maintain proper redox signaling underlies some basic mechanisms of biological aging, during which inflammatory and catabolic pathways eventually predominate. Physical exercise has been shown to activate various redox signaling pathways that control the adaptation and remodeling process. Although this stimulatory effect of exercise declines with aging, it is not completed abolished. Thus, aged people can still benefit from regular physical activity in the appropriate forms and at proper intensity to preserve muscle function. Copyright © 2015 The American Physiological Society.

Telomeres and cardiovascular disease risk: an update 2013.

PubMed

Nilsson, Peter M; Tufvesson, Hanna; Leosdottir, Margrét; Melander, Olle

2013-12-01

Leukocyte telomere length (LTL) has been regarded as a potential marker of biologic aging because it usually shortens in a predictable way with age. Recently, a growing interest in cardiovascular aging has led to a number of new epidemiologic studies investigating LTL in various disease conditions. Some methodological problems exist because there are different methods available to determine LTL, and standardization is much needed. For example, in the majority of studies, patients with early-onset coronary heart disease have been shown to have shorter LTL. In addition, patients with diabetes mellitus complications tend to have shorter LTL than control subjects. On the other hand, increased left ventricular hypertrophy or mass is associated with longer LTL, and studies investigating hypertension have reported both shorter and longer LTL than found in normotensive control subjects. There is, therefore, a need for longitudinal studies to elucidate these complicated relationships further, to provide estimations of telomere attrition rates, and to overcome analytical problems when only cross-sectional studies are used. The understanding of cardiovascular aging and telomere biology may open up new avenues for interventions, such as stem cell therapy or agents that could retard this aging process over and beyond conventional risk factor control. Copyright © 2013 Mosby, Inc. All rights reserved.

Vocal aging and adductor spasmodic dysphonia: Response to botulinum toxin injection

PubMed Central

Cannito, Michael P; Kahane, Joel C; Chorna, Lesya

2008-01-01

Aging of the larynx is characterized by involutional changes which alter its biomechanical and neural properties and create a biological environment that is different from younger counterparts. Illustrative anatomical examples are presented. This natural, non-disease process appears to set conditions which may influence the effectiveness of botulinum toxin injection and our expectations for its success. Adductor spasmodic dysphonia, a type of laryngeal dystonia, is typically treated using botulinum toxin injections of the vocal folds in order to suppress adductory muscle spasms which are disruptive to production of speech and voice. A few studies have suggested diminished response to treatment in older patients with adductor spasmodic dysphonia. This retrospective study provides a reanalysis of existing pre-to-post treatment data as function of age. Perceptual judgments of speech produced by 42 patients with ADSD were made by two panels of professional listeners with expertise in voice or fluency of speech. Results demonstrate a markedly reduced positive response to botulinum toxin treatment in the older patients. Perceptual findings are further elucidated by means of acoustic spectrography. Literature on vocal aging is reviewed to provide a specific set of biological mechanisms that best account for the observed interaction of botulinum toxin treatment with advancing age. PMID:18488884

Inflammation, aging, and cancer: tumoricidal versus tumorigenesis of immunity: a common denominator mapping chronic diseases.

PubMed

Khatami, Mahin

2009-01-01

Acute inflammation is a highly regulated defense mechanism of immune system possessing two well-balanced and biologically opposing arms termed apoptosis ('Yin') and wound healing ('Yang') processes. Unresolved or chronic inflammation (oxidative stress) is perhaps the loss of balance between 'Yin' and 'Yang' that would induce co-expression of exaggerated or 'mismatched' apoptotic and wound healing factors in the microenvironment of tissues ('immune meltdown'). Unresolved inflammation could initiate the genesis of many age-associated chronic illnesses such as autoimmune and neurodegenerative diseases or tumors/cancers. In this perspective 'birds' eye' view of major interrelated co-morbidity risk factors that participate in biological shifts of growth-arresting ('tumoricidal') or growth-promoting ('tumorigenic') properties of immune cells and the genesis of chronic inflammatory diseases and cancer will be discussed. Persistent inflammation is perhaps a common denominator in the genesis of nearly all age-associated health problems or cancer. Future challenging opportunities for diagnosis, prevention, and/or therapy of chronic illnesses will require an integrated understanding and identification of developmental phases of inflammation-induced immune dysfunction and age-associated hormonal and physiological readjustments of organ systems. Designing suitable cohort studies to establish the oxido-redox status of adults may prove to be an effective strategy in assessing individual's health toward developing personal medicine for healthy aging.

The Use of Informative Priors in Bayesian Modeling Age-at-death; a Quick Look at Chronological and Biological Age Changes in the Sacroiliac Joint in American Males

PubMed Central

Godde, Kanya

2017-01-01

The aim of this study is to examine how well different informative priors model age-at-death in Bayesian statistics, which will shed light on how the skeleton ages, particularly at the sacroiliac joint. Data from four samples were compared for their performance as informative priors for auricular surface age-at-death estimation: (1) American population from US Census data; (2) county data from the US Census data; (3) a local cemetery; and (4) a skeletal collection. The skeletal collection and cemetery are located within the county that was sampled. A Gompertz model was applied to compare survivorship across the four samples. Transition analysis parameters, coupled with the generated Gompertz parameters, were input into Bayes' theorem to generate highest posterior density ranges from posterior density functions. Transition analysis describes the age at which an individual transitions from one age phase to another. The result is age ranges that should describe the chronological age of 90% of the individuals who fall in a particular phase. Cumulative binomial tests indicate the method performed lower than 90% at capturing chronological age as assigned to a biological phase, despite wide age ranges at older ages. The samples performed similarly overall, despite small differences in survivorship. Collectively, these results show that as we age, the senescence pattern becomes more variable. More local samples performed better at describing the aging process than more general samples, which implies practitioners need to consider sample selection when using the literature to diagnose and work with patients with sacroiliac joint pain. PMID:29546217

[Comparative biochemistry of process of ageing in men and women].

PubMed

Miakotnykh, V S; Berezina, D A; Borovkova, T A; Gavrilov, I V

2014-01-01

In the research of a number of biochemical indicators in 858 men and 899 women aged from 20 till 70 years divided into 6 compared groups depending on age and gender clear distinctions in the dynamics of the components of the lipid status, status of lipid peroxidation and antioxidant activity of the blood system, the content of middlemolecular peptides are revealed. Simultaneous determination of the biological age of the subjects also revealed a distinct gender differencies testifying to lower rate of aging of men, despite the probability of earlier, in comparison with women, development of dislipidemia and atherosclerosis. Association of the received gender distinctions both with changes of level of estrogen in women due to menopause and with the peculiarities of stressful impacts on male and female organism in different age periods is supposed.

Autophagy and cardiovascular aging: lesson learned from rapamycin.

PubMed

Nair, Sreejayan; Ren, Jun

2012-06-01

The biological aging process is commonly associated with increased risk of cardiovascular diseases. Several theories have been put forward for aging-associated deterioration in ventricular function, including attenuation of growth hormone (insulin-like growth factors and insulin) signaling, loss of DNA replication and repair, histone acetylation and accumulation of reactive oxygen species. Recent evidence has depicted a rather unique role of autophagy as another important pathway in the regulation of longevity and senescence. Autophagy is a predominant cytoprotective (rather than self-destructive) process. It carries a prominent role in determination of lifespan. Reduced autophagy has been associated with aging, leading to accumulation of dysfunctional or damaged proteins and organelles. To the contrary, measures such as caloric restriction and exercise may promote autophagy to delay aging and associated comorbidities. Stimulation of autophagy using rapamycin may represent a novel strategy to prolong lifespan and combat aging-associated diseases. Rapamycin regulates autophagy through inhibition of the nutrient-sensing molecule mammalian target of rapamycin (mTOR). Inhibition of mTOR through rapamycin and caloric restriction promotes longevity. The purpose of this review is to recapitulate some of the recent advances in an effort to better understand the interplay between rapamycin-induced autophagy and decelerating cardiovascular aging.

Animal and human models to understand ageing.

PubMed

Lees, Hayley; Walters, Hannah; Cox, Lynne S

2016-11-01

Human ageing is the gradual decline in organ and tissue function with increasing chronological time, leading eventually to loss of function and death. To study the processes involved over research-relevant timescales requires the use of accessible model systems that share significant similarities with humans. In this review, we assess the usefulness of various models, including unicellular yeasts, invertebrate worms and flies, mice and primates including humans, and highlight the benefits and possible drawbacks of each model system in its ability to illuminate human ageing mechanisms. We describe the strong evolutionary conservation of molecular pathways that govern cell responses to extracellular and intracellular signals and which are strongly implicated in ageing. Such pathways centre around insulin-like growth factor signalling and integration of stress and nutritional signals through mTOR kinase. The process of cellular senescence is evaluated as a possible underlying cause for many of the frailties and diseases of human ageing. Also considered is ageing arising from systemic changes that cannot be modelled in lower organisms and instead require studies either in small mammals or in primates. We also touch briefly on novel therapeutic options arising from a better understanding of the biology of ageing. Copyright © 2016. Published by Elsevier Ireland Ltd.

Effects of sugar concentration processes in grapes and wine aging on aroma compounds of sweet wines—a review.

PubMed

Reboredo-Rodríguez, Patricia; González-Barreiro, Carmen; Rial-Otero, Raquel; Cancho-Grande, Beatriz; Simal-Gándara, Jesús

2015-01-01

Dessert sweet wines from Europe and North America are described in this review from two points of view: both their aroma profile and also their sensorial description. There are growing literature data about the chemical composition and sensory properties of these wines. Wines were grouped according to the production method (concentration of sugars in grapes) and to the aging process of wine (oxidative, biological, or a combination of both and aging in the bottle). It was found that wines natively sweets and wines fortified with liquors differ in their volatile compounds. Sensory properties of these wines include those of dried fruit (raisins), red berries, honey, chocolate and vanilla, which is contributing to their growing sales. However, there is still a need for scientific research on the understanding of the mechanisms for wine flavor enhancement.

The Scientific Quest for Lasting Youth: Prospects for Curing Aging

PubMed Central

2014-01-01

Abstract People have always sought eternal life and everlasting youth. Recent technological breakthroughs and our growing understanding of aging have given strength to the idea that a cure for human aging can eventually be developed. As such, it is crucial to debate the long-term goals and potential impact of the field. Here, I discuss the scientific prospect of eradicating human aging. I argue that curing aging is scientifically possible and not even the most challenging enterprise in the biosciences. Developing the means to abolish aging is also an ethical endeavor because the goal of biomedical research is to allow people to be as healthy as possible for as long as possible. There is no evidence, however, that we are near to developing the technologies permitting radical life extension. One major difficulty in aging research is the time and costs it takes to do experiments and test interventions. I argue that unraveling the functioning of the genome and developing predictive computer models of human biology and disease are essential to increase the accuracy of medical interventions, including in the context of life extension, and exponential growth in informatics and genomics capacity might lead to rapid progress. Nonetheless, developing the tools for significantly modifying human biology is crucial to intervening in a complex process like aging. Yet in spite of advances in areas like regenerative medicine and gene therapy, the development of clinical applications has been slow and this remains a key hurdle for achieving radical life extension in the foreseeable future. PMID:25132068

Long-term exposure to air pollution is associated with biological aging.

PubMed

Ward-Caviness, Cavin K; Nwanaji-Enwerem, Jamaji C; Wolf, Kathrin; Wahl, Simone; Colicino, Elena; Trevisi, Letizia; Kloog, Itai; Just, Allan C; Vokonas, Pantel; Cyrys, Josef; Gieger, Christian; Schwartz, Joel; Baccarelli, Andrea A; Schneider, Alexandra; Peters, Annette

2016-11-15

Long-term exposure to air pollution is associated with age-related diseases. We explored the association between accelerated biological aging and air pollution, a potential mechanism linking air pollution and health. We estimated long-term exposure to PM10, PM2.5, PM2.5 absorbance/black carbon (BC), and NOx via land-use regression models in individuals from the KORA F4 cohort. Accelerated biological aging was assessed using telomere length (TeloAA) and three epigenetic measures: DNA methylation age acceleration (DNAmAA), extrinsic epigenetic age acceleration (correlated with immune cell counts, EEAA), and intrinsic epigenetic age acceleration (independent of immune cell counts, IEAA). We also investigated sex-specific associations between air pollution and biological aging, given the published association between sex and aging measures. In KORA an interquartile range (0.97 µg/m3) increase in PM2.5 was associated with a 0.33 y increase in EEAA (CI = 0.01, 0.64; P = 0.04). BC and NOx (indicators or traffic exposure) were associated with DNAmAA and IEAA in women, while TeloAA was inversely associated with BC in men. We replicated this inverse BC-TeloAA association in the Normative Aging Study, a male cohort based in the USA. A multiple phenotype analysis in KORA F4 combining all aging measures showed that BC and PM10 were broadly associated with biological aging in men. Thus, we conclude that long-term exposure to air pollution is associated with biological aging measures, potentially in a sex-specific manner. However, many of the associations were relatively weak and further replication of overall and sex-specific associations is warranted.

Long-term exposure to air pollution is associated with biological aging

PubMed Central

Ward-Caviness, Cavin K.; Nwanaji-Enwerem, Jamaji C.; Wolf, Kathrin; Wahl, Simone; Colicino, Elena; Trevisi, Letizia; Kloog, Itai; Just, Allan C.; Vokonas, Pantel; Cyrys, Josef; Gieger, Christian; Schwartz, Joel; Baccarelli, Andrea A.; Schneider, Alexandra; Peters, Annette

2016-01-01

Long-term exposure to air pollution is associated with age-related diseases. We explored the association between accelerated biological aging and air pollution, a potential mechanism linking air pollution and health. We estimated long-term exposure to PM10, PM2.5, PM2.5 absorbance/black carbon (BC), and NOx via land-use regression models in individuals from the KORA F4 cohort. Accelerated biological aging was assessed using telomere length (TeloAA) and three epigenetic measures: DNA methylation age acceleration (DNAmAA), extrinsic epigenetic age acceleration (correlated with immune cell counts, EEAA), and intrinsic epigenetic age acceleration (independent of immune cell counts, IEAA). We also investigated sex-specific associations between air pollution and biological aging, given the published association between sex and aging measures. In KORA an interquartile range (0.97 μg/m3) increase in PM2.5 was associated with a 0.33 y increase in EEAA (CI = 0.01, 0.64; P = 0.04). BC and NOx (indicators or traffic exposure) were associated with DNAmAA and IEAA in women, while TeloAA was inversely associated with BC in men. We replicated this inverse BC-TeloAA association in the Normative Aging Study, a male cohort based in the USA. A multiple phenotype analysis in KORA F4 combining all aging measures showed that BC and PM10 were broadly associated with biological aging in men. Thus, we conclude that long-term exposure to air pollution is associated with biological aging measures, potentially in a sex-specific manner. However, many of the associations were relatively weak and further replication of overall and sex-specific associations is warranted. PMID:27793020

Sex differences in processing printed advertisements.

PubMed

Putrevu, Sanjay

2004-06-01

The success of using biological sex to divide or segment markets requires a thorough understanding of how men and women process and respond to advertisements and other persuasive communications. Toward this end, this research (N=64; 32 men and 32 women) studied how college-age men and women respond to printed advertisements. There were no differences between the sexes in recall and recognition of claims in advertisements, but men and women generated different types of message relevant thoughts-women generated more category thoughts and men generated more attribute thoughts, suggesting that, while women and men might not differ in the depth of processing, they might use different processing styles.

Source Separation of Urine as an Alternative Solution to Nutrient Management in Biological Nutrient Removal Treatment Plants.

PubMed

Jimenez, Jose; Bott, Charles; Love, Nancy; Bratby, John

2015-12-01

Municipal wastewater contains a mixture of brown (feces and toilet paper), yellow (urine), and gray (kitchen, bathroom and wash) waters. Urine contributes approximately 70-80% of the nitrogen (N), 50-70% of the phosphorus (P) load and 60-70% of the pharmaceutical residues in normal domestic sewage. This study evaluated the impact of different levels of source separation of urine on an existing biological nutrient removal (BNR) process. A process model of an existing biological nutrient removal (BNR) plant was used. Increasing the amount of urine diverted from the water reclamation facilities, has little impact on effluent ammonia (NH₃-N) concentration, but effluent nitrate (NO₃-N) concentration decreases. If nitrification is necessary then no reduction in the sludge age can be realized. However, a point is reached where the remaining influent nitrogen load matches the nitrogen requirements for biomass growth, and no residual nitrogen needs to be nitrified. That allows a significant reduction in sludge age, implying reduced process volume requirements. In situations where nitrification is required, lower effluent nitrate (NO₃-N) concentrations were realized due to both the lower influent nitrogen content in the wastewater and a more favorable nitrogen-to-carbon ratio for denitrification. The external carbon requirement for denitrification decreases as the urine separation efficiency increases due to the lower influent nitrogen content in the wastewater and a more favorable nitrogen-to-carbon ratio for denitrification. The effluent phosphorus concentration decreases when the amount of urine sent to water reclamation facilities is decreased due to lower influent phosphorus concentrations. In the case of chemical phosphate removal, urine separation reduces the amount of chemicals required.

Defining age- and lactocrine-sensitive elements of the neonatal porcine uterine microRNA–mRNA interactome†,‡

PubMed Central

George, Ashley F.; Rahman, Kathleen M.; Camp, Meredith E.; Prasad, Nripesh; Bartol, Frank F.; Bagnell, Carol A.

2017-01-01

Abstract Factors delivered to offspring in colostrum within 2 days of birth support neonatal porcine uterine development. The uterine mRNA transcriptome is affected by age and nursing during this period. Whether uterine microRNA (miRNA) expression is affected similarly is unknown. Objectives were to (1) determine effects of age and nursing on porcine uterine miRNA expression between birth and postnatal day (PND) 2 using miRNA sequencing (miRNAseq) and; (2) define affected miRNA–mRNA interactions and associated biological processes using integrated target prediction analysis. At birth (PND 0), gilts were euthanized, nursed ad libitum, or gavage-fed milk replacer for 48 h. Uteri were collected at birth or 50 h postnatal. MicroRNAseq data were validated using quantitative real-time PCR. Targets were predicted using an established mRNA database generated from the same tissues. For PND 2 versus PND 0 comparisons, 31 differentially expressed (DE) miRNAs were identified for nursed, and 42 DE miRNAs were identified for replacer-fed gilts. Six DE miRNAs were identified for nursed versus replacer-fed gilts on PND 2. Target prediction for inversely correlated DE miRNA–mRNA pairings indicated 20 miRNAs targeting 251 mRNAs in nursed, versus 29 miRNAs targeting 585 mRNAs in replacer-fed gilts for PND 2 versus PND 0 comparisons, and 5 miRNAs targeting 81 mRNAs for nursed versus replacer-fed gilts on PND 2. Biological processes predicted to be affected by age and nursing included cell-to-cell signaling, cell morphology, and tissue morphology. Results indicate novel age- and lactocrine-sensitive miRNA–mRNA relationships associated with porcine neonatal uterine development between birth and PND 2. PMID:28203709

Chronobiology of the neuroimmunoendocrine system and aging.

PubMed

Mate, Ianire; Madrid, Juan Antonio; De la Fuente, Mónica

2014-01-01

The health maintenance depends on the preservation of the homeostatic systems, such as nervous, endocrine and immune system, and a proper communication between them. In this regard, the circadian system, which promotes a better physiological system functions and thus well being, could be considered part of that homeostatic complex, since the neuroimmunoendocrine system possesses circadian patterns in most variables, as well as circannual or seasonal variations. With aging, an impairment of the homeostatic systems occurs and an alteration of circadian system regulation has been demonstrated. In the immune system, several function parameters, which are good markers of health and of the rate of aging, change not only with age (immunosenescence) but also throughout the day and year. Indeed, with advancing age there is a modification of immune cell circadian function especially in lymphocytes. Moreover, immune functions at early afternoon correspond to more aged values than at morning, especially in mature subjects (60-79 years of age). In addition, these mature men and women showed a significant impaired immune cell function, which is especially remarkable in the winter. It is noteworthy the role of immunomodulatory hormones, such as melatonin, in the regulation of biological rhythms and their involvement in the aging process. Furthermore, the evidence of a neuroimmune regulation of the circadian system and its disturbance with aging, highlights the importance of proinflammatory cytokines in this complex cross-talk. The biological rhythms disruption with age and some diseases (jet lag, cancer and seasonal affective disorder), could contribute increasing the immune system impairment and consequently the loss of health.

The biospeckle method for the investigation of agricultural crops: A review

NASA Astrophysics Data System (ADS)

Zdunek, Artur; Adamiak, Anna; Pieczywek, Piotr M.; Kurenda, Andrzej

2014-01-01

Biospeckle is a nondestructive method for the evaluation of living objects. It has been applied to medicine, agriculture and microbiology for monitoring processes related to the movement of material particles. Recently, this method is extensively used for evaluation of quality of agricultural crops. In the case of botanical materials, the sources of apparent biospeckle activity are the Brownian motions and biological processes such as cyclosis, growth, transport, etc. Several different applications have been shown to monitor aging and maturation of samples, organ development and the detection and development of defects and diseases. This review will focus on three aspects: on the image analysis and mathematical methods for biospeckle activity evaluation, on published applications to botanical samples, with special attention to agricultural crops, and on interpretation of the phenomena from a biological point of view.

Clinical Trials Targeting Aging and Age-Related Multimorbidity

PubMed Central

Crimmins, Eileen M; Grossardt, Brandon R; Crandall, Jill P; Gelfond, Jonathan A L; Harris, Tamara B; Kritchevsky, Stephen B; Manson, JoAnn E; Robinson, Jennifer G; Rocca, Walter A; Temprosa, Marinella; Thomas, Fridtjof; Wallace, Robert; Barzilai, Nir

2017-01-01

Abstract Background There is growing interest in identifying interventions that may increase health span by targeting biological processes underlying aging. The design of efficient and rigorous clinical trials to assess these interventions requires careful consideration of eligibility criteria, outcomes, sample size, and monitoring plans. Methods Experienced geriatrics researchers and clinical trialists collaborated to provide advice on clinical trial design. Results Outcomes based on the accumulation and incidence of age-related chronic diseases are attractive for clinical trials targeting aging. Accumulation and incidence rates of multimorbidity outcomes were developed by selecting at-risk subsets of individuals from three large cohort studies of older individuals. These provide representative benchmark data for decisions on eligibility, duration, and assessment protocols. Monitoring rules should be sensitive to targeting aging-related, rather than disease-specific, outcomes. Conclusions Clinical trials targeting aging are feasible, but require careful design consideration and monitoring rules. PMID:28364543

Biological Aging - Criteria for Modeling and a New Mechanistic Model

NASA Astrophysics Data System (ADS)

Pletcher, Scott D.; Neuhauser, Claudia

To stimulate interaction and collaboration across scientific fields, we introduce a minimum set of biological criteria that theoretical models of aging should satisfy. We review results of several recent experiments that examined changes in age-specific mortality rates caused by genetic and environmental manipulation. The empirical data from these experiments is then used to test mathematical models of aging from several different disciplines, including molecular biology, reliability theory, physics, and evolutionary biology/population genetics. We find that none of the current models are consistent with all of the published experimental findings. To provide an example of how our criteria might be applied in practice, we develop a new conceptual model of aging that is consistent with our observations.

Brain aging phenomena in migrating sockeye salmon Oncorhynchus nerka nerka.

PubMed

Götz, M E; Malz, C R; Dirr, A; Blum, D; Gsell, W; Schmidt, S; Burger, R; Pohli, S; Riederer, P

2005-09-01

Aging, a process occurring in all vertebrates, is closely related to a loss in physical and functional abilities. There is widespread interest in clarifying the relevance of environmental, metabolic, and genetic factors for vertebrate aging. In the Pacific salmon a dramatic example of aging is known. Looking for changes in the salmon brain, perhaps even in the role of initiating the aging processes, we investigated several biochemical parameters that should reflect brain functional activity and stress response such as the neurotransmitters dopamine, and serotonin, and two of their respective metabolites 3,4-dihydroxyphenylacetic acid, and 5-hydroxyindole acetic acid, as well as glutathione, glutathione disulfide, and the extent of terminal deoxynucleotidyltransferase-mediated dUTP nick end-labelling. The aging of migrating sockeye salmon (Oncorhynchus nerka nerka) is accompanied by gradual increase in dopamine and serotonin turnover and a gradual decrease of brain total protein and glutathione levels. There appears to be an increased need for detoxification of reactive biological intermediates since activities of superoxide dismutase and catalase increase with age. However, our data do not support a major increase in apoptotic cell death during late aging but rather implicate an age related downward regulation of protein and glutathione synthesis and proteolysis increasing the need for autophagocytosis or heterophagocytosis in the course of cell death.

The natural phytochemical dehydroabietic acid is an anti-aging reagent that mediates the direct activation of SIRT1.

PubMed

Kim, Juewon; Kang, Young-Gyu; Lee, Jee-young; Choi, Dong-hwa; Cho, Young-uk; Shin, Jae-Min; Park, Jun Seong; Lee, John Hwan; Kim, Wan Gi; Seo, Dae Bang; Lee, Tae Ryong; Miyamoto, Yusei; No, Kyoung Tai

2015-09-05

Dehydroabietic acid (DAA) is a naturally occurring diterpene resin acid of confers, such as pinus species (P. densiflora, P. sylvestris) and grand fir (Abies grandis), and it induces various biological actions including antimicrobial, antiulcer, and cardiovascular activities. The cellular targets that mediate these actions are largely unknown yet. In this report, we suggest that DAA is an anti-aging reagent. DAA has lifespan extension effects in Caenorhabditis elegans, prevents lipofuscin accumulation, and prevents collagen secretion in human dermal fibroblasts. We found that these anti-aging effects are primarily mediated by SIRT1 activation. Lifespan extension effects by DAA were ameliorated in sir-2.1 mutants and SIRT1 protein expression was increased, resulting in the deacetylation of SIRT1 target protein PGC-1α. Moreover, DAA binds directly to the SIRT1 protein independent of the SIRT1 substrate NAD(+) levels. Through a molecular docking study, we also propose a binding model for DAA-SIRT1. Taken together, our results demonstrate that the anti-aging effects are the first identified biological property of DAA and that the direct activation of SIRT1 enzymatic activity suggests the potential use of this natural diterpene, or related compounds, in age-related diseases or as a preventive reagent against the aging process. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[The influence of different types of physical exertions on the mature males' biological age].

PubMed

Sirotin, A B; Belozerova, L M; Sergeeva, I G; Zhukov, V N; Kolegova, N G

2014-01-01

We studied the biological age according to anthropometric indexes, mental, physical and both the types of working efficiency in 122 males at the age of 50-59 years. All of them were devided into 5 groups: untrained individuals, going in for general physical training, sport veterans, specializing in endurance training, sport plays representatives, weight-lifters. We found out a younger biological age in sport veterans, who were carrying out dynamic exertions.

Analysing Students' Shared Activity while Modeling a Biological Process in a Computer-Supported Educational Environment

ERIC Educational Resources Information Center

Ergazaki, M.; Zogza, V.; Komis, V.

2007-01-01

This paper reports on a case study with three dyads of high school students (age 14 years) each collaborating on a plant growth modeling task in the computer-supported educational environment "ModelsCreator". Following a qualitative line of research, the present study aims at highlighting the ways in which the collaborating students as well as the…

A Simple Interactive Introduction to Teaching Genetic Engineering

ERIC Educational Resources Information Center

Child, Paula

2013-01-01

In the UK, at key stage 4, students aged 14-15 studying GCSE Core Science or Unit 1 of the GCSE Biology course are required to be able to describe the process of genetic engineering to produce bacteria that can produce insulin. The simple interactive introduction described in this article allows students to consider the problem, devise a model and…

Young People's Risk of Suicide Attempts in Relation to Parental Death: A Population-Based Register Study

ERIC Educational Resources Information Center

Jakobsen, Ida Skytte; Christiansen, Erik

2011-01-01

Background: The objective of this study was to examine the association between the death of a biological parent and subsequent suicide attempts by young people (aged 10-22 years), and to explore sociodemographic factors as modifying factors in the process. Methods: The study used a nested case-control design. The full study population was obtained…

On the relationship between cell cycle analysis with ergodic principles and age-structured cell population models.

PubMed

Kuritz, K; Stöhr, D; Pollak, N; Allgöwer, F

2017-02-07

Cyclic processes, in particular the cell cycle, are of great importance in cell biology. Continued improvement in cell population analysis methods like fluorescence microscopy, flow cytometry, CyTOF or single-cell omics made mathematical methods based on ergodic principles a powerful tool in studying these processes. In this paper, we establish the relationship between cell cycle analysis with ergodic principles and age structured population models. To this end, we describe the progression of a single cell through the cell cycle by a stochastic differential equation on a one dimensional manifold in the high dimensional dataspace of cell cycle markers. Given the assumption that the cell population is in a steady state, we derive transformation rules which transform the number density on the manifold to the steady state number density of age structured population models. Our theory facilitates the study of cell cycle dependent processes including local molecular events, cell death and cell division from high dimensional "snapshot" data. Ergodic analysis can in general be applied to every process that exhibits a steady state distribution. By combining ergodic analysis with age structured population models we furthermore provide the theoretic basis for extensions of ergodic principles to distribution that deviate from their steady state. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nitrones as Therapeutics

PubMed Central

Floyd, Robert A.; Kopke, Richard D.; Choi, Chul-Hee; Foster, Steven B.; Doblas, Sabrina; Towner, Rheal A.

2008-01-01

Nitrones have the general chemical formula X-CH=NO-Y. They were first used to trap free radicals in chemical systems and then subsequently in biochemical systems. More recently several nitrones including PBN (α-phenyl-tert-butylnitrone) have been shown to have potent biological activity in many experimental animal models. Many diseases of aging including stroke, cancer development, Parkinson’s disease and Alzheimer’s disease are known to have enhanced levels of free radicals and oxidative stress. Some derivatives of PBN are significantly more potent than PBN and have undergone extensive commercial development in stroke. Recent research has shown that PBN-related nitrones also have anti-cancer activity in several experimental cancer models and have potential as therapeutics in some cancers. Also in recent observations nitrones have been shown to act synergistically in combination with antioxidants in the prevention of acute acoustic noise induced hearing loss. The mechanistic basis of the potent biological activity of PBN-related nitrones is not known. Even though PBN-related nitrones do decrease oxidative stress and oxidative damage, their potent biological anti-inflammatory activity and their ability to alter cellular signaling processes can not readily be explained by conventional notions of free radical trapping biochemistry. This review is focused on our observations and others where the use of selected nitrones as novel therapeutics have been evaluated in experimental models in the context of free radical biochemical and cellular processes considered important in pathologic conditions and age-related diseases. PMID:18793715

Identifying Exosome-Derived MicroRNAs as Candidate Biomarkers of Frailty.

PubMed

Ipson, B R; Fletcher, M B; Espinoza, S E; Fisher, A L

2018-01-01

Frailty is a geriatric syndrome associated with progressive physical decline and significantly increases risk for falls, disability, hospitalizations, and death. However, much remains unknown regarding the biological mechanisms that contribute to aging and frailty, and to date, there are no clinically used prognostic or diagnostic molecular biomarkers. The present study profiled exosome-derived microRNAs isolated from the plasma of young, robust older, and frail older individuals and identified eight miRNAs that are uniquely enriched in frailty: miR-10a-3p, miR-92a-3p, miR-185-3p, miR-194-5p, miR-326, miR-532-5p, miR-576-5p, and miR-760. Furthermore, since exosomes can deliver miRNAs to alter cellular activity and behavior, these miRNAs may also provide insights into the biological mechanisms underlying frailty; KEGG analysis of their target genes revealed multiple pathways implicated in aging and age-related processes. Although further validation and research studies are warranted, our study identified eight novel candidate biomarkers of frailty that may help to elucidate the multifactorial pathogenesis of frailty.

Biological maturity at birth, the course of the subsequent ontogenetic stages and age at menarche.

PubMed

Szwed, A; Kosińska, M

2012-08-01

The main aim of the study was to assess the influence of biological maturity at birth on growth processes in the subsequent years and during puberty in girls. The material of this study comes from the outpatient clinic cards and cross-sectional research on girls from the province of Wielkopolska in Poland. It includes data of 527 girls. The influence of perinatal maturity on body weight in the later stages of ontogeny was determined with the use of the Kruskal-Wallis test and the Mann-Whitney U test. In order to determine the relationship between perinatal maturity and age at menarche, the survival analysis module was used. The results show a diverse influence of perinatal maturity on the values of body weight achieved in later years of life. The indicated predictive factors included both birth weight and gestational age. In the examined girls menarche occurred between the 10th year and the 17th year of life (X¯=12.87, s=1.26; Me=13 years). The comparison showed a significant variation in age at menarche depending on the length of pregnancy (log-rank χ(2)(2)=27.068, p<0.0001) and birth weight (log-rank χ(2)(2)=23.241, p<0.0001). There was no variation in maturation of the examined girls conditioned by the occurrence of intra-uterine growth retardation (log-rank χ(2)(2)=2.046, p>0.05). Remote prognoses as to the postnatal development of preterm-born children and/or children with low birth weight indicate adverse influence of these variables on age at menarche. Perinatal biological maturity of a newborn conditions the course of postnatal development. Copyright © 2012 Elsevier GmbH. All rights reserved.

Proton irradiation impacts age-driven modulations of cancer progression influenced by immune system transcriptome modifications from splenic tissue.

PubMed

Wage, Justin; Ma, Lili; Peluso, Michael; Lamont, Clare; Evens, Andrew M; Hahnfeldt, Philip; Hlatky, Lynn; Beheshti, Afshin

2015-09-01

Age plays a crucial role in the interplay between tumor and host, with additional impact due to irradiation. Proton irradiation of tumors induces biological modulations including inhibition of angiogenic and immune factors critical to 'hallmark' processes impacting tumor development. Proton irradiation has also provided promising results for proton therapy in cancer due to targeting advantages. Additionally, protons may contribute to the carcinogenesis risk from space travel (due to the high proportion of high-energy protons in space radiation). Through a systems biology approach, we investigated how host tissue (i.e. splenic tissue) of tumor-bearing mice was altered with age, with or without whole-body proton exposure. Transcriptome analysis was performed on splenic tissue from adolescent (68-day) versus old (736-day) C57BL/6 male mice injected with Lewis lung carcinoma cells with or without three fractionations of 0.5 Gy (1-GeV) proton irradiation. Global transcriptome analysis indicated that proton irradiation of adolescent hosts caused significant signaling changes within splenic tissues that support carcinogenesis within the mice, as compared with older subjects. Increases in cell cycling and immunosuppression in irradiated adolescent hosts with CDK2, MCM7, CD74 and RUVBL2 indicated these were the key genes involved in the regulatory changes in the host environment response (i.e. the spleen). Collectively, these results suggest that a significant biological component of proton irradiation is modulated by host age through promotion of carcinogenesis in adolescence and resistance to immunosuppression, carcinogenesis and genetic perturbation associated with advancing age. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Human RecQL4 helicase plays multifaceted roles in the genomic stability of normal and cancer cells.

PubMed

Mo, Dongliang; Zhao, Yongliang; Balajee, Adayabalam S

2018-01-28

Human RecQ helicases that share homology with E. coli RecQ helicase play critical roles in diverse biological activities such as DNA replication, transcription, recombination and repair. Mutations in three of the five human RecQ helicases (RecQ1, WRN, BLM, RecQL4 and RecQ5) result in autosomal recessive syndromes characterized by accelerated aging symptoms and cancer incidence. Mutational inactivation of Werner (WRN) and Bloom (BLM) genes results in Werner syndrome (WS) and Bloom syndrome (BS) respectively. However, mutations in RecQL4 result in three human disorders: (I) Rothmund-Thomson syndrome (RTS), (II) RAPADILINO and (III) Baller-Gerold syndrome (BGS). Cells from WS, BS and RTS are characterized by a unique chromosomal anomaly indicating that each of the RecQ helicases performs specialized function(s) in a non-redundant manner. Elucidating the biological functions of RecQ helicases will enable us to understand not only the aging process but also to determine the cause for age-associated human diseases. Recent biochemical and molecular studies have given new insights into the multifaceted roles of RecQL4 that range from genomic stability to carcinogenesis and beyond. This review summarizes some of the existing and emerging knowledge on diverse biological functions of RecQL4 and its significance as a potential molecular target for cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Low but significant genetic differentiation underlies biologically meaningful phenotypic divergence in a large Atlantic salmon population.

PubMed

Aykanat, Tutku; Johnston, Susan E; Orell, Panu; Niemelä, Eero; Erkinaro, Jaakko; Primmer, Craig R

2015-10-01

Despite decades of research assessing the genetic structure of natural populations, the biological meaning of low yet significant genetic divergence often remains unclear due to a lack of associated phenotypic and ecological information. At the same time, structured populations with low genetic divergence and overlapping boundaries can potentially provide excellent models to study adaptation and reproductive isolation in cases where high-resolution genetic markers and relevant phenotypic and life history information are available. Here, we combined single nucleotide polymorphism (SNP)-based population inference with extensive phenotypic and life history data to identify potential biological mechanisms driving fine-scale subpopulation differentiation in Atlantic salmon (Salmo salar) from the Teno River, a major salmon river in Europe. Two sympatrically occurring subpopulations had low but significant genetic differentiation (FST  = 0.018) and displayed marked differences in the distribution of life history strategies, including variation in juvenile growth rate, age at maturity and size within age classes. Large, late-maturing individuals were virtually absent from one of the two subpopulations, and there were significant differences in juvenile growth rates and size at age after oceanic migration between individuals in the respective subpopulations. Our findings suggest that different evolutionary processes affect each subpopulation and that hybridization and subsequent selection may maintain low genetic differentiation without hindering adaptive divergence. © 2015 John Wiley & Sons Ltd.

Endogenous longevity, biological deterioration and economic growth.

PubMed

Sanso, Marcos; Aísa, Rosa M

2006-05-01

The identification of the types of bidirectional interactions that take place between longevity and economic growth in the long-run is carried out by means of the integration of human capital accumulation, innovation in medical technology, a health goods sector, and individual decisions on health and longevity in a dynamic general equilibrium set-up. In this context, in which individual agents decide not only on their "quality" of life but also on its "quantity", the mere process of biological deterioration, that is to say, the continuous loss of health goods effectiveness in maintaining a given level of health as individuals age, provides the reason for an additional, and new, engine of growth.

Intrinsic and extrinsic mortality reunited.

PubMed

Koopman, Jacob J E; Wensink, Maarten J; Rozing, Maarten P; van Bodegom, David; Westendorp, Rudi G J

2015-07-01

Intrinsic and extrinsic mortality are often separated in order to understand and measure aging. Intrinsic mortality is assumed to be a result of aging and to increase over age, whereas extrinsic mortality is assumed to be a result of environmental hazards and be constant over age. However, allegedly intrinsic and extrinsic mortality have an exponentially increasing age pattern in common. Theories of aging assert that a combination of intrinsic and extrinsic stressors underlies the increasing risk of death. Epidemiological and biological data support that the control of intrinsic as well as extrinsic stressors can alleviate the aging process. We argue that aging and death can be better explained by the interaction of intrinsic and extrinsic stressors than by classifying mortality itself as being either intrinsic or extrinsic. Recognition of the tight interaction between intrinsic and extrinsic stressors in the causation of aging leads to the recognition that aging is not inevitable, but malleable through the environment. Copyright © 2015 Elsevier Inc. All rights reserved.

Convergent molecular defects underpin diverse neurodegenerative diseases.

PubMed

Tofaris, George K; Buckley, Noel J

2018-02-19

In our ageing population, neurodegenerative disorders carry an enormous personal, societal and economic burden. Although neurodegenerative diseases are often thought of as clinicopathological entities, increasing evidence suggests a considerable overlap in the molecular underpinnings of their pathogenesis. Such overlapping biological processes include the handling of misfolded proteins, defective organelle trafficking, RNA processing, synaptic health and neuroinflammation. Collectively but in different proportions, these biological processes in neurons or non-neuronal cells lead to regionally distinct patterns of neuronal vulnerability and progression of pathology that could explain the disease symptomology. With the advent of patient-derived cellular models and novel genetic manipulation tools, we are now able to interrogate this commonality despite the cellular complexity of the brain in order to develop novel therapeutic strategies to prevent or arrest neurodegeneration. Here, we describe broadly these concepts and their relevance across neurodegenerative diseases. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Postnatal brain development: Structural imaging of dynamic neurodevelopmental processes

PubMed Central

Jernigan, Terry L.; Baaré, William F. C.; Stiles, Joan; Madsen, Kathrine Skak

2013-01-01

After birth, there is striking biological and functional development of the brain’s fiber tracts as well as remodeling of cortical and subcortical structures. Behavioral development in children involves a complex and dynamic set of genetically guided processes by which neural structures interact constantly with the environment. This is a protracted process, beginning in the third week of gestation and continuing into early adulthood. Reviewed here are studies using structural imaging techniques, with a special focus on diffusion weighted imaging, describing age-related brain maturational changes in children and adolescents, as well as studies that link these changes to behavioral differences. Finally, we discuss evidence for effects on the brain of several factors that may play a role in mediating these brain–behavior associations in children, including genetic variation, behavioral interventions, and hormonal variation associated with puberty. At present longitudinal studies are few, and we do not yet know how variability in individual trajectories of biological development in specific neural systems map onto similar variability in behavioral trajectories. PMID:21489384

A systems biology approach to studying Tai Chi, physiological complexity and healthy aging: design and rationale of a pragmatic randomized controlled trial.

PubMed

Wayne, Peter M; Manor, Brad; Novak, Vera; Costa, Madelena D; Hausdorff, Jeffrey M; Goldberger, Ary L; Ahn, Andrew C; Yeh, Gloria Y; Peng, C-K; Lough, Matthew; Davis, Roger B; Quilty, Mary T; Lipsitz, Lewis A

2013-01-01

Aging is typically associated with progressive multi-system impairment that leads to decreased physical and cognitive function and reduced adaptability to stress. Due to its capacity to characterize complex dynamics within and between physiological systems, the emerging field of complex systems biology and its array of quantitative tools show great promise for improving our understanding of aging, monitoring senescence, and providing biomarkers for evaluating novel interventions, including promising mind-body exercises, that treat age-related disease and promote healthy aging. An ongoing, two-arm randomized clinical trial is evaluating the potential of Tai Chi mind-body exercise to attenuate age-related loss of complexity. A total of 60 Tai Chi-naïve healthy older adults (aged 50-79) are being randomized to either six months of Tai Chi training (n=30), or to a waitlist control receiving unaltered usual medical care (n=30). Our primary outcomes are complexity-based measures of heart rate, standing postural sway and gait stride interval dynamics assessed at 3 and 6months. Multiscale entropy and detrended fluctuation analysis are used as entropy- and fractal-based measures of complexity, respectively. Secondary outcomes include measures of physical and psychological function and tests of physiological adaptability also assessed at 3 and 6months. Results of this study may lead to novel biomarkers that help us monitor and understand the physiological processes of aging and explore the potential benefits of Tai Chi and related mind-body exercises for healthy aging. Copyright © 2012 Elsevier Inc. All rights reserved.

Ontogeny of the spheno-occipital synchondrosis in a modern Queensland, Australian population using computed tomography.

PubMed

Lottering, Nicolene; MacGregor, Donna M; Alston, Clair L; Gregory, Laura S

2015-05-01

Due to disparity regarding the age at which skeletal maturation of the spheno-occipital synchondrosis occurs in forensic and biological literature, this study provides recalibrated multislice computed tomography (MSCT) age standards for the Australian (Queensland) population, using a Bayesian statistical approach. The sample comprises retrospective cranial/cervical MSCT scans obtained from 448 males and 416 females aged birth to 20 years from the Skeletal Biology and Forensic Anthropology Research Osteological Database. Fusion status of the synchondrosis was scored using a modified six-stage scoring tier on an MSCT platform, with negligible observer error (κ = 0.911 ± 0.04, intraclass correlation coefficient = 0.994). Bayesian transition analysis indicates that females are most likely to transition to complete fusion at 13.1 years and males at 15.6 years. Posterior densities were derived for each morphological stage, with complete fusion of the synchondrosis attained in all Queensland males over 16.3 years of age and females aged 13.8 years and older. The results demonstrate significant sexual dimorphism in synchondrosis fusion and are suggestive of intrapopulation variation between major geographic regions in Australia. This study contributes to the growing repository of contemporary anthropological standards calibrated for the Queensland milieu to improve the efficacy of the coronial process for medicolegal death investigation. As a stand-alone age indicator, the basicranial synchondrosis may be consulted as an exclusion criterion when determining the age of majority that constitutes 17 years in Queensland forensic practice. © 2014 Wiley Periodicals, Inc.

Dietary Epigenetics in Cancer and Aging

PubMed Central

Tollefsbol, Trygve O.

2013-01-01

Although epigenetic aberrations frequently occur in aging and cancer and form a core component of these conditions, perhaps the most useful aspect of epigenetic processes is that they are readily reversible. Unlike genetic effects that also play a role in cancer and aging, epigenetic aberrations can be relatively easily corrected. One of the most widespread approaches to the epigenetic alterations in cancer and aging is dietary control. This can be achieved not only through the quality of the diet, but also through the quantity of calories that are consumed. Many phytochemicals such as sulforaphane from cruciferous vegetables and green tea have anticancer epigenetic effects and are also efficacious for preventing or treating the epigenetic aberrations of other age-associated diseases besides cancer. Likewise, the quantity of calories that are consumed have proven to be advantageous in preventing cancer and extending the lifespan through control of epigenetic mediators. The purpose of this chapter is to review some of the most recent advances in the epigenetics of cancer and aging and to provide insights into advances being made with respect to dietary intervention into these biological processes that have vast health implications and high translational potential. PMID:24114485

The Biology of Aging and Cancer: Frailty, Inflammation, and Immunity.

PubMed

Zhang, Xinwen; Meng, Xin; Chen, Yiyin; Leng, Sean X; Zhang, Haiyan

The majority of patients with common malignancies are older adults. Intrinsic complex biological changes of aging along with inflammation, immunosenescence, age-associated chronic diseases, and extrinsic environmental and psychosocial factors have significant impact on not only development and behavior of individual malignancies, but also physiologic reserve and vulnerability of older patients who suffer from them. As a result, clinical practice of geriatric oncology demands integration of careful geriatric assessment and management. This article provides an overview of basic biology of aging and its relationship with cancer. After a brief introduction about the definition and mechanisms of aging, as well as age-related biological and physiological changes, the discussion mainly focuses on recent development and insights into the relationship of frailty, inflammation, and immunity with cancer, highlighting how the new knowledge can help further improve assessment and treatment of older patients with malignancies and promote cancer research.

Quantification of biological aging in young adults

PubMed Central

Belsky, Daniel W.; Caspi, Avshalom; Houts, Renate; Cohen, Harvey J.; Corcoran, David L.; Danese, Andrea; Harrington, HonaLee; Israel, Salomon; Levine, Morgan E.; Schaefer, Jonathan D.; Sugden, Karen; Williams, Ben; Yashin, Anatoli I.; Poulton, Richie; Moffitt, Terrie E.

2015-01-01

Antiaging therapies show promise in model organism research. Translation to humans is needed to address the challenges of an aging global population. Interventions to slow human aging will need to be applied to still-young individuals. However, most human aging research examines older adults, many with chronic disease. As a result, little is known about aging in young humans. We studied aging in 954 young humans, the Dunedin Study birth cohort, tracking multiple biomarkers across three time points spanning their third and fourth decades of life. We developed and validated two methods by which aging can be measured in young adults, one cross-sectional and one longitudinal. Our longitudinal measure allows quantification of the pace of coordinated physiological deterioration across multiple organ systems (e.g., pulmonary, periodontal, cardiovascular, renal, hepatic, and immune function). We applied these methods to assess biological aging in young humans who had not yet developed age-related diseases. Young individuals of the same chronological age varied in their “biological aging” (declining integrity of multiple organ systems). Already, before midlife, individuals who were aging more rapidly were less physically able, showed cognitive decline and brain aging, self-reported worse health, and looked older. Measured biological aging in young adults can be used to identify causes of aging and evaluate rejuvenation therapies. PMID:26150497

Quantitative Machine Learning Analysis of Brain MRI Morphology throughout Aging.

PubMed

Shamir, Lior; Long, Joe

2016-01-01

While cognition is clearly affected by aging, it is unclear whether the process of brain aging is driven solely by accumulation of environmental damage, or involves biological pathways. We applied quantitative image analysis to profile the alteration of brain tissues during aging. A dataset of 463 brain MRI images taken from a cohort of 416 subjects was analyzed using a large set of low-level numerical image content descriptors computed from the entire brain MRI images. The correlation between the numerical image content descriptors and the age was computed, and the alterations of the brain tissues during aging were quantified and profiled using machine learning. The comprehensive set of global image content descriptors provides high Pearson correlation of ~0.9822 with the chronological age, indicating that the machine learning analysis of global features is sensitive to the age of the subjects. Profiling of the predicted age shows several periods of mild changes, separated by shorter periods of more rapid alterations. The periods with the most rapid changes were around the age of 55, and around the age of 65. The results show that the process of brain aging of is not linear, and exhibit short periods of rapid aging separated by periods of milder change. These results are in agreement with patterns observed in cognitive decline, mental health status, and general human aging, suggesting that brain aging might not be driven solely by accumulation of environmental damage. Code and data used in the experiments are publicly available.

The special status of sad infant faces: age and valence differences in adults' cortical face processing.

PubMed

Colasante, Tyler; Mossad, Sarah I; Dudek, Joanna; Haley, David W

2017-04-01

Understanding the relative and joint prioritization of age- and valence-related face characteristics in adults' cortical face processing remains elusive because these two characteristics have not been manipulated in a single study of neural face processing. We used electroencephalography to investigate adults' P1, N170, P2 and LPP responses to infant and adult faces with happy and sad facial expressions. Viewing infant vs adult faces was associated with significantly larger P1, N170, P2 and LPP responses, with hemisphere and/or participant gender moderating this effect in select cases. Sad faces were associated with significantly larger N170 responses than happy faces. Sad infant faces were associated with significantly larger N170 responses in the right hemisphere than all other combinations of face age and face valence characteristics. We discuss the relative and joint neural prioritization of infant face characteristics and negative facial affect, and their biological value as distinct caregiving and social cues. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Behavioral characteristics of very-low-birth-weight infants of varying biologic risk at 6, 15, and 24 months of age.

PubMed

Oehler, J M; Thompson, R J; Goldstein, R F; Gustafson, K E; Brazy, J E

1996-01-01

To explore the relationship between developmental outcome and behavior of very-low-birth-weight (VLBW) infants (< or = 1500 g) at high and low biologic risk. Descriptive, ex post facto. Clinic for follow-up of infants at high risk. A convenience sample of 102 VLBW infants, free of major congenital anomalies, who completed 6-, 15-, and 24-month developmental testing and who were part of a larger study of 274 VLBW infants. Bayley Scales of Infant Development. Infants at high biologic risk, versus infants at low biologic risk, were less attentive and active through age 15 months and were less adept in gross and fine motor skills through age 24 months (p < or = 0.05-0.001). Infants with continuous delay were less attentive than infants with no delay or late delay through age 24 months, less active through age 15 months (p < or = 0.001-0.001), and less skilled in motor behaviors through age 24 months (p < or = 0.05-0.001). Infants at high biologic risk and infants with developmental delays are less attentive, less active, and less skilled in motor tasks during the first 15-24 months of life, suggesting an association between biologic risk and behavior and developmental delay and behavior.

Bringing life to soil physical processes

NASA Astrophysics Data System (ADS)

Hallett, P. D.

2013-12-01

When Oklahoma's native prairie grass roots were replaced by corn, the greatest environmental (and social) disaster ever to hit America ensued. The soils lost structure, physical binding by roots was annihilated and when drought came the Great Dust Bowl commenced. This form of environmental disaster has repeated over history and although not always apparent, similar processes drive the degradation of seemingly productive farmland and forests. But just as negative impacts on biology are deleterious to soil physical properties, positive impacts could reverse these trends. In finding solutions to soil sustainability and food security, we should be able to exploit biological processes to improve soil physical properties. This talk will focus on a quantitative understanding of how biology changes soil physical behaviour. Like the Great Dust Bowl, it starts with reinforcement mechanisms by plant roots. We found that binding of soil by cereal (barley) roots within 5 weeks of planting can more than double soil shear strength, with greater plant density causing greater reinforcement. With time, however, the relative impact of root reinforcement diminishes due to root turnover and aging of the seedbed. From mechanical tests of individual roots, reasonable predictions of reinforcement by tree roots are possible with fibre bundle models. With herbaceous plants like cereals, however, the same parameters (root strength, stiffness, size and distribution) result in a poor prediction. We found that root type, root age and abiotic factors such as compaction and waterlogging affect mechanical behaviour, further complicating the understanding and prediction of root reinforcement. For soil physical stability, the interface between root and soil is an extremely important zone in terms of resistance of roots to pull-out and rhizosphere formation. Compounds analogous to root exudates have been found with rheological tests to initially decrease the shear stress where wet soils flow, but after decomposition of these exudates by microbes the shear stress increases. This suggests an initial dispersion, followed by aggregation of the soil, which explains the structural arrangement of soil particles in the rhizosphere observed by microscopy. Dispersion of soil minerals in the root zone is important to release bound nutrients from mineral surfaces. Using fracture mechanics we measured large impacts of biological exudates on the toughness and interparticle bond energy of soils. Now novel tests are being developed to quantify interparticle bonding by biological exudates on single and multiple particle contacts, including mechanical test specimens that can be inoculated with specific bacteria or fungi. This will allow for clay mineralogy, water potential and solution chemistry impacts on interparticle bonding to be quantified directly. Wettability experiments with the same samples measure hydrological properties such as contact angle. Basic information from these tests will help explain biological processes that drive soil structure formation and stabilisation, providing data for models of soil structure dynamics.

Protein glycation, diabetes, and aging.

PubMed

Ulrich, P; Cerami, A

2001-01-01

Biological amines react with reducing sugars to form a complex family of rearranged and dehydrated covalent adducts that are often yellow-brown and/or fluorescent and include many cross-linked structures. Food chemists have long studied this process as a source of flavor, color, and texture changes in cooked, processed, and stored foods. During the 1970s and 1980s, it was realized that this process, called the Maillard reaction or advanced glycation, also occurs slowly in vivo. Advanced glycation endproducts (AGEs) that form are implicated, causing the complications of diabetes and aging, primarily via adventitious and crosslinking of proteins. Long-lived proteins such as structural collagen and lens crystallins particularly are implicated as pathogenic targets of AGE processes. AGE formation in vascular wall collagen appears to be an especially deleterious event, causing crosslinking of collagen molecules to each other and to circulating proteins. This leads to plaque formation, basement membrane thickening, and loss of vascular elasticity. The chemistry of these later-stage, glycation-derived crosslinks is still incompletely understood but, based on the hypothesis that AGE formation involves reactive carbonyl groups, the authors introduced the carbonyl reagent aminoguanidine hydrochloride as an inhibitor of AGE formation in vivo in the mid 1980s. Subsequent studies by many researchers have shown the effectiveness of aminoguanidine in slowing or preventing a wide range of complications of diabetes and aging in animals and, recently, in humans. Since, the authors have developed a new class of agents, exemplified by 4,5-dimethyl-3-phenacylthiazolium chloride (DPTC), which can chemically break already-formed AGE protein-protein crosslinks. These agents are based on a new theory of AGE crosslinking that postulates that alpha-dicarbonyl structures are present in AGE protein-protein crosslinks. In studies in aged animals, DPTC has been shown to be capable of reverting indices of vascular compliance to levels seen in younger animals. Human clinical trials are underway.

Foster Mother-Infant Bonding: Associations between Foster Mothers' Oxytocin Production, Electrophysiological Brain Activity, Feelings of Commitment, and Caregiving Quality

ERIC Educational Resources Information Center

Bick, Johanna; Dozier, Mary; Bernard, Kristin; Grasso, Damion; Simons, Robert

2013-01-01

This study examined the biological processes associated with foster mother-infant bonding. In an examination of foster mother-infant dyads ("N" = 41, mean infant age = 8.5 months), foster mothers' oxytocin production was associated with their expressions of behavioral delight toward their foster infant and their average P3 response to…

Molecular Age-Related Changes in the Anterior Segment of the Eye

PubMed Central

Gulias-Cañizo, Rosario; Martínez-Báez, Blanca Elizabeth; Quiroz-Mercado, Hugo

2017-01-01

Purpose To examine the current knowledge about the age-related processes in the anterior segment of the eye at a biological, clinical, and molecular level. Methods We reviewed the available published literature that addresses the aging process of the anterior segment of the eye and its associated molecular and physiological events. We performed a search on PubMed, CINAHL, and Embase using the MeSH terms “eye,” “anterior segment,” and “age.” We generated searches to account for synonyms of these keywords and MESH headings as follows: (1) “Eye” AND “ageing process” OR “anterior segment ageing” and (2) “Anterior segment” AND “ageing process” OR “anterior segment” AND “molecular changes” AND “age.” Results. Among the principal causes of age-dependent alterations in the anterior segment of the eye, we found the mutation of the TGF-β gene and loss of autophagy in addition to oxidative stress, which contributes to the pathogenesis of degenerative diseases. Conclusions In this review, we summarize the current knowledge regarding some of the molecular mechanisms related to aging in the anterior segment of the eye. We also introduce and propose potential roles of autophagy, an important mechanism responsible for maintaining homeostasis and proteostasis under stress conditions in the anterior segment during aging. PMID:29147580

Modality-specificity of sensory aging in vision and audition: evidence from event-related potentials.

PubMed

Ceponiene, R; Westerfield, M; Torki, M; Townsend, J

2008-06-18

Major accounts of aging implicate changes in processing external stimulus information. Little is known about differential effects of auditory and visual sensory aging, and the mechanisms of sensory aging are still poorly understood. Using event-related potentials (ERPs) elicited by unattended stimuli in younger (M=25.5 yrs) and older (M=71.3 yrs) subjects, this study examined mechanisms of sensory aging under minimized attention conditions. Auditory and visual modalities were examined to address modality-specificity vs. generality of sensory aging. Between-modality differences were robust. The earlier-latency responses (P1, N1) were unaffected in the auditory modality but were diminished in the visual modality. The auditory N2 and early visual N2 were diminished. Two similarities between the modalities were age-related enhancements in the late P2 range and positive behavior-early N2 correlation, the latter suggesting that N2 may reflect long-latency inhibition of irrelevant stimuli. Since there is no evidence for salient differences in neuro-biological aging between the two sensory regions, the observed between-modality differences are best explained by the differential reliance of auditory and visual systems on attention. Visual sensory processing relies on facilitation by visuo-spatial attention, withdrawal of which appears to be more disadvantageous in older populations. In contrast, auditory processing is equipped with powerful inhibitory capacities. However, when the whole auditory modality is unattended, thalamo-cortical gating deficits may not manifest in the elderly. In contrast, ERP indices of longer-latency, stimulus-level inhibitory modulation appear to diminish with age.

New tools for redox biology: From imaging to manipulation.

PubMed

Bilan, Dmitry S; Belousov, Vsevolod V

2017-08-01

Redox reactions play a key role in maintaining essential biological processes. Deviations in redox pathways result in the development of various pathologies at cellular and organismal levels. Until recently, studies on transformations in the intracellular redox state have been significantly hampered in living systems. The genetically encoded indicators, based on fluorescent proteins, have provided new opportunities in biomedical research. The existing indicators already enable monitoring of cellular redox parameters in different processes including embryogenesis, aging, inflammation, tissue regeneration, and pathogenesis of various diseases. In this review, we summarize information about all genetically encoded redox indicators developed to date. We provide the description of each indicator and discuss its advantages and limitations, as well as points that need to be considered when choosing an indicator for a particular experiment. One chapter is devoted to the important discoveries that have been made by using genetically encoded redox indicators. Copyright © 2016 Elsevier Inc. All rights reserved.

Examining the sex difference in lateralisation for processing facial emotion: does biological sex or psychological gender identity matter?

PubMed

Bourne, Victoria J; Maxwell, Adele M

2010-04-01

The research examining sex differences in functional lateralisation has shown varying results. While some provide evidence for males being more strongly lateralised than females, a number have shown either no relationship or the opposite pattern of findings. In this study we consider whether psychological gender identity might clarify some of the conflicting results in this area of research. Eight five participants (39 males) aged from 18 to 49 years old were tested. We found that psychological masculinity was associated with stronger patterns of lateralisation for the processing of a range of emotional expressions. We also found an interaction between biological sex and psychological gender identity, with a positive relationship between psychological masculinity and lateralisation found for males, but a negative relationship found for females. The possible role of hormonal exposure in this relationship is discussed. (c) 2010 Elsevier Ltd. All rights reserved.

Beyond the PhD: Putting the Right Tools in Your Research Toolbox

PubMed Central

Downs, Charles A.; Morrison, Helena W.

2013-01-01

Postdoctoral training is vital to a successful career for nurse researchers with a biological or biobehavioral focus. Such training provides structured time to devote to gaining substantive knowledge, expanding one’s biological-methods repertoire, and writing grants. However, for unknown reasons, relatively few nurses pursue postdoctoral training. A few plausible explanations include a near critical shortage of nursing faculty coupled with an aging population in need of health care, a lack of available mentoring for predoctoral students to pursue postdoctoral training, and the difficulty of navigating the process of finding and choosing the right match for a postdoctoral experience. The purposes of this article are to provide a rationale for choosing postdoctoral training, review common fellowship opportunities, and discuss the process of finding and choosing the right match for postdoctoral training. The authors provide two prospective plans for postdoctoral training and include a plan for staying on track during the postdoctoral experience. PMID:20026452

PARPs and ADP-Ribosylation: 50 Years … and Counting.

PubMed

Kraus, W Lee

2015-06-18

Over 50 years ago, the discovery of poly(ADP-ribose) (PAR) set a new field of science in motion-the field of poly(ADP-ribosyl) transferases (PARPs) and ADP-ribosylation. The field is still flourishing today. The diversity of biological processes now known to require PARPs and ADP-ribosylation was practically unimaginable even two decades ago. From an initial focus on DNA damage detection and repair in response to genotoxic stresses, the field has expanded to include the regulation of chromatin structure, gene expression, and RNA processing in a wide range of biological systems, including reproduction, development, aging, stem cells, inflammation, metabolism, and cancer. This special focus issue of Molecular Cell includes a collection of three Reviews, three Perspectives, and a SnapShot, which together summarize the current state of the field and suggest where it may be headed. Copyright © 2015 Elsevier Inc. All rights reserved.

Beyond the PhD: putting the right tools in your research toolbox.

PubMed

Downs, Charles A; Morrison, Helena W

2011-01-01

Postdoctoral training is vital to a successful career for nurse researchers with a biological or biobehavioral focus. Such training provides structured time to devote to gaining substantive knowledge, expanding one's biological-methods repertoire, and writing grants. However, for unknown reasons, relatively few nurses pursue postdoctoral training. A few plausible explanations include a near critical shortage of nursing faculty coupled with an aging population in need of health care, a lack of available mentoring for predoctoral students to pursue postdoctoral training, and the difficulty of navigating the process of finding and choosing the right match for a postdoctoral experience. The purposes of this article are to provide a rationale for choosing postdoctoral training, review common fellowship opportunities, and discuss the process of finding and choosing the right match for postdoctoral training. The authors provide two prospective plans for postdoctoral training and include a plan for staying on track during the postdoctoral experience.

AGEs, RAGEs and s-RAGE; friend or foe for cancer.

PubMed

Ahmad, Saheem; Khan, Hamda; Siddiqui, Zeba; Khan, Mohd Yasir; Rehman, Shahnawaz; Shahab, Uzma; Godovikova, Tatyana; Silnikov, Vladimir; Moinuddin

2018-04-01

Impaired awareness of glycation biology in cancer initiation and progression is one of the fundamental reasons for its meticulous investigation of the molecules involved in signalling pathway. Glycation of biological macromolecules results in the progression of advanced glycation end-products (AGEs) that proliferates the process of carcinogenesis by activation of transcription factors and release of cytokines. The receptor for advanced glycation end-products (RAGEs) with the binding of its different ligands like; AGEs, HMGB1 and S100 activate the signalling arrays. The activation of downstream signalling pathway ultimately leads to the pathophysiological conditions of diabetes, ageing, neurological disorders and cancers as well as a result of the activation of transcription factors which is discussed in the main body text of this review. However, there might be a likelihood of the positive effect of the HMGB1 and S100 proteins in cancer. Still, some untouched mechanisms might be responsible for the establishment of the function of AGE-RAGE or AGE-sRAGE axis activation that leads to the friend-foe association with the cancers. The levels of RAGE and s-RAGE may be a useful biomarker of ligand-RAGE pathway activation and cancer. Thus, the possibility of providing a potential complement to carcinogenesis is very high which might be an interesting target for therapeutic interventions. This article is an insightful assessment on AGE, RAGE and s-RAGE for its possible role in cancer onset and progression. The novel therapeutic targets for cancer prevention or inhibition are also explained in brief in relation to AGE and RAGE. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mirror me: Imitative responses in adults with autism.

PubMed

Schunke, Odette; Schöttle, Daniel; Vettorazzi, Eik; Brandt, Valerie; Kahl, Ursula; Bäumer, Tobias; Ganos, Christos; David, Nicole; Peiker, Ina; Engel, Andreas K; Brass, Marcel; Münchau, Alexander

2016-02-01

Dysfunctions of the human mirror neuron system have been postulated to underlie some deficits in autism spectrum disorders including poor imitative performance and impaired social skills. Using three reaction time experiments addressing mirror neuron system functions under simple and complex conditions, we examined 20 adult autism spectrum disorder participants and 20 healthy controls matched for age, gender and education. Participants performed simple finger-lifting movements in response to (1) biological finger and non-biological dot movement stimuli, (2) acoustic stimuli and (3) combined visual-acoustic stimuli with different contextual (compatible/incompatible) and temporal (simultaneous/asynchronous) relation. Mixed model analyses revealed slower reaction times in autism spectrum disorder. Both groups responded faster to biological compared to non-biological stimuli (Experiment 1) implying intact processing advantage for biological stimuli in autism spectrum disorder. In Experiment 3, both groups had similar 'interference effects' when stimuli were presented simultaneously. However, autism spectrum disorder participants had abnormally slow responses particularly when incompatible stimuli were presented consecutively. Our results suggest imitative control deficits rather than global imitative system impairments. © The Author(s) 2015.

Association of Aging-Related Endophenotypes With Mortality in 2 Cohort Studies: the Long Life Family Study and the Health, Aging and Body Composition Study.

PubMed

Singh, Jatinder; Schupf, Nicole; Boudreau, Robert; Matteini, Amy M; Prasad, Tanushree; Newman, Anne B; Liu, YongMei; Christensen, Kaare; Kammerer, Candace M

2015-12-01

One method by which to identify fundamental biological processes that may contribute to age-related disease and disability, instead of disease-specific processes, is to construct endophenotypes comprising linear combinations of physiological measures. Applying factor analyses methods to phenotypic data (2006-2009) on 28 traits representing 5 domains (cognitive, cardiovascular, metabolic, physical, and pulmonary) from 4,472 US and Danish individuals in 574 pedigrees from the Long Life Family Study (United States and Denmark), we constructed endophenotypes and assessed their relationship with mortality. The most dominant endophenotype primarily reflected the physical activity and pulmonary domains, was heritable, was significantly associated with mortality, and attenuated the association of age with mortality by 24.1%. Using data (1997-1998) on 1,794 Health, Aging and Body Composition Study participants from Memphis, Tennessee, and Pittsburgh, Pennsylvania, we obtained strikingly similar endophenotypes and relationships to mortality. We also reproduced the endophenotype constructs, especially the dominant physical activity and pulmonary endophenotype, within demographic subpopulations of these 2 cohorts. Thus, this endophenotype construct may represent an underlying phenotype related to aging. Additional genetic studies of this endophenotype may help identify genetic variants or networks that contribute to the aging process. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Telomere length is a biomarker of cumulative oxidative stress, biologic age, and an independent predictor of survival and therapeutic treatment requirement associated with smoking behavior.

PubMed

Babizhayev, Mark A; Savel'yeva, Ekaterina L; Moskvina, Svetlana N; Yegorov, Yegor E

2011-11-01

Globally, tobacco use is associated with 5 million deaths per annum and is regarded as one of the leading causes of premature death. Major chronic disorders associated with smoking include cardiovascular diseases, several types of cancer, and chronic obstructive pulmonary disease (lung problems). Cigarette smoking (CS) generates a cumulative oxidative stress, which may contribute to the pathogenesis of chronic diseases. Mainstream and side stream gas-phase smoke each have about the same concentration of reactive free radical species, about 1 × 10(16) radicals per cigarette (or 5 × 10(14) per puff). This effect is critical in understanding the biologic effects of smoke. Several lines of evidence suggest that cigarette smoke constituents can directly activate vascular reactive oxygen species production. In this work we present multiple evidence that CS provide the important risk factors in many age-related diseases, and is associated with increased cumulative and systemic oxidative stress and inflammation. The cited processes are marked by increased white blood cell (leucocytes, WBCs) turnover. The data suggest an alteration of the circulating WBCs by CS, resulting in increased adherence to endothelial cells. Telomeres are complex DNA-protein structures located at the end of eukaryotic chromosomes. Telomere length shortens with biologic age in all replicating somatic cells. It has been shown that tobacco smoking enhances telomere shortening in circulating human WBCs. Telomere attrition (expressed in WBCs) can serve as a biomarker of the cumulative oxidative stress and inflammation induced by smoking and, consequently, show the pace of biologic aging. We originally propose that patented specific oral formulations of nonhydrolized carnosine and carcinine provide a powerful tool for targeted therapeutic inhibition of cumulative oxidative stress and inflammation and protection of telomere attrition associated with smoking. The longitudinal studies of the clinical population groups described in this study including elderly support the hypothesis that telomere length is a predictor of survival and therapeutic treatment requirement associated with smoking behavior.

Before the long journey: Development of Soviet space biology and medicine

NASA Technical Reports Server (NTRS)

Gazenko, O. G.

1978-01-01

Academician O. Gazenko, Chief of the Institute of Biomedical Problems, USSR Ministry of Public Health, reviewed the short but intense history of Soviet research in space biology and medicine. The solid academic approach of the Soviet Academy of Sciences in giving a good start at the very beginning of the space age is stressed and key people and institutions who initiated these studies are named. The basic feature of the first period of space biology is seen as the search for answers to a few fundamental questions of survival in space. It is pointed out that the initiated investigations were replaced by refined, in-depth studies of the biological, biophysical, and biochemical processes in human organism in the space environment and the search for methods which should enable cosmonaut crews to live in space for several years during interplanetary journeys. Discussing the typical problems of this effort, Gazenko each time showed how they benefit medical science and practice in general.

Biological and Organic Chemical Decomposition of Silicates. Chapter 7.2

NASA Technical Reports Server (NTRS)

Silverman, M. P.

1979-01-01

The weathering of silicate rocks and minerals, an important concern of geologists and geochemists for many years, traditionally has been approached from strictly physical and chemical points of view. Biological effects were either unrecognized, ignored, or were mentioned in passing to account for such phenomena as the accumulation of organic matter in sediments or the generation of reducing environments. A major exception occurred in soil science where agricultural scientists, studying the factors important in the development of soils and their ability to nourish and sustain various crops, laid the foundation for much of what is known of the biological breakdown of silicate rocks and minerals. The advent of the space age accelerated the realization that many environmental problems and geo- chemical processes on Earth can only be understood in terms of ecosystems. This in turn, spurred renewed interest and activity among modem biologists, geologists and soil scientists attempting to unravel the intimate relations between biology and the weathering of silicate rocks and minerals of the earth surface.

Biological and Organic Chemical Decomposition of Silicates. Chapter 7.2

NASA Technical Reports Server (NTRS)

Sliverman, M. P.

1979-01-01

The weathering of silicate rocks and minerals, an important concern of geologists and geochemists for many years, traditionally has been approached from strictly physical and chemical points of view. Biological effects were either unrecognized, ignored, or were mentioned in passing to account for such phenomena as the accumulation of organic matter in sediments or the generation of reducing environments. A major exception occurred in soil science where agricultural scientists, studying the factors important in the development of soils and their ability to nourish and sustain various crops, laid the foundation for much of what is known of the biological breakdown of silicate rocks and minerals. The advent of the space age accelerated the realization that many environmental problems and geochemical processes on Earth can only be understood in terms of ecosystems. This in turn, spurred renewed interest and activity among modem biologists, geologists and soil scientists attempting to unravel the intimate relations between biology and the weathering of silicate rocks and minerals of the earth's surface.

Relationship of senescence of pulmonary system to chronic obstructive pulmonary disease in the advanced life.

PubMed

Donma, O; Donma, M M

2002-08-01

Chronic obstructive pulmonary disease (COPD) is a major worldwide health problem. There exists a relationship between COPD and increased oxidative stress, and oxidants may be involved in lung damage during the course of COPD. Polymorphonuclear (PMN) cell recruitment at lung level plays an important role in free radical overproduction, impact inflammatory processes and may alter oxidant-antioxidant balance. Biological aging is thought to be influenced by free radical generation, aging, and the diseases. All the components of the respiratory system are affected by aging. Nutrition, smoking habits and sleep-related disorders also affect the respiratory system. Whether these changes are due to aging or associated with aging is a matter of debate. Since alterations caused by aging and cigarette smoke in lungs of various species were informed to be partly simulated with age-related alterations in human lung, the effects of oxidative agents and antioxidative parameters on both COPD and aging were evaluated.

Telomere biology in aging and cancer: early history and perspectives.

PubMed

Hayashi, Makoto T

2018-01-20

The ends of eukaryotic linear chromosomes are protected from undesired enzymatic activities by a nucleoprotein complex called the telomere. Expanding evidence indicates that telomeres have central functions in human aging and tumorigenesis. While it is undoubtedly important to follow current advances in telomere biology, it is also fruitful to be well informed in seminal historical studies for a comprehensive understanding of telomere biology, and for the anticipation of future directions. With this in mind, I here summarize the early history of telomere biology and current advances in the field, mostly focusing on mammalian studies relevant to aging and cancer.

The oxidative hypothesis of senescence.

PubMed

Gilca, M; Stoian, I; Atanasiu, V; Virgolici, B

2007-01-01

The oxidative hypothesis of senescence, since its origin in 1956, has garnered significant evidence and growing support among scientists for the notion that free radicals play an important role in ageing, either as "damaging" molecules or as signaling molecules. Age-increasing oxidative injuries induced by free radicals, higher susceptibility to oxidative stress in short-lived organisms, genetic manipulations that alter both oxidative resistance and longevity and the anti-ageing effect of caloric restriction and intermittent fasting are a few examples of accepted scientific facts that support the oxidative theory of senescence. Though not completely understood due to the complex "network" of redox regulatory systems, the implication of oxidative stress in the ageing process is now well documented. Moreover, it is compatible with other current ageing theories (e.g, those implicating the mitochondrial damage/mitochondrial-lysosomal axis, stress-induced premature senescence, biological "garbage" accumulation, etc). This review is intended to summarize and critically discuss the redox mechanisms involved during the ageing process: sources of oxidant agents in ageing (mitochondrial -electron transport chain, nitric oxide synthase reaction- and non-mitochondrial- Fenton reaction, microsomal cytochrome P450 enzymes, peroxisomal beta -oxidation and respiratory burst of phagocytic cells), antioxidant changes in ageing (enzymatic- superoxide dismutase, glutathione-reductase, glutathion peroxidase, catalase- and non-enzymatic glutathione, ascorbate, urate, bilirubine, melatonin, tocopherols, carotenoids, ubiquinol), alteration of oxidative damage repairing mechanisms and the role of free radicals as signaling molecules in ageing.

Contributions of Nonhuman Primates to Research on Aging

PubMed Central

Didier, E. S.; MacLean, A. G.; Mohan, M.; Didier, P. J.; Lackner, A. A.; Kuroda, M. J.

2016-01-01

Aging is the biological process of declining physiologic function associated with increasing mortality rate during advancing age. Humans and higher nonhuman primates exhibit unusually longer average life spans as compared with mammals of similar body mass. Furthermore, the population of humans worldwide is growing older as a result of improvements in public health, social services, and health care systems. Comparative studies among a wide range of organisms that include nonhuman primates contribute greatly to our understanding about the basic mechanisms of aging. Based on their genetic and physiologic relatedness to humans, nonhuman primates are especially important for better understanding processes of aging unique to primates, as well as for testing intervention strategies to improve healthy aging and to treat diseases and disabilities in older people. Rhesus and cynomolgus macaques are the predominant monkeys used in studies on aging, but research with lower nonhuman primate species is increasing. One of the priority topics of research about aging in nonhuman primates involves neurologic changes associated with cognitive decline and neurodegenerative diseases. Additional areas of research include osteoporosis, reproductive decline, caloric restriction, and their mimetics, as well as immune senescence and chronic inflammation that affect vaccine efficacy and resistance to infections and cancer. The purpose of this review is to highlight the findings from nonhuman primate research that contribute to our understanding about aging and health span in humans. PMID:26869153

Contributions of Nonhuman Primates to Research on Aging.

PubMed

Didier, E S; MacLean, A G; Mohan, M; Didier, P J; Lackner, A A; Kuroda, M J

2016-03-01

Aging is the biological process of declining physiologic function associated with increasing mortality rate during advancing age. Humans and higher nonhuman primates exhibit unusually longer average life spans as compared with mammals of similar body mass. Furthermore, the population of humans worldwide is growing older as a result of improvements in public health, social services, and health care systems. Comparative studies among a wide range of organisms that include nonhuman primates contribute greatly to our understanding about the basic mechanisms of aging. Based on their genetic and physiologic relatedness to humans, nonhuman primates are especially important for better understanding processes of aging unique to primates, as well as for testing intervention strategies to improve healthy aging and to treat diseases and disabilities in older people. Rhesus and cynomolgus macaques are the predominant monkeys used in studies on aging, but research with lower nonhuman primate species is increasing. One of the priority topics of research about aging in nonhuman primates involves neurologic changes associated with cognitive decline and neurodegenerative diseases. Additional areas of research include osteoporosis, reproductive decline, caloric restriction, and their mimetics, as well as immune senescence and chronic inflammation that affect vaccine efficacy and resistance to infections and cancer. The purpose of this review is to highlight the findings from nonhuman primate research that contribute to our understanding about aging and health span in humans. © The Author(s) 2016.

Hepatocyte polyploidization and its association with pathophysiological processes.

PubMed

Wang, Min-Jun; Chen, Fei; Lau, Joseph T Y; Hu, Yi-Ping

2017-05-18

A characteristic cellular feature of the mammalian liver is the progressive polyploidization of the hepatocytes, where individual cells acquire more than two sets of chromosomes. Polyploidization results from cytokinesis failure that takes place progressively during the course of postnatal development. The proportion of polyploidy also increases with the aging process or with cellular stress such as surgical resection, toxic stimulation, metabolic overload, or oxidative damage, to involve as much as 90% of the hepatocytes in mice and 40% in humans. Hepatocyte polyploidization is generally considered an indicator of terminal differentiation and cellular senescence, and related to the dysfunction of insulin and p53/p21 signaling pathways. Interestingly, the high prevalence of hepatocyte polyploidization in the aged mouse liver can be reversed when the senescent hepatocytes are serially transplanted into young mouse livers. Here we review the current knowledge on the mechanism of hepatocytes polyploidization during postnatal growth, aging, and liver diseases. The biologic significance of polyploidization in senescent reversal, within the context of new ways to think of liver aging and liver diseases is considered.

Hepatocyte polyploidization and its association with pathophysiological processes

PubMed Central

Wang, Min-Jun; Chen, Fei; Lau, Joseph T Y; Hu, Yi-Ping

2017-01-01

A characteristic cellular feature of the mammalian liver is the progressive polyploidization of the hepatocytes, where individual cells acquire more than two sets of chromosomes. Polyploidization results from cytokinesis failure that takes place progressively during the course of postnatal development. The proportion of polyploidy also increases with the aging process or with cellular stress such as surgical resection, toxic stimulation, metabolic overload, or oxidative damage, to involve as much as 90% of the hepatocytes in mice and 40% in humans. Hepatocyte polyploidization is generally considered an indicator of terminal differentiation and cellular senescence, and related to the dysfunction of insulin and p53/p21 signaling pathways. Interestingly, the high prevalence of hepatocyte polyploidization in the aged mouse liver can be reversed when the senescent hepatocytes are serially transplanted into young mouse livers. Here we review the current knowledge on the mechanism of hepatocytes polyploidization during postnatal growth, aging, and liver diseases. The biologic significance of polyploidization in senescent reversal, within the context of new ways to think of liver aging and liver diseases is considered. PMID:28518148

Efficacy of a composite biological age score to predict ten-year survival among Kansas and Nebraska Mennonites.

PubMed

Uttley, M; Crawford, M H

1994-02-01

In 1980 and 1981 Mennonite descendants of a group of Russian immigrants participated in a multidisciplinary study of biological aging. The Mennonites live in Goessel, Kansas, and Henderson, Nebraska. In 1991 the survival status of the participants was documented by each church secretary. Data are available for 1009 individuals, 177 of whom are now deceased. They ranged from 20 to 95 years in age when the data were collected. Biological ages were computed using a stepwise multiple regression procedure based on 38 variables previously identified as being related to survival, with chronological age as the dependent variable. Standardized residuals place participants in either a predicted-younger or a predicted-older group. The independence of the variables biological age and survival status is tested with the chi-square statistic. The significance of biological age differences between surviving and deceased Mennonites is determined by t test values. The two statistics provide consistent results. Predicted age group classification and survival status are related. The group of deceased participants is generally predicted to be older than the group of surviving participants, although neither statistic is significant for all subgroups of Mennonites. In most cases, however, individuals in the predicted-older groups are at a relatively higher risk of dying compared with those in the predicted-younger groups, although the increased risk is not always significant.

Physical Activity-Related Injury Profile in Children and Adolescents According to Their Age, Maturation, and Level of Sports Participation.

PubMed

Costa E Silva, Lara; Fragoso, Maria Isabel; Teles, Júlia

Physical activity (PA) is beneficial, enhancing healthy development. However, one-third of school-age children practicing sports regularly suffer from an injury. These injuries are associated with sex, chronological age, and PA level. To identify the importance of age, PA level, and maturity as predictors of injury in Portuguese youth. Descriptive epidemiological study. Level 3. Information about injury and PA level was assessed via 2 questionnaires (LESADO RAPIL II) from 647 subjects aged 10 to 17 years. Maturity offset according to Mirwald (time before or after peak height velocity) and Tanner-Whitehouse III bone age estimates were used to evaluate maturation. Binary logistic regression and gamma regression were used to determine significant predictors of injury and injury rate. Injury occurrence was higher for both sexes in recreational, school, and federated athletes (athletes engaged in sports that are regulated by their respective federations, with formal competition). These injuries also increased with age in boys and in the higher maturity offset group in girls. Injury rate was higher for both sexes in the no sports participation group. Early-maturing girls, with higher bone age and lower maturity offset, showed higher injury rate. Injuries in Portuguese youth were related to PA level, age, and biological maturation. Recreational, school, and federated athletes had more injury ocurrences while subjects with no sports participation had higher injury risk. Older subjects had more injuries. Early-maturing girls that had just passed peak height velocity may be particularly vulnerable to risk of sports injury because of the growing process. Increased knowledge about injury with specific PA exposure data is important to an overall risk management strategy. This study has deepened the association between injury and biological maturation variables.

An Autistic Endophenotype and Testosterone Are Involved in an Atypical Decline in Selective Attention and Visuospatial Processing in Middle-Aged Women.

PubMed

Ángel, Romero-Martínez; Luis, Moya-Albiol

2015-12-15

Mothers of offspring with autism spectrum disorders (ASD) could present mild forms of their children's cognitive characteristics, resulting from prenatal brain exposure and sensitivity to testosterone (T). Indeed, their cognition is frequently characterized by hyper-systemizing, outperforming in tests that assess cognitive domains such as selective attention, and fine motor and visuospatial skills. In the general population, all these start to decline around the mid-forties. This study aimed to characterize whether middle-aged women who are biological mothers of individuals with ASD had better performance in the aforementioned cognitive skills than mothers of normative children (in both groups n = 22; mean age = 45), using the standardized Stroop and mirror-drawing tests. We also examined the role of T in their performance in the aforementioned tests. ASD mothers outperformed controls in both tests, giving more correct answers and making fewer mistakes. In addition, they presented higher T levels, which have been associated with better cognitive performance. Cognitive decline in specific skills with aging could be delayed in these middle-aged women, corresponding to a cognitive endophenotype, T playing an important role in this process.

Age-related shifts in hemispheric dominance for syntactic processing.

PubMed

Leckey, Michelle; Federmeier, Kara D

2017-12-01

Recent ERP data from young adults have revealed that simple syntactic anomalies elicit different patterns of lateralization in right-handed participants depending upon their familial sinistrality profile (whether or not they have left-handed biological relatives). Right-handed participants who do not have left-handed relatives showed a strongly lateralized response pattern, with P600 responses following left-hemisphere-biased presentations and N400 responses following right-hemisphere-biased presentations. Given that the literature on aging has documented a tendency to change across adulthood from asymmetry of function to a more bilateral pattern, we tested the stability of this asymmetric response to syntactic violations by recording ERPs as 24 older adults (age 60+) with no history of familial sinistrality made grammaticality judgments on simple two-word phrases. Results showed that the asymmetric pattern observed in right-handed adults without familial sinistrality indeed changes with age, such that P600 responses come to be elicited not only with left-hemisphere-biased but also with right-hemisphere-biased presentations in older adults. These findings suggest that, as with many other cognitive functions, syntactic processing becomes more bilateral with age. © 2017 Society for Psychophysiological Research.

The glia doctrine: addressing the role of glial cells in healthy brain ageing.

PubMed

Nagelhus, Erlend A; Amiry-Moghaddam, Mahmood; Bergersen, Linda H; Bjaalie, Jan G; Eriksson, Jens; Gundersen, Vidar; Leergaard, Trygve B; Morth, J Preben; Storm-Mathisen, Jon; Torp, Reidun; Walhovd, Kristine B; Tønjum, Tone

2013-10-01

Glial cells in their plurality pervade the human brain and impact on brain structure and function. A principal component of the emerging glial doctrine is the hypothesis that astrocytes, the most abundant type of glial cells, trigger major molecular processes leading to brain ageing. Astrocyte biology has been examined using molecular, biochemical and structural methods, as well as 3D brain imaging in live animals and humans. Exosomes are extracelluar membrane vesicles that facilitate communication between glia, and have significant potential for biomarker discovery and drug delivery. Polymorphisms in DNA repair genes may indirectly influence the structure and function of membrane proteins expressed in glial cells and predispose specific cell subgroups to degeneration. Physical exercise may reduce or retard age-related brain deterioration by a mechanism involving neuro-glial processes. It is most likely that additional information about the distribution, structure and function of glial cells will yield novel insight into human brain ageing. Systematic studies of glia and their functions are expected to eventually lead to earlier detection of ageing-related brain dysfunction and to interventions that could delay, reduce or prevent brain dysfunction. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

An Autistic Endophenotype and Testosterone Are Involved in an Atypical Decline in Selective Attention and Visuospatial Processing in Middle-Aged Women

PubMed Central

Ángel, Romero-Martínez; Luis, Moya-Albiol

2015-01-01

Mothers of offspring with autism spectrum disorders (ASD) could present mild forms of their children’s cognitive characteristics, resulting from prenatal brain exposure and sensitivity to testosterone (T). Indeed, their cognition is frequently characterized by hyper-systemizing, outperforming in tests that assess cognitive domains such as selective attention, and fine motor and visuospatial skills. In the general population, all these start to decline around the mid-forties. This study aimed to characterize whether middle-aged women who are biological mothers of individuals with ASD had better performance in the aforementioned cognitive skills than mothers of normative children (in both groups n = 22; mean age = 45), using the standardized Stroop and mirror-drawing tests. We also examined the role of T in their performance in the aforementioned tests. ASD mothers outperformed controls in both tests, giving more correct answers and making fewer mistakes. In addition, they presented higher T levels, which have been associated with better cognitive performance. Cognitive decline in specific skills with aging could be delayed in these middle-aged women, corresponding to a cognitive endophenotype, T playing an important role in this process. PMID:26694433

Serum profiling of healthy aging identifies phospho- and sphingolipid species as markers of human longevity.

PubMed

Montoliu, Ivan; Scherer, Max; Beguelin, Fiona; DaSilva, Laeticia; Mari, Daniela; Salvioli, Stefano; Martin, Francois-Pierre J; Capri, Miriam; Bucci, Laura; Ostan, Rita; Garagnani, Paolo; Monti, Daniela; Biagi, Elena; Brigidi, Patrizia; Kussmann, Martin; Rezzi, Serge; Franceschi, Claudio; Collino, Sebastiano

2014-01-01

As centenarians well represent the model of healthy aging, there are many important implications in revealing the underlying molecular mechanisms behind such successful aging. By combining NMR metabonomics and shot-gun lipidomics in serum we analyzed metabolome and lipidome composition of a group of centenarians with respect to elderly individuals. Specifically, NMR metabonomics profiling of serum revealed that centenarians are characterized by a metabolic phenotype distinct from that of elderly subjects, in particular regarding amino acids and lipid species. Shot- gun lipidomics approach displays unique changes in lipids biosynthesis in centenarians, with 41 differently abundant lipid species with respect to elderly subjects. These findings reveal phospho/sphingolipids as putative markers and biological modulators of healthy aging, in humans. Considering the particular actions of these metabolites, these data are suggestive of a better counteractive antioxidant capacity and a well-developed membrane lipid remodelling process in the healthy aging phenotype.

Too old to have children? Lessons from natural fertility populations.

PubMed

Eijkemans, Marinus J C; van Poppel, Frans; Habbema, Dik F; Smith, Ken R; Leridon, Henri; te Velde, Egbert R

2014-06-01

Is it possible to construct an age curve denoting the ages above which women are biologically too old to reproduce? We constructed a curve based on the distribution of female age at last birth in natural fertility populations reflecting the ages above which women have become biologically too old to have children. The median age at last birth (ALB) for females is ∼40-41 years of age across a range of natural fertility populations. This suggests that there is a fairly universal pattern of age-related fertility decline. However, little is known about the distribution of female ALB and in the present era of modern birth control, it is impossible to assess the age-specific distribution of ALB. Reliable information is lacking that could benefit couples who envisage delaying childbearing. This study is a review of high-quality historical data sets of natural fertility populations in which the distributions of female age at last birth were analysed. The studies selected used a retrospective cohort design where women were followed as they age through their reproductive years. Using a common set of eligibility criteria, large data files of natural fertility populations were prepared such that the analysis could be performed in parallel across all populations. Data on the ALB and confounding variables are presented as box and whisker plots denoting the 5th, 25th, 50th, 75th and 95th percentile distribution of the age at last birth for each population. The analysis includes the estimation of Kaplan-Meier curves for age at last birth of each population. The hazard curve for ALB was obtained by plotting the smoothed hazard curve of each population and taking the lowest hazard within a time period of at least 5 years. This lowest hazard curve was then transformed into a cumulative distribution function representing the composite curve of the end of biological fertility. This curve was based on the data from three of the six populations, having the lowest hazards of end of fertility. We selected six natural fertility populations comprising 58 051 eligible women. While these populations represent different historical time periods, the distribution of the ages at last birth is remarkably similar. The curve denoting the end of fertility indicates that <3% of women had their last birth at age 20 years meaning that almost 98% were able to have at least one child thereafter. The cumulative curve for the end of fertility slowly increases from 4.5% at age 25 years, 7% at age 30 years, 12% at age 35 years and 20% at age 38 years. Thereafter, it rises rapidly to about 50% at age 41, almost 90% at age 45 years and approaching 100% at age 50 years. It may be argued that these historical fertility data do not apply to the present time; however, the age-dependent decline in fertility is similar to current populations and is consistent with the pattern seen in women treated by donor insemination. Furthermore, for reproductive ageing, we note that it is unlikely that such a conserved biological process with a high degree of heritability would have changed significantly within a century or two. We argue that the age-specific ALB curve can be used to counsel couples who envisage having children in the future. Our findings challenge the unsubstantiated pessimism regarding the possibility of natural conception after age 35 years. No external funding was either sought or obtained for this study. There are no conflicts of interest to be declared.

Proteins involved in flor yeast carbon metabolism under biofilm formation conditions.

PubMed

Moreno-García, Jaime; García-Martínez, Teresa; Moreno, Juan; Mauricio, Juan Carlos

2015-04-01

A lack of sugars during the production of biologically aged wines after fermentation of grape must causes flor yeasts to metabolize other carbon molecules formed during fermentation (ethanol and glycerol, mainly). In this work, a proteome analysis involving OFFGEL fractionation prior to LC/MS detection was used to elucidate the carbon metabolism of a flor yeast strain under biofilm formation conditions (BFC). The results were compared with those obtained under non-biofilm formation conditions (NBFC). Proteins associated to processes such as non-fermentable carbon uptake, the glyoxylate and TCA cycles, cellular respiration and inositol metabolism were detected at higher concentrations under BFC than under the reference conditions (NBFC). This study constitutes the first attempt at identifying the flor yeast proteins responsible for the peculiar sensory profile of biologically aged wines. A better metabolic knowledge of flor yeasts might facilitate the development of effective strategies for improved production of these special wines. Copyright © 2014 Elsevier Ltd. All rights reserved.

Role of macrophage migration inhibitory factor in age-related lung disease

PubMed Central

Sauler, Maor; Bucala, Richard

2015-01-01

The prevalence of many common respiratory disorders, including pneumonia, chronic obstructive lung disease, pulmonary fibrosis, and lung cancer, increases with age. Little is known of the host factors that may predispose individuals to such diseases. Macrophage migration inhibitory factor (MIF) is a potent upstream regulator of the immune system. MIF is encoded by variant alleles that occur commonly in the population. In addition to its role as a proinflammatory cytokine, a growing body of literature demonstrates that MIF influences diverse molecular processes important for the maintenance of cellular homeostasis and may influence the incidence or clinical manifestations of a variety of chronic lung diseases. This review highlights the biological properties of MIF and its implication in age-related lung disease. PMID:25957294

A flame burning within.

PubMed

Ferrucci, Luigi; Ble, Alessandro; Bandinelli, Stefania; Lauretani, Fulvio; Suthers, Kristen; Guralnik, Jack M

2004-06-01

Inflammation is a human being's primary defense against threats to homeostasis that are encountered every day. Especially in old age, when regulatory mechanisms responsible for inflammatory responses may be ineffective or damaged, the result can be adverse pathological conditions, and an increased risk of morbidity and mortality. The inflammation response is a plastic network composed of redundant signaling among several different mediators. These mediators have a reciprocal relationship with other biological sub-systems, including hormone regulation, the autonomic nervous system, and oxidative/anti-oxidant balance. Studying this complex architecture requires parallel and multiple research strategies from epidemiological to biochemical level, from observational studies to innovative intervention approaches. Given that the inflammatory response is a critical age-related process, understanding its regulatory action is essential in avoiding hazardous consequences in old age.

Oxidative stress and protein aggregation during biological aging.

PubMed

Squier, T C

2001-09-01

Biological aging is a fundamental process that represents the major risk factor with respect to the development of cancer, neurodegenerative, and cardiovascular diseases in vertebrates. It is, therefore, evident that the molecular mechanisms of aging are fundamental to understand many disease processes. In this regard, the oxidation and nitration of intracellular proteins and the formation of protein aggregates have been suggested to underlie the loss of cellular function and the reduced ability of senescent animals to withstand physiological stresses. Since oxidatively modified proteins are thermodynamically unstable and assume partially unfolded tertiary structures that readily form aggregates, it is likely that oxidized proteins are intermediates in the formation of amyloid fibrils. It is, therefore, of interest to identify oxidatively sensitive protein targets that may play a protective role through their ability to down-regulate energy metabolism and the consequent generation of reactive oxygen species (ROS). In this respect, the maintenance of cellular calcium gradients represents a major energetic expense, which links alterations in intracellular calcium levels to ATP utilization and the associated generation of ROS through respiratory control mechanisms. The selective oxidation or nitration of the calcium regulatory proteins calmodulin and Ca-ATPase that occurs in vivo during aging and under conditions of oxidative stress may represent an adaptive response to oxidative stress that functions to down-regulate energy metabolism and the associated generation of ROS. Since these calcium regulatory proteins are also preferentially oxidized or nitrated under in vitro conditions, these results suggest an enhanced sensitivity of these critical calcium regulatory proteins, which modulate signal transduction processes and intracellular energy metabolism, to conditions of oxidative stress. Thus, the selective oxidation of critical signal transduction proteins probably represents a regulatory mechanism that functions to minimize the generation of ROS through respiratory control mechanisms. The reduction of the rate of ROS generation, in turn, will promote cellular survival under conditions of oxidative stress, when reactive oxygen and nitrogen species overwhelm cellular antioxidant defense systems, by minimizing the non-selective oxidation of a range of biomolecules. Since protein aggregation occurs if protein repair and degradative systems are unable to act upon oxidized proteins and restore cellular function, the reduction of the oxidative load on the cell by the down-regulation of the electron transport chain functions to minimize protein aggregation. Thus, ROS function as signaling molecules that fine-tune cellular metabolism through the selective oxidation or nitration of calcium regulatory proteins in order to minimize wide-spread oxidative damage and protein aggregation. Oxidative damage to cellular proteins, the loss of calcium homeostasis and protein aggregation contribute to the formation of amyloid deposits that accumulate during biological aging. Critical to understand the relationship between these processes and biological aging is the identification of oxidatively sensitive proteins that modulate energy utilization and the associated generation of ROS. In this latter respect, oxidative modifications to the calcium regulatory proteins calmodulin (CaM) and the sarco/endoplasmic reticulum Ca-ATPase (SERCA) function to down-regulate ATP utilization and the associated generation of ROS associated with replenishing intracellular ATP through oxidative phosphorylation. Reductions in the rate of ROS generation, in turn, will minimize protein oxidation and facilitate intracellular repair and degradative systems that function to eliminate damaged and partially unfolded proteins. Since the rates of protein repair or degradation compete with the rate of protein aggregation, the modulation of intracellular calcium concentrations and energy metabolism through the selective oxidation or nitration of critical signal transduction proteins (i.e. CaM or SERCA) is thought to maintain cellular function by minimizing protein aggregation and amyloid formation. Age-dependent increases in the rate of ROS generation or declines in cellular repair or degradation mechanisms will increase the oxidative load on the cell, resulting in corresponding increases in the concentrations of oxidized proteins and the associated formation of amyloid.

The Age of the Earth & Its Importance to Biology

ERIC Educational Resources Information Center

Senter, Phil

2013-01-01

Biology textbooks tend to assert the correctness of evolutionary concepts but mention very little of the evidence that supports them. This gives the impression that evolutionary theory is poorly supported, which discourages acceptance of the theory. A case in point is the age of the Earth. Biology textbooks usually mention that the planet is…

Does Aging or Endothelial Dysfunction Pose a Threat to Military Crewmembers

DTIC Science & Technology

1999-10-01

that have proven its vulnerable to oxidation. Eicosapentaenoic and primary medical effect to ameliorate or even docosahexaenoic acids in marine lipids...and a family of 21-amino acid peptide prostanoids like thromboxane A2, prostaglandin BIOLOGY OF ENDOTHELIUM H2 and components of renin-angiotensin...oxidizable compounds like LDL-cholesterol and Moreover, the whole process is influenced unsaturated fatty acids . There is a battery of negatively by

Bivalent rLP2086 (Trumenba®): Development of a well-characterized vaccine through commercialization.

PubMed

Sunasara, Khurram; Cundy, John; Srinivasan, Sriram; Evans, Brad; Sun, Weiqiang; Cook, Scott; Bortell, Eric; Farley, John; Griffin, Daniel; Bailey Piatchek, Michele; Arch-Douglas, Katherine

2018-05-24

The phrase "Process is the Product" is often applied to biologics, including multicomponent vaccines composed of complex components that evade complete characterization. Vaccine production processes must be defined and locked early in the development cycle to ensure consistent quality of the vaccine throughout scale-up, clinical studies, and commercialization. This approach of front-loading the development work helped facilitate the accelerated approval of the Biologic License Application for the well-characterized vaccine bivalent rLP2086 (Trumenba®, Pfizer Inc) in 2014 under Breakthrough Therapy Designation. Bivalent rLP2086 contains two rLP2086 antigens and is licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B in individuals 10-25years of age in the United States. This paper discusses the development of the manufacturing process of the two antigens for the purpose of making it amenable to any manufacturing facility. For the journey to commercialization, the operating model used to manage this highly accelerated program led to a framework that ensured "right the first time" execution, robust process characterization, and proactive process monitoring. This framework enabled quick problem identification and proactive resolutions, resulting in a robust control strategy for the commercial process. Copyright © 2017 Elsevier Ltd. All rights reserved.

Framing the inborn aging process and longevity science.

PubMed

Farrelly, Colin

2010-06-01

The medical sciences are currently dominated by the "disease-model" approach to health extension, an approach that prioritizes the study of pathological mechanisms with the goal of discovering treatment modalities for specific diseases. This approach has marginalized research on the aging process itself, research that could lead to an intervention that retards aging, thus conferring health dividends that would far exceed what could be expected by eliminating any specific disease of aging. This paper offers a diagnosis of how this sub-optimal approach to health extension arose and some general prescriptions concerning how progress could be made in terms of adopting a more rational approach to health extension. Drawing on empirical findings from psychology and economics, "prospect theory" is applied to the challenges of "framing" the inborn aging process given the cognitive capacities of real (rather than rational) decision-makers under conditions of risk and uncertainty. Prospect theory reveals that preferences are in fact dependent on whether particular outcomes of a choice are regarded as "a loss" or "a gain", relative to a reference point (or "aspiration level for survival"). And this has significant consequences for the way biogerontologists ought to characterise the central aspirations of the field (i.e. to prevent disease versus extend lifespan). Furthermore, it reveals the importance of shifting the existing reference point of the medical sciences to one that is shaped by the findings of evolutionary biology and biodemography.

Aging and efficiency in living systems: Complexity, adaptation and self-organization.

PubMed

Chatterjee, Atanu; Georgiev, Georgi; Iannacchione, Germano

2017-04-01

Living systems are open, out-of-equilibrium thermodynamic entities, that maintain order by locally reducing their entropy. Aging is a process by which these systems gradually lose their ability to maintain their out-of-equilibrium state, as measured by their free-energy rate density, and hence, their order. Thus, the process of aging reduces the efficiency of those systems, making them fragile and less adaptive to the environmental fluctuations, gradually driving them towards the state of thermodynamic equilibrium. In this paper, we discuss the various metrics that can be used to understand the process of aging from a complexity science perspective. Among all the metrics that we propose, action efficiency, is observed to be of key interest as it can be used to quantify order and self-organization in any physical system. Based upon our arguments, we present the dependency of other metrics on the action efficiency of a system, and also argue as to how each of the metrics, influences all the other system variables. In order to support our claims, we draw parallels between technological progress and biological growth. Such parallels are used to support the universal applicability of the metrics and the methodology presented in this paper. Therefore, the results and the arguments presented in this paper throw light on the finer nuances of the science of aging. Copyright © 2017 Elsevier B.V. All rights reserved.

Advanced glycation end-products: a biological consequence of lifestyle contributing to cancer disparity

PubMed Central

Turner, David P.

2015-01-01

Low income, poor diet, obesity and a lack of exercise are inter-related lifestyle factors that can profoundly alter our biological make-up to increase cancer risk, growth and development. We recently reported a potential mechanistic link between carbohydrate derived metabolites and cancer which may provide a biological consequence of lifestyle that can directly impact tumor biology. Advanced glycation end-products (AGEs) are reactive metabolites produced as a by-product of sugar metabolism. Failure to remove these highly reactive metabolites can lead to protein damage, aberrant cell signaling, increased stress responses, and decreased genetic fidelity. Critically, AGE accumulation is also directly affected by our lifestyle choices and shows a race specific, tumor dependent pattern of accumulation in cancer patients. This review will discuss the contribution of AGEs to the cancer phenotype with a particular emphasis on their biological links with the socioeconomic and environmental risk factors that drive cancer disparity. Given the potential benefits of lifestyle changes and the potential biological role of AGEs in promoting cancer, opportunities exist for collaborations impacting basic, translational, epidemiological and cancer prevention initiatives. PMID:25920350

Advanced glycation end-products: a biological consequence of lifestyle contributing to cancer disparity.

PubMed

Turner, David P

2015-05-15

Low income, poor diet, obesity, and a lack of exercise are interrelated lifestyle factors that can profoundly alter our biologic make up to increase cancer risk, growth, and development. We recently reported a potential mechanistic link between carbohydrate-derived metabolites and cancer, which may provide a biologic consequence of lifestyle that can directly affect tumor biology. Advanced glycation end-products (AGE) are reactive metabolites produced as a by-product of sugar metabolism. Failure to remove these highly reactive metabolites can lead to protein damage, aberrant cell signaling, increased stress responses, and decreased genetic fidelity. Critically, AGE accumulation is also directly affected by our lifestyle choices and shows a race-specific, tumor-dependent pattern of accumulation in cancer patients. This review will discuss the contribution of AGEs to the cancer phenotype, with a particular emphasis on their biologic links with the socioeconomic and environmental risk factors that drive cancer disparity. Given the potential benefits of lifestyle changes and the potential biologic role of AGEs in promoting cancer, opportunities exist for collaborations affecting basic, translational, epidemiologic, and cancer prevention initiatives. ©2015 American Association for Cancer Research.

Validation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function.

PubMed

Perco, Paul; Heinzel, Andreas; Leierer, Johannes; Schneeberger, Stefan; Bösmüller, Claudia; Oberhuber, Rupert; Wagner, Silvia; Engler, Franziska; Mayer, Gert

2018-05-03

Donor organ quality affects long term outcome after renal transplantation. A variety of prognostic molecular markers is available, yet their validity often remains undetermined. A network-based molecular model reflecting donor kidney status based on transcriptomics data and molecular features reported in scientific literature to be associated with chronic allograft nephropathy was created. Significantly enriched biological processes were identified and representative markers were selected. An independent kidney pre-implantation transcriptomics dataset of 76 organs was used to predict estimated glomerular filtration rate (eGFR) values twelve months after transplantation using available clinical data and marker expression values. The best-performing regression model solely based on the clinical parameters donor age, donor gender, and recipient gender explained 17% of variance in post-transplant eGFR values. The five molecular markers EGF, CD2BP2, RALBP1, SF3B1, and DDX19B representing key molecular processes of the constructed renal donor organ status molecular model in addition to the clinical parameters significantly improved model performance (p-value = 0.0007) explaining around 33% of the variability of eGFR values twelve months after transplantation. Collectively, molecular markers reflecting donor organ status significantly add to prediction of post-transplant renal function when added to the clinical parameters donor age and gender.

Factors and processes governing the C-14 content of carbonate in desert soils

NASA Technical Reports Server (NTRS)

Amundson, Ronald; Wang, Yang; Chadwick, Oliver; Trumbore, Susan; Mcfadden, Leslie; Mcdonald, Eric; Wells, Steven; Deniro, Michael

1994-01-01

A model is presented describing the factors and processes which determine the measured C-14 ages of soil calcium carbonate. Pedogenic carbonate forms in isotopic equilium with soil CO2. Carbon dioxide in soils is a mixture of CO2 derived from two biological sources: respiration by living plant roots and respiration of microorganisms decomposing soil humus. The relative proportion of these two CO2 sources can greatly affect the initial C-14 content of pedogenic carbonate: the greater the contribution of humus-derived CO2, the greater the initial C-14 age of the carbonate mineral. For any given mixture of CO2 sources, the steady-state (14)CO2 distribution vs. soil depth can be described by a production/diffusion model. As a soil ages, the C-14 age of soil humus increases, as does the steady-state C-14 age of soil CO2 and the initial C-14 age of any pedogenic carbonate which forms. The mean C-14 age of a complete pedogenic carbonate coating or nodule will underestimate the true age of the soil carbonate. This discrepancy increases the older a soil becomes. Partial removal of outer (and younger) carbonate coatings greatly improves the relationship between measured C-14 age and true age. Although the production/diffusion model qualitatively explains the C-14 age of pedogenic carbonate vs. soil depth in many soils, other factors, such as climate change, may contribute to the observed trends, particularily in soils older than the Holocene.

The neurocognitive consequences of sleep restriction: A meta-analytic review.

PubMed

Lowe, Cassandra J; Safati, Adrian; Hall, Peter A

2017-09-01

The current meta-analytic review evaluated the effects of experimentally manipulated sleep restriction on neurocognitive functioning. Random-effects models were employed to estimate the overall effect size and the differential effect size across cognitive domains. Age, time of day, age-adjusted sleep deficit, cumulative days of restricted sleep, sleep latency, subjective sleepiness, and biological sex were examined as potential moderators of the effect. Based on a sample of 61 studies, from 71 different populations, findings revealed a significant negative effect of sleep restriction on cognitive processing across cognitive domains (g=-0.383, p<0.001). This effect held for executive functioning (g=-0.324, p<0.001), sustained attention (g=-0.409, p<0.001), and long-term memory (g=-0.192, p=0.002). There was insufficient evidence to detect an effect within the domains of attention, multitask, impulsive decision-making or intelligence. Age group, time of day, cumulative days of restricted sleep, sleep latency, subjective sleepiness, and biological sex were all significant moderators of the overall effect. In conclusion, the current meta-analysis is the first comprehensive review to provide evidence that short-term sleep restriction significantly impairs waking neurocognitive functioning. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chronic alcoholism and bone remodeling processes: Caveats and considerations for the forensic anthropologist.

PubMed

Michael, Amy R; Bengtson, Jennifer D

2016-02-01

Clinical literature provides substantial information on the effects of chronic alcohol abuse on bone remodeling and related skeletal disease processes. This biomedical information is seldom considered in detail by forensic anthropologists, who often rely on normative macroscopic models of bone remodeling and traditional macroscopic age estimation methods in the creation of biological profiles. The case study presented here considers the ways that alcoholism disrupts normal bone remodeling processes, thus skewing estimations of age-at-death. Alcoholism affects bone macroscopically, resulting in a porous appearance and an older estimation of age, while simultaneously inhibiting osteoblastic activity and resulting in a younger microscopic appearance. Forensic anthropologists must also be cognizant of pathological remodeling stemming from alcoholism in cases where trauma analysis is critical to the reconstruction of events leading up to death, as fracture healing rates can be affected. Beyond the case study, we also consider how forensic anthropologists and practitioners can recognize and account for osteological signatures of alcoholism in medico-legal contexts. In order to best estimate age at death, a combined macroscopic and microscopic approach should be employed whenever possible alcohol and drug abuse is known or suspected. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Adipose tissue NAD+ biology in obesity and insulin resistance: From mechanism to therapy.

PubMed

Yamaguchi, Shintaro; Yoshino, Jun

2017-05-01

Nicotinamide adenine dinucleotide (NAD + ) biosynthetic pathway, mediated by nicotinamide phosphoribosyltransferase (NAMPT), a key NAD + biosynthetic enzyme, plays a pivotal role in controlling many biological processes, such as metabolism, circadian rhythm, inflammation, and aging. Over the past decade, NAMPT-mediated NAD + biosynthesis, together with its key downstream mediator, namely the NAD + -dependent protein deacetylase SIRT1, has been demonstrated to regulate glucose and lipid metabolism in a tissue-dependent manner. These discoveries have provided novel mechanistic and therapeutic insights into obesity and its metabolic complications, such as insulin resistance, an important risk factor for developing type 2 diabetes and cardiovascular disease. This review will focus on the importance of adipose tissue NAMPT-mediated NAD + biosynthesis and SIRT1 in the pathophysiology of obesity and insulin resistance. We will also critically explore translational and clinical aspects of adipose tissue NAD + biology. © 2017 WILEY Periodicals, Inc.

Mitochondria and ageing: role in heart, skeletal muscle and adipose tissue

PubMed Central

Boengler, Kerstin; Kosiol, Maik; Mayr, Manuel; Schulz, Rainer

2017-01-01

Abstract Age is the most important risk factor for most diseases. Mitochondria play a central role in bioenergetics and metabolism. In addition, several lines of evidence indicate the impact of mitochondria in lifespan determination and ageing. The best‐known hypothesis to explain ageing is the free radical theory, which proposes that cells, organs, and organisms age because they accumulate reactive oxygen species (ROS) damage over time. Mitochondria play a central role as the principle source of intracellular ROS, which are mainly formed at the level of complex I and III of the respiratory chain. Dysfunctional mitochondria generating less ATP have been observed in various aged organs. Mitochondrial dysfunction comprises different features including reduced mitochondrial content, altered mitochondrial morphology, reduced activity of the complexes of the electron transport chain, opening of the mitochondrial permeability transition pore, and increased ROS formation. Furthermore, abnormalities in mitochondrial quality control or defects in mitochondrial dynamics have also been linked to senescence. Among the tissues affected by mitochondrial dysfunction are those with a high‐energy demand and thus high mitochondrial content. Therefore, the present review focuses on the impact of mitochondria in the ageing process of heart and skeletal muscle. In this article, we review different aspects of mitochondrial dysfunction and discuss potential therapeutic strategies to improve mitochondrial function. Finally, novel aspects of adipose tissue biology and their involvement in the ageing process are discussed. PMID:28432755

Assessing older adults in civil litigation cases.

PubMed

Kohutis, Eileen A

With the population aging, the legal and mental health systems need to be prepared for cases that involve older adults beyond the customary matters of guardianship and competency. Assessing older adults with the current tests raises concerns because these measures may not be adequately normed for this age group. Malingering, factitious disorders, and somatoform disorders are discussed due to health-related issues of normal aging. These topics complicate the assessment procedure and need consideration because they may affect the claimant's performance or symptom presentation. Although claims of posttraumatic stress disorder (PTSD) are common in civil litigation cases, it can be additionally complex in older adults. The evaluator needs to weigh not only factors related to the normal biological process of aging but also those that are attendant with the litigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Extracellular vesicles and their synthetic analogues in aging and age-associated brain diseases

PubMed Central

Smith, J. A.; Leonardi, T.; Huang, B.; Iraci, N.; Vega, B.; Pluchino, S.

2015-01-01

Multicellular organisms rely upon diverse and complex intercellular communications networks for a myriad of physiological processes. Disruption of these processes is implicated in the onset and propagation of disease and disorder, including the mechanisms of senescence at both cellular and organismal levels. In recent years, secreted extracellular vesicles (EVs) have been identified as a particularly novel vector by which cell-to-cell communications are enacted. EVs actively and specifically traffic bioactive proteins, nucleic acids, and metabolites between cells at local and systemic levels, modulating cellular responses in a bidirectional manner under both homeostatic and pathological conditions. EVs are being implicated not only in the generic aging process, but also as vehicles of pathology in a number of age-related diseases, including cancer and neurodegenerative and disease. Thus, circulating EVs—or specific EV cargoes—are being utilised as putative biomarkers of disease. On the other hand, EVs, as targeted intercellular shuttles of multipotent bioactive payloads, have demonstrated promising therapeutic properties, which can potentially be modulated and enhanced through cellular engineering. Furthermore, there is considerable interest in employing nanomedicinal approaches to mimic the putative therapeutic properties of EVs by employing synthetic analogues for targeted drug delivery. Herein we describe what is known about the origin and nature of EVs and subsequently review their putative roles in biology and medicine (including the use of synthetic EV analogues), with a particular focus on their role in aging and age-related brain diseases. PMID:24973266

Extracellular vesicles and their synthetic analogues in aging and age-associated brain diseases.

PubMed

Smith, J A; Leonardi, T; Huang, B; Iraci, N; Vega, B; Pluchino, S

2015-04-01

Multicellular organisms rely upon diverse and complex intercellular communications networks for a myriad of physiological processes. Disruption of these processes is implicated in the onset and propagation of disease and disorder, including the mechanisms of senescence at both cellular and organismal levels. In recent years, secreted extracellular vesicles (EVs) have been identified as a particularly novel vector by which cell-to-cell communications are enacted. EVs actively and specifically traffic bioactive proteins, nucleic acids, and metabolites between cells at local and systemic levels, modulating cellular responses in a bidirectional manner under both homeostatic and pathological conditions. EVs are being implicated not only in the generic aging process, but also as vehicles of pathology in a number of age-related diseases, including cancer and neurodegenerative and disease. Thus, circulating EVs-or specific EV cargoes-are being utilised as putative biomarkers of disease. On the other hand, EVs, as targeted intercellular shuttles of multipotent bioactive payloads, have demonstrated promising therapeutic properties, which can potentially be modulated and enhanced through cellular engineering. Furthermore, there is considerable interest in employing nanomedicinal approaches to mimic the putative therapeutic properties of EVs by employing synthetic analogues for targeted drug delivery. Herein we describe what is known about the origin and nature of EVs and subsequently review their putative roles in biology and medicine (including the use of synthetic EV analogues), with a particular focus on their role in aging and age-related brain diseases.

Foundations of Forensic Meteoritics

NASA Astrophysics Data System (ADS)

Treiman, A. H.

1992-07-01

It may be useful to know if a meteorite was found at the site where it fell. For instance, the polymict ureilites North Haig and Nilpena were found 1100 km apart, yet are petrologically identical [1]. Could this distance represent transport from a single strewn field, or does it represent distinct fall sites? A meteorite may contain sufficient clues to suggest some characteristics of its fall site. If these inferences are inconsistent with the find site, one may infer that the meteorite has been transported. It will likely be impossible to determine the exact fall site of a transported meteorite. Data relevant to a meteorite's fall site may be intrinsic to the meteorite, or acquired at the site. For instance, an intrinsic property is terrestrial residence age (from abundances of cosmogenic radioisotopes and their decay products); a meteorite's terrestrial residence age must be the same or less than that of the surface on which it fell. After falling, a meteorite may acquire characteristic telltales of terrestrial geological, geochemical, and biological processes. These telltale clues may include products of chemical weathering, adhering geological materials, biological organisms living (or once living) on the meteorite, and biological materials adhering to (but never living on) the meteorite. The effects of chemical weathering, present in all but the freshest finds, range from slight rusting to extensive decomposition and veining The ages of weathering materials and veins, as with terrestrial residence ages above, must be less than the age of the fall surface. The mineralogy and chemistry, elemental and isotopic, of weathering materials will differ according to the mineralogy and composition of the meteorite, and the mineralogy, geochemistry, hydrology, and climate of the fall site. Weathering materials may also vary as climate changes and may vary among the microenvironments associated with a meteorite on the Earth's surface. Geological materials (rock, sediment, soil) adhering to a meteorite are samples of the actual physical environment in which the meteorite rested. Adhesion may derive from chemical cementation (incl. rust from the meteorite), biologic activity (incl. desert varnish?), or impact processes [2]. Given the wide diversity of geological materials and processes on the Earth, adhering geological materials may be useful forensic tools. For instance, fall in a volcanic terrane may be inconsistent with adhering sediments of clean quartz sand. Biologic matter on meteorites includes animal and vegetable matter mixed with the adhering geological materials, lichens and other plants growing in place, and purposefully attached animal matter (e.g. insect eggs). The most useful biological data may be provided by pollen, which can often be referred unambiguously to genera and species of plants. For example, sediments adhering to meteorites from the central Nullabor Plain (W. Australia) are different from sediments from the Plain's margin in S. Australia. Sediment on meteorites from the central Nullabor (e.g. Mundrabilla) lacks quartz sand and consists almost entirely of clay-sized particles, consistent with derivation from the local saprolitic soil. Sediment on meteorites from the eastern Nullabor (e.g. Hughes and Cook, S.A.) contains a significant fraction of quartz sand, 1/4- to 1/2-mm grains, probably blown from the Great Victoria Desert to the north and northwest. However, sedimentologic data alone may be misleading. For instance, sediments adhering to Nuevo Mercurio stones (H5; Zacatecas, Mexico) are clay-sized and lack coarser material. But sediment on Nuevo Mercurio (b), a ureilite found in the Nuevo Mercurio strewn field, consists of quartz sand and clay pellets, 1/4 to 1/2 mm diameter. Clearly, local environments may affect the character of sediment adhering to a meteorite, and careful detailed study may be required to determine whether a meteorite has been transported. I am grateful to R. Farrell and D. New for availability of samples. References: 1. Prinz et al. (1986) Lunar Planet. Sci. XVII, 681. [2] Koeberl and Schultz (1992) Lunar Planet. Sci. XXIII, 707.

Vitamin D, Cognition and Alzheimer’s Disease: The Therapeutic Benefit is in the D-Tails

PubMed Central

Landel, Véréna; Annweiler, Cédric; Millet, Pascal; Morello, Maria; Féron, François

2016-01-01

Since its discovery during the epidemic of rickets in the early 1920s, the physiological effects of vitamin D on calcium/phosphorus homeostasis have been thoroughly studied. Along with the understanding of its actions on skeletal diseases and advances in cellular and molecular biology, this misnamed vitamin has gained attention as a potential player in a growing number of physiological processes and a variety of diseases. During the last 25 years, vitamin D has emerged as a serious candidate in nervous system development and function and a therapeutic tool in a number of neurological pathologies. More recently, experimental and pre-clinical data suggest a link between vitamin D status and cognitive function. Human studies strongly support a correlation between low levels of circulating 25-hydroxyvitamin D (25(OH)D) and cognitive impairment or dementia in aging populations. In parallel, animal studies show that supplementation with vitamin D is protective against biological processes associated with Alzheimer’s disease (AD) and enhances learning and memory performance in various animal models of aging and AD. These experimental observations support multiple mechanisms by which vitamin D can act against neurodegenerative processes. However, clinical interventional studies are disappointing and fail to associate increased 25(OH)D levels with improved cognitive outcomes. This review collects the current available data from both animal and human studies and discusses the considerations that future studies examining the effects of vitamin D status on neurocognitive function might consider. PMID:27176073

40 CFR 63.138 - Process wastewater provisions-performance standards for treatment processes managing Group 1...

Code of Federal Regulations, 2010 CFR

2010-07-01

.../or Table 9 compounds are similar and often identical. (3) Biological treatment processes. Biological treatment processes in compliance with this section may be either open or closed biological treatment processes as defined in § 63.111. An open biological treatment process in compliance with this section need...

Analyzing the dynamics of cell cycle processes from fixed samples through ergodic principles.

PubMed

Wheeler, Richard John

2015-11-05

Tools to analyze cyclical cellular processes, particularly the cell cycle, are of broad value for cell biology. Cell cycle synchronization and live-cell time-lapse observation are widely used to analyze these processes but are not available for many systems. Simple mathematical methods built on the ergodic principle are a well-established, widely applicable, and powerful alternative analysis approach, although they are less widely used. These methods extract data about the dynamics of a cyclical process from a single time-point "snapshot" of a population of cells progressing through the cycle asynchronously. Here, I demonstrate application of these simple mathematical methods to analysis of basic cyclical processes--cycles including a division event, cell populations undergoing unicellular aging, and cell cycles with multiple fission (schizogony)--as well as recent advances that allow detailed mapping of the cell cycle from continuously changing properties of the cell such as size and DNA content. This includes examples using existing data from mammalian, yeast, and unicellular eukaryotic parasite cell biology. Through the ongoing advances in high-throughput cell analysis by light microscopy, electron microscopy, and flow cytometry, these mathematical methods are becoming ever more important and are a powerful complementary method to traditional synchronization and time-lapse cell cycle analysis methods. © 2015 Wheeler. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety

PubMed Central

Mukherjee, Siddharth; Date, Abhijit; Patravale, Vandana; Korting, Hans Christian; Roeder, Alexander; Weindl, Günther

2006-01-01

Aging of skin is an intricate biological process consisting of two types. While intrinsic or chronological aging is an inevitable process, photoaging involves the premature aging of skin occurring due to cumulative exposure to ultraviolet radiation. Chronological and photoaging both have clinically differentiable manifestations. Various natural and synthetic retinoids have been explored for the treatment of aging and many of them have shown histological and clinical improvement, but most of the studies have been carried out in patients presenting with photoaged skin. Amongst the retinoids, tretinoin possibly is the most potent and certainly the most widely investigated retinoid for photoaging therapy. Although retinoids show promise in the treatment of skin aging, irritant reactions such as burning, scaling or dermatitis associated with retinoid therapy limit their acceptance by patients. This problem is more prominent with tretinoin and tazarotene whereas other retinoids mainly represented by retinaldehyde and retinol are considerably less irritating. In order to minimize these side effects, various novel drug delivery systems have been developed. In particular, nanoparticles have shown a good potential in improving the stability, tolerability and efficacy of retinoids like tretinoin and retinol. However, more elaborate clinical studies are required to confirm their advantage in the delivery of topical retinoids. PMID:18046911

Secular change in chert distribution: a reflection of evolving biological participation in the silica cycle

NASA Technical Reports Server (NTRS)

Maliva, R. G.; Knoll, A. H.; Siever, R.

1989-01-01

In the modern oceans, the removal of dissolved silica from sea water is principally a biological process carried out by diatoms, with lesser contributions from radiolaria, silicoflagellates, and sponges. Because such silica in sediments is often redistributed locally during diagenesis to from nodular or bedded chert, stratigraphic changes in the facies distribution of early diagenetic chert provide important insights into the development of biological participation in the silica cycle. The abundance of chert in upper Proterozoic peritidal carbonates suggests that at this time silica was removed from seawater principally by abiological processes operating in part of the margins of the oceans. With the evolution of demosponges near the beginning of the Cambrian Period, subtidal biogenetic cherts became increasingly common, and with the Ordovician rise of radiolaria to ecological and biogeochemical prominence, sedimented skeletons became a principal sink for oceanic silica. Cherts of Silurian to Cretaceous age share many features of facies distribution and petrography but they differ from Cenozoic siliceous deposits. These differences are interpreted to reflect the mid-Cretaceous radiation of diatoms and their subsequent rise to domination of the silica cycle. Biogeochemical cycles provide an important framework for the paleobiological interpretation of the organisms that participate in them.

Physical Growth, Biological Age, and Nutritional Transitions of Adolescents Living at Moderate Altitudes in Peru

PubMed Central

Cossio-Bolaños, Marco; Gómez Campos, Rossana; Andruske, Cynthia Lee; Flores, Antonio Viveros; Luarte-Rocha, Cristian; Olivares, Pedro R.; Garcia-Rubio, Javier; de Arruda, Miguel

2015-01-01

Background: Peru is experiencing a stage of nutritional transition where the principal characteristics are typical of countries undergoing development. Objectives: The objectives of this study were the following: (a) compare physical growth patterns with an international standard; (b) determine biological age; and (c) analyze the double nutritional burden of adolescents living at a moderate altitude in Peru. Design: Weight, standing height, and sitting height were measured in 551 adolescents of both sexes (12.0 to 17.9 years old) from an urban area of Arequipa, Peru (2328 m). Physical growth was compared with the international standard of the CDC-2000. Biological age was determined by using a non-invasive transversal technique based on years from age at peak height velocity (APHV). Nutritional state was determined by means of weight for age and height for age. Z scores were calculated using international standards from the CDC-2000. Results: Body weight for both sexes was similar to the CDC-2000 international standards. At all ages, the girls’ height (p < 0.05) was below the standards. However, the boys’ height (p < 0.05) was less at ages, 15, 16, and 17. Biological age showed up in girls at age 12.7 years and for boys at 15.2 years. Stunted growth (8.7% boys and 18.0% girls) and over weight (11.3% boys and 8.8% girls) occurred in both groups. A relationship existed in both sexes between the categories of weight for the age and stunted growth by sex. Conclusions: Adolescents living at a moderate altitude exhibited stunted linear growth and biological maturation. Furthermore, adolescents of both sexes showed the presence of the double nutritional burden (stunted growth and excessive weight). PMID:26404334

Physical Growth, Biological Age, and Nutritional Transitions of Adolescents Living at Moderate Altitudes in Peru.

PubMed

Cossio-Bolaños, Marco; Campos, Rossana Gómez; Andruske, Cynthia Lee; Flores, Antonio Viveros; Luarte-Rocha, Cristian; Olivares, Pedro R; Garcia-Rubio, Javier; de Arruda, Miguel

2015-09-25

Peru is experiencing a stage of nutritional transition where the principal characteristics are typical of countries undergoing development. The objectives of this study were the following: (a) compare physical growth patterns with an international standard; (b) determine biological age; and (c) analyze the double nutritional burden of adolescents living at a moderate altitude in Peru. Weight, standing height, and sitting height were measured in 551 adolescents of both sexes (12.0 to 17.9 years old) from an urban area of Arequipa, Peru (2328 m). Physical growth was compared with the international standard of the CDC-2000. Biological age was determined by using a non-invasive transversal technique based on years from age at peak height velocity (APHV). Nutritional state was determined by means of weight for age and height for age. Z scores were calculated using international standards from the CDC-2000. Body weight for both sexes was similar to the CDC-2000 international standards. At all ages, the girls' height (p < 0.05) was below the standards. However, the boys' height (p < 0.05) was less at ages, 15, 16, and 17. Biological age showed up in girls at age 12.7 years and for boys at 15.2 years. Stunted growth (8.7% boys and 18.0% girls) and over weight (11.3% boys and 8.8% girls) occurred in both groups. A relationship existed in both sexes between the categories of weight for the age and stunted growth by sex. Adolescents living at a moderate altitude exhibited stunted linear growth and biological maturation. Furthermore, adolescents of both sexes showed the presence of the double nutritional burden (stunted growth and excessive weight).

Fieldwork in UK Secondary Schools: Influences and Provision

ERIC Educational Resources Information Center

Tilling, Steve

2004-01-01

The paper describes a national survey of biology teachers visiting Field Studies Council (FSC) centres in England and Wales. It provides data on levels of biology fieldwork at ages 11-16 (Years 7-11), and factors affecting A-level biology fieldwork provision at ages 16-19 (Years 12 and 13). The results are compared with similar data from geography…

Ca cycling and isotopic fluxes in forested ecosystems in Hawaii

USGS Publications Warehouse

Wiegand, B.A.; Chadwick, O.A.; Vitousek, P.M.; Wooden, J.L.

2005-01-01

Biogeochemical processes fractionate Ca isotopes in plants and soils along a 4 million year developmental sequence in the Hawaiian Islands. We observed that plants preferentially take up 40Ca relative to 44Ca, and that biological fractionation and changes in the relative contributions from volcanic and marine sources produce a significant increase in 44Ca in soil exchangeable pools. Our results imply moderate fluxes enriched in 44Ca from strongly nutrient-depleted old soils, in contrast with high 40Ca fluxes in young and little weathered environments. In addition, biological fractionation controls divergent geochemical pathways of Ca and Sr in the plant-soil system. While Ca depletes progressively with increasing soil age, Sr/Ca ratios increase systematically. Sr isotope ratios provide a valuable tracer for provenance studies of alkaline earth elements in forested ecosystems, but its usefulness is limited when deciphering biogeochemical processes involved in the terrestrial Ca cycle. Ca isotopes in combination with Sr/ Ca ratios reveal more complex processes involved in the biogeochemistry of Ca and Sr. Copyright 2005 by the American Geophysical Union.

Using Nonlinear Stochastic Evolutionary Game Strategy to Model an Evolutionary Biological Network of Organ Carcinogenesis Under a Natural Selection Scheme

PubMed Central

Chen, Bor-Sen; Tsai, Kun-Wei; Li, Cheng-Wei

2015-01-01

Molecular biologists have long recognized carcinogenesis as an evolutionary process that involves natural selection. Cancer is driven by the somatic evolution of cell lineages. In this study, the evolution of somatic cancer cell lineages during carcinogenesis was modeled as an equilibrium point (ie, phenotype of attractor) shifting, the process of a nonlinear stochastic evolutionary biological network. This process is subject to intrinsic random fluctuations because of somatic genetic and epigenetic variations, as well as extrinsic disturbances because of carcinogens and stressors. In order to maintain the normal function (ie, phenotype) of an evolutionary biological network subjected to random intrinsic fluctuations and extrinsic disturbances, a network robustness scheme that incorporates natural selection needs to be developed. This can be accomplished by selecting certain genetic and epigenetic variations to modify the network structure to attenuate intrinsic fluctuations efficiently and to resist extrinsic disturbances in order to maintain the phenotype of the evolutionary biological network at an equilibrium point (attractor). However, during carcinogenesis, the remaining (or neutral) genetic and epigenetic variations accumulate, and the extrinsic disturbances become too large to maintain the normal phenotype at the desired equilibrium point for the nonlinear evolutionary biological network. Thus, the network is shifted to a cancer phenotype at a new equilibrium point that begins a new evolutionary process. In this study, the natural selection scheme of an evolutionary biological network of carcinogenesis was derived from a robust negative feedback scheme based on the nonlinear stochastic Nash game strategy. The evolvability and phenotypic robustness criteria of the evolutionary cancer network were also estimated by solving a Hamilton–Jacobi inequality – constrained optimization problem. The simulation revealed that the phenotypic shift of the lung cancer-associated cell network takes 54.5 years from a normal state to stage I cancer, 1.5 years from stage I to stage II cancer, and 2.5 years from stage II to stage III cancer, with a reasonable match for the statistical result of the average age of lung cancer. These results suggest that a robust negative feedback scheme, based on a stochastic evolutionary game strategy, plays a critical role in an evolutionary biological network of carcinogenesis under a natural selection scheme. PMID:26244004

Potential biomarkers of ageing.

PubMed

Simm, Andreas; Nass, Norbert; Bartling, Babett; Hofmann, Britt; Silber, Rolf-Edgar; Navarrete Santos, Alexander

2008-03-01

Life span in individual humans is very heterogeneous.Thus, the ageing rate, measured as the decline of functional capacity and stress resistance, is different in every individual. There have been attempts made to analyse this individual age, the so-called biological age, in comparison to chronological age. Biomarkers of ageing should help to characterise this biological age and, as age is a major risk factor in many degenerative diseases,could be subsequently used to identify individuals at high risk of developing age-associated diseases or disabilities. Markers based on oxidative stress, protein glycation,inflammation, cellular senescence and hormonal deregulation are discussed.

A Hierarchical Bayesian Model for Calibrating Estimates of Species Divergence Times

PubMed Central

Heath, Tracy A.

2012-01-01

In Bayesian divergence time estimation methods, incorporating calibrating information from the fossil record is commonly done by assigning prior densities to ancestral nodes in the tree. Calibration prior densities are typically parametric distributions offset by minimum age estimates provided by the fossil record. Specification of the parameters of calibration densities requires the user to quantify his or her prior knowledge of the age of the ancestral node relative to the age of its calibrating fossil. The values of these parameters can, potentially, result in biased estimates of node ages if they lead to overly informative prior distributions. Accordingly, determining parameter values that lead to adequate prior densities is not straightforward. In this study, I present a hierarchical Bayesian model for calibrating divergence time analyses with multiple fossil age constraints. This approach applies a Dirichlet process prior as a hyperprior on the parameters of calibration prior densities. Specifically, this model assumes that the rate parameters of exponential prior distributions on calibrated nodes are distributed according to a Dirichlet process, whereby the rate parameters are clustered into distinct parameter categories. Both simulated and biological data are analyzed to evaluate the performance of the Dirichlet process hyperprior. Compared with fixed exponential prior densities, the hierarchical Bayesian approach results in more accurate and precise estimates of internal node ages. When this hyperprior is applied using Markov chain Monte Carlo methods, the ages of calibrated nodes are sampled from mixtures of exponential distributions and uncertainty in the values of calibration density parameters is taken into account. PMID:22334343

Systems Biology Approaches to the Study of Biological Networks Underlying Alzheimer's Disease: Role of miRNAs.

PubMed

Roth, Wera; Hecker, David; Fava, Eugenio

2016-01-01

MicroRNAs (miRNAs) are emerging as significant regulators of mRNA complexity in the human central nervous system (CNS) thereby controlling distinct gene expression profiles in a spatio-temporal manner during development, neuronal plasticity, aging and (age-related) neurodegeneration, including Alzheimer's disease (AD). Increasing effort is expended towards dissecting and deciphering the molecular and genetic mechanisms of neurobiological and pathological functions of these brain-enriched miRNAs. Along these lines, recent data pinpoint distinct miRNAs and miRNA networks being linked to APP splicing, processing and Aβ pathology (Lukiw et al., Front Genet 3:327, 2013), and furthermore, to the regulation of tau and its cellular subnetworks (Lau et al., EMBO Mol Med 5:1613, 2013), altogether underlying the onset and propagation of Alzheimer's disease. MicroRNA profiling studies in Alzheimer's disease suffer from poor consensus which is an acknowledged concern in the field, and constitutes one of the current technical challenges. Hence, a strong demand for experimental and computational systems biology approaches arises, to incorporate and integrate distinct levels of information and scientific knowledge into a complex system of miRNA networks in the context of the transcriptome, proteome and metabolome in a given cellular environment. Here, we will discuss the state-of-the-art technologies and computational approaches on hand that may lead to a deeper understanding of the complex biological networks underlying the pathogenesis of Alzheimer's disease.

An epigenetic biomarker of aging for lifespan and healthspan

PubMed Central

Levine, Morgan E.; Lu, Ake T.; Quach, Austin; Chen, Brian H.; Assimes, Themistocles L.; Bandinelli, Stefania; Hou, Lifang; Baccarelli, Andrea A.; Stewart, James D.; Li, Yun; Whitsel, Eric A.; Wilson, James G; Reiner, Alex P; Aviv, Abraham; Lohman, Kurt; Liu, Yongmei; Ferrucci, Luigi

2018-01-01

Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. While this biomarker was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. Based on an in-depth transcriptional analysis in sorted cells, we find that increased epigenetic, relative to chronological age, is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important pathways in aging. PMID:29676998

Effects of Aging on the Digestive System

MedlinePlus

... switch to the Professional version Home Digestive Disorders Biology of the Digestive System Effects of Aging on ... Version. DOCTORS: Click here for the Professional Version Biology of the Digestive System Overview of the Digestive ...

Clinical implications of somatic mutations in aplastic anemia and myelodysplastic syndrome in genomic age.

PubMed

Maciejewski, Jaroslaw P; Balasubramanian, Suresh K

2017-12-08

Recent technological advances in genomics have led to the discovery of new somatic mutations and have brought deeper insights into clonal diversity. This discovery has changed not only the understanding of disease mechanisms but also the diagnostics and clinical management of bone marrow failure. The clinical applications of genomics include enhancement of current prognostic schemas, prediction of sensitivity or refractoriness to treatments, and conceptualization and selective application of targeted therapies. However, beyond these traditional clinical aspects, complex hierarchical clonal architecture has been uncovered and linked to the current concepts of leukemogenesis and stem cell biology. Detection of clonal mutations, otherwise typical of myelodysplastic syndrome, in the course of aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria has led to new pathogenic concepts in these conditions and created a new link between AA and its clonal complications, such as post-AA and paroxysmal nocturnal hemoglobinuria. Distinctions among founder vs subclonal mutations, types of clonal evolution (linear or branching), and biological features of individual mutations (sweeping, persistent, or vanishing) will allow for better predictions of the biologic impact they impart in individual cases. As clonal markers, mutations can be used for monitoring clonal dynamics of the stem cell compartment during physiologic aging, disease processes, and leukemic evolution. © 2016 by The American Society of Hematology. All rights reserved.

Differential Proteome Analysis of a Flor Yeast Strain under Biofilm Formation

PubMed Central

Moreno-García, Jaime; Mauricio, Juan Carlos; Moreno, Juan; García-Martínez, Teresa

2017-01-01

Several Saccharomyces cerevisiae strains (flor yeasts) form a biofilm (flor velum) on the surface of Sherry wines after fermentation, when glucose is depleted. This flor velum is fundamental to biological aging of these particular wines. In this study, we identify abundant proteins in the formation of the biofilm of an industrial flor yeast strain. A database search to enrich flor yeast “biological process” and “cellular component” according to Gene Ontology Terminology (GO Terms) and, “pathways” was carried out. The most abundant proteins detected were largely involved in respiration, translation, stress damage prevention and repair, amino acid metabolism (glycine, isoleucine, leucine and arginine), glycolysis/gluconeogenesis and biosynthesis of vitamin B9 (folate). These proteins were located in cellular components as in the peroxisome, mitochondria, vacuole, cell wall and extracellular region; being these two last directly related with the flor formation. Proteins like Bgl2p, Gcv3p, Hyp2p, Mdh1p, Suc2p and Ygp1p were quantified in very high levels. This study reveals some expected processes and provides new and important information for the design of conditions and genetic constructions of flor yeasts for improving the cellular survival and, thus, to optimize biological aging of Sherry wine production. PMID:28350350

UV fluorescence excitation spectroscopy as a non-invasive predictor of epidermal proliferation and clinical performance of cosmetic formulations

NASA Astrophysics Data System (ADS)

Maidhof, Robert; Liebel, Frank; Hwang, Cheng; Ruvolo, Eduardo; Lyga, John

2017-02-01

The epidermis is the outermost layer of skin and is composed of cells primarily containing keratin. It consists of about ten layers of living cells (keratinocytes) and ten layers of dead cells (corneocytes). These cells are continually shed from the outside and replaced from the inside in a process called desquamation which is controlled by two biological events - proliferation and differentiation. One method to non-invasively study biological changes in the skin is using fluorescence excitation spectroscopy. Several characteristic excitation-emission peaks occur in skin that have been related to the epidermal and dermal composition. The magnitude of the peak that occurs at 295nm excitation (F295) has been linked to changes in skin proliferation, cell turnover, epidermal thickening, and skin aging. We hypothesize that changes in this fluorescent signal could be used to assess the potential activity of cosmetic anti-aging compounds to deliver a benefit to skin. Previous work with retinol and glycolic acid, two commonly used actives that effect epidermal proliferation and exfoliation, has demonstrated an increase in F295 (attributed to tryptophan excitation fluorescence). In this study we present the results of a placebo controlled study that aims to correlate changes in F295 with biological performance (epidermal thickening and Ki67 expression).

Biological and Rearing Mother Influences on Child ADHD Symptoms: Revisiting the Developmental Interface between Nature and Nurture

PubMed Central

Harold, Gordon T.; Leve, Leslie D.; Barrett, Douglas; Elam, Kit; Neiderhiser, Jenae M.; Natsuaki, Misaki N.; Shaw, Daniel S.; Reiss, David; Thapar, Anita

2013-01-01

Background Families of children with attention deficit hyperactivity disorder (ADHD) report more negative family relationships than families of children without ADHD. Questions remain as to the role of genetic factors underlying associations between family relationships and children’s ADHD symptoms, and the role of children’s ADHD symptoms as an evocative influence on the quality of relationships experienced within such families. Utilizing the attributes of two genetically sensitive research designs, the present study examined associations between biologically related and non-biologically related maternal ADHD symptoms, parenting practices, child impulsivity/activation, and child ADHD symptoms. The combined attributes of the study designs permit assessment of associations while controlling for passive genotype-environment correlation and directly examining evocative genotype-environment correlation (rGE); two relatively under examined confounds of past research in this area. Methods A cross-sectional adoption-at-conception design (Cardiff IVF Study; C-IVF) and a longitudinal adoption-at-birth design (Early Growth and Development Study; EGDS) were used. The C-IVF sample included 160 mothers and children (age 5–8 years). The EGDS sample included 320 linked sets of adopted children (age 6 years), adoptive-, and biologically-related mothers. Questionnaires were used to assess maternal ADHD symptoms, parenting practices, child impulsivity/activation, and child ADHD symptoms. A cross-rater approach was used across measures of maternal behavior (mother reports) and child ADHD symptoms (father reports). Results Significant associations were revealed between rearing mother ADHD symptoms, hostile parenting behavior, and child ADHD symptoms in both samples. Because both samples consisted of genetically-unrelated mothers and children, passive rGE was removed as a possible explanatory factor underlying these associations. Further, path analysis revealed evidence for evocative rGE processes in the longitudinal adoption-at-birth study (EGDS) from biologically-related maternal ADHD symptoms to biologically-unrelated maternal hostile parenting through early disrupted child behavior (impulsivity/activation), with maternal hostile parenting and disrupted child behavior associated with later child ADHD symptoms, controlling for concurrent adoptive mother ADHD symptoms. Conclusions Results highlight the importance of genetically-influenced child ADHD-related temperamental attributes on genetically-unrelated maternal hostility that in turn links to later child ADHD symptoms. Implications for intervention programs focusing on early family processes and the precursors of child ADHD symptoms are discussed. PMID:24007415

Does age difference really matter? Facial markers of biological quality and age difference between husband and wife.

PubMed

Danel, D P; Dziedzic-Danel, A; Kleisner, K

2016-08-01

Information conveyed by facial attractiveness markers such as averageness, bilateral symmetry, and secondary sexual characteristics may play an important adaptive role in human sexual selection. Nonetheless, mate choice also relies on other non-physical characteristics such as, for instance, an individual's age. Women prefer and enter in relationships with older partners, whereas in men the inverse relation is observed. Surprisingly, the link between facial morphological markers of biological quality on the one hand and age disparity between partners on the other hand has been as yet subject of very little research. This study aims to fill this gap. We had used facial photographs and demographic data of heterosexual marriages. Facial cues of biological quality, such as averageness, bilateral symmetry, and sexual dimorphism, were digitally measured using geometric morphometric methods and then associated with spouses' age difference. It turned out that a greater age disparity between spouses correlates, in both partners, with higher scores in facial measures which indicate partners' biological quality. One exception is female facial masculinity - generally regarded as an unattractive marker of a low biological quality - which, too, is associated with higher spouse age disparity. In general, our results show that facial symmetry, averageness, and secondary sexual characteristics may play a role in age-dependent mate choice. We suggest that in marriages where the wife is considerably younger than the husband, wife's greater facial masculinity may increase her perceived age and with it, her perceived maturity. Copyright © 2016 Elsevier GmbH. All rights reserved.

Reversible modulation of SIRT1 activity in a mouse strain

PubMed Central

Clark-Knowles, Katherine V.; He, Xiaohong; Jardine, Karen; Coulombe, Josée; Dewar-Darch, Danielle; Caron, Annabelle Z.

2017-01-01

The SIRT1 protein deacetylase is reported to have a remarkably wide spectrum of biological functions affecting such varied processes as aging, cancer, metabolism, neurodegeneration and immunity. However, the SIRT1 literature is also full of contradictions. To help establish the role(s) of SIRT1 in these and other biological processes, we set out to create a mouse in which the SIRT1 activity could be toggled between on and off states by fusing the estrogen receptor ligand-binding domain (ER) to the C terminus of the SIRT1 protein. We found that the catalytic activity of the SIRT1-ER fusion protein increased 4–5 fold in cells treated with its ligand, 4-hydroxy-tamoxifen (4OHT). The 4OHT-induced activation of SIRT1-ER was due in large part to a 2 to 4-fold increase in abundance of the SIRT1-ER protein in cells in culture and in tissues in vivo. This increase is reversible and is a consequence of 4OHT-induced stabilization of the SIRT1-ER protein. Since changes in SIRT1 level or activity of 2–4 fold are frequently reported to be sufficient to affect its biological functions, this mouse should be helpful in establishing the causal relationships between SIRT1 and the diseases and processes it affects. PMID:28273169

Unified theory of Alzheimer's disease (UTAD): implications for prevention and curative therapy.

PubMed

Nehls, Michael

2016-01-01

The aim of this review is to propose a Unified Theory of Alzheimer's disease (UTAD) that integrates all key behavioural, genetic and environmental risk factors in a causal chain of etiological and pathogenetic events. It is based on three concepts that emanate from human's evolutionary history: (1) The grandmother-hypothesis (GMH), which explains human longevity due to an evolutionary advantage in reproduction by trans-generational transfer of acquired knowledge. Consequently it is argued that mental health at old-age must be the default pathway of humans' genetic program and not development of AD. (2) Therefore, mechanism like neuronal rejuvenation (NRJ) and adult hippocampal neurogenesis (AHN) that still function efficiently even at old age provide the required lifelong ability to memorize personal experiences important for survival. Cumulative evidence from a multitude of experimental and epidemiological studies indicate that behavioural and environmental risk factors, which impair productive AHN, result in reduced episodic memory performance and in reduced psychological resilience. This leads to avoidance of novelty, dysregulation of the hypothalamic-pituitary-adrenal (HPA)-axis and cortisol hypersecretion, which drives key pathogenic mechanisms of AD like the accumulation and oligomerization of synaptotoxic amyloid beta, chronic neuroinflammation and neuronal insulin resistance. (3) By applying to AHN the law of the minimum (LOM), which defines the basic requirements of biological growth processes, the UTAD explains why and how different lifestyle deficiencies initiate the AD process by impairing AHN and causing dysregulation of the HPA-axis, and how environmental and genetic risk factors such as toxins or ApoE4, respectively, turn into disease accelerators under these unnatural conditions. Consequently, the UTAD provides a rational strategy for the prevention of mental decline and a system-biological approach for the causal treatment of AD, which might even be curative if the systemic intervention is initiated early enough in the disease process. Hence an individualized system-biological treatment of patients with early AD is proposed as a test for the validity of UTAD and outlined in this review.

From the bush to the bench: the annual Nothobranchius fishes as a new model system in biology.

PubMed

Cellerino, Alessandro; Valenzano, Dario R; Reichard, Martin

2016-05-01

African annual fishes from the genus Nothobranchius are small teleosts that inhabit temporary water bodies subject to annual desiccation due to the alternation of the monsoon seasons. Given their unique biology, these fish have emerged as a model taxon in several biological disciplines. Their increasing popularity stems from the extremely short lifespan that is the result of their specific life-history adaptations and is retained under laboratory conditions. Nothobranchius furzeri, the most popular laboratory species, is the vertebrate species with the shortest lifespan recorded in captivity. In the laboratory, adults of different Nothobranchius species and populations live between 3 and 18 months and, notably, there is a negative correlation between the captive lifespan of a species and the aridity of their habitat. Their short lifespan is coupled to rapid age-dependent functional decline and expression of cellular and molecular changes comparable to those observed in other vertebrates, including humans. The recent development of transgenesis in this species makes it possible to insert specific constructs into their genome, and the establishment of transgenic lines is facilitated by their very rapid generation time, which can be as short as 1 month. This makes Nothobranchius species particularly suited for investigating biological and molecular aspects of ageing and ageing-associated dysfunctions. At the same time, they also represent a unique model taxon to investigate the evolution of life-history adaptations and their genetic architecture. We review their natural history, including phylogenetic relationships, distribution in relation to habitat conditions and natural selection for differential longevity, population structure and demography, and life cycle with emphasis on diapause that may occur at three stages during embryonic development. We further critically evaluate their use as a laboratory model for understanding the evolution of a rapid ageing rate and its consequences for other life-history traits, for cellular, molecular and integrative traits associated with the ageing process, high incidence of neoplasias, their utility for genome-wide gene-expression studies, and as a model for quantitative genetics. We summarize recent achievements in fostering Nothobranchius species as a widely applicable model system, including an annotated transcriptome, successful transgenesis, and existence of viable inbred lines. We compare the conditions they experience in the wild and in captivity and suggest that they are an ideal taxon to investigate natural genetic variation in a laboratory setting. We conclude that Nothobranchius species - and N. furzeri in particular - could become a unique model taxon that bridges interests in ecological and biomedical research. We hope that a conceptual and methodological integration of these two branches of biology will provide important new insights. © 2015 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.

Quantitative measures of healthy aging and biological age

PubMed Central

Kim, Sangkyu; Jazwinski, S. Michal

2015-01-01

Numerous genetic and non-genetic factors contribute to aging. To facilitate the study of these factors, various descriptors of biological aging, including ‘successful aging’ and ‘frailty’, have been put forth as integrative functional measures of aging. A separate but related quantitative approach is the ‘frailty index’, which has been operationalized and frequently used. Various frailty indices have been constructed. Although based on different numbers and types of health variables, frailty indices possess several common properties that make them useful across different studies. We have been using a frailty index termed FI34 based on 34 health variables. Like other frailty indices, FI34 increases non-linearly with advancing age and is a better indicator of biological aging than chronological age. FI34 has a substantial genetic basis. Using FI34, we found elevated levels of resting metabolic rate linked to declining health in nonagenarians. Using FI34 as a quantitative phenotype, we have also found a genomic region on chromosome 12 that is associated with healthy aging and longevity. PMID:26005669

Applications of physiological bases of ageing to forensic sciences. Estimation of age-at-death.

PubMed

C Zapico, Sara; Ubelaker, Douglas H

2013-03-01

Age-at-death estimation is one of the main challenges in forensic sciences since it contributes to the identification of individuals. There are many anthropological techniques to estimate the age at death in children and adults. However, in adults this methodology is less accurate and requires population specific references. For that reason, new methodologies have been developed. Biochemical methods are based on the natural process of ageing, which induces different biochemical changes that lead to alterations in cells and tissues. In this review, we describe different attempts to estimate the age in adults based on these changes. Chemical approaches imply modifications in molecules or accumulation of some products. Molecular biology approaches analyze the modifications in DNA and chromosomes. Although the most accurate technique appears to be aspartic acid racemization, it is important to take into account the other techniques because the forensic context and the human remains available will determine the possibility to apply one or another methodology. Copyright © 2013 Elsevier B.V. All rights reserved.

Selected Issues on Aging.

ERIC Educational Resources Information Center

Gordon, Ruby D.

Aging is a continuum which begins at birth and ends at death. A multidisciplinary approach is necessary to the study of aging as a part of developmental psychology. The individual is a biological organism as well as a member of society. Biological adjustments to life are affected by physical changes which influence motives and emotions. Some of…

Longer leukocyte telomere length in Costa Rica's Nicoyan Peninsula: A population-based study

PubMed Central

Rehkopf, David H; Dow, William H; Rosero-Bixby, Luis; Lin, Jue; Epel, Elissa S; Blackburn, Elizabeth H

2013-01-01

Studies in humans suggest that leukocyte telomere length may act as a marker of biological aging. We investigated whether individuals in the Nicoya region of Costa Rica, known for exceptional longevity, had longer telomere length than those in other parts of the country. After controlling for age, age squared, rurality, rainy season and gender, mean leukocyte telomere length in Nicoya was substantially longer (81 base pairs, p<0.05) than in other areas of Costa Rica, providing evidence of a biological pathway to which this notable longevity may be related. This relationship remains unchanged (79 base pairs, p<0.05) after statistically controlling for nineteen potential biological, dietary and social and demographic mediators. Thus the difference in mean leukocyte telomere length that characterizes this unique region does not appear to be explainable by traditional behavioral and biological risk factors. More detailed examination of mean leukocyte telomere length by age shows that the regional telomere length difference declines at older ages. PMID:23988653

Age Effects on Hypocotyl Mechanics.

PubMed

Saxe, Friederike; Weichold, Susann; Reinecke, Antje; Lisec, Jan; Döring, Anett; Neumetzler, Lutz; Burgert, Ingo; Eder, Michaela

2016-01-01

Numerous studies deal with composition and molecular processes involved in primary cell wall formation and alteration in Arabidopsis. However, it still remains difficult to assess the relation between physiological properties and mechanical function at the cell wall level. The thin and fragile structure of primary cell walls and their large biological variability, partly related to structural changes during growth, make mechanical experiments challenging. Since, to the best of our knowledge, there is no reliable data in the literature about how the properties of the fully elongated zone of hypocotyls change with age. We studied in a series of experiments on two different seed batches the tensile properties the region below the growth zone of 4 to 7 day old etiolated Arabidopsis hypocotyls. Additionally, we analysed geometrical parameters, hypocotyl density and cellulose content as individual traits and their relation to tissue mechanics. No significant differences of the mechanical parameters of the non-growing region between 5-7 day old plants could be found whereas in 4 day old plants both tensile stiffness and ultimate tensile stress were significantly lower than in the older plants. Furthermore hypocotyl diameters and densities remain almost the same for 5, 6 and 7 day old seedlings. Naturally, hypocotyl lengths increase with age. The evaluation whether the choice-age or length-influences the mechanical properties showed that both are equally applicable sampling parameters. Additionally, our detailed study allows for the estimation of biological variability, connections between mechanics and hypocotyl age could be established and complement the knowledge on biochemistry and genetics affecting primary plant cell wall growth. The application of two different micromechanical devices for testing living Arabidopsis hypocotyls allows for emphasizing and discussing experimental limitations and for presenting a wide range of possibilities to address current and future questions related to plant cell wall mechanics, synthesis and growth in combination with molecular biology methodologies.

Ultraviolet light treatment for the restoration of age-related degradation of titanium bioactivity.

PubMed

Hori, Norio; Ueno, Takeshi; Suzuki, Takeo; Yamada, Masahiro; Att, Wael; Okada, Shunsaku; Ohno, Akinori; Aita, Hideki; Kimoto, Katsuhiko; Ogawa, Takahiro

2010-01-01

To examine the bioactivity of differently aged titanium (Ti) disks and to determine whether ultraviolet (UV) light treatment reverses the possible adverse effects of Ti aging. Ti disks with three different surface topographies were prepared: machined, acid-etched, and sandblasted. The disks were divided into three groups: disks tested for biologic capacity immediately after processing (fresh surfaces), disks stored under dark ambient conditions for 4 weeks, and disks stored for 4 weeks and treated with UV light. The protein adsorption capacity of Ti was examined using albumin and fibronectin. Cell attraction to Ti was evaluated by examining migration, attachment, and spreading behaviors of human osteoblasts on Ti disks. Osteoblast differentiation was evaluated by examining alkaline phosphatase activity, the expression of bone-related genes, and mineralized nodule area in the culture. Four-week-old Ti disks showed = or < 50% protein adsorption after 6 hours of incubation compared with fresh disks, regardless of surface topography. Total protein adsorption for 4-week-old surfaces did not reach the level of fresh surfaces, even after 24 hours of incubation. Fifty percent fewer human osteoblasts migrated and attached to 4-week-old surfaces compared with fresh surfaces. Alkaline phosphatase activity, gene expression, and mineralized nodule area were substantially reduced on the 4-week-old surfaces. The reduction of these biologic parameters was associated with the conversion of Ti disks from superhydrophilicity to hydrophobicity during storage for 4 weeks. UV-treated 4-week-old disks showed even higher protein adsorption, osteoblast migration, attachment, differentiation, and mineralization than fresh surfaces, and were associated with regenerated superhydrophilicity. Time-related degradation of Ti bioactivity is substantial and impairs the recruitment and function of human osteoblasts as compared to freshly prepared Ti surfaces, suggesting a "biologic aging"-like change of Ti. UV treatment of aged Ti, however, restores and even enhances bioactivity, exceeding its innate levels.

Music models aberrant rule decoding and reward valuation in dementia

PubMed Central

Clark, Camilla N; Golden, Hannah L; McCallion, Oliver; Nicholas, Jennifer M; Cohen, Miriam H; Slattery, Catherine F; Paterson, Ross W; Fletcher, Phillip D; Mummery, Catherine J; Rohrer, Jonathan D; Crutch, Sebastian J; Warren, Jason D

2018-01-01

Abstract Aberrant rule- and reward-based processes underpin abnormalities of socio-emotional behaviour in major dementias. However, these processes remain poorly characterized. Here we used music to probe rule decoding and reward valuation in patients with frontotemporal dementia (FTD) syndromes and Alzheimer’s disease (AD) relative to healthy age-matched individuals. We created short melodies that were either harmonically resolved (‘finished’) or unresolved (‘unfinished’); the task was to classify each melody as finished or unfinished (rule processing) and rate its subjective pleasantness (reward valuation). Results were adjusted for elementary pitch and executive processing; neuroanatomical correlates were assessed using voxel-based morphometry. Relative to healthy older controls, patients with behavioural variant FTD showed impairments of both musical rule decoding and reward valuation, while patients with semantic dementia showed impaired reward valuation but intact rule decoding, patients with AD showed impaired rule decoding but intact reward valuation and patients with progressive non-fluent aphasia performed comparably to healthy controls. Grey matter associations with task performance were identified in anterior temporal, medial and lateral orbitofrontal cortices, previously implicated in computing diverse biological and non-biological rules and rewards. The processing of musical rules and reward distils cognitive and neuroanatomical mechanisms relevant to complex socio-emotional dysfunction in major dementias. PMID:29186630

Cancer and genetics: what we need to know now.

PubMed

Ruccione, K

1999-07-01

Profound changes brought about by discoveries in molecular biology may enable us in the future to treat cancer without causing late effects or to prevent cancer altogether. Even before that happens, the age of molecular medicine has arrived. Molecular biology is the study of biological processes at the level of the molecule. A major aspect of molecular biology is molecular genetics--the science that deals with DNA and RNA. Most of the progress in molecular biology has been made in the second half of the 20th century. Each discovery or technological innovation has built on previous discoveries and paved the way for the next, culminating in the current effort to map, sequence, and understand the functions of the entire human genome. In the past 20 years, many pieces of the cancer puzzle have been found, showing us how the normal cellular control mechanisms go awry to cause cancer and setting the stage for genetic testing and disease treatment. These new discoveries bring both promise and peril. To provide comprehensive care for survivors of childhood cancer and care in other settings as well, health care providers must now be familiar with the concepts and language of molecular biology, understand its applications to cancer care, and be fully informed about its implications for clinical practice, research, and education.

Adoption consideration and concerns among young adult female cancer survivors.

PubMed

Gorman, Jessica R; Whitcomb, Brian W; Standridge, Daniel; Malcarne, Vanessa L; Romero, Sally A D; Roberts, Samantha A; Su, H Irene

2017-02-01

We compared adoption consideration between female young adult cancer survivors and women of the same age in the general US population, hypothesizing that cancer survivors who desired children would report greater interest in adoption than an age-adjusted general population sample who desired children. After age-standardizing the cancer survivor cohort to match the age distribution of the 2006-2010 National Survey for Family Growth (NSFG), we estimated adoption consideration among women age 18-35 years who wanted a (another) child in the two cohorts overall and within age groups. We assessed characteristics and concerns related to adoption consideration among cancer survivors. Among cancer survivors, 81.6 % (95 % CI 75.7-87.6) reported that they would consider adoption compared to 40.3 % (95 % CI 40.3-40.3) of women in the general population. While over 80 % of the cancer survivor sample reported that they would consider adoption, only 15 % of cancer survivors reported no concerns about adoption. The most common concerns were desire for a biological child (48 %), expense (45 %), adoption agency candidacy (41 %), and needing more information (39 %). We observed a twofold higher interest in adoption when comparing the cancer survivor with the general population, suggesting that adoption is a consideration for many young women who have survived cancer. Adoption is an important family-building option for those who want to have a child but are unable to or choose not to have a biological child. However, young adult survivors may need more support to understand and navigate this process.

An Overview of Non-pathological Geroneuropsychology: Implications for Nursing Practice and Research

PubMed Central

Graham, Martha A.; Fazeli, Pariya L.; Heaton, Karen; Moneyham, Linda

2011-01-01

One aspect of successful aging is maintaining cognitive functioning; that includes both subjective cognitive functioning and objective cognitive functioning even in lieu of subtle cognitive deficits that occur with normal, non-pathological aging. Age-related cognitive deficits emerge across several domains including attention, memory, language, speed of processing, executive, and psychomotor, just to name a few. A primary theory explaining such cognitive deficits is cognitive reserve theory; it posits that biological factors such as demyelination and oxidative stress interfere with neuronal communication which eventually produces observable deficits in cognitive functioning. Therefore, it is important to maintain or improve cognitive reserve in order to augment cognitive functioning in later life. This article provides a general overview of the principles of geroneuropsychology along with implications for nursing practice and research. PMID:22210304

Effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients.

PubMed

Hung, Man-Hsin; Liu, Chun-Yu; Shiau, Cheng-Ying; Hsu, Chin-Yi; Tsai, Yi-Fang; Wang, Yu-Ling; Tai, Ling-Chen; King, Kuang-Liang; Chao, Ta-Chung; Chiu, Jen-Hwey; Su, Cheng-Hsi; Lo, Su-Shun; Tzeng, Cheng-Hwai; Shyr, Yi-Ming; Tseng, Ling-Ming

2014-01-01

Brain metastasis is a major complication of breast cancer. This study aimed to analyze the effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients. We identified subtypes of invasive ductal carcinoma of the breast by determining estrogen receptor, progesterone receptor and HER2 status. Time to brain metastasis according to age and cancer subtype was analyzed by Cox proportional hazard analysis. Of the 2248 eligible patients, 164 (7.3%) developed brain metastasis over a median follow-up of 54.2 months. Age 35 or younger, HER2-enriched subtype, and triple-negative breast cancer were significant risk factors of brain metastasis. Among patients aged 35 or younger, the risk of brain metastasis was independent of biological subtype (P = 0.507). Among patients aged 36-59 or >60 years, those with triple-negative or HER2-enriched subtypes had consistently increased risk of brain metastasis, as compared with those with luminal A tumors. Patients with luminal B tumors had higher risk of brain metastasis than luminal A only in patients >60 years. Breast cancer subtypes are associated with differing risks of brain metastasis among different age groups. Patients age 35 or younger are particularly at risk of brain metastasis independent of biological subtype.

Matrix ageing and vascular impacts: focus on elastin fragmentation.

PubMed

Duca, Laurent; Blaise, Sébastien; Romier, Béatrice; Laffargue, Muriel; Gayral, Stéphanie; El Btaouri, Hassan; Kawecki, Charlotte; Guillot, Alexandre; Martiny, Laurent; Debelle, Laurent; Maurice, Pascal

2016-06-01

Cardiovascular diseases (CVDs) are the leading cause of death worldwide and represent a major problem of public health. Over the years, life expectancy has considerably increased throughout the world, and the prevalence of CVD is inevitably rising with the growing ageing of the population. The normal process of ageing is associated with progressive deterioration in structure and function of the vasculature, commonly called vascular ageing. At the vascular level, extracellular matrix (ECM) ageing leads to molecular alterations in long half-life proteins, such as elastin and collagen, and have critical effects on vascular diseases. This review highlights ECM alterations occurring during vascular ageing with a specific focus on elastin fragmentation and also the contribution of elastin-derived peptides (EDP) in age-related vascular complications. Moreover, current and new pharmacological strategies aiming at minimizing elastin degradation, EDP generation, and associated biological effects are discussed. These strategies may be of major relevance for preventing and/or delaying vascular ageing and its complications. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

The Aging of Iron Man

PubMed Central

Ashraf, Azhaar; Clark, Maryam; So, Po-Wah

2018-01-01

Brain iron is tightly regulated by a multitude of proteins to ensure homeostasis. Iron dyshomeostasis has become a molecular signature associated with aging which is accompanied by progressive decline in cognitive processes. A common theme in neurodegenerative diseases where age is the major risk factor, iron dyshomeostasis coincides with neuroinflammation, abnormal protein aggregation, neurodegeneration, and neurobehavioral deficits. There is a great need to determine the mechanisms governing perturbations in iron metabolism, in particular to distinguish between physiological and pathological aging to generate fruitful therapeutic targets for neurodegenerative diseases. The aim of the present review is to focus on the age-related alterations in brain iron metabolism from a cellular and molecular biology perspective, alongside genetics, and neuroimaging aspects in man and rodent models, with respect to normal aging and neurodegeneration. In particular, the relationship between iron dyshomeostasis and neuroinflammation will be evaluated, as well as the effects of systemic iron overload on the brain. Based on the evidence discussed here, we suggest a synergistic use of iron-chelators and anti-inflammatories as putative anti-brain aging therapies to counteract pathological aging in neurodegenerative diseases. PMID:29593525

Family-centered prevention ameliorates the longitudinal association between risky family processes and epigenetic aging.

PubMed

Brody, Gene H; Yu, Tianyi; Chen, Edith; Beach, Steven R H; Miller, Gregory E

2016-05-01

Research has suggested that 'risky' family processes have unforeseen negative consequences for health later in life. The purpose of this study was to further understanding of risky family environments and development of health vulnerabilities by (a) examining the likelihood that elevated levels of parental depressive symptoms when children are age 11 forecast accelerated epigenetic aging 9 years later at age 20; (b) determining whether participation in an efficacious family-centered prevention program focused on enhancing supportive parenting and strengthening family relationships will ameliorate this association; and (c) testing a moderation-mediation hypothesis that prevention-induced reductions in harsh parenting across adolescence will account for prevention effects in reducing accelerated epigenetic aging. In the rural southeastern United States, parents and 11-year-old children from 399 families participated in the Strong African American Families (SAAF) program or a control condition. Parents reported their own depressive symptoms when their children were 11, and both youths and parents reported youth exposure to harsh parenting at ages 11 and 16. Blood was drawn from youths at age 20 to measure accelerated epigenetic aging using a marker derived from the DNA methylation of cells. Elevated parental depressive symptoms forecast accelerated epigenetic aging among youths in the control condition, but not among SAAF participants. Moderated-mediation analyses confirmed that reductions in harsh parenting accounted for SAAF's protective effects on epigenetic aging. Subsequent exploratory analyses indicated that accelerated epigenetic aging forecast emotional distress among young adults in the control condition but not among those who participated in SAAF. This study is unique in using a randomized prevention trial to test hypotheses about the ways risky family processes contribute to accelerated epigenetic aging. The results suggest that developmentally appropriate family-centered interventions designed to enhance parenting and strengthen families can buffer the biological residue of life in a risky family. © 2015 Association for Child and Adolescent Mental Health.

MicroRNAs (MiRs) Precisely Regulate Immune System Development and Function in Immunosenescence Process.

PubMed

Aalaei-Andabili, Seyed Hossein; Rezaei, Nima

2016-01-01

Human aging is a complex process with pivotal changes in gene expression of biological pathways. Immune system dysfunction has been recognized as one of the most important abnormalities induced by senescent names immunosenescence. Emerging evidences suggest miR role in immunosenescence. We aimed to systemically review all relevant reports to clearly state miR effects on immunosenescence process. Sensitive electronic searches carried out. Quality assessment has been performed. Since majority of the included studies were laboratory works, and therefore heterogen, we discussed miR effects on immunological aging process nonstatically. Forty-six articles were found in the initial search. After exclusion of 34 articles, 12 studies enrolled to the final stage. We found that miRs have crucial roles in exact function of immune system. MiRs are involved in the regulation of the aging process in the immune system components and target certain genes, promoting or inhibiting immune system reaction to invasion. Also, miRs control life span of the immune system members by regulation of the genes involved in the apoptosis. Interestingly, we found that immunosenescence is controllable by proper manipulation of the various miRs expression. DNA methylation and histone acetylation have been discovered as novel strategies, altering NF-κB binding ability to the miR promoter sites. Effect of miRs on impairment of immune system function due to the aging is emerging. Although it has been accepted that miRs have determinant roles in the regulation of the immunosenescence; however, most of the reports are concluded from animal/laboratory works, suggesting the necessity of more investigations in human.

Integration of chemical and toxicological tools to assess the bioavailability of copper derived from different copper-based fungicides in soil.

PubMed

Wang, Quan-Ying; Sun, Jing-Yue; Xu, Xing-Jian; Yu, Hong-Wen

2018-06-20

Because the extensive use of Cu-based fungicides, the accumulation of Cu in agricultural soil has been widely reported. However, little information is known about the bioavailability of Cu deriving from different fungicides in soil. This paper investigated both the distribution behaviors of Cu from two commonly used fungicides (Bordeaux mixture and copper oxychloride) during the aging process and the toxicological effects of Cu on earthworms. Copper nitrate was selected as a comparison during the aging process. The distribution process of exogenous Cu into different soil fractions involved an initial rapid retention (the first 8 weeks) and a following slow continuous retention. Moreover, Cu mainly moved from exchangeable and carbonate fractions to Fe-Mn oxides-combined fraction during the aging process. The Elovich model fit well with the available Cu aging process, and the transformation rate was in the order of Cu(NO 3 ) 2 > Bordeaux mixture > copper oxychloride. On the other hand, the biological responses of earthworms showed that catalase activities and malondialdehyde contents of the copper oxychloride treated earthworms were significantly higher than those of Bordeaux mixture treated earthworms. Also, body Cu loads of earthworms from different Cu compounds spiked soils were in the following order: copper oxychloride > Bordeaux mixture. Thus, the bioavailability of Cu from copper oxychloride in soil was significantly higher than that of Bordeaux mixture, and different Cu compounds should be taken into consideration when studying the bioavailability of Cu-based fungicides in the soil. Copyright © 2018 Elsevier Inc. All rights reserved.

Controversy in Biology Classrooms-Citizen Science Approaches to Evolution and Applications to Climate Change Discussions.

PubMed

Yoho, Rachel A; Vanmali, Binaben H

2016-03-01

The biological sciences encompass topics considered controversial by the American public, such as evolution and climate change. We believe that the development of climate change education in the biology classroom is better informed by an understanding of the history of the teaching of evolution. A common goal for science educators should be to engender a greater respect for and appreciation of science among students while teaching specific content knowledge. Citizen science has emerged as a viable yet underdeveloped method for engaging students of all ages in key scientific issues that impact society through authentic data-driven scientific research. Where successful, citizen science may open avenues of communication and engagement with the scientific process that would otherwise be more difficult to achieve. Citizen science projects demonstrate versatility in education and the ability to test hypotheses by collecting large amounts of often publishable data. We find a great possibility for science education research in the incorporation of citizen science projects in curriculum, especially with respect to "hot topics" of socioscientific debate based on our review of the findings of other authors. Journal of Microbiology & Biology Education.

[Therapy for childhood uveitis: biologics: too often--too late?].

PubMed

Mackensen, F; Lutz, T

2011-03-01

Pediatric uveitis differs from uveitis seen in adulthood not only because of the uveitis presentation and severity of disease but also by a worse prognosis and age-specific problems that may occur under therapy. Biologics are selective acting proteins that are manufactured by biotechnology. The greatest amount of knowledge to date exists for the TNF alpha blocking agents. Experimental and clinical studies showed that TNF alpha plays a significant role in the process of intraocular inflammation, so it was a logical step to use TNF blocking agents in uveitis therapy. Randomized controlled studies are rare, but pooled data (as presented here) of case series published show good evidence for the efficacy especially of infliximab and adalimumab. It is to be hoped that blindness and severe sight disabilities can be further reduced by this treatment in the future. From pediatric rheumatology we have learned about even newer biologics. With this review we want to show the weaknesses and strengths of therapy with biologics and want to help in choosing this treatment at the indicated time point in the disease.

An open future for ecological and evolutionary data?

PubMed

Kenall, Amye; Harold, Simon; Foote, Christopher

2014-04-02

As part of BioMed Central's open science mission, we are pleased to announce that two of our journals have integrated with the open data repository Dryad. Authors submitting their research to either BMC Ecology or BMC Evolutionary Biology will now have the opportunity to deposit their data directly into the Dryad archive and will receive a permanent, citable link to their dataset. Although this does not affect any of our current data deposition policies at these journals, we hope to encourage a more widespread adoption of open data sharing in the fields of ecology and evolutionary biology by facilitating this process for our authors. We also take this opportunity to discuss some of the wider issues that may concern researchers when making their data openly available. Although we offer a number of positive examples from different fields of biology, we also recognise that reticence to data sharing still exists, and that change must be driven from within research communities in order to create future science that is fit for purpose in the digital age. This editorial was published jointly in both BMC Ecology and BMC Evolutionary Biology.

Physiological links of circadian clock and biological clock of aging.

PubMed

Liu, Fang; Chang, Hung-Chun

2017-07-01

Circadian rhythms orchestrate biochemical and physiological processes in living organisms to respond the day/night cycle. In mammals, nearly all cells hold self-sustained circadian clocks meanwhile couple the intrinsic rhythms to systemic changes in a hierarchical manner. The suprachiasmatic nucleus (SCN) of the hypothalamus functions as the master pacemaker to initiate daily synchronization according to the photoperiod, in turn determines the phase of peripheral cellular clocks through a variety of signaling relays, including endocrine rhythms and metabolic cycles. With aging, circadian desynchrony occurs at the expense of peripheral metabolic pathologies and central neurodegenerative disorders with sleep symptoms, and genetic ablation of circadian genes in model organisms resembled the aging-related features. Notably, a number of studies have linked longevity nutrient sensing pathways in modulating circadian clocks. Therapeutic strategies that bridge the nutrient sensing pathways and circadian clock might be rational designs to defy aging.

Sensory Perception and Aging in Model Systems: From the Outside In

PubMed Central

Linford, Nancy J.; Kuo, Tsung-Han; Chan, Tammy P.; Pletcher, Scott D.

2014-01-01

Sensory systems provide organisms from bacteria to human with the ability to interact with the world. Numerous senses have evolved that allow animals to detect and decode cues from sources in both their external and internal environments. Recent advances in understanding the central mechanisms by which the brains of simple organisms evaluate different cues and initiate behavioral decisions, coupled with observations that sensory manipulations are capable of altering organism lifespan, have opened the door for powerful new research into aging. While direct links between sensory perception and aging have been established only recently, here we discuss these initial discoveries and evaluate the potential for different forms of sensory processing to modulate lifespan across taxa. Harnessing the neurobiology of simple model systems to study the biological impact of sensory experiences will yield insights into the broad influence of sensory perception in mammals and may help uncover new mechanisms of healthy aging. PMID:21756108

Sensory perception and aging in model systems: from the outside in.

PubMed

Linford, Nancy J; Kuo, Tsung-Han; Chan, Tammy P; Pletcher, Scott D

2011-01-01

Sensory systems provide organisms from bacteria to humans with the ability to interact with the world. Numerous senses have evolved that allow animals to detect and decode cues from sources in both their external and internal environments. Recent advances in understanding the central mechanisms by which the brains of simple organisms evaluate different cues and initiate behavioral decisions, coupled with observations that sensory manipulations are capable of altering organismal lifespan, have opened the door for powerful new research into aging. Although direct links between sensory perception and aging have been established only recently, here we discuss these initial discoveries and evaluate the potential for different forms of sensory processing to modulate lifespan across taxa. Harnessing the neurobiology of simple model systems to study the biological impact of sensory experiences will yield insights into the broad influence of sensory perception in mammals and may help uncover new mechanisms of healthy aging.

An Old Problem: Aging and Skeletal-Muscle-Strain Injury.

PubMed

Baker, Brent A

2017-04-01

Clinical Scenario: Even though chronological aging is an inevitable phenomenological consequence occurring in every living organism, it is biological aging that may be the most significant factor challenging our quality of life. Development of functional limitations, resulting from improper maintenance and restoration of various organ systems, ultimately leads to reduced health and independence. Skeletal muscle is an organ system that, when challenged, is often injured in response to varying stimuli. Overt muscle-strain injury can be traumatic, clinically diagnosable, properly managed, and a remarkably common event, yet our contemporary understanding of how age and environmental stressors affect the initial and subsequent induction of injury and how the biological processes resulting from this event are modifiable and, eventually, lead to functional restoration and healing of skeletal muscle and adjacent tissues is presently unclear. Even though the secondary injury response to and recovery from "contraction-induced" skeletal-muscle injury are impaired with aging, there is no scientific consensus as to the exact mechanism responsible for this event. Given the multitude of investigative approaches, particular consideration given to the appropriateness of the muscle-injury model, or research paradigm, is critical so that outcomes may be physiologically relevant and translational. In this case, methods implementing stretch-shortening contractions, the most common form of muscle movements used by all mammals during physical movement, work, and activity, are highlighted. Understanding the fundamental evidence regarding how aging influences the responsivity of skeletal muscle to strain injury is vital for informing how clinicians approach and implement preventive strategies, as well as therapeutic interventions. From a practical perspective, maintaining or improving the overall health and tissue quality of skeletal muscle as one ages will positively affect skeletal muscle's safety threshold and responsivity, which may reduce incidence of injury, improve recovery time, and lessen overall fiscal burdens.

Adverse Childhood and Recent Negative Life Events: Contrasting Associations With Cognitive Decline in Older Persons.

PubMed

Korten, Nicole C M; Penninx, Brenda W J H; Pot, Anne Margriet; Deeg, Dorly J H; Comijs, Hannie C

2014-06-01

To examine whether persons who experienced adverse childhood events or recent negative life events have a worse cognitive performance and faster cognitive decline and the role of depression and apolipoprotein E-∊4 in this relationship. The community-based sample consisted of 10-year follow-up data of 1312 persons participating in the Longitudinal Aging Study Amsterdam (age range 65-85 years). Persons who experienced adverse childhood events showed a faster 10-year decline in processing speed but only when depressive symptoms were experienced. Persons with more recent negative life events showed slower processing speed at baseline but no faster decline. Childhood adversity may cause biological or psychological vulnerability, which is associated with both depressive symptoms and cognitive decline in later life. The accumulation of recent negative life events did not affect cognitive functioning over a longer time period. © The Author(s) 2014.

Clock-like mutational processes in human somatic cells

DOE PAGES

Alexandrov, Ludmil B.; Jones, Philip H.; Wedge, David C.; ...

2015-11-09

During the course of a lifetime, somatic cells acquire mutations. Different mutational processes may contribute to the mutations accumulated in a cell, with each imprinting a mutational signature on the cell's genome. Some processes generate mutations throughout life at a constant rate in all individuals, and the number of mutations in a cell attributable to these processes will be proportional to the chronological age of the person. Using mutations from 10,250 cancer genomes across 36 cancer types, we investigated clock-like mutational processes that have been operating in normal human cells. Two mutational signatures show clock-like properties. Both exhibit different mutationmore » rates in different tissues. However, their mutation rates are not correlated, indicating that the underlying processes are subject to different biological influences. For one signature, the rate of cell division may influence its mutation rate. This paper provides the first survey of clock-like mutational processes operating in human somatic cells.« less

Clock-like mutational processes in human somatic cells

PubMed Central

Alexandrov, Ludmil B.; Jones, Philip H.; Wedge, David C.; Sale, Julian E.; Campbell, Peter J.; Nik-Zainal, Serena; Stratton, Michael R.

2016-01-01

During the course of a lifetime somatic cells acquire mutations. Different mutational processes may contribute to the mutations accumulated in a cell, with each imprinting a mutational signature on the cell’s genome. Some processes generate mutations throughout life at a constant rate in all individuals and the number of mutations in a cell attributable to these processes will be proportional to the chronological age of the person. Using mutations from 10,250 cancer genomes across 36 cancer types, we investigated clock-like mutational processes that have been operating in normal human cells. Two mutational signatures show clock-like properties. Both exhibit different mutation rates in different tissues. However, their mutation rates are not correlated indicating that the underlying processes are subject to different biological influences. For one signature, the rate of cell division may influence its mutation rate. This study provides the first survey of clock-like mutational processes operative in human somatic cells. PMID:26551669

Genomic signatures of adaptation to wine biological ageing conditions in biofilm-forming flor yeasts.

PubMed

Coi, A L; Bigey, F; Mallet, S; Marsit, S; Zara, G; Gladieux, P; Galeote, V; Budroni, M; Dequin, S; Legras, J L

2017-04-01

The molecular and evolutionary processes underlying fungal domestication remain largely unknown despite the importance of fungi to bioindustry and for comparative adaptation genomics in eukaryotes. Wine fermentation and biological ageing are performed by strains of S. cerevisiae with, respectively, pelagic fermentative growth on glucose and biofilm aerobic growth utilizing ethanol. Here, we use environmental samples of wine and flor yeasts to investigate the genomic basis of yeast adaptation to contrasted anthropogenic environments. Phylogenetic inference and population structure analysis based on single nucleotide polymorphisms revealed a group of flor yeasts separated from wine yeasts. A combination of methods revealed several highly differentiated regions between wine and flor yeasts, and analyses using codon-substitution models for detecting molecular adaptation identified sites under positive selection in the high-affinity transporter gene ZRT1. The cross-population composite likelihood ratio revealed selective sweeps at three regions, including in the hexose transporter gene HXT7, the yapsin gene YPS6 and the membrane protein coding gene MTS27. Our analyses also revealed that the biological ageing environment has led to the accumulation of numerous mutations in proteins from several networks, including Flo11 regulation and divalent metal transport. Together, our findings suggest that the tuning of FLO11 expression and zinc transport networks are a distinctive feature of the genetic changes underlying the domestication of flor yeasts. Our study highlights the multiplicity of genomic changes underlying yeast adaptation to man-made habitats and reveals that flor/wine yeast lineage can serve as a useful model for studying the genomics of adaptive divergence. © 2017 John Wiley & Sons Ltd.

svdPPCS: an effective singular value decomposition-based method for conserved and divergent co-expression gene module identification.

PubMed

Zhang, Wensheng; Edwards, Andrea; Fan, Wei; Zhu, Dongxiao; Zhang, Kun

2010-06-22

Comparative analysis of gene expression profiling of multiple biological categories, such as different species of organisms or different kinds of tissue, promises to enhance the fundamental understanding of the universality as well as the specialization of mechanisms and related biological themes. Grouping genes with a similar expression pattern or exhibiting co-expression together is a starting point in understanding and analyzing gene expression data. In recent literature, gene module level analysis is advocated in order to understand biological network design and system behaviors in disease and life processes; however, practical difficulties often lie in the implementation of existing methods. Using the singular value decomposition (SVD) technique, we developed a new computational tool, named svdPPCS (SVD-based Pattern Pairing and Chart Splitting), to identify conserved and divergent co-expression modules of two sets of microarray experiments. In the proposed methods, gene modules are identified by splitting the two-way chart coordinated with a pair of left singular vectors factorized from the gene expression matrices of the two biological categories. Importantly, the cutoffs are determined by a data-driven algorithm using the well-defined statistic, SVD-p. The implementation was illustrated on two time series microarray data sets generated from the samples of accessory gland (ACG) and malpighian tubule (MT) tissues of the line W118 of M. drosophila. Two conserved modules and six divergent modules, each of which has a unique characteristic profile across tissue kinds and aging processes, were identified. The number of genes contained in these models ranged from five to a few hundred. Three to over a hundred GO terms were over-represented in individual modules with FDR < 0.1. One divergent module suggested the tissue-specific relationship between the expressions of mitochondrion-related genes and the aging process. This finding, together with others, may be of biological significance. The validity of the proposed SVD-based method was further verified by a simulation study, as well as the comparisons with regression analysis and cubic spline regression analysis plus PAM based clustering. svdPPCS is a novel computational tool for the comparative analysis of transcriptional profiling. It especially fits the comparison of time series data of related organisms or different tissues of the same organism under equivalent or similar experimental conditions. The general scheme can be directly extended to the comparisons of multiple data sets. It also can be applied to the integration of data sets from different platforms and of different sources.

DNA mismatch repair gene MSH6 implicated in determining age at natural menopause

PubMed Central

Perry, John R.B.; Hsu, Yi-Hsiang; Chasman, Daniel I.; Johnson, Andrew D.; Elks, Cathy; Albrecht, Eva; Andrulis, Irene L.; Beesley, Jonathan; Berenson, Gerald S.; Bergmann, Sven; Bojesen, Stig E.; Bolla, Manjeet K.; Brown, Judith; Buring, Julie E.; Campbell, Harry; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Corre, Tanguy; Couch, Fergus J.; Cox, Angela; Czene, Kamila; D'adamo, Adamo Pio; Davies, Gail; Deary, Ian J.; Dennis, Joe; Easton, Douglas F.; Engelhardt, Ellen G.; Eriksson, Johan G.; Esko, Tõnu; Fasching, Peter A.; Figueroa, Jonine D.; Flyger, Henrik; Fraser, Abigail; Garcia-Closas, Montse; Gasparini, Paolo; Gieger, Christian; Giles, Graham; Guenel, Pascal; Hägg, Sara; Hall, Per; Hayward, Caroline; Hopper, John; Ingelsson, Erik; Kardia, Sharon L.R.; Kasiman, Katherine; Knight, Julia A.; Lahti, Jari; Lawlor, Debbie A.; Magnusson, Patrik K.E.; Margolin, Sara; Marsh, Julie A.; Metspalu, Andres; Olson, Janet E.; Pennell, Craig E.; Polasek, Ozren; Rahman, Iffat; Ridker, Paul M.; Robino, Antonietta; Rudan, Igor; Rudolph, Anja; Salumets, Andres; Schmidt, Marjanka K.; Schoemaker, Minouk J.; Smith, Erin N.; Smith, Jennifer A.; Southey, Melissa; Stöckl, Doris; Swerdlow, Anthony J.; Thompson, Deborah J.; Truong, Therese; Ulivi, Sheila; Waldenberger, Melanie; Wang, Qin; Wild, Sarah; Wilson, James F; Wright, Alan F.; Zgaga, Lina; Ong, Ken K.; Murabito, Joanne M.; Karasik, David; Murray, Anna

2014-01-01

The length of female reproductive lifespan is associated with multiple adverse outcomes, including breast cancer, cardiovascular disease and infertility. The biological processes that govern the timing of the beginning and end of reproductive life are not well understood. Genetic variants are known to contribute to ∼50% of the variation in both age at menarche and menopause, but to date the known genes explain <15% of the genetic component. We have used genome-wide association in a bivariate meta-analysis of both traits to identify genes involved in determining reproductive lifespan. We observed significant genetic correlation between the two traits using genome-wide complex trait analysis. However, we found no robust statistical evidence for individual variants with an effect on both traits. A novel association with age at menopause was detected for a variant rs1800932 in the mismatch repair gene MSH6 (P = 1.9 × 10−9), which was also associated with altered expression levels of MSH6 mRNA in multiple tissues. This study contributes to the growing evidence that DNA repair processes play a key role in ovarian ageing and could be an important therapeutic target for infertility. PMID:24357391

[Impacts of biological and family factors on lexical and intellectual development in Mandarin-speaking children].

PubMed

Niu, Jie; Chen, Yong-Xiang; Zhu, Li-Qi

2015-07-01

To investigate the impacts of biological factors (age and sex) and family factors (socioeconomic status and parenting style) on the early lexical and intellectual development of children in a longitudinal tracking study. A total of 38 Mandarin-speaking children aged from 18 to 24 months were surveyed using the Putonghua Chinese Communicative Development Inventory (PCDI), the Ages and Stages Questionnaire (ASQ), and a self-designed Questionnaire for Parents. All of the subjects were retested using PCDI and ASQ after 6 months. Biological factors accounted for 65% of the variance in lexical development, 10% of which was attributed to gender, in the first survey. After six months, the contribution of age decreased to 26% and gender had no significant impact. Lexical development could positively predict the intellectual development of children. When age and gender were controlled, it accounted for 22% of the variance in intellectual development. Family socioeconomic factors had no significant impacts on lexical and intellectual development. Children's recognition of people and objects around them with guidance of parents in parenting styles could positively predict the intellectual development of children six months later, which accounted for 10% of the variance. Biological factors play an important role in the early lexical development of children. However, the influence decreases with the increase of age (months). Biological factors, lexical development, and parenting style have a combined influence on children's intellectual development.

Biological processes modulating longevity across primates: a phylogenetic genome-phenome analysis.

PubMed

Muntané, Gerard; Farré, Xavier; Antonio Rodríguez, Juan; Pegueroles, Cinta; Hughes, David A; de Magalhães, João Pedro; Gabaldón, Toni; Navarro, Arcadi

2018-05-21

Aging is a complex process affecting different species and individuals in different ways. Comparing genetic variation across species with their aging phenotypes will help understanding the molecular basis of aging and longevity. Although most studies on aging have so far focused on short-lived model organisms, recent comparisons of genomic, transcriptomic, and metabolomic data across lineages with different lifespans are unveiling molecular signatures associated with longevity. Here, we examine the relationship between genomic variation and maximum lifespan (MLS) across primate species. We used two different approaches. First, we searched for parallel amino acid mutations that co-occur with increases in longevity across the primate linage. Twenty-five such amino acid variants were identified, several of which have been previously reported by studies with different experimental setups and in different model organisms. The genes harboring these mutations are mainly enriched in functional categories such as Wound Healing, Blood Coagulation and Cardiovascular Disorders. We demonstrate that these pathways are highly enriched for pleiotropic effects, as predicted by the Antagonistic Pleiotropy (AP) theory of aging. A second approach was focused on changes in rates of protein evolution across the primate phylogeny. Using the Phylogenetic Generalized Least Squares (PGLS) we show that some genes exhibit strong correlations between their evolutionary rates and longevity-associated traits. These include genes in the Sphingosine 1-phosphate pathway, PI3K signaling and the Thrombin/protease-activated receptor pathway, among other cardiovascular processes. Together, these results shed light into human senescence patterns and underscore the power of comparative genomics to identify pathways related to aging and longevity.

Age-related striatal BOLD changes without changes in behavioral loss aversion.

PubMed

Viswanathan, Vijay; Lee, Sang; Gilman, Jodi M; Kim, Byoung Woo; Lee, Nick; Chamberlain, Laura; Livengood, Sherri L; Raman, Kalyan; Lee, Myung Joo; Kuster, Jake; Stern, Daniel B; Calder, Bobby; Mulhern, Frank J; Blood, Anne J; Breiter, Hans C

2015-01-01

Loss aversion (LA), the idea that negative valuations have a higher psychological impact than positive ones, is considered an important variable in consumer research. The literature on aging and behavior suggests older individuals may show more LA, although it is not clear if this is an effect of aging in general (as in the continuum from age 20 and 50 years), or of the state of older age (e.g., past age 65 years). We also have not yet identified the potential biological effects of aging on the neural processing of LA. In the current study we used a cohort of subjects with a 30 year range of ages, and performed whole brain functional MRI (fMRI) to examine the ventral striatum/nucleus accumbens (VS/NAc) response during a passive viewing of affective faces with model-based fMRI analysis incorporating behavioral data from a validated approach/avoidance task with the same stimuli. Our a priori focus on the VS/NAc was based on (1) the VS/NAc being a central region for reward/aversion processing; (2) its activation to both positive and negative stimuli; (3) its reported involvement with tracking LA. LA from approach/avoidance to affective faces showed excellent fidelity to published measures of LA. Imaging results were then compared to the behavioral measure of LA using the same affective faces. Although there was no relationship between age and LA, we observed increasing neural differential sensitivity (NDS) of the VS/NAc to avoidance responses (negative valuations) relative to approach responses (positive valuations) with increasing age. These findings suggest that a central region for reward/aversion processing changes with age, and may require more activation to produce the same LA behavior as in younger individuals, consistent with the idea of neural efficiency observed with high IQ individuals showing less brain activation to complete the same task.

Age-related striatal BOLD changes without changes in behavioral loss aversion

PubMed Central

Viswanathan, Vijay; Lee, Sang; Gilman, Jodi M.; Kim, Byoung Woo; Lee, Nick; Chamberlain, Laura; Livengood, Sherri L.; Raman, Kalyan; Lee, Myung Joo; Kuster, Jake; Stern, Daniel B.; Calder, Bobby; Mulhern, Frank J.; Blood, Anne J.; Breiter, Hans C.

2015-01-01

Loss aversion (LA), the idea that negative valuations have a higher psychological impact than positive ones, is considered an important variable in consumer research. The literature on aging and behavior suggests older individuals may show more LA, although it is not clear if this is an effect of aging in general (as in the continuum from age 20 and 50 years), or of the state of older age (e.g., past age 65 years). We also have not yet identified the potential biological effects of aging on the neural processing of LA. In the current study we used a cohort of subjects with a 30 year range of ages, and performed whole brain functional MRI (fMRI) to examine the ventral striatum/nucleus accumbens (VS/NAc) response during a passive viewing of affective faces with model-based fMRI analysis incorporating behavioral data from a validated approach/avoidance task with the same stimuli. Our a priori focus on the VS/NAc was based on (1) the VS/NAc being a central region for reward/aversion processing; (2) its activation to both positive and negative stimuli; (3) its reported involvement with tracking LA. LA from approach/avoidance to affective faces showed excellent fidelity to published measures of LA. Imaging results were then compared to the behavioral measure of LA using the same affective faces. Although there was no relationship between age and LA, we observed increasing neural differential sensitivity (NDS) of the VS/NAc to avoidance responses (negative valuations) relative to approach responses (positive valuations) with increasing age. These findings suggest that a central region for reward/aversion processing changes with age, and may require more activation to produce the same LA behavior as in younger individuals, consistent with the idea of neural efficiency observed with high IQ individuals showing less brain activation to complete the same task. PMID:25983682

Sexual Dimorphism and Aging in the Human Hyppocampus: Identification, Validation, and Impact of Differentially Expressed Genes by Factorial Microarray and Network Analysis.

PubMed

Guebel, Daniel V; Torres, Néstor V

2016-01-01

Motivation: In the brain of elderly-healthy individuals, the effects of sexual dimorphism and those due to normal aging appear overlapped. Discrimination of these two dimensions would powerfully contribute to a better understanding of the etiology of some neurodegenerative diseases, such as "sporadic" Alzheimer. Methods: Following a system biology approach, top-down and bottom-up strategies were combined. First, public transcriptome data corresponding to the transition from adulthood to the aging stage in normal, human hippocampus were analyzed through an optimized microarray post-processing (Q-GDEMAR method) together with a proper experimental design (full factorial analysis). Second, the identified genes were placed in context by building compatible networks. The subsequent ontology analyses carried out on these networks clarify the main functionalities involved. Results: Noticeably we could identify large sets of genes according to three groups: those that exclusively depend on the sex, those that exclusively depend on the age, and those that depend on the particular combinations of sex and age (interaction). The genes identified were validated against three independent sources (a proteomic study of aging, a senescence database, and a mitochondrial genetic database). We arrived to several new inferences about the biological functions compromised during aging in two ways: by taking into account the sex-independent effects of aging, and considering the interaction between age and sex where pertinent. In particular, we discuss the impact of our findings on the functions of mitochondria, autophagy, mitophagia, and microRNAs. Conclusions: The evidence obtained herein supports the occurrence of significant neurobiological differences in the hippocampus, not only between adult and elderly individuals, but between old-healthy women and old-healthy men. Hence, to obtain realistic results in further analysis of the transition from the normal aging to incipient Alzheimer, the features derived from the sexual dimorphism in hippocampus should be explicitly considered.

Sexual Dimorphism and Aging in the Human Hyppocampus: Identification, Validation, and Impact of Differentially Expressed Genes by Factorial Microarray and Network Analysis

PubMed Central

Guebel, Daniel V.; Torres, Néstor V.

2016-01-01

Motivation: In the brain of elderly-healthy individuals, the effects of sexual dimorphism and those due to normal aging appear overlapped. Discrimination of these two dimensions would powerfully contribute to a better understanding of the etiology of some neurodegenerative diseases, such as “sporadic” Alzheimer. Methods: Following a system biology approach, top-down and bottom-up strategies were combined. First, public transcriptome data corresponding to the transition from adulthood to the aging stage in normal, human hippocampus were analyzed through an optimized microarray post-processing (Q-GDEMAR method) together with a proper experimental design (full factorial analysis). Second, the identified genes were placed in context by building compatible networks. The subsequent ontology analyses carried out on these networks clarify the main functionalities involved. Results: Noticeably we could identify large sets of genes according to three groups: those that exclusively depend on the sex, those that exclusively depend on the age, and those that depend on the particular combinations of sex and age (interaction). The genes identified were validated against three independent sources (a proteomic study of aging, a senescence database, and a mitochondrial genetic database). We arrived to several new inferences about the biological functions compromised during aging in two ways: by taking into account the sex-independent effects of aging, and considering the interaction between age and sex where pertinent. In particular, we discuss the impact of our findings on the functions of mitochondria, autophagy, mitophagia, and microRNAs. Conclusions: The evidence obtained herein supports the occurrence of significant neurobiological differences in the hippocampus, not only between adult and elderly individuals, but between old-healthy women and old-healthy men. Hence, to obtain realistic results in further analysis of the transition from the normal aging to incipient Alzheimer, the features derived from the sexual dimorphism in hippocampus should be explicitly considered. PMID:27761111

The Geology and Astrobiology of Europa (Invited)

NASA Astrophysics Data System (ADS)

Chyba, C. F.; Hand, K. P.

2009-12-01

Galileo’s discovery of the jovian moons was a crucial step in the process, completed by Newton, that overthrew the Aristotelian dichotomy between the physics of the terrestrial realm and the physics of the heavens. Now, 400 years later, we know of one kind of biology, Earth biology (DNA-protein life) and have glimpses of other possibilities more closely or distantly related (e.g., the RNA world). The galilean satellite Europa is one of the most likely venues in our solar system for presenting us with another example of life, and life likely from an entirely separate origin. Europa therefore gives us a chance to extend our understanding of biology beyond Earth biology to a more generalized biology, providing a biological counterpart to the galilean/newtonian revolution. This possibility is the reason that Europa is one of the highest priorities in solar system exploration. It is a still entirely speculative but credible possibility, because of Europa’s extraordinary geophysics and chemistry. First, radiogenic decay and tidal energy appear sufficient to maintain a subsurface liquid water ocean on Europa that resides between an ice shell and a rocky mantle. Gravity measurements confirm this differentiation, and magnetometer measurements seem to confirm the liquidity of the ocean. Magnetometer measurements further put strong limits on the thickness of the ice shell overlying the ocean and on the salinity of the ocean itself. Because the ocean is covered by kilometers of ice, the enormous free energy of sunlight is rarely available for chemistry or possible biology, but radiolytic chemistry at the surface ice may provide a powerful oxidizing arrow for the ocean that, coupled with deep hydrothermal activity, maintains a supply of electron acceptor and donor pairs that could be used by life. The details of this scenario depend on surface impact gardening and sputtering rates, and on the interaction of the ice shell with the ocean. Current estimates based on cratering rates suggest an ice shell age 1-2 orders of magnitude less than the age of the solar system; sufficiently frequent melting into the ocean could lead to an oxidized, rather than a reduced ocean. Europa likely formed with a chondritic composition and, in addition, accumulated some material (while losing much in erosion) from impacts over the age of the solar system, so that the biologically essential elements should all be present. It is this combination of liquid water, essential elements, and available energy, all in contact with potentially catalytic mineral surfaces, that makes Europa so biologically attractive and gives its ocean the appearance of habitability, at least for some potential Earth-analog organisms. Of course, habitability for life and prospects for the origin of life are two distinct issues.

Proteomics analysis for asymmetric inheritance of preexisting proteins between mother and daughter cells in budding yeast.

PubMed

Okada, Mitsuhiro; Kusunoki, Shunta; Ishibashi, Yuko; Kito, Keiji

2017-06-01

In budding yeast, a mother cell can produce a finite number of daughter cells over its life. The accumulation of a variety of types of damaged components has an impact on the aging process. Asymmetrical inheritance during cell division causes these aberrant intracellular constituents to be retained in mother cells and prevents them from segregating to daughter cells. However, the understanding of asymmetrical inheritance of individual proteins that are damaged or old age, and their relevance to the aging process, has been limited. The aim of this study is to propose a proteomics strategy for asymmetrical inheritance of preexisting proteins between mother and daughter cells. During synchronous culture for one generation, newly synthesized proteins were labeled with stable isotope amino acids to discriminate preexisting proteins originally expressed in mother cells, followed by separation of mother and daughter cells using a conventional method based on biotin labeling. Isotope incorporation ratios for individual proteins were quantified using mass spectrometry. We successfully identified 21 proteins whose preexisting versions were asymmetrically inherited in mother cells, including plasma membrane transporter involved in the aging process and organelle-anchoring proteins related to the stress response to misfolded proteins. Thus, our approach would be useful for making catalog of asymmetrically inherited proteins. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Molecular and biological hallmarks of ageing.

PubMed

Aunan, J R; Watson, M M; Hagland, H R; Søreide, K

2016-01-01

Ageing is the inevitable time-dependent decline in physiological organ function that eventually leads to death. Age is a major risk factor for many of the most common medical conditions, such as cardiovascular disease, cancer, diabetes and Alzheimer's disease. This study reviews currently known hallmarks of ageing and their clinical implications. A literature search of PubMed/MEDLINE was conducted covering the last decade. Average life expectancy has increased dramatically over the past century and is estimated to increase even further. Maximum longevity, however, appears unchanged, suggesting a universal limitation to the human organism. Understanding the underlying molecular processes of ageing and health decline may suggest interventions that, if used at an early age, can prevent, delay, alleviate or even reverse age-related diseases. Hallmarks of ageing can be grouped into three main categories. The primary hallmarks cause damage to cellular functions: genomic instability, telomere attrition, epigenetic alterations and loss of proteostasis. These are followed by antagonistic responses to such damage: deregulated nutrient sensing, altered mitochondrial function and cellular senescence. Finally, integrative hallmarks are possible culprits of the clinical phenotype (stem cell exhaustion and altered intercellular communication), which ultimately contribute to the clinical effects of ageing as seen in physiological loss of reserve, organ decline and reduced function. The sum of these molecular hallmarks produces the clinical picture of the elderly surgical patient: frailty, sarcopenia, anaemia, poor nutrition and a blunted immune response system. Improved understanding of the ageing processes may give rise to new biomarkers of risk or prognosis, novel treatment targets and translational approaches across disciplines that may improve outcomes. © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

Accelerated ageing and renal dysfunction links lower socioeconomic status and dietary phosphate intake.

PubMed

McClelland, Ruth; Christensen, Kelly; Mohammed, Suhaib; McGuinness, Dagmara; Cooney, Josephine; Bakshi, Andisheh; Demou, Evangelia; MacDonald, Ewan; Caslake, Muriel; Stenvinkel, Peter; Shiels, Paul G

2016-05-01

We have sought to explore the impact of dietary Pi intake on human age related health in the pSoBid cohort (n=666) to explain the disparity between health and deprivation status in this cohort. As hyperphosphataemia is a driver of accelerated ageing in rodent models of progeria we tested whether variation in Pi levels in man associate with measures of biological ageing and health. We observed significant relationships between serum Pi levels and markers of biological age (telomere length (p=0.040) and DNA methylation content (p=0.028), gender and chronological age (p=0.032). When analyses were adjusted for socio-economic status and nutritional factors, associations were observed between accelerated biological ageing (telomere length, genomic methylation content) and dietary derived Pi levels among the most deprived males, directly related to the frequency of red meat consumption. Accelerated ageing is associated with high serum Pi levels and frequency of red meat consumption. Our data provide evidence for a mechanistic link between high intake of Pi and age-related morbidities tied to socio-economic status.

Basic Biology of Skeletal Aging: Role of Stress Response Pathways

PubMed Central

2013-01-01

Although a decline in bone formation and loss of bone mass are common features of human aging, the molecular mechanisms mediating these effects have remained unclear. Evidence from pharmacological and genetic studies in mice has provided support for a deleterious effect of oxidative stress in bone and has strengthened the idea that an increase in reactive oxygen species (ROS) with advancing age represents a pathophysiological mechanism underlying age-related bone loss. Mesenchymal stem cells and osteocytes are long-lived cells and, therefore, are more susceptible than other types of bone cells to the molecular changes caused by aging, including increased levels of ROS and decreased autophagy. However, short-lived cells like osteoblast progenitors and mature osteoblasts and osteoclasts are also affected by the altered aged environment characterized by lower levels of sex steroids, increased endogenous glucocorticoids, and higher oxidized lipids. This article reviews current knowledge on the effects of the aging process on bone, with particular emphasis on the role of ROS and autophagy in cells of the osteoblast lineage in mice. PMID:23825036

A microRNA feedback loop regulates global microRNA abundance during aging.

PubMed

Inukai, Sachi; Pincus, Zachary; de Lencastre, Alexandre; Slack, Frank J

2018-02-01

Expression levels of many microRNAs (miRNAs) change during aging, notably declining globally in a number of organisms and tissues across taxa. However, little is known about the mechanisms or the biological relevance for this change. We investigated the network of genes that controls miRNA transcription and processing during C. elegans aging. We found that miRNA biogenesis genes are highly networked with transcription factors and aging-associated miRNAs. In particular, miR-71, known to influence life span and itself up-regulated during aging, represses alg-1 /Argonaute expression post-transcriptionally during aging. Increased ALG-1 abundance in mir-71 loss-of-function mutants led to globally increased miRNA expression. Interestingly, these mutants demonstrated widespread mRNA expression dysregulation and diminished levels of variability both in gene expression and in overall life span. Thus, the progressive molecular decline often thought to be the result of accumulated damage over an organism's life may be partially explained by a miRNA-directed mechanism of age-associated decline. © 2018 Inukai et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Perinatally acquired HIV infection accelerates epigenetic aging in South African adolescents.

PubMed

Horvath, Steve; Phillips, Nicole; Heany, Sarah J; Kobor, Michael S; Lin, David Ts; Myer, Landon; Zar, Heather J; Stein, Dan J; Levine, Andrew J; Hoare, Jacqueline

2018-05-08

Recent studies demonstrate that infection with the Human Immunodeficiency Virus-1 (HIV) is associated with accelerated aging effects in adults according to a highly accurate epigenetic biomarker of aging known as epigenetic clock. However, it not yet known whether epigenetic age acceleration occurs as early as adolescence in perinatally HIV-infected (PHIV+) youth. Observational study of PHIV and HIV-uninfected adolescents enrolled in the Cape Town Adolescent Antiretroviral Cohort (CTAAC) Study. The Illumina EPIC array was used to generate blood DNA methylation data from 204 PHIV and 44 age-matched, uninfected (HIV-) adolescents aged 9 to 12 years old. The epigenetic clock software and method was used to estimate two measures of epigenetic age acceleration. Each participant completed a comprehensive neuropsychological test battery upon enrolment to CTAAC. HIV is associated with biologically older blood in PHIV+ adolescents according to both measures of epigenetic age acceleration. One of the measures, extrinsic epigenetic age acceleration, is negatively correlated with measures of cognitive functioning (executive functioning, working memory, processing speed). Overall, our results indicate that epigenetic age acceleration in blood can be observed in PHIV+ adolescents and that these epigenetic changes accompany poorer cognitive functioning.

Family Structure Instability, Genetic Sensitivity and Child Wellbeing

PubMed Central

Mitchell, Colter; McLanahan, Sara; Hobcraft, John; Brooks-Gunn, Jeanne; Garfinkel, Irwin; Notterman, Daniel

2016-01-01

The association between family structure instability and children’s life chances is well documented, with children reared in stable, two-parent families experiencing more favorable outcomes than children reared in other family arrangements. This study extends prior research by distinguishing between father-entrances into and father-exits from the household, by distinguishing between the entrance of a biological father and a social-father, and by testing for interactions between family structure instability and children’s age, gender and genetic characteristics. Using data from the Fragile Families and Child Wellbeing Study (n=2493) and focusing on changes in family structure between birth and age 9, we find that father-exits are associated with increases in children’s anti-social behavior, which is a strong predictor of health and wellbeing in adulthood. The pattern for father-entrances is more complicated, with biological father entrances being associated with lower anti-social behavior among boys, and social-father entrances being associated with higher anti-social behavior among boys with certain genetic variants. Child’s age at the time of family change does not moderate the association with children’s behavior. However, incorporating genetic information into our models sharpens the findings substantially, showing how such data can enrich our understanding of the intergenerational mobility process. PMID:26046228

Redox Biology in Neurological Function, Dysfunction, and Aging.

PubMed

Franco, Rodrigo; Vargas, Marcelo R

2018-04-23

Reduction oxidation (redox) reactions are central to life and when altered, they can promote disease progression. In the brain, redox homeostasis is recognized to be involved in all aspects of central nervous system (CNS) development, function, aging, and disease. Recent studies have uncovered the diverse nature by which redox reactions and homeostasis contribute to brain physiology, and when dysregulated to pathological consequences. Redox reactions go beyond what is commonly described as oxidative stress and involve redox mechanisms linked to signaling and metabolism. In contrast to the nonspecific nature of oxidative damage, redox signaling involves specific oxidation/reduction reactions that regulate a myriad of neurological processes such as neurotransmission, homeostasis, and degeneration. This Forum is focused on the role of redox metabolism and signaling in the brain. Six review articles from leading scientists in the field that appraise the role of redox metabolism and signaling in different aspects of brain biology including neurodevelopment, neurotransmission, aging, neuroinflammation, neurodegeneration, and neurotoxicity are included. An original research article exemplifying these concepts uncovers a novel link between oxidative modifications, redox signaling, and neurodegeneration. This Forum highlights the recent advances in the field and we hope it encourages future research aimed to understand the mechanisms by which redox metabolism and signaling regulate CNS physiology and pathophysiology. Antioxid. Redox Signal. 00, 000-000.

Dynamic contrast-enhanced magnetic resonance imaging of the sarcopenic muscle

PubMed Central

Nicolato, Elena; Farace, Paolo; Asperio, Roberto M; Marzola, Pasquina; Lunati, Ernesto; Sbarbati, Andrea; Osculati, Francesco

2002-01-01

Background Studies about capillarity of the aged muscle provided conflicting results and no data are currently available about the magnetic resonance imaging (MRI) in vivo characteristics of the microvascular bed in aged rats. We have studied age-related modifications of the skeletal muscle by in vivo T2-relaxometry and dynamic contrast-enhanced magnetic resonance imaging (CE-MRI) at high field intensity (4.7 T). The aim of the work was to test the hypothesis that the ageing process involves microvessels in skeletal muscle. Methods The study was performed in 4-month-old (n = 6) and 20-month-old (n = 6) rats. Results At MRI examination, the relaxation time T2 of the gastrocnemius muscle showed no significant difference between these two groups. The kinetic of contrast penetration in the tissue showed that in 4-month-old rats the enhancement values of the signal intensity at different time-points were significantly higher than those found in senescent rats. Conclusion The reported finding suggests that there is a modification of the microcirculatory function in skeletal muscle of aged rats. This work also demonstrates that CE-MRI allows for an in vivo quantification of the multiple biological processes involving the skeletal muscle during aging. Therefore, CE-MRI could represent a further tool for the follow up of tissue modification and therapeutic intervention both in patients with sarcopenia and in experimental models of this pathology. PMID:12049675

Slowed ageing, welfare, and population problems.

PubMed

Wareham, Christopher

2015-10-01

Biological studies have demonstrated that it is possible to slow the ageing process and extend lifespan in a wide variety of organisms, perhaps including humans. Making use of the findings of these studies, this article examines two problems concerning the effect of life extension on population size and welfare. The first--the problem of overpopulation--is that as a result of life extension too many people will co-exist at the same time, resulting in decreases in average welfare. The second--the problem of underpopulation--is that life extension will result in too few people existing across time, resulting in decreases in total welfare. I argue that overpopulation is highly unlikely to result from technologies that slow ageing. Moreover, I claim that the problem of underpopulation relies on claims about life extension that are false in the case of life extension by slowed ageing. The upshot of these arguments is that the population problems discussed provide scant reason to oppose life extension by slowed ageing.

Visualization of aging-associated chromatin alterations with an engineered TALE system

PubMed Central

Ren, Ruotong; Deng, Liping; Xue, Yanhong; Suzuki, Keiichiro; Zhang, Weiqi; Yu, Yang; Wu, Jun; Sun, Liang; Gong, Xiaojun; Luan, Huiqin; Yang, Fan; Ju, Zhenyu; Ren, Xiaoqing; Wang, Si; Tang, Hong; Geng, Lingling; Zhang, Weizhou; Li, Jian; Qiao, Jie; Xu, Tao; Qu, Jing; Liu, Guang-Hui

2017-01-01

Visualization of specific genomic loci in live cells is a prerequisite for the investigation of dynamic changes in chromatin architecture during diverse biological processes, such as cellular aging. However, current precision genomic imaging methods are hampered by the lack of fluorescent probes with high specificity and signal-to-noise contrast. We find that conventional transcription activator-like effectors (TALEs) tend to form protein aggregates, thereby compromising their performance in imaging applications. Through screening, we found that fusing thioredoxin with TALEs prevented aggregate formation, unlocking the full power of TALE-based genomic imaging. Using thioredoxin-fused TALEs (TTALEs), we achieved high-quality imaging at various genomic loci and observed aging-associated (epi) genomic alterations at telomeres and centromeres in human and mouse premature aging models. Importantly, we identified attrition of ribosomal DNA repeats as a molecular marker for human aging. Our study establishes a simple and robust imaging method for precisely monitoring chromatin dynamics in vitro and in vivo. PMID:28139645

The role and control of sludge age in biological nutrient removal activated sludge systems.

PubMed

Ekama, G A

2010-01-01

The sludge age is the most fundamental and important parameter in the design, operation and control of biological nutrient removal (BNR) activated sludge (AS) systems. Generally, the better the effluent and waste sludge quality required from the system, the longer the sludge age, the larger the biological reactor and the more wastewater characteristics need to be known. Controlling the reactor concentration does not control sludge age, only the mass of sludge in the system. When nitrification is a requirement, sludge age control becomes a requirement and the secondary settling tanks can no longer serve the dual purpose of clarifier and waste activated sludge thickeners. The easiest and most practical way to control sludge age is with hydraulic control by wasting a defined proportion of the reactor volume daily. In AS plants with reactor concentration control, nitrification fails first. With hydraulic control of sludge age, nitrification will not fail, rather the plant fails by shedding solids over the secondary settling tank effluent weirs.

Muscle Stem Cells: A Model System for Adult Stem Cell Biology.

PubMed

Cornelison, Ddw; Perdiguero, Eusebio

2017-01-01

Skeletal muscle stem cells, originally termed satellite cells for their position adjacent to differentiated muscle fibers, are absolutely required for the process of skeletal muscle repair and regeneration. In the last decade, satellite cells have become one of the most studied adult stem cell systems and have emerged as a standard model not only in the field of stem cell-driven tissue regeneration but also in stem cell dysfunction and aging. Here, we provide background in the field and discuss recent advances in our understanding of muscle stem cell function and dysfunction, particularly in the case of aging, and the potential involvement of muscle stem cells in genetic diseases such as the muscular dystrophies.

Discovery of plant extracts that greatly delay yeast chronological aging and have different effects on longevity-defining cellular processes

PubMed Central

Samson, Eugenie; Arlia-Ciommo, Anthony; Dakik, Pamela; Cortes, Berly; Feldman, Rachel; Mohtashami, Sadaf; McAuley, Mélissa; Chancharoen, Marisa; Rukundo, Belise; Simard, Éric; Titorenko, Vladimir I.

2016-01-01

We discovered six plant extracts that increase yeast chronological lifespan to a significantly greater extent than any of the presently known longevity-extending chemical compounds. One of these extracts is the most potent longevity-extending pharmacological intervention yet described. We show that each of the six plant extracts is a geroprotector which delays the onset and decreases the rate of yeast chronological aging by eliciting a hormetic stress response. We also show that each of these extracts has different effects on cellular processes that define longevity in organisms across phyla. These effects include the following: 1) increased mitochondrial respiration and membrane potential; 2) augmented or reduced concentrations of reactive oxygen species; 3) decreased oxidative damage to cellular proteins, membrane lipids, and mitochondrial and nuclear genomes; 4) enhanced cell resistance to oxidative and thermal stresses; and 5) accelerated degradation of neutral lipids deposited in lipid droplets. Our findings provide new insights into mechanisms through which chemicals extracted from certain plants can slow biological aging. PMID:26918729

Senescence and the pro-tumorigenic stroma.

PubMed

Alspach, Elise; Fu, Yujie; Stewart, Sheila A

2013-01-01

Hayflick and Moorhead first described senescence in the late 1960's as a permanent growth arrest that primary cells underwent after a defined number of cellular divisions in culture. This observation gave rise to the hypothesis that cells contained an internal counting mechanism that limited cellular division and that this limit was an important barrier to cellular transformation. What began as an in vitro observation has led to an immense body of work that reaches into all fields of biology and is of particular interest in the areas of aging, tissue regeneration, and tumorigenesis. The initially simplistic view that senescence limits cellular division and contributes to aging while stymying tumorigenesis has now evolved into an important and complex biological process that has numerous caveats and often opposing effects on tumorigenesis. In this review, we limit our discussion to the complex role senescence plays in tumorigenesis. Throughout the review we attempt to draw many parallels to other systems including the role senescent cells play in the tumor microenvironment and their significant molecular and phenotypic similarities to cancer associated fibroblasts (CAFs).

Single molecular biology: coming of age in DNA replication.

PubMed

Liu, Xiao-Jing; Lou, Hui-Qiang

2017-09-20

DNA replication is an essential process of the living organisms. To achieve precise and reliable replication, DNA polymerases play a central role in DNA synthesis. Previous investigations have shown that the average rates of DNA synthesis on the leading and lagging strands in a replisome must be similar to avoid the formation of significant gaps in the nascent strands. The underlying mechanism has been assumed to be coordination between leading- and lagging-strand polymerases. However, Kowalczykowski's lab members recently performed single molecule techniques in E. coli and showed the real-time behavior of a replisome. The leading- and lagging-strand polymerases function stochastically and independently. Furthermore, when a DNA polymerase is paused, the helicase slows down in a self-regulating fail-safe mechanism, akin to a ''dead-man's switch''. Based on the real-time single-molecular observation, the authors propose that leading- and lagging-strand polymerases synthesize DNA stochastically within a Gaussian distribution. Along with the development and application of single-molecule techniques, we will witness a new age of DNA replication and other biological researches.

Ageing induced vascular smooth muscle cell senescence in atherosclerosis.

PubMed

Uryga, Anna K; Bennett, Martin R

2016-04-15

Atherosclerosis is a disease of ageing in that its incidence and prevalence increase with age. However, atherosclerosis is also associated with biological ageing, manifest by a number of typical hallmarks of ageing in the atherosclerotic plaque. Thus, accelerated biological ageing may be superimposed on the effects of chronological ageing in atherosclerosis. Tissue ageing is seen in all cells that comprise the plaque, but particularly in vascular smooth muscle cells (VSMCs). Hallmarks of ageing include evidence of cell senescence, DNA damage (including telomere attrition), mitochondrial dysfunction, a pro-inflammatory secretory phenotype, defects in proteostasis, epigenetic changes, deregulated nutrient sensing, and exhaustion of progenitor cells. In this model, initial damage to DNA (genomic, telomeric, mitochondrial and epigenetic changes) results in a number of cellular responses (cellular senescence, deregulated nutrient sensing and defects in proteostasis). Ultimately, ongoing damage and attempts at repair by continued proliferation overwhelm reparative capacity, causing loss of specialised cell functions, cell death and inflammation. This review summarises the evidence for accelerated biological ageing in atherosclerosis, the functional consequences of cell ageing on cells comprising the plaque, and the causal role that VSMC senescence plays in atherogenesis. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

KSC-98pc864

NASA Image and Video Library

1998-07-16

KENNEDY SPACE CENTER, FLA. -- STS-95 Mission Specialist Stephen K. Robinson injects water into the base of the seed container where plants will grow during the upcoming mission. This is part of the Biological Research in Canisters (BRIC) experiment which is at the SPACEHAB Payload Processing Facility, Cape Canaveral, Fla. This experiment will fly in SPACEHAB in Discovery’s payload bay. STS-95 is scheduled to launch from pad 39B at KSC on Oct. 29, 1998. The mission also includes research payloads such as the Spartan solar-observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as experiments on space flight and the aging process

The Health Significance of Positive Emotions in Adulthood and Later Life.

PubMed

Ong, Anthony D; Mroczek, Daniel K; Riffin, Catherine

2011-08-01

A growing body of literature supports a link between positive emotions and health in older adults. In this article, we review evidence of the effects of positive emotions on downstream biological processes and meaningful clinical endpoints, such as adult morbidity and mortality. We then present relevant predictions from lifespan theories that suggest changes in cognition and motivation may play an important role in explaining how positive emotions are well maintained in old age, despite pervasive declines in cognitive processes. We conclude by discussing how the application of psychological theory can inform greater understanding of the adaptive significance of positive emotions in adulthood and later life.

The Health Significance of Positive Emotions in Adulthood and Later Life

PubMed Central

Ong, Anthony D.; Mroczek, Daniel K.; Riffin, Catherine

2011-01-01

A growing body of literature supports a link between positive emotions and health in older adults. In this article, we review evidence of the effects of positive emotions on downstream biological processes and meaningful clinical endpoints, such as adult morbidity and mortality. We then present relevant predictions from lifespan theories that suggest changes in cognition and motivation may play an important role in explaining how positive emotions are well maintained in old age, despite pervasive declines in cognitive processes. We conclude by discussing how the application of psychological theory can inform greater understanding of the adaptive significance of positive emotions in adulthood and later life. PMID:21927620

Rethinking differentiation: Stem cells, regeneration, and plasticity

PubMed Central

Alvarado, Alejandro Sánchez; Yamanaka, Shinya

2014-01-01

Cell differentiation is an essential process for the development, growth, reproduction and longevity of all multicellular organisms, and its regulation has been the focus of intense investigation for the past 4 decades. The study of natural and induced stem cells has ushered an age of re-examination of what it means to be a stem or a differentiated cell. Past and recent discoveries in plants and animals, as well as novel experimental manipulations are beginning to erode many of these established concepts, and are forcing a re-evaluation of the experimental systems and paradigms presently being used to explore these and other biological process. PMID:24679530

Evolving Relevance of Neuroproteomics in Alzheimer's Disease.

PubMed

Lista, Simone; Zetterberg, Henrik; O'Bryant, Sid E; Blennow, Kaj; Hampel, Harald

2017-01-01

Substantial progress in the understanding of the biology of Alzheimer's disease (AD) has been achieved over the past decades. The early detection and diagnosis of AD and other age-related neurodegenerative diseases, however, remain a challenging scientific frontier. Therefore, the comprehensive discovery (relating to all individual, converging or diverging biochemical disease mechanisms), development, validation, and qualification of standardized biological markers with diagnostic and prognostic functions with a precise performance profile regarding specificity, sensitivity, and positive and negative predictive value are warranted.Methodological innovations in the area of exploratory high-throughput technologies, such as sequencing, microarrays, and mass spectrometry-based analyses of proteins/peptides, have led to the generation of large global molecular datasets from a multiplicity of biological systems, such as biological fluids, cells, tissues, and organs. Such methodological progress has shifted the attention to the execution of hypothesis-independent comprehensive exploratory analyses (opposed to the classical hypothesis-driven candidate approach), with the aim of fully understanding the biological systems in physiology and disease as a whole. The systems biology paradigm integrates experimental biology with accurate and rigorous computational modelling to describe and foresee the dynamic features of biological systems. The use of dynamically evolving technological platforms, including mass spectrometry, in the area of proteomics has enabled to rush the process of biomarker discovery and validation for refining significantly the diagnosis of AD. Currently, proteomics-which is part of the systems biology paradigm-is designated as one of the dominant matured sciences needed for the effective exploratory discovery of prospective biomarker candidates expected to play an effective role in aiding the early detection, diagnosis, prognosis, and therapy development in AD.

76 FR 573 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-05

..., [email protected] . Name of Committee: Biology of Development and Aging Integrated Review Group... Committee: Biology of Development and Aging Integrated Review Group, Development--1 Study Section. Date..., Metabolism, Nutrition and Reproductive Sciences Integrated Review Group, Integrative Physiology of Obesity...

Normal form from biological motion despite impaired ventral stream function.

PubMed

Gilaie-Dotan, S; Bentin, S; Harel, M; Rees, G; Saygin, A P

2011-04-01

We explored the extent to which biological motion perception depends on ventral stream integration by studying LG, an unusual case of developmental visual agnosia. LG has significant ventral stream processing deficits but no discernable structural cortical abnormality. LG's intermediate visual areas and object-sensitive regions exhibit abnormal activation during visual object perception, in contrast to area V5/MT+ which responds normally to visual motion (Gilaie-Dotan, Perry, Bonneh, Malach, & Bentin, 2009). Here, in three studies we used point light displays, which require visual integration, in adaptive threshold experiments to examine LG's ability to detect form from biological and non-biological motion cues. LG's ability to detect and discriminate form from biological motion was similar to healthy controls. In contrast, he was significantly deficient in processing form from non-biological motion. Thus, LG can rely on biological motion cues to perceive human forms, but is considerably impaired in extracting form from non-biological motion. Finally, we found that while LG viewed biological motion, activity in a network of brain regions associated with processing biological motion was functionally correlated with his V5/MT+ activity, indicating that normal inputs from V5/MT+ might suffice to activate his action perception system. These results indicate that processing of biologically moving form can dissociate from other form processing in the ventral pathway. Furthermore, the present results indicate that integrative ventral stream processing is necessary for uncompromised processing of non-biological form from motion. Copyright © 2011 Elsevier Ltd. All rights reserved.

Theoretical considerations concerning the effect of relativistic velocities on the rate of biological processes.

PubMed

Heneine, I F

1997-06-01

Theoretical considerations were advanced on the reaction rate of biological systems in a rocket accelerated at fractional levels of the velocity of light. The values of mass increase in reacting molecules and length contraction of space under these relativistic velocities attained by the hypothetical rocket were inserted in equations of the absolute reaction rate theory. The equations employed were for the frequency of collisions, and for the internal kinetic energy of molecular reactions. Results of both sets of equations indicated that reduction of reaction rates were correlated to the mass increase. This would imply a general slowing of all chemical, biochemical and biological processes taking place. A human would suffer a related decrease in metabolic rate. Contrary to what is generally accepted, the biological aging of the space traveler under velocities bearable by humans, namely under 0.50c, would follow a pace very similar to that of an observer remaining in the resting frame of reference. With increased increments of the velocity, the space traveler would display a more intense lowering of the metabolic rate, with signs and symptoms comparable to body core hypothermia. Metabolic rates at insufficient levels to maintain the vital functions would be attained at 0.70c and higher, leading swiftly to coma and death. The presence of an endocrine dysfunction such as hypothyroidism or obesity in the space traveler would aggravate the signs and symptoms. Space travel at efficient velocities would be unbearable for a warm-blooded animal.

Analyzing the dynamics of cell cycle processes from fixed samples through ergodic principles

PubMed Central

Wheeler, Richard John

2015-01-01

Tools to analyze cyclical cellular processes, particularly the cell cycle, are of broad value for cell biology. Cell cycle synchronization and live-cell time-lapse observation are widely used to analyze these processes but are not available for many systems. Simple mathematical methods built on the ergodic principle are a well-established, widely applicable, and powerful alternative analysis approach, although they are less widely used. These methods extract data about the dynamics of a cyclical process from a single time-point “snapshot” of a population of cells progressing through the cycle asynchronously. Here, I demonstrate application of these simple mathematical methods to analysis of basic cyclical processes—cycles including a division event, cell populations undergoing unicellular aging, and cell cycles with multiple fission (schizogony)—as well as recent advances that allow detailed mapping of the cell cycle from continuously changing properties of the cell such as size and DNA content. This includes examples using existing data from mammalian, yeast, and unicellular eukaryotic parasite cell biology. Through the ongoing advances in high-throughput cell analysis by light microscopy, electron microscopy, and flow cytometry, these mathematical methods are becoming ever more important and are a powerful complementary method to traditional synchronization and time-lapse cell cycle analysis methods. PMID:26543196

Asynchrony of senescence among phenotypic traits in a wild mammal population

PubMed Central

Hayward, Adam D.; Moorad, Jacob; Regan, Charlotte E.; Berenos, Camillo; Pilkington, Jill G.; Pemberton, Josephine M.; Nussey, Daniel H.

2015-01-01

The degree to which changes in lifespan are coupled to changes in senescence in different physiological systems and phenotypic traits is a central question in biogerontology. It is underpinned by deeper biological questions about whether or not senescence is a synchronised process, or whether levels of synchrony depend on species or environmental context. Understanding how natural selection shapes patterns of synchrony in senescence across physiological systems and phenotypic traits demands the longitudinal study of many phenotypes under natural conditions. Here, we examine the patterns of age-related variation in late adulthood in a wild population of Soay sheep (Ovis aries) that have been the subject of individual-based monitoring for thirty years. We examined twenty different phenotypic traits in both males and females, encompassing vital rates (survival and fecundity), maternal reproductive performance (offspring birth weight, birth date and survival), male rutting behaviour, home range measures, parasite burdens, and body mass. We initially quantified age-related variation in each trait having controlled for annual variation in the environment, among-individual variation and selective disappearance effects. We then standardised our age-specific trait means and tested whether age trajectories could be meaningfully grouped according to sex or the type of trait. Whilst most traits showed age-related declines in later life, we found striking levels of asynchrony both within and between the sexes. Of particular note, female fecundity and reproductive performance declined with age, but male annual reproductive success did not. We also discovered that whilst home range size and quality decline with age in females, home range size increases with age in males. Our findings highlight the complexity of phenotypic ageing under natural conditions and, along with emerging data from other wild populations and laboratory models, suggest that the long-standing hypothesis within evolutionary biology that fitness-related traits should senesce in a synchronous manner is seriously flawed. PMID:26277618

[The characteristics of the geroprotective action of magnetotherapy in elderly patients with combined cardiovascular pathology].

PubMed

Abramovich, S G; Fedotchenko, A A; Koriakina, A V; Pogodin, K V; Smirnov, S N

1999-01-01

Central hemodynamics, diastolic and pumping functions of the heart, myocardial reactivity, microcirculation and biological age of cardiovascular system were studied in 66 elderly patients suffering from hypertension and ischemic heart disease. The patients received systemic magnetotherapy which produced a geroprotective effect as shown by improved microcirculation, myocardial reactivity, central hemodynamics reducing biological age of cardiovascular system and inhibiting its ageing.

Current Trends in Biology Education.

ERIC Educational Resources Information Center

Wivagg, Daniel E.; Moore, Randy

1987-01-01

This newsletter reports on the status of biology education in the United States. It states that biology has entered its "golden age" because of the emergence of biotechnology, ecology, agricultural productivity, and human biology as major societal issues. This report discusses the status of the informal national curriculum of biology, involving…

Telomere Length Attrition, a Marker of Biological Senescence, Is Inversely Correlated with Triglycerides and Cholesterol in South Asian Males with Type 2 Diabetes Mellitus

PubMed Central

Harte, Alison L.; da Silva, Nancy F.; Miller, Michelle A.; Cappuccio, Francesco P.; Kelly, Ann; O'Hare, Joseph P.; Barnett, Anthony H.; Al-Daghri, Nasser M.; Al-Attas, Omar; Alokail, Majed; Sabico, Shaun; Tripathi, Gyanendra; Bellary, Srikanth; Kumar, Sudhesh; McTernan, Philip G.

2012-01-01

South Asians have a higher risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) than white Caucasians, for a given BMI. Premature biological ageing, assessed by reduction in telomere length (TL), may be mediated by factors resulting from altered metabolic profiles associated with obesity. We hypothesise that ethnicity and metabolic status represent detrimental factors contributing to premature biological ageing. Therefore we assessed TL in two South Asian, age and BMI-matched cohorts [T2DM (n = 142) versus non-T2DM (n = 76)] to determine the effects of BMI, gender, lipid and CVD profile on biological ageing. Genomic DNA was obtained from the UKADS cohort; biochemical and anthropometric data was collected and TL was measured by quantitative real-time PCR. Our findings indicated a gender-specific effect with reduced TL in T2DM men compared with non-T2DM men (P = 0.006). Additionally, in T2DM men, TL was inversely correlated with triglycerides and total cholesterol (r = −0.419, P < 0.01; r = −0.443, P < 0.01). In summary, TL was reduced amongst South Asian T2DM men and correlated with triglycerides and total cholesterol. This study highlights enhanced biological ageing among South Asian, T2DM men, which appears to be tracked by changes in lipids and BMI, suggesting that raised lipids and BMI may directly contribute to premature ageing. PMID:22474429

Reconstructing the evolution of first-row transition metal minerals by GeoDeepDive

NASA Astrophysics Data System (ADS)

Liu, C.; Peters, S. E.; Ross, I.; Golden, J. J.; Downs, R. T.; Hazen, R. M.

2016-12-01

Terrestrial mineralogy evolves as a consequence of a range of physical, chemical, and biological processes [1]. Evolution of the first-row transition metal minerals could mirror the evolution of Earth's oxidation state and life, since these elements mostly are redox-sensitive and/or play critical roles in biology. The fundamental building blocks to reconstruct mineral evolution are the mineral species, locality, and age data, which are typically dispersed in sentences in scientific and technical publications. These data can be tracked down in a brute-force way, i.e., human retrieval, reading, and recording all relevant literature. Alternatively, they can be extracted automatically by GeoDeepDive. In GeoDeepDive, scientific and technical articles from publishers, including Elsevier, Wiley, USGS, SEPM, GSA and Canada Science Publishing, have been parsed into a Javascript database with NLP tags. Sentences containing data of mineral names, locations, and ages can be recognized and extracted by user-developed applications. In a preliminary search for cobalt mineral ages, we successfully extracted 678 citations with >1000 mentions of cobalt minerals, their locations, and ages. The extracted results are in agreement with brute-force search results. What is more, GeoDeepDive provides 40 additional data points that were not recovered by the brute-force approach. The extracted mineral locality-age data suggest that the evolution of Co minerals is controlled by global supercontinent cycles, i.e., more Co minerals form during episodes of supercontinent assembly. Mineral evolution of other first-row transition elements is being investigated through GeoDeepDive. References: [1] Hazen et al. (2008) Mineral evolution. American Mineralogist, 93, 1693-1720

Human Ageing Genomic Resources: new and updated databases

PubMed Central

Tacutu, Robi; Thornton, Daniel; Johnson, Emily; Budovsky, Arie; Barardo, Diogo; Craig, Thomas; Diana, Eugene; Lehmann, Gilad; Toren, Dmitri; Wang, Jingwei; Fraifeld, Vadim E

2018-01-01

Abstract In spite of a growing body of research and data, human ageing remains a poorly understood process. Over 10 years ago we developed the Human Ageing Genomic Resources (HAGR), a collection of databases and tools for studying the biology and genetics of ageing. Here, we present HAGR’s main functionalities, highlighting new additions and improvements. HAGR consists of six core databases: (i) the GenAge database of ageing-related genes, in turn composed of a dataset of >300 human ageing-related genes and a dataset with >2000 genes associated with ageing or longevity in model organisms; (ii) the AnAge database of animal ageing and longevity, featuring >4000 species; (iii) the GenDR database with >200 genes associated with the life-extending effects of dietary restriction; (iv) the LongevityMap database of human genetic association studies of longevity with >500 entries; (v) the DrugAge database with >400 ageing or longevity-associated drugs or compounds; (vi) the CellAge database with >200 genes associated with cell senescence. All our databases are manually curated by experts and regularly updated to ensure a high quality data. Cross-links across our databases and to external resources help researchers locate and integrate relevant information. HAGR is freely available online (http://genomics.senescence.info/). PMID:29121237

Topics in space gerontology: Effects of altered gravity and the problem of biological age

NASA Technical Reports Server (NTRS)

Economos, A. C.

1982-01-01

The use of altered gravity experimentation as a gerontological research tool is examined and a rationale for a systems approach to the adaptation to spaceflight is presented. The dependence of adaptation capacity on biological age is also discussed.

Scalable Parameter Estimation for Genome-Scale Biochemical Reaction Networks

PubMed Central

Kaltenbacher, Barbara; Hasenauer, Jan

2017-01-01

Mechanistic mathematical modeling of biochemical reaction networks using ordinary differential equation (ODE) models has improved our understanding of small- and medium-scale biological processes. While the same should in principle hold for large- and genome-scale processes, the computational methods for the analysis of ODE models which describe hundreds or thousands of biochemical species and reactions are missing so far. While individual simulations are feasible, the inference of the model parameters from experimental data is computationally too intensive. In this manuscript, we evaluate adjoint sensitivity analysis for parameter estimation in large scale biochemical reaction networks. We present the approach for time-discrete measurement and compare it to state-of-the-art methods used in systems and computational biology. Our comparison reveals a significantly improved computational efficiency and a superior scalability of adjoint sensitivity analysis. The computational complexity is effectively independent of the number of parameters, enabling the analysis of large- and genome-scale models. Our study of a comprehensive kinetic model of ErbB signaling shows that parameter estimation using adjoint sensitivity analysis requires a fraction of the computation time of established methods. The proposed method will facilitate mechanistic modeling of genome-scale cellular processes, as required in the age of omics. PMID:28114351

[Clinical, morphological and molecular biological characteristics of the aging eye].

PubMed

Böhm, M R R; Thomasen, H; Parnitzke, F; Steuhl, K-P

2017-02-01

The physiological aging of the eye is associated with loss of visual function. Age-related changes of the eye can result in ophthalmological diseases. The aim of this article is to display morphological, histological and molecular biological alterations of the aging eye. A web-based search and review of the literature for aging of the visual system including cornea, lens, vitreous humor, retina, retinal pigment epithelium (RPE), choroidea and optic nerve were carried out. The most important results related to morphological, histological and molecular biological changes are summarized. Age-related, morphological alterations can be found in preretinal structures, e. g. cornea, lens and vitreous humor, as well as neuronal structures, such as the retina. In addition to negligible clinical signs of the aging eye, there are clinically relevant changes which can develop into pathological ophthalmological diseases. These transitions from age-related alterations to relevant ophthalmological diseases, e. g. age-related macular degeneration and glaucoma are continuous. An understanding of aging could provide predictive factors to detect the conversion of physiological aging into pathological conditions. The derivation of physiological markers or new approaches to detection and treatment of disease-related entities associated with the risk factor aging are desirable. Translational approaches in clinical and basic science are necessary to provide new therapeutic options for relevant ophthalmological diseases in the future.

Sex differences in social cognition: The case of face processing.

PubMed

Proverbio, Alice Mado

2017-01-02

Several studies have demonstrated that women show a greater interest for social information and empathic attitude than men. This article reviews studies on sex differences in the brain, with particular reference to how males and females process faces and facial expressions, social interactions, pain of others, infant faces, faces in things (pareidolia phenomenon), opposite-sex faces, humans vs. landscapes, incongruent behavior, motor actions, biological motion, erotic pictures, and emotional information. Sex differences in oxytocin-based attachment response and emotional memory are also mentioned. In addition, we investigated how 400 different human faces were evaluated for arousal and valence dimensions by a group of healthy male and female University students. Stimuli were carefully balanced for sensory and perceptual characteristics, age, facial expression, and sex. As a whole, women judged all human faces as more positive and more arousing than men. Furthermore, they showed a preference for the faces of children and the elderly in the arousal evaluation. Regardless of face aesthetics, age, or facial expression, women rated human faces higher than men. The preference for opposite- vs. same-sex faces strongly interacted with facial age. Overall, both women and men exhibited differences in facial processing that could be interpreted in the light of evolutionary psychobiology. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Anterior cingulate activation is related to a positivity bias and emotional stability in successful aging.

PubMed

Brassen, Stefanie; Gamer, Matthias; Büchel, Christian

2011-07-15

Behavioral studies consistently reported an increased preference for positive experiences in older adults. The socio-emotional selectivity theory explains this positivity effect with a motivated goal shift in emotion regulation, which probably depends on available cognitive resources. The present study investigates the neurobiological mechanism underlying this hypothesis. Functional magnetic resonance imaging data were acquired in 21 older and 22 young subjects while performing a spatial-cueing paradigm that manipulates attentional load on emotional face distracters. We focused our analyses on the anterior cingulate cortex as a key structure of cognitive control of emotion. Elderly subjects showed a specifically increased distractibility by happy faces when more attentional resources were available for face processing. This effect was paralleled by an increased engagement of the rostral anterior cingulate cortex, and this frontal engagement was significantly correlated with emotional stability. The current study highlights how the brain might mediate the tendency to preferentially engage in positive information processing in healthy aging. The finding of a resource-dependency of this positivity effect suggests demanding self-regulating processes that are related to emotional well-being. These findings are of particular relevance regarding implications for the understanding, treatment, and prevention of nonsuccessful aging like highly prevalent late-life depression. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Advanced glycation end products and their receptor in age-related, non-communicable chronic inflammatory diseases; Overview of clinical evidence and potential contributions to disease.

PubMed

Reynaert, Niki L; Gopal, Poornima; Rutten, Erica P A; Wouters, Emiel F M; Schalkwijk, Casper G

2016-12-01

Age-related, non-communicable chronic inflammatory diseases represent the major 21st century health problem. Especially in Western countries, the prevalence of non-communicable diseases like chronic obstructive pulmonary disease, cardiovascular disease, type 2 diabetes and osteoporosis are exponentially rising as the population ages. These diseases are determined by common risk factors and share an age-related onset. The affected organs display evidence of accelerated ageing, and are hallmarked by chronic inflammation and oxidative stress. The receptor for advanced glycation end products (RAGE) has been implicated in a number of inflammatory diseases and plays a central role in amplifying inflammatory responses. Advanced glycation end product (AGE) formation and accumulation is accelerated under these conditions. Advanced glycation end products are not only linked to RAGE signaling and inflammation, but to various hallmarks of the ageing process. In addition to these biological functions, circulating levels of the soluble form of RAGE and of advanced glycation end products are candidate biomarkers for many age-related inflammatory diseases. The purpose of this review is to provide an overview of the mechanistic connections between RAGE and advanced glycation end products and the processes of inflammation and ageing. Furthermore, through the presented overview of AGE-RAGE alterations that have been described in clinical studies in chronic obstructive pulmonary disease, cardiovascular disease, type 2 diabetes and osteoporosis, and insight obtained from mechanistic in vitro and animal studies, it can be concluded that these AGE-RAGE disturbances are a common contributing factor to the inflammatory state and pathogenesis of these various conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Visual event-related potentials to biological motion stimuli in autism spectrum disorders

PubMed Central

Bletsch, Anke; Krick, Christoph; Siniatchkin, Michael; Jarczok, Tomasz A.; Freitag, Christine M.; Bender, Stephan

2014-01-01

Atypical visual processing of biological motion contributes to social impairments in autism spectrum disorders (ASD). However, the exact temporal sequence of deficits of cortical biological motion processing in ASD has not been studied to date. We used 64-channel electroencephalography to study event-related potentials associated with human motion perception in 17 children and adolescents with ASD and 21 typical controls. A spatio-temporal source analysis was performed to assess the brain structures involved in these processes. We expected altered activity already during early stimulus processing and reduced activity during subsequent biological motion specific processes in ASD. In response to both, random and biological motion, the P100 amplitude was decreased suggesting unspecific deficits in visual processing, and the occipito-temporal N200 showed atypical lateralization in ASD suggesting altered hemispheric specialization. A slow positive deflection after 400 ms, reflecting top-down processes, and human motion-specific dipole activation differed slightly between groups, with reduced and more diffuse activation in the ASD-group. The latter could be an indicator of a disrupted neuronal network for biological motion processing in ADS. Furthermore, early visual processing (P100) seems to be correlated to biological motion-specific activation. This emphasizes the relevance of early sensory processing for higher order processing deficits in ASD. PMID:23887808

Immune dysregulation and cognitive vulnerability in the aging brain: Interactions of microglia, IL-1β, BDNF and synaptic plasticity.

PubMed

Patterson, Susan L

2015-09-01

Older individuals often experience declines in cognitive function after events (e.g. infection, or injury) that trigger activation of the immune system. This occurs at least in part because aging sensitizes the response of microglia (the brain's resident immune cells) to signals triggered by an immune challenge. In the aging brain, microglia respond to these signals by producing more pro-inflammatory cytokines (e.g. interleukin-1beta or IL-1β) and producing them for longer than microglia in younger brains. This exaggerated inflammatory response can compromise processes critical for optimal cognitive functioning. Interleukin-1β is central to the inflammatory response and is a key mediator and modulator of an array of associated biological functions; thus its production and release is usually very tightly regulated. This review will focus on the impact of dysregulated production of IL-1β on hippocampus dependent-memory systems and associated synaptic plasticity processes. The neurotrophin brain-derived neurotrophic factor (BNDF) helps to protect neurons from damage caused by infection or injury, and it plays a critical role in many of the same memory and hippocampal plasticity processes compromised by dysregulated production of IL-1β. This suggests that an exaggerated brain inflammatory response, arising from aging and a secondary immune challenge, may erode the capacity to provide the BDNF needed for memory-related plasticity processes at hippocampal synapses. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'. Copyright © 2014 Elsevier Ltd. All rights reserved.

The use of information theory for the evaluation of biomarkers of aging and physiological age.

PubMed

Blokh, David; Stambler, Ilia

2017-04-01

The present work explores the application of information theoretical measures, such as entropy and normalized mutual information, for research of biomarkers of aging. The use of information theory affords unique methodological advantages for the study of aging processes, as it allows evaluating non-linear relations between biological parameters, providing the precise quantitative strength of those relations, both for individual and multiple parameters, showing cumulative or synergistic effect. Here we illustrate those capabilities utilizing a dataset on heart disease, including diagnostic parameters routinely available to physicians. The use of information-theoretical methods, utilizing normalized mutual information, revealed the exact amount of information that various diagnostic parameters or their combinations contained about the persons' age. Based on those exact informative values for the correlation of measured parameters with age, we constructed a diagnostic rule (a decision tree) to evaluate physiological age, as compared to chronological age. The present data illustrated that younger subjects suffering from heart disease showed characteristics of people of higher age (higher physiological age). Utilizing information-theoretical measures, with additional data, it may be possible to create further clinically applicable information-theory-based markers and models for the evaluation of physiological age, its relation to age-related diseases and its potential modifications by therapeutic interventions. Copyright © 2017 Elsevier B.V. All rights reserved.

[Estimation of the biological age in males of the taiga tick (Ixodes persulcatus: Ixodinae) by fat reserves in the midgut].

PubMed

Grigor'eva, L A

2012-01-01

Some criteria for the estimation of the biological and calendar age by the fat storage in midgut cells of Ixodes persulcatus males were established on the basis of examination of ticks from the laboratory culture.

Aging: Molecular Pathways and Implications on the Cardiovascular System.

PubMed

de Almeida, Arthur José Pontes Oliveira; Ribeiro, Thaís Porto; de Medeiros, Isac Almeida

2017-01-01

The world's population over 60 years is growing rapidly, reaching 22% of the global population in the next decades. Despite the increase in global longevity, individual healthspan needs to follow this growth. Several diseases have their prevalence increased by age, such as cardiovascular diseases, the leading cause of morbidity and mortality worldwide. Understanding the aging biology mechanisms is fundamental to the pursuit of cardiovascular health. In this way, aging is characterized by a gradual decline in physiological functions, involving the increased number in senescent cells into the body. Several pathways lead to senescence, including oxidative stress and persistent inflammation, as well as energy failure such as mitochondrial dysfunction and deregulated autophagy, being ROS, AMPK, SIRTs, mTOR, IGF-1, and p53 key regulators of the metabolic control, connecting aging to the pathways which drive towards diseases. In addition, senescence can be induced by cellular replication, which resulted from telomere shortening. Taken together, it is possible to draw a common pathway unifying aging to cardiovascular diseases, and the central point of this process, senescence, can be the target for new therapies, which may result in the healthspan matching the lifespan.

Whole genome sequences of two octogenarians with sustained cognitive abilities

PubMed Central

Nickles, Dorothee; Madireddy, Lohith; Patel, Nihar; Isobe, Noriko; Miller, Bruce L.; Baranzini, Sergio E.; Kramer, Joel H.; Oksenberg, Jorge R.

2014-01-01

Although numerous genetic variants affecting aging and mortality have been identified, e.g. APOE ε4, the genetic component influencing cognitive aging has not been fully defined yet. A better knowledge of the genetics of aging will prove helpful in understanding the underlying biological processes. Here, we describe the whole genome sequences of two female octogenarians. We provide the repertoire of genomic variants that the two octogenarians have in common. We also describe the overlap with the previously reported genomes of two supercentenarians - individuals aged ≥ 110 years. We assessed the genetic disease propensities of the octogenarians and non-aged control genomes and could not find support for the hypothesis that long-lived healthy individuals might exhibit greater genetic fitness than the general population. Furthermore, there is no evidence for an accumulation of previously described variants promoting longevity in the two octogenarians. These findings suggest that genetic fitness, as currently defined, is not the sole factor enabling an increased lifespan. We identified a number of healthy-cognitive-aging candidate genetic loci awaiting confirmation in larger studies. PMID:25618617

Whole genome sequences of 2 octogenarians with sustained cognitive abilities.

PubMed

Nickles, Dorothee; Madireddy, Lohith; Patel, Nihar; Isobe, Noriko; Miller, Bruce L; Baranzini, Sergio E; Kramer, Joel H; Oksenberg, Jorge R

2015-03-01

Although numerous genetic variants affecting aging and mortality have been identified, for example, apolipoprotein E ε4, the genetic component influencing cognitive aging has not been fully defined yet. A better knowledge of the genetics of aging will prove helpful in understanding the underlying biological processes. Here, we describe the whole genome sequences of 2 female octogenarians. We provide the repertoire of genomic variants that the 2 octogenarians have in common. We also describe the overlap with the previously reported genomes of 2 supercentenarians—individuals aged ≥110 years. We assessed the genetic disease propensities of the octogenarians and non-aged control genomes and could not find support for the hypothesis that long-lived healthy individuals might exhibit greater genetic fitness than the general population. Furthermore, there is no evidence for an accumulation of previously described variants promoting longevity in the 2 octogenarians. These findings suggest that genetic fitness, as currently defined, is not the sole factor enabling an increased life span. We identified a number of healthy-cognitive-aging candidate genetic loci awaiting confirmation in larger studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Biological and rearing mother influences on child ADHD symptoms: revisiting the developmental interface between nature and nurture.

PubMed

Harold, Gordon T; Leve, Leslie D; Barrett, Douglas; Elam, Kit; Neiderhiser, Jenae M; Natsuaki, Misaki N; Shaw, Daniel S; Reiss, David; Thapar, Anita

2013-10-01

Families of children with attention deficit hyperactivity disorder (ADHD) report more negative family relationships than families of children without ADHD. Questions remain as to the role of genetic factors underlying associations between family relationships and children's ADHD symptoms, and the role of children's ADHD symptoms as an evocative influence on the quality of relationships experienced within such families. Utilizing the attributes of two genetically sensitive research designs, the present study examined associations between biologically related and nonbiologically related maternal ADHD symptoms, parenting practices, child impulsivity/activation, and child ADHD symptoms. The combined attributes of the study designs permit assessment of associations while controlling for passive genotype-environment correlation and directly examining evocative genotype-environment correlation (rGE); two relatively under examined confounds of past research in this area. A cross-sectional adoption-at-conception design (Cardiff IVF Study; C-IVF) and a longitudinal adoption-at-birth design (Early Growth and Development Study; EGDS) were used. The C-IVF sample included 160 mothers and children (age 5-8 years). The EGDS sample included 320 linked sets of adopted children (age 6 years), adoptive-, and biologically related mothers. Questionnaires were used to assess maternal ADHD symptoms, parenting practices, child impulsivity/activation, and child ADHD symptoms. A cross-rater approach was used across measures of maternal behavior (mother reports) and child ADHD symptoms (father reports). Significant associations were revealed between rearing mother ADHD symptoms, hostile parenting behavior, and child ADHD symptoms in both samples. Because both samples consisted of genetically unrelated mothers and children, passive rGE was removed as a possible explanatory factor underlying these associations. Further, path analysis revealed evidence for evocative rGE processes in the longitudinal adoption-at-birth study (EGDS) from biologically related maternal ADHD symptoms to biologically unrelated maternal hostile parenting through early disrupted child behavior (impulsivity/activation), with maternal hostile parenting and disrupted child behavior associated with later child ADHD symptoms, controlling for concurrent adoptive mother ADHD symptoms. Results highlight the importance of genetically influenced child ADHD-related temperamental attributes on genetically unrelated maternal hostility that in turn links to later child ADHD symptoms. Implications for intervention programs focusing on early family processes and the precursors of child ADHD symptoms are discussed. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

The Emergence of Geroscience as an Interdisciplinary Approach to the Enhancement of Health Span and Life Span

PubMed Central

Sierra, Felipe

2016-01-01

Research on the biology of aging has accelerated rapidly in the last two decades. It is now at the point where translation of the findings into useful approaches to improve the health of the elderly population seems possible. In trying to fill that gap, a new field termed geroscience will be articulated here that attempts to identify the biological underpinnings for the age-dependency of most chronic diseases. Herein, I will review the major conceptual issues leading to the formulation of geroscience as a field, as well as give examples of current areas of inquiry in which basic aging biology research could lead to therapeutic approaches to address age-related chronic diseases, not one at a time, but most of them in unison. PMID:26931460

Investigation of Age Polyethism in Food Processing of the Fungus-Growing Termite Odontotermes formosanus (Blattodea: Termitidae) Using a Laboratory Artificial Rearing System.

PubMed

Li, Hongjie; Yang, Mengyi; Chen, Yonger; Zhu, Na; Lee, Chow-Yang; Wei, Ji-Qian; Mo, Jianchu

2015-02-01

Laboratory rearing systems are useful models for studying Rhinotermitid behavior. Information on the biology of fungus-growing termites, however, is limited because of the difficulty of rearing colonies in the laboratory settings. The physical structure of termite nests makes it impossible to photograph or to observe colonies in the field. In this study, an artificial rearing system for field-collected colonies of the fungus-growing termite Odontotermes formosanus (Shiraki) was developed to facilitate observation in the laboratory. We recorded colony activity within the artificial rearing system and documented a variety of social behaviors that occurred throughout the food processing of the colony. This complex miniature ecosystem was cooperatively organized via division of labor in the foraging and processing of plant materials, and the observed patterns largely resembled the caste and age-based principles present in Macrotermes colonies. This work extends our insights into polyethism in the subfamily Macrotermitinae. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Gingival wound healing: an essential response disturbed by aging?

PubMed

Smith, P C; Cáceres, M; Martínez, C; Oyarzún, A; Martínez, J

2015-03-01

Gingival wound healing comprises a series of sequential responses that allow the closure of breaches in the masticatory mucosa. This process is of critical importance to prevent the invasion of microbes or other agents into tissues, avoiding the establishment of a chronic infection. Wound healing may also play an important role during cell and tissue reaction to long-term injury, as it may occur during inflammatory responses and cancer. Recent experimental data have shown that gingival wound healing is severely affected by the aging process. These defects may alter distinct phases of the wound-healing process, including epithelial migration, granulation tissue formation, and tissue remodeling. The cellular and molecular defects that may explain these deficiencies include several biological responses such as an increased inflammatory response, altered integrin signaling, reduced growth factor activity, decreased cell proliferation, diminished angiogenesis, reduced collagen synthesis, augmented collagen remodeling, and deterioration of the proliferative and differentiation potential of stem cells. In this review, we explore the cellular and molecular basis of these defects and their possible clinical implications. © International & American Associations for Dental Research 2014.

Analysis of sensory processing in preterm infants.

PubMed

Cabral, Thais Invenção; da Silva, Louise Gracelli Pereira; Martinez, Cláudia Maria Simões; Tudella, Eloisa

2016-12-01

Premature birth suggests condition of biological vulnerability, predisposing to neurological injuries, requiring hospitalization in Neonatal Intensive Care Units, which, while contributing to increase the survival rates, expose infants to sensory stimuli harmful to the immature organism. To evaluate the sensory processing at 4 and 6months' corrected age. This was a descriptive cross-sectional study with a sample of 30 infants divided into an experimental group composed of preterm infants (n=15), and a control group composed of full-term infants (n=15). The infants were assessed using the Test of Sensory Functions in Infants. The preterm infants showed poor performance in the total score of the test in reactivity to tactile deep pressure and reactivity to vestibular stimulation. When groups were compared, significant differences in the total score (p=0.0113) and in the reactivity to tactile deep pressure (p<0.0001) were found. At 4 and 6months of corrected age, the preterm infants showed alterations in sensory processing. These changes were most evident in reactivity to tactile deep pressure and vestibular stimulation. Copyright © 2016. Published by Elsevier Ireland Ltd.

Aging and Parkinson's disease: Different sides of the same coin?

PubMed

Collier, Timothy J; Kanaan, Nicholas M; Kordower, Jeffrey H

2017-07-01

Despite abundant epidemiological evidence in support of aging as the primary risk factor for PD, biological correlates of a connection have been elusive. In this article, we address the following question: does aging represent biology accurately characterized as pre-PD? We present evidence from our work on midbrain dopamine neurons of aging nonhuman primates that demonstrates that markers of known correlates of dopamine neuron degeneration in PD, including impaired proteasome/lysosome function, oxidative/nitrative damage, and inflammation, all increase with advancing age and are exaggerated in the ventral tier substantia nigra dopamine neurons most vulnerable to degeneration in PD. Our findings support the view that aging-related changes in the dopamine system approach the biological threshold for parkinsonism, actively producing a vulnerable pre-parkinsonian state. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Reevaluation of immune activation in the era of cART and an aging HIV-infected population

PubMed Central

de Armas, Lesley R.; Pallikkuth, Suresh; George, Varghese; Rinaldi, Stefano; Pahwa, Rajendra; Arheart, Kristopher L.

2017-01-01

Biological aging is associated with immune activation (IA) and declining immunity due to systemic inflammation. It is widely accepted that HIV infection causes persistent IA and premature immune senescence despite effective antiretroviral therapy and virologic suppression; however, the effects of combined HIV infection and aging are not well defined. Here, we assessed the relationship between markers of IA and inflammation during biological aging in HIV-infected and -uninfected populations. Antibody response to seasonal influenza vaccination was implemented as a measure of immune competence and relationships between IA, inflammation, and antibody responses were explored using statistical modeling appropriate for integrating high-dimensional data sets. Our results show that markers of IA, such as coexpression of HLA antigen D related (HLA-DR) and CD38 on CD4+ T cells, exhibit strong associations with HIV infection but not with biological age. Certain variables that showed a strong relationship with aging, such as declining naive and CD38+ CD4 and CD8+ T cells, did so regardless of HIV infection. Interestingly, the variable of biological age was not identified in a predictive model as significantly impacting vaccine responses in either group, while distinct IA and inflammatory variables were closely associated with vaccine response in HIV-infected and -uninfected populations. These findings shed light on the most relevant and persistent immune defects during virological suppression with antiretroviral therapy. PMID:29046481

Reevaluation of immune activation in the era of cART and an aging HIV-infected population.

PubMed

de Armas, Lesley R; Pallikkuth, Suresh; George, Varghese; Rinaldi, Stefano; Pahwa, Rajendra; Arheart, Kristopher L; Pahwa, Savita

2017-10-19

Biological aging is associated with immune activation (IA) and declining immunity due to systemic inflammation. It is widely accepted that HIV infection causes persistent IA and premature immune senescence despite effective antiretroviral therapy and virologic suppression; however, the effects of combined HIV infection and aging are not well defined. Here, we assessed the relationship between markers of IA and inflammation during biological aging in HIV-infected and -uninfected populations. Antibody response to seasonal influenza vaccination was implemented as a measure of immune competence and relationships between IA, inflammation, and antibody responses were explored using statistical modeling appropriate for integrating high-dimensional data sets. Our results show that markers of IA, such as coexpression of HLA antigen D related (HLA-DR) and CD38 on CD4+ T cells, exhibit strong associations with HIV infection but not with biological age. Certain variables that showed a strong relationship with aging, such as declining naive and CD38+ CD4 and CD8+ T cells, did so regardless of HIV infection. Interestingly, the variable of biological age was not identified in a predictive model as significantly impacting vaccine responses in either group, while distinct IA and inflammatory variables were closely associated with vaccine response in HIV-infected and -uninfected populations. These findings shed light on the most relevant and persistent immune defects during virological suppression with antiretroviral therapy.

Out-of-School Experience Categories Influencing Interest in Biology of Secondary School Students by Gender: Exploration on an Abu Dhabi Sample

ERIC Educational Resources Information Center

Badri, Masood; Yang, Guang; Al Mazroui, Karima; Mohaidat, Jihad; Al Rashedi, Asma; Al Housani, Najwa

2017-01-01

This study employed the international Relevance of Science Education questionnaire to survey the interest in biology and the out-of-school experiences of Abu Dhabi secondary school students (median age 17, mean age 17.53 and mode age of 16) in the third semester of 2014. It included 3100 participants. An exploratory factor analysis was used to…

The Effect of Executive Function on Biological Reasoning in Young Children: An Individual Differences Study

ERIC Educational Resources Information Center

Zaitchik, Deborah; Iqbal, Yeshim; Carey, Susan

2014-01-01

There is substantial variance in the age at which children construct and deploy their first explicit theory of biology. This study tests the hypothesis that this variance is due, at least in part, to individual differences in their executive function (EF) abilities. A group of 79 boys and girls aged 5-7 years (with a mean age of 6½ years) were…

Computational biology for ageing

PubMed Central

Wieser, Daniela; Papatheodorou, Irene; Ziehm, Matthias; Thornton, Janet M.

2011-01-01

High-throughput genomic and proteomic technologies have generated a wealth of publicly available data on ageing. Easy access to these data, and their computational analysis, is of great importance in order to pinpoint the causes and effects of ageing. Here, we provide a description of the existing databases and computational tools on ageing that are available for researchers. We also describe the computational approaches to data interpretation in the field of ageing including gene expression, comparative and pathway analyses, and highlight the challenges for future developments. We review recent biological insights gained from applying bioinformatics methods to analyse and interpret ageing data in different organisms, tissues and conditions. PMID:21115530

Health, Health Care, and Systems Science: Emerging Paradigm.

PubMed

Janecka, Ivo

2017-02-15

Health is a continuum of an optimized state of a biologic system, an outcome of positive relationships with the self and others. A healthy system follows the principles of systems science derived from observations of nature, highlighting the character of relationships as the key determinant. Relationships evolve from our decisions, which are consequential to the function of our own biologic system on all levels, including the genome, where epigenetics impact our morphology. In healthy systems, decisions emanate from the reciprocal collaboration of hippocampal memory and the executive prefrontal cortex. We can decide to change relationships through choices. What is selected, however, only represents the cognitive interpretation of our limited sensory perception; it strongly reflects inherent biases toward either optimizing state, making a biologic system healthy, or not. Health or its absence is then the outcome; there is no inconsequential choice. Public health effort should not focus on punitive steps (e.g. taxation of unhealthy products or behaviors) in order to achieve a higher level of public's health. It should teach people the process of making healthy decisions; otherwise, people will just migrate/shift from one unhealthy product/behavior to another, and well-intended punitive steps will not make much difference. Physical activity, accompanied by nutrition and stress management, have the greatest impact on fashioning health and simultaneously are the most cost-effective measures. Moderate-to-vigorous exercise not only improves aerobic fitness but also positively influences cognition, including memory and senses. Collective, rational societal decisions can then be anticipated. Health care is a business system principally governed by self-maximizing decisions of its components; uneven and contradictory outcomes are the consequences within such a non-optimized system. Health is not health care. We are biologic systems subject to the laws of biology in spite of our incongruous decisions that are detrimental to health. A biologic system/a human body originates from structural, deterministic genes as well as shared epigenetic memory of our ancestors affecting our bodily function and structure. The political governing systems' vertical hierarchy has control over money and laws, neither of which materially affect individual lifestyle/behavioral choices toward health. Improved health comes from focusing on enhancing the biologic age and not the chronologic one, which simply represents a linear time from a birth certificate to a death certificate and is applicable only in its extremes. "Age-related diseases" are simply reflections of a given culture. Biologic age, reflecting the actual state of health, could be used in all health-related assessments including health-life insurance premiums, licensing of job categories, etc., all with a broader and healthy societal impact.

Health, Health Care, and Systems Science: Emerging Paradigm

PubMed Central

2017-01-01

Health is a continuum of an optimized state of a biologic system, an outcome of positive relationships with the self and others. A healthy system follows the principles of systems science derived from observations of nature, highlighting the character of relationships as the key determinant. Relationships evolve from our decisions, which are consequential to the function of our own biologic system on all levels, including the genome, where epigenetics impact our morphology. In healthy systems, decisions emanate from the reciprocal collaboration of hippocampal memory and the executive prefrontal cortex. We can decide to change relationships through choices. What is selected, however, only represents the cognitive interpretation of our limited sensory perception; it strongly reflects inherent biases toward either optimizing state, making a biologic system healthy, or not. Health or its absence is then the outcome; there is no inconsequential choice. Public health effort should not focus on punitive steps (e.g. taxation of unhealthy products or behaviors) in order to achieve a higher level of public’s health. It should teach people the process of making healthy decisions; otherwise, people will just migrate/shift from one unhealthy product/behavior to another, and well-intended punitive steps will not make much difference. Physical activity, accompanied by nutrition and stress management, have the greatest impact on fashioning health and simultaneously are the most cost-effective measures. Moderate-to-vigorous exercise not only improves aerobic fitness but also positively influences cognition, including memory and senses. Collective, rational societal decisions can then be anticipated. Health care is a business system principally governed by self-maximizing decisions of its components; uneven and contradictory outcomes are the consequences within such a non-optimized system. Health is not health care. We are biologic systems subject to the laws of biology in spite of our incongruous decisions that are detrimental to health. A biologic system/a human body originates from structural, deterministic genes as well as shared epigenetic memory of our ancestors affecting our bodily function and structure. The political governing systems’ vertical hierarchy has control over money and laws, neither of which materially affect individual lifestyle/behavioral choices toward health. Improved health comes from focusing on enhancing the biologic age and not the chronologic one, which simply represents a linear time from a birth certificate to a death certificate and is applicable only in its extremes. “Age-related diseases” are simply reflections of a given culture. Biologic age, reflecting the actual state of health, could be used in all health-related assessments including health-life insurance premiums, licensing of job categories, etc., all with a broader and healthy societal impact. PMID:28357162

Telomeres in aging and disease: lessons from zebrafish.

PubMed

Carneiro, Madalena C; de Castro, Inês Pimenta; Ferreira, Miguel Godinho

2016-07-01

Age is the highest risk factor for some of the most prevalent human diseases, including cancer. Telomere shortening is thought to play a central role in the aging process in humans. The link between telomeres and aging is highlighted by the fact that genetic diseases causing telomerase deficiency are associated with premature aging and increased risk of cancer. For the last two decades, this link has been mostly investigated using mice that have long telomeres. However, zebrafish has recently emerged as a powerful and complementary model system to study telomere biology. Zebrafish possess human-like short telomeres that progressively decline with age, reaching lengths in old age that are observed when telomerase is mutated. The extensive characterization of its well-conserved molecular and cellular physiology makes this vertebrate an excellent model to unravel the underlying relationship between telomere shortening, tissue regeneration, aging and disease. In this Review, we explore the advantages of using zebrafish in telomere research and discuss the primary discoveries made in this model that have contributed to expanding our knowledge of how telomere attrition contributes to cellular senescence, organ dysfunction and disease. © 2016. Published by The Company of Biologists Ltd.

Multiple biological pathways link cognitive lifestyle to protection from dementia.

PubMed

Valenzuela, Michael J; Matthews, Fiona E; Brayne, Carol; Ince, Paul; Halliday, Glenda; Kril, Jillian J; Dalton, Marshall A; Richardson, Kathryn; Forster, Gill; Sachdev, Perminder S

2012-05-01

An active cognitive lifestyle is linked to diminished dementia risk, but the underlying mechanisms are poorly understood. Potential mechanisms include disease modification, neuroprotection, and compensation. Prospective, population-based brain series provide the rare opportunity to test the plausibility of these mechanisms in humans. Participants came from the United Kingdom Medical Research Council Cognitive Function and Ageing Study, comprising 13,004 individuals aged over 65 years and followed for 14 years. In study 1, a Cognitive Lifestyle Score (CLS) was computed on all Cognitive Function and Ageing Study subjects to define low, middle, and high groups. By August 2004, 329 individuals with CLS data had come to autopsy and underwent Consortium to Establish a Registry of Alzheimer's Disease assessment. Study 2 involved more detailed quantitative histology in the hippocampus and Brodmann area 9 in 72 clinically matched individuals with high and low CLS. CLS groups did not differ on several Alzheimer disease neuropathologic measures; however, high CLS men had less cerebrovascular disease after accounting for vascular risk factors, and women had greater brain weight. No group differences were evident in hippocampal neuronal density. In Brodmann area 9, cognitively active individuals had significantly greater neuronal density, as well as correlated increases in cortical thickness. An active cognitive lifestyle was associated with protection from cerebrovascular disease in men, but there was no evidence for Alzheimer disease modification or hippocampal neuroprotection. Men and women both exhibited neurotrophic changes in the prefrontal lobe linked to cognitive lifestyle, consistent with a compensatory process. Lifespan complex cognitive activity may therefore protect against dementia through multiple biological pathways. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Behaviour of telomere and telomerase during aging and regeneration in zebrafish.

PubMed

Anchelin, Monique; Murcia, Laura; Alcaraz-Pérez, Francisca; García-Navarro, Esther M; Cayuela, María L

2011-02-09

Telomere length and telomerase activity are important factors in the pathobiology of human diseases. Age-related diseases and premature aging syndromes are characterized by short telomeres, which can compromise cell viability, whereas tumour cells can prevent telomere loss by aberrantly upregulating telomerase. The zebrafish (Danio rerio) offers multiple experimental manipulation advantages over other vertebrate models and, therefore, it has been recently considered as a potential model for aging, cancer, and regeneration studies. However, it has only partially been exploited to shed light on these fundamental biological processes. The aim of this study was, therefore, to investigate telomere length and telomerase expression and activity in different strains of zebrafish obtained from different stock centres to determine whether they undergo any changes during aging and regeneration. We found that although both telomerase expression and telomere length increased from embryo to adulthood stages, they drastically declined in aged fish despite telomerase activity was detected in different tissues of old fish. In addition, we observed a weaker upregulation of telomerase expression in regenerating fins of old fish, which well correlates with their impaired regeneration capacity. Strikingly, telomeres were elongated or maintained during the fin regeneration process at all ages and after repeated amputations, likely to support high cell proliferation rates. We conclude that the expression of telomerase and telomere length are closely related during the entire life cycle of the fish and that these two parameters can be used as biomarkers of aging in zebrafish. Our results also reveal a direct relationship between the expression of telomerase, telomere length and the efficiency of tissue regeneration.