Telomerase-mediated life-span extension of human primary fibroblasts by human artificial chromosome (HAC) vector

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

Shitara, Shingo; Kakeda, Minoru; Nagata, Keiko

2008-05-09

Telomerase-mediated life-span extension enables the expansion of normal cells without malignant transformation, and thus has been thought to be useful in cell therapies. Currently, integrating vectors including the retrovirus are used for human telomerase reverse transcriptase (hTERT)-mediated expansion of normal cells; however, the use of these vectors potentially causes unexpected insertional mutagenesis and/or activation of oncogenes. Here, we established normal human fibroblast (hPF) clones retaining non-integrating human artificial chromosome (HAC) vectors harboring the hTERT expression cassette. In hTERT-HAC/hPF clones, we observed the telomerase activity and the suppression of senescent-associated SA-{beta}-galactosidase activity. Furthermore, the hTERT-HAC/hPF clones continued growing beyond 120 daysmore » after cloning, whereas the hPF clones retaining the silent hTERT-HAC senesced within 70 days. Thus, hTERT-HAC-mediated episomal expression of hTERT allows the extension of the life-span of human primary cells, implying that gene delivery by non-integrating HAC vectors can be used to control cellular proliferative capacity of primary cultured cells.« less

Neuronal inhibition of the autophagy nucleation complex extends life span in post-reproductive C. elegans

PubMed Central

Byrne, Jonathan; Medina, Rebeca; Kolundžić, Ena; Geisinger, Johannes; Hajduskova, Martina; Tursun, Baris; Richly, Holger

2017-01-01

Autophagy is a ubiquitous catabolic process that causes cellular bulk degradation of cytoplasmic components and is generally associated with positive effects on health and longevity. Inactivation of autophagy has been linked with detrimental effects on cells and organisms. The antagonistic pleiotropy theory postulates that some fitness-promoting genes during youth are harmful during aging. On this basis, we examined genes mediating post-reproductive longevity using an RNAi screen. From this screen, we identified 30 novel regulators of post-reproductive longevity, including pha-4. Through downstream analysis of pha-4, we identified that the inactivation of genes governing the early stages of autophagy up until the stage of vesicle nucleation, such as bec-1, strongly extend both life span and health span. Furthermore, our data demonstrate that the improvements in health and longevity are mediated through the neurons, resulting in reduced neurodegeneration and sarcopenia. We propose that autophagy switches from advantageous to harmful in the context of an age-associated dysfunction. PMID:28882853

Dysfunction of different cellular degradation pathways contributes to specific β-amyloid42-induced pathologies.

PubMed

Ji, Xuan-Ru; Cheng, Kuan-Chung; Chen, Yu-Ru; Lin, Tzu-Yu; Cheung, Chun Hei Antonio; Wu, Chia-Lin; Chiang, Hsueh-Cheng

2018-03-01

The endosomal-lysosomal system (ELS), autophagy, and ubiquitin-proteasome system (UPS) are cellular degradation pathways that each play a critical role in the removal of misfolded proteins and the prevention of the accumulation of abnormal proteins. Recent studies on Alzheimer's disease (AD) pathogenesis have suggested that accumulation of aggregated β-amyloid (Aβ) peptides in the AD brain results from a dysfunction in these cellular clearance systems. However, the specific roles of these pathways in the removal of Aβ peptides and the pathogenesis underlying AD are unclear. Our in vitro and in vivo genetic approaches revealed that ELS mainly removed monomeric β-amyloid42 (Aβ42), while autophagy and UPS clear oligomeric Aβ42. Although overproduction of phosphatidylinositol 4-phosphate-5 increased Aβ42 clearance, it reduced the life span of Aβ42 transgenic flies. Our behavioral studies further demonstrated impaired autophagy and UPS-enhanced Aβ42-induced learning and memory deficits, but there was no effect on Aβ42-induced reduction in life span. Results from genetic fluorescence imaging showed that these pathways were damaged in the following order: UPS, autophagy, and finally ELS. The results of our study demonstrate that different degradation pathways play distinct roles in the removal of Aβ42 aggregates and in disease progression. These findings also suggest that pharmacologic treatments that are designed to stimulate cellular degradation pathways in patients with AD should be used with caution.-Ji, X.-R., Cheng, K.-C., Chen, Y.-R., Lin, T.-Y., Cheung, C. H. A., Wu, C.-L., Chiang, H.-C. Dysfunction of different cellular degradation pathways contributes to specific β-amyloid42-induced pathologies.

SIP-ing the elixir of youth.

PubMed

Mair, William; Steffen, Kristan K; Dillin, Andrew

2011-09-16

AMP-activated protein kinase (AMPK) is a conserved cellular fuel gauge previously implicated in aging. In this issue, Lu et al. (2011) describe how age-related deacetylation of Sip2, a subunit of the AMPK homolog in yeast, acts as a life span clock that can be wound backward or forward to modulate longevity. Copyright © 2011 Elsevier Inc. All rights reserved.

Interplay between Selenium Levels, Selenoprotein Expression, and Replicative Senescence in WI-38 Human Fibroblasts*

PubMed Central

Legrain, Yona; Touat-Hamici, Zahia; Chavatte, Laurent

2014-01-01

Selenium is an essential trace element, which is incorporated as selenocysteine into at least 25 selenoproteins using a unique translational UGA-recoding mechanism. Selenoproteins are important enzymes involved in antioxidant defense, redox homeostasis, and redox signaling pathways. Selenium levels decline during aging, and its deficiency is associated with a marked increase in mortality for people over 60 years of age. Here, we investigate the relationship between selenium levels in the culture medium, selenoprotein expression, and replicative life span of human embryonic lung fibroblast WI-38 cells. Selenium levels regulate the entry into replicative senescence and modify the cellular markers characteristic for senescent cells. Whereas selenium supplementation extends the number of population doublings, its deficiency impairs the proliferative capacity of WI-38 cells. We observe that the expression of several selenoproteins involved in antioxidant defense is specifically affected in response to cellular senescence. Their expression is selectively controlled by the modulation of mRNA levels and translational recoding efficiencies. Our data provide novel mechanistic insights into how selenium impacts the replicative life span of mammalian cells by identifying several selenoproteins as new targets of senescence. PMID:24425862

Altered Lipid Synthesis by Lack of Yeast Pah1 Phosphatidate Phosphatase Reduces Chronological Life Span*

PubMed Central

Park, Yeonhee; Han, Gil-Soo; Mileykovskaya, Eugenia; Garrett, Teresa A.; Carman, George M.

2015-01-01

In Saccharomyces cerevisiae, Pah1 phosphatidate phosphatase, which catalyzes the dephosphorylation of phosphatidate to yield diacylglycerol, plays a crucial role in the synthesis of the storage lipid triacylglycerol. This evolutionarily conserved enzyme also plays a negative regulatory role in controlling de novo membrane phospholipid synthesis through its consumption of phosphatidate. We found that the pah1Δ mutant was defective in the utilization of non-fermentable carbon sources but not in oxidative phosphorylation; the mutant did not exhibit major changes in oxygen consumption rate, mitochondrial membrane potential, F1F0-ATP synthase activity, or gross mitochondrial morphology. The pah1Δ mutant contained an almost normal complement of major mitochondrial phospholipids with some alterations in molecular species. Although oxidative phosphorylation was not compromised in the pah1Δ mutant, the cellular levels of ATP in quiescent cells were reduced by 2-fold, inversely correlating with a 4-fold increase in membrane phospholipids. In addition, the quiescent pah1Δ mutant cells had 3-fold higher levels of mitochondrial superoxide and cellular lipid hydroperoxides, had reduced activities of superoxide dismutase 2 and catalase, and were hypersensitive to hydrogen peroxide. Consequently, the pah1Δ mutant had a shortened chronological life span. In addition, the loss of Tsa1 thioredoxin peroxidase caused a synthetic growth defect with the pah1Δ mutation. The shortened chronological life span of the pah1Δ mutant along with its growth defect on non-fermentable carbon sources and hypersensitivity to hydrogen peroxide was suppressed by the loss of Dgk1 diacylglycerol kinase, indicating that the underpinning of pah1Δ mutant defects was the excess synthesis of membrane phospholipids. PMID:26338708

Proteotoxicity and the contrasting effects of oxaloacetate and glycerol on Caenorhabditis elegans life span: a role for methylglyoxal?

PubMed

Hipkiss, Alan R

2010-10-01

Because accumulation of altered proteins is the most common biochemical symptom of aging, it is at least possible that such proteotoxicity may cause aging and influence life span. The life span of the nematode worm Caenorhabditis elegans is strongly influenced by changes in the intracellular concentration of methylglyoxal (MG), a putative source of much age-related proteotoxicity and organelle, cellular, and molecular dysfunction. Glycerol has recently been shown to shorten, whereas oxaloacetate has been found to extend, life span in C. elegans. It is suggested here that glycerol and oxaloacetate exert opposing effects on MG formation in C. elegans. It is proposed that, if not secreted by aquaporin, glycerol is converted to glycerol phosphate and then to dihydroxyacetone phosphate (DHAP) via a reaction requiring nicotinamide adenine dinucleotide (NAD(+)). This inhibits operation of the glycerol phosphate cycle in which DHAP is converted into glycerol phosphate, which concomitantly regenerates NAD(+) from NADH, thereby ensuring glycolytic oxidation of glyceraldehyde-3-phosphate (G3P). Because DHAP and G3P spontaneously decompose into MG, and NAD(+) is required for conversion of G3P into phosphoglycerate, the glycerol-induced increased DHAP formation and decreased NAD(+) availability will increase the potential for MG generation. In contrast, oxaloacetate may decrease MG generation by stimulating the operation of the malate-oxaloacetate shuttle, in which oxaloacetate is converted to malate, which regenerates NAD(+) from NADH. By the ensuing G3P oxidation, increased NAD(+) availability will decrease the potential for MG formation. It should be noted that mitochondria are involved in the operation of the above cycle/shuttles and that increased NAD(+) availability also stimulates those sirtuin activities that increase mitogenesis and mitochondrial activity via effects on signal transduction and gene expression, which frequently accompany dietary restriction-induced life span extension.

A Phylogenomic Census of Molecular Functions Identifies Modern Thermophilic Archaea as the Most Ancient Form of Cellular Life

PubMed Central

Kim, Kyung Mo; Caetano-Anollés, Gustavo

2014-01-01

The origins of diversified life remain mysterious despite considerable efforts devoted to untangling the roots of the universal tree of life. Here we reconstructed phylogenies that described the evolution of molecular functions and the evolution of species directly from a genomic census of gene ontology (GO) definitions. We sampled 249 free-living genomes spanning organisms in the three superkingdoms of life, Archaea, Bacteria, and Eukarya, and used the abundance of GO terms as molecular characters to produce rooted phylogenetic trees. Results revealed an early thermophilic origin of Archaea that was followed by genome reduction events in microbial superkingdoms. Eukaryal genomes displayed extraordinary functional diversity and were enriched with hundreds of novel molecular activities not detected in the akaryotic microbial cells. Remarkably, the majority of these novel functions appeared quite late in evolution, synchronized with the diversification of the eukaryal superkingdom. The distribution of GO terms in superkingdoms confirms that Archaea appears to be the simplest and most ancient form of cellular life, while Eukarya is the most diverse and recent. PMID:25249790

Oxidative damage and cellular defense mechanisms in sea urchin models of aging.

PubMed

Du, Colin; Anderson, Arielle; Lortie, Mae; Parsons, Rachel; Bodnar, Andrea

2013-10-01

The free radical, or oxidative stress, theory of aging proposes that the accumulation of oxidative cellular damage is a major contributor to the aging process and a key determinant of species longevity. This study investigates the oxidative stress theory in a novel model for aging research, the sea urchin. Sea urchins present a unique model for the study of aging because of the existence of species with tremendously different natural life spans, including some species with extraordinary longevity and negligible senescence. Cellular oxidative damage, antioxidant capacity, and proteasome enzyme activities were measured in the tissues of three sea urchin species: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus, and Strongylocentrotus purpuratus, which has an intermediate life span. Levels of protein carbonyls and 4-hydroxynonenal measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2'-deoxyguanosine measured in cell-free coelomic fluid showed no general increase with age. The fluorescent age pigment lipofuscin, measured in muscle, nerve, and esophagus, increased with age; however, it appeared to be predominantly extracellular. Antioxidant mechanisms (total antioxidant capacity, superoxide dismutase) and proteasome enzyme activities were maintained with age. In some instances, levels of oxidative damage were lower and antioxidant activity higher in cells or tissues of the long-lived species compared to the short-lived species; however, further studies are required to determine the relationship between oxidative damage and longevity in these animals. Consistent with the predictions of the oxidative stress theory of aging, the results suggest that negligible senescence is accompanied by a lack of accumulation of cellular oxidative damage with age, and maintenance of antioxidant capacity and proteasome enzyme activities may be important mechanisms to mitigate damage. Copyright © 2013 Elsevier Inc. All rights reserved.

Linkages between mitochondrial lipids and life history in temperate and tropical birds.

PubMed

Calhoon, Elisabeth A; Jimenez, Ana Gabriela; Harper, James M; Jurkowitz, Marianne S; Williams, Joseph B

2014-01-01

Temperate birds tend to have a fast pace of life and short life spans with high reproductive output, whereas tropical birds tend to have a slower pace of life, invest fewer resources in reproduction, and have higher adult survival rates. How these differences in life history at the organismal level are rooted in differences at the cellular level is a major focus of current research. Here, we cultured fibroblasts from phylogenetically paired tropical and temperate species, isolated mitochondria from each, and compared their mitochondrial membrane lipids. We also correlated the amounts of these lipids with an important life history parameter, clutch size. We found that tropical birds tended to have less mitochondrial lipid per cell, especially less cardiolipin per cell, suggesting that cells from tropical birds have fewer mitochondria or less inner mitochondrial membrane per cell. We also found that the mitochondria of tropical birds and the species with the smallest clutch sizes had higher amounts of plasmalogens, a lipid that could serve as an antioxidant. Overall, our findings are consistent with the idea that there are underlying molecular and cellular physiological traits that could account for the differences in whole-animal physiology between animals with different life histories.

CTT1 overexpression increases life span of calorie-restricted Saccharomyces cerevisiae deficient in Sod1.

PubMed

Rona, Germana; Herdeiro, Ricardo; Mathias, Cristiane Juliano; Torres, Fernando Araripe; Pereira, Marcos Dias; Eleutherio, Elis

2015-06-01

Studies using different organisms revealed that reducing calorie intake, without malnutrition, known as calorie restriction (CR), increases life span, but its mechanism is still unkown. Using the yeast Saccharomyces cerevisiae as eukaryotic model, we observed that Cu, Zn-superoxide dismutase (Sod1p) is required to increase longevity, as well as to confer protection against lipid and protein oxidation under CR. Old cells of sod1 strain also presented a premature induction of apoptosis. However, when CTT1 (which codes for cytosolic catalase) was overexpressed, sod1 and WT strains showed similar survival rates. Furthermore, CTT1 overexpression decreased lipid peroxidation and delayed the induction of apoptotic process. Superoxide is rapidly converted to hydrogen peroxide by superoxide dismutase, but it also undergoes spontaneous dismutation albeit at a slower rate. However, the quantity of peroxide produced from superoxide in this way is two-fold higher. Peroxide degradation, catalyzed by catalase, is of vital importance, because in the presence of a reducer transition metal peroxide is reduced to the highly reactive hydroxyl radical, which reacts indiscriminately with most cellular constituents. These findings might explain why overexpression of catalase was able to overcome the deficiency of Sod1p, increasing life span in response to CR.

The parkin Mutant Phenotype in the Fly Is Largely Rescued by Metal-Responsive Transcription Factor (MTF-1) ▿ †

PubMed Central

Saini, Nidhi; Georgiev, Oleg; Schaffner, Walter

2011-01-01

The gene for Parkin, an E3 ubiquitin ligase, is mutated in some familial forms of Parkinson's disease, a severe neurodegenerative disorder. A homozygous mutant of the Drosophila ortholog of human parkin is viable but results in severe motoric impairment including an inability to fly, female and male sterility, and a decreased life span. We show here that a double mutant of the genes for Parkin and the metal-responsive transcription factor 1 (MTF-1) is not viable. MTF-1, which is conserved from insects to mammals, is a key regulator of heavy metal homeostasis and detoxification and plays additional roles in other stress conditions, notably oxidative stress. In contrast to the synthetic lethality of the double mutant, elevated expression of MTF-1 dramatically ameliorates the parkin mutant phenotype, as evidenced by a prolonged life span, motoric improvement including short flight episodes, and female fertility. At the cellular level, muscle and mitochondrial structures are substantially improved. A beneficial effect is also seen with a transgene encoding human MTF-1. We propose that Parkin and MTF-1 provide complementary functions in metal homeostasis, oxidative stress and other cellular stress responses. Our findings also raise the possibility that MTF-1 gene polymorphisms in humans could affect the severity of Parkinson's disease. PMID:21383066

Interpreting the universal phylogenetic tree

NASA Technical Reports Server (NTRS)

Woese, C. R.

2000-01-01

The universal phylogenetic tree not only spans all extant life, but its root and earliest branchings represent stages in the evolutionary process before modern cell types had come into being. The evolution of the cell is an interplay between vertically derived and horizontally acquired variation. Primitive cellular entities were necessarily simpler and more modular in design than are modern cells. Consequently, horizontal gene transfer early on was pervasive, dominating the evolutionary dynamic. The root of the universal phylogenetic tree represents the first stage in cellular evolution when the evolving cell became sufficiently integrated and stable to the erosive effects of horizontal gene transfer that true organismal lineages could exist.

Senescence in chronic liver disease: Is the future in aging?

PubMed

Aravinthan, Aloysious D; Alexander, Graeme J M

2016-10-01

Cellular senescence is a fundamental, complex mechanism with an important protective role present from embryogenesis to late life across all species. It limits the proliferative potential of damaged cells thus protecting against malignant change, but at the expense of substantial alterations to the microenvironment and tissue homeostasis, driving inflammation, fibrosis and paradoxically, malignant disease if the process is sustained. Cellular senescence has attracted considerable recent interest with recognition of pathways linking aging, malignancy and insulin resistance and the current focus on therapeutic interventions to extend health-span. There are major implications for hepatology in the field of fibrosis and cancer, where cellular senescence of hepatocytes, cholangiocytes, stellate cells and immune cells has been implicated in chronic liver disease progression. This review focuses on cellular senescence in chronic liver disease and explores therapeutic opportunities. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Biological impact of auditory expertise across the life span: musicians as a model of auditory learning

PubMed Central

Strait, Dana L.; Kraus, Nina

2013-01-01

Experience-dependent characteristics of auditory function, especially with regard to speech-evoked auditory neurophysiology, have garnered increasing attention in recent years. This interest stems from both pragmatic and theoretical concerns as it bears implications for the prevention and remediation of language-based learning impairment in addition to providing insight into mechanisms engendering experience-dependent changes in human sensory function. Musicians provide an attractive model for studying the experience-dependency of auditory processing in humans due to their distinctive neural enhancements compared to nonmusicians. We have only recently begun to address whether these enhancements are observable early in life, during the initial years of music training when the auditory system is under rapid development, as well as later in life, after the onset of the aging process. Here we review neural enhancements in musically trained individuals across the life span in the context of cellular mechanisms that underlie learning, identified in animal models. Musicians’ subcortical physiologic enhancements are interpreted according to a cognitive framework for auditory learning, providing a model by which to study mechanisms of experience-dependent changes in auditory function in humans. PMID:23988583

Caloric restriction and intermittent fasting: Two potential diets for successful brain aging

PubMed Central

Martin, Bronwen; Mattson, Mark P.; Maudsley, Stuart

2008-01-01

The vulnerability of the nervous system to advancing age is all too often manifest in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. In this review article we describe evidence suggesting that two dietary interventions, caloric restriction (CR) and intermittent fasting (IF), can prolong the health-span of the nervous system by impinging upon fundamental metabolic and cellular signaling pathways that regulate life-span. CR and IF affect energy and oxygen radical metabolism, and cellular stress response systems, in ways that protect neurons against genetic and environmental factors to which they would otherwise succumb during aging. There are multiple interactive pathways and molecular mechanisms by which CR and IF benefit neurons including those involving insulin-like signaling, FoxO transcription factors, sirtuins and peroxisome proliferator-activated receptors. These pathways stimulate the production of protein chaperones, neurotrophic factors and antioxidant enzymes, all of which help cells cope with stress and resist disease. A better understanding of the impact of CR and IF on the aging nervous system will likely lead to novel approaches for preventing and treating neurodegenerative disorders. PMID:16899414

Mice Producing Reduced Levels of Insulin-Like Growth Factor Type 1 Display an Increase in Maximum, but not Mean, Life Span

PubMed Central

2014-01-01

Reduced signaling through the IGF type 1 (IGF-1) receptor increases life span in multiple invertebrate organisms. Studies on mammalian longevity suggest that reducing levels of IGF-1 may also increase life span. However, the data are conflicting and complicated by the physiology of the mammalian neuroendocrine system. We have performed life-span analysis on mice homozygous for an insertion in the Igf1 gene. These mice produce reduced levels of IGF-1 and display a phenotype consistent with a significant decrease in IGF-1. Life-span analysis was carried out at three independent locations. Although the life-span data varied between sites, the maximum life span of the IGF-1-deficient mice was significantly increased and age-specific mortality rates were reduced in the IGF-1-deficient mice; however, mean life span did not differ except at one site, where mean life span was increased in female IGF-1-deficient animals. Early life mortality was noted in one cohort of IGF-1-deficient mice. The results are consistent with a significant role for IGF-1 in the modulation of life span but contrast with the published life-span data for the hypopituitary Ames and Snell dwarf mice and growth hormone receptor null mice, indicating that a reduction in IGF-1 alone is insufficient to increase both mean and maximal life span in mice. PMID:23873963

Adding the Third Dimension to Virus Life Cycles: Three-Dimensional Reconstruction of Icosahedral Viruses from Cryo-Electron Micrographs

PubMed Central

Baker, T. S.; Olson, N. H.; Fuller, S. D.

1999-01-01

Viruses are cellular parasites. The linkage between viral and host functions makes the study of a viral life cycle an important key to cellular functions. A deeper understanding of many aspects of viral life cycles has emerged from coordinated molecular and structural studies carried out with a wide range of viral pathogens. Structural studies of viruses by means of cryo-electron microscopy and three-dimensional image reconstruction methods have grown explosively in the last decade. Here we review the use of cryo-electron microscopy for the determination of the structures of a number of icosahedral viruses. These studies span more than 20 virus families. Representative examples illustrate the use of moderate- to low-resolution (7- to 35-Å) structural analyses to illuminate functional aspects of viral life cycles including host recognition, viral attachment, entry, genome release, viral transcription, translation, proassembly, maturation, release, and transmission, as well as mechanisms of host defense. The success of cryo-electron microscopy in combination with three-dimensional image reconstruction for icosahedral viruses provides a firm foundation for future explorations of more-complex viral pathogens, including the vast number that are nonspherical or nonsymmetrical. PMID:10585969

Longevity of guard cell chloroplasts in falling leaves: implication for stomatal function and cellular aging.

PubMed

Zeiger, E; Schwartz, A

1982-11-12

Guard cell chloroplasts in senescing leaves from 12 species of perennial trees and three species of annual plants survived considerably longer than their mesophyll counterparts. In Ginkgo biloba, stomata from yellow leaves opened during the day and closed at night; guard cell chloroplasts from these leaves showed fluorescence transients associated with electron transport and photophosphorylation. These findings indicate that guard cell chloroplasts are highly conserved throughout the life-span of the leaf and that leaves retain stomatal control during senescence.

Longevity of guard cell chloroplasts in falling leaves: implication for stomatal function and cellular aging

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

Zeiger, E.; Schwartz, A.

1982-11-12

Guard cell chloroplasts in senescing leaves from 12 species of perennial trees and three species of annual plants survived considerably longer than their mesophyll counterparts. In Ginkgo biloba, stomata from yellow leaves opened during the day and closed at night; guard cell chloroplasts from these leaves showed fluorescence transients associated with electron transport and photophosphorylation. These findings indicate that guard cell chloroplasts are highly conserved throughout the life-span of the leaf and that leaves retain stomatal control during senescence.

Partial uncoupling of oxidative phosphorylation induces premature senescence in human fibroblasts and yeast mother cells.

PubMed

Stöckl, Petra; Zankl, Christina; Hütter, Eveline; Unterluggauer, Hermann; Laun, Peter; Heeren, Gino; Bogengruber, Edith; Herndler-Brandstetter, Dietmar; Breitenbach, Michael; Jansen-Dürr, Pidder

2007-09-15

The mitochondrial theory of aging predicts that functional alterations in mitochondria leading to reactive oxygen species (ROS) production contribute to the aging process in most if not all species. Using cellular senescence as a model for human aging, we have recently reported partial uncoupling of the respiratory chain in senescent human fibroblasts. In the present communication, we address a potential cause-effect relationship between impaired mitochondrial coupling and premature senescence. Chronic exposure of human fibroblasts to the chemical uncoupler carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) led to a temporary, reversible uncoupling of oxidative phosphorylation. FCCP inhibited cell proliferation in a dose-dependent manner, and a significant proportion of the cells entered premature senescence within 12 days. Unexpectedly, chronic exposure of cells to FCCP led to a significant increase in ROS production, and the inhibitory effect of FCCP on cell proliferation was eliminated by the antioxidant N-acetyl-cysteine. However, antioxidant treatment did not prevent premature senescence, suggesting that a reduction in the level of oxidative phosphorylation contributes to phenotypical changes characteristic of senescent human fibroblasts. To assess whether this mechanism might be conserved in evolution, the influence of mitochondrial uncoupling on replicative life span of yeast cells was also addressed. Similar to our findings in human fibroblasts, partial uncoupling of oxidative phsophorylation in yeast cells led to a substantial decrease in the mother-cell-specific life span and a concomitant incrase in ROS, indicating that life span shortening by mild mitochondrial uncoupling may represent a "public" mechanism of aging.

The nucleus- and endoplasmic reticulum-targeted forms of protein tyrosine phosphatase 61F regulate Drosophila growth, life span, and fecundity.

PubMed

Buszard, Bree J; Johnson, Travis K; Meng, Tzu-Ching; Burke, Richard; Warr, Coral G; Tiganis, Tony

2013-04-01

The protein tyrosine phosphatases (PTPs) T cell PTP (TCPTP) and PTP1B share a high level of catalytic domain sequence and structural similarity yet display distinct differences in substrate recognition and function. Their noncatalytic domains contribute to substrate selectivity and function by regulating TCPTP nucleocytoplasmic shuttling and targeting PTP1B to the endoplasmic reticulum (ER). The Drosophila TCPTP/PTP1B orthologue PTP61F has two variants with identical catalytic domains that are differentially targeted to the ER and nucleus. Here we demonstrate that the PTP61F variants differ in their ability to negatively regulate insulin signaling in vivo, with the nucleus-localized form (PTP61Fn) being more effective than the ER-localized form (PTP61Fm). We report that PTP61Fm is reliant on the adaptor protein Dock to attenuate insulin signaling in vivo. Also, we show that the PTP61F variants differ in their capacities to regulate growth, with PTP61Fn but not PTP61Fm attenuating cellular proliferation. Furthermore, we generate a mutant lacking both PTP61F variants, which displays a reduction in median life span and a decrease in female fecundity, and show that both variants are required to rescue these mutant phenotypes. Our findings define the role of PTP61F in life span and fecundity and reinforce the importance of subcellular localization in mediating PTP function in vivo.

Life-Span Learning: A Developmental Perspective

ERIC Educational Resources Information Center

Thornton, James E.

2003-01-01

The article discusses learning as embedded processes of development and aging, and as social activity over the life course. The concept of life-span learning is proposed and outlined to discuss these processes as aspects of and propositions in life-span development and aging theory. Life-span learning processes arise and continuously develop in a…

Elixir of Life: Thwarting Aging With Regenerative Reprogramming.

PubMed

Beyret, Ergin; Martinez Redondo, Paloma; Platero Luengo, Aida; Izpisua Belmonte, Juan Carlos

2018-01-05

All living beings undergo systemic physiological decline after ontogeny, characterized as aging. Modern medicine has increased the life expectancy, yet this has created an aged society that has more predisposition to degenerative disorders. Therefore, novel interventions that aim to extend the healthspan in parallel to the life span are needed. Regeneration ability of living beings maintains their biological integrity and thus is the major leverage against aging. However, mammalian regeneration capacity is low and further declines during aging. Therefore, modalities that reinforce regeneration can antagonize aging. Recent advances in the field of regenerative medicine have shown that aging is not an irreversible process. Conversion of somatic cells to embryonic-like pluripotent cells demonstrated that the differentiated state and age of a cell is not fixed. Identification of the pluripotency-inducing factors subsequently ignited the idea that cellular features can be reprogrammed by defined factors that specify the desired outcome. The last decade consequently has witnessed a plethora of studies that modify cellular features including the hallmarks of aging in addition to cellular function and identity in a variety of cell types in vitro. Recently, some of these reprogramming strategies have been directly used in animal models in pursuit of rejuvenation and cell replacement. Here, we review these in vivo reprogramming efforts and discuss their potential use to extend the longevity by complementing or augmenting the regenerative capacity. © 2017 American Heart Association, Inc.

[Autoradiographic study of the renewal rate of neutrophils and thrombocytes in summer and winter frogs].

PubMed

Goryshina, E N

1984-04-01

In early August frogs were injected with 3H-thymidine and observed during 10 months under conditions close to natural. Individual changes of neutrophil and thrombocyte contents in the blood, those of the number of labeled cells among them, and the density of labeling were studied. The life span of neutrophils in the active frogs was found as long as 2-3 weeks, while that of thrombocytes lasted for several months. In September the hibernating cell populations are formed and cell proliferation ceases. This process is suggested to be regulated by some complex centralized mechanisms rather than by a direct action of temperature. The size of circulating populations of both the cell types decreases during hibernation, part of the cells is deposited outside of circulation. The life span of cells rises considerably, their renewal begins only in spring. The ability of cells of the neutrophilic lineage to proliferate is preserved at low temperatures and is realized in pathological conditions. The similarities in seasonal adaptations are stated between amphibians and hibernating mammals at the level of cellular populations.

Mitochondrial Reactive Oxygen Species Trigger Hypoxia-Inducible Factor-Dependent Extension of the Replicative Life Span during Hypoxia▿

PubMed Central

Bell, Eric L.; Klimova, Tatyana A.; Eisenbart, James; Schumacker, Paul T.; Chandel, Navdeep S.

2007-01-01

Physiological hypoxia extends the replicative life span of human cells in culture. Here, we report that hypoxic extension of replicative life span is associated with an increase in mitochondrial reactive oxygen species (ROS) in primary human lung fibroblasts. The generation of mitochondrial ROS is necessary for hypoxic activation of the transcription factor hypoxia-inducible factor (HIF). The hypoxic extension of replicative life span is ablated by a dominant negative HIF. HIF is sufficient to induce telomerase reverse transcriptase mRNA and telomerase activity and to extend replicative life span. Furthermore, the down-regulation of the von Hippel-Lindau tumor suppressor protein by RNA interference increases HIF activity and extends replicative life span under normoxia. These findings provide genetic evidence that hypoxia utilizes mitochondrial ROS as signaling molecules to activate HIF-dependent extension of replicative life span. PMID:17562866

Life-Span Extension by Caloric Restriction Is Determined by Type and Level of Food Reduction and by Reproductive Mode in Brachionus manjavacas (Rotifera)

PubMed Central

2013-01-01

We measured life span and fecundity of three reproductive modes in a clone of the monogonont rotifer Brachionus manjavacas subjected to chronic caloric restriction (CCR) over a range of food concentrations or to intermittent fasting (IF). IF increased life span 50%–70% for all three modes, whereas CCR increased life span of asexual females derived from sexually or asexually produced eggs, but not that of sexual females. The main effect of CR on both asexual modes was to delay death at young ages, rather than to prevent death at middle ages or to greatly extend maximum life span; in contrast CR in sexual females greatly increased the life span of a few long-lived individuals. Lifetime fecundity did not decrease with CCR, suggesting a lack of resource allocation trade-off between somatic maintenance and reproduction. Multiple outcomes for a clonal lineage indicate that different responses are established through epigenetic programming, whereas differences in life-span allocations suggest that multiple genetic mechanisms mediate life-span extension. PMID:22904096

Life-span extension by caloric restriction is determined by type and level of food reduction and by reproductive mode in Brachionus manjavacas (Rotifera).

PubMed

Gribble, Kristin E; Welch, David B Mark

2013-04-01

We measured life span and fecundity of three reproductive modes in a clone of the monogonont rotifer Brachionus manjavacas subjected to chronic caloric restriction (CCR) over a range of food concentrations or to intermittent fasting (IF). IF increased life span 50%-70% for all three modes, whereas CCR increased life span of asexual females derived from sexually or asexually produced eggs, but not that of sexual females. The main effect of CR on both asexual modes was to delay death at young ages, rather than to prevent death at middle ages or to greatly extend maximum life span; in contrast CR in sexual females greatly increased the life span of a few long-lived individuals. Lifetime fecundity did not decrease with CCR, suggesting a lack of resource allocation trade-off between somatic maintenance and reproduction. Multiple outcomes for a clonal lineage indicate that different responses are established through epigenetic programming, whereas differences in life-span allocations suggest that multiple genetic mechanisms mediate life-span extension.

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.

Genetic mouse models of brain ageing and Alzheimer's disease.

PubMed

Bilkei-Gorzo, Andras

2014-05-01

Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

Detrimental effects of proteasome inhibition activity in Drosophila melanogaster: implication of ER stress, autophagy, and apoptosis.

PubMed

Velentzas, Panagiotis D; Velentzas, Athanassios D; Mpakou, Vassiliki E; Antonelou, Marianna H; Margaritis, Lukas H; Papassideri, Issidora S; Stravopodis, Dimitrios J

2013-02-01

In eukaryotes, the ubiquitin-proteasome machinery regulates a number of fundamental cellular processes through accurate and tightly controlled protein degradation pathways. We have, herein, examined the effects of proteasome functional disruption in Dmp53 (+/+) (wild-type) and Dmp53 (-/-) Drosophila melanogaster fly strains through utilization of Bortezomib, a proteasome-specific inhibitor. We report that proteasome inhibition drastically shortens fly life-span and impairs climbing performance, while it also causes larval lethality and activates developmentally irregular cell death programs during oogenesis. Interestingly, Dmp53 gene seems to play a role in fly longevity and climbing ability. Moreover, Bortezomib proved to induce endoplasmic reticulum (ER) stress that was able to result in the engagement of unfolded protein response (UPR) signaling pathway, as respectively indicated by fly Xbp1 activation and Ref(2)P-containing protein aggregate formation. Larva salivary gland and adult brain both underwent strong ER stress in response to Bortezomib, thus underscoring the detrimental role of proteasome inhibition in larval development and brain function. We also propose that the observed upregulation of autophagy operates as a protective mechanism to "counterbalance" Bortezomib-induced systemic toxicity, which is tightly associated, besides ER stress, with activation of apoptosis, mainly mediated by functional Drice caspase and deregulated dAkt kinase. The reduced life-span of exposed to Bortezomib flies overexpressing Atg1_RNAi or Atg18_RNAi supports the protective nature of autophagy against proteasome inhibition-induced stress. Our data reveal the in vivo significance of proteasome functional integrity as a major defensive system against cellular toxicity likely occurring during critical biological processes and morphogenetic courses.

Comparative transcriptional profiling identifies takeout as a gene that regulates life span

PubMed Central

Bauer, Johannes; Antosh, Michael; Chang, Chengyi; Schorl, Christoph; Kolli, Santharam; Neretti, Nicola; Helfand, Stephen L.

2010-01-01

A major challenge in translating the positive effects of dietary restriction (DR) for the improvement of human health is the development of therapeutic mimics. One approach to finding DR mimics is based upon identification of the proximal effectors of DR life span extension. Whole genome profiling of DR in Drosophila shows a large number of changes in gene expression, making it difficult to establish which changes are involved in life span determination as opposed to other unrelated physiological changes. We used comparative whole genome expression profiling to discover genes whose change in expression is shared between DR and two molecular genetic life span extending interventions related to DR, increased dSir2 and decreased Dmp53 activity. We find twenty-one genes shared among the three related life span extending interventions. One of these genes, takeout, thought to be involved in circadian rhythms, feeding behavior and juvenile hormone binding is also increased in four other life span extending conditions: Rpd3, Indy, chico and methuselah. We demonstrate takeout is involved in longevity determination by specifically increasing adult takeout expression and extending life span. These studies demonstrate the power of comparative whole genome transcriptional profiling for identifying specific downstream elements of the DR life span extending pathway. PMID:20519778

The meaning of death: some simulations of a model of healthy and unhealthy consumption.

PubMed

Forster, M

2001-07-01

Simulations of a model of healthy and unhealthy consumption are used to investigate the impact of various terminal conditions on life-span, pathways of health-related consumption and health. A model in which life-span and the 'death' stock of health are fixed is compared to versions in which (i) the 'death' stock of health is freely chosen; (ii) life-span is freely chosen; (iii) both the 'death' stock of health and life-span are freely chosen. The choice of terminal conditions has a striking impact on optimal plans. Results are discussed with reference to the existing demand for health literature and illustrate the application of iterative processes to determine optimal life-span, the role played by the marginal value of health capital in determining optimal plans, and the importance of checking the second-order conditions for the optimal choice of life-span.

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 Motivational Theory of Life-Span Development

PubMed Central

Heckhausen, Jutta; Wrosch, Carsten; Schulz, Richard

2010-01-01

This article had four goals. First, the authors identified a set of general challenges and questions that a life-span theory of development should address. Second, they presented a comprehensive account of their Motivational Theory of Life-Span Development. They integrated the model of optimization in primary and secondary control and the action-phase model of developmental regulation with their original life-span theory of control to present a comprehensive theory of development. Third, they reviewed the relevant empirical literature testing key propositions of the Motivational Theory of Life-Span Development. Finally, because the conceptual reach of their theory goes far beyond the current empirical base, they pointed out areas that deserve further and more focused empirical inquiry. PMID:20063963

Longevity and age-related lesions in a laboratory colony of grasshopper mice, Onychomys leucogaster

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

O'Farrell, T.P.; Cosgrove, G.E.

1975-07-01

Mated pairs of northern grasshopper mice, Onychomys leucogaster fuscogriseus, were maintained in a laboratory colony to determine their median longevity, maximum life span, and age-related pathologies. Median life span for both sexes and four cohorts was 1411 days and the maximum life span was 1915 days. There were no significant differences between sexes, but cohorts 5-7 generations removed from wild-caught parents had shorter median life spans. (auth)

Genetics and pharmacology of longevity: the road to therapeutics for healthy aging.

PubMed

Castillo-Quan, Jorge Iván; Kinghorn, Kerri J; Bjedov, Ivana

2015-01-01

Aging can be defined as the progressive decline in tissue and organismal function and the ability to respond to stress that occurs in association with homeostatic failure and the accumulation of molecular damage. Aging is the biggest risk factor for human disease and results in a wide range of aging pathologies. Although we do not completely understand the underlying molecular basis that drives the aging process, we have gained exceptional insights into the plasticity of life span and healthspan from the use of model organisms such as the worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Single-gene mutations in key cellular pathways that regulate environmental sensing, and the response to stress, have been identified that prolong life span across evolution from yeast to mammals. These genetic manipulations also correlate with a delay in the onset of tissue and organismal dysfunction. While the molecular genetics of aging will remain a prosperous and attractive area of research in biogerontology, we are moving towards an era defined by the search for therapeutic drugs that promote healthy aging. Translational biogerontology will require incorporation of both therapeutic and pharmacological concepts. The use of model organisms will remain central to the quest for drug discovery, but as we uncover molecular processes regulated by repurposed drugs and polypharmacy, studies of pharmacodynamics and pharmacokinetics, drug-drug interactions, drug toxicity, and therapeutic index will slowly become more prevalent in aging research. As we move from genetics to pharmacology and therapeutics, studies will not only require demonstration of life span extension and an underlying molecular mechanism, but also the translational relevance for human health and disease prevention. Copyright © 2015 Elsevier Inc. All rights reserved.

Resveratrol induces mitochondrial dysfunction and decreases chronological life span of Saccharomyces cerevisiae in a glucose-dependent manner.

PubMed

Ramos-Gomez, Minerva; Olivares-Marin, Ivanna Karina; Canizal-García, Melina; González-Hernández, Juan Carlos; Nava, Gerardo M; Madrigal-Perez, Luis Alberto

2017-06-01

A broad range of health benefits have been attributed to resveratrol (RSV) supplementation in mammalian systems, including the increases in longevity. Nonetheless, despite the growing number of studies performed with RSV, the molecular mechanism by which it acts still remains unknown. Recently, it has been proposed that inhibition of the oxidative phosphorylation activity is the principal mechanism of RSV action. This mechanism suggests that RSV might induce mitochondrial dysfunction resulting in oxidative damage to cells with a concomitant decrease of cell viability and cellular life span. To prove this hypothesis, the chronological life span (CLS) of Saccharomyces cerevisiae was studied as it is accepted as an important model of oxidative damage and aging. In addition, oxygen consumption, mitochondrial membrane potential, and hydrogen peroxide (H 2 O 2 ) release were measured in order to determine the extent of mitochondrial dysfunction. The results demonstrated that the supplementation of S. cerevisiae cultures with 100 μM RSV decreased CLS in a glucose-dependent manner. At high-level glucose, RSV supplementation increased oxygen consumption during the exponential phase yeast cultures, but inhibited it in chronologically aged yeast cultures. However, at low-level glucose, oxygen consumption was inhibited in yeast cultures in the exponential phase as well as in chronologically aged cultures. Furthermore, RSV supplementation promoted the polarization of the mitochondrial membrane in both cultures. Finally, RSV decreased the release of H 2 O 2 with high-level glucose and increased it at low-level glucose. Altogether, this data supports the hypothesis that RSV supplementation decreases CLS as a result of mitochondrial dysfunction and this phenotype occurs in a glucose-dependent manner.

Sirtuins of parasitic protozoa: In search of function(s)

PubMed Central

Religa, Agnieszka A.; Waters, Andrew P.

2012-01-01

The SIR2 family of NAD+-dependent protein deacetylases, collectively called sirtuins, has been of central interest due to their proposed roles in life-span regulation and ageing. Sirtuins are one group of environment sensors of a cell interpreting external information and orchestrating internal responses at the sub-cellular level, through participation in gene regulation mechanisms. Remarkably conserved across all kingdoms of life SIR2 proteins in several protozoan parasites appear to have both conserved and intriguing unique functions. This review summarises our current knowledge of the members of the sirtuin families in Apicomplexa, including Plasmodium, and other protozoan parasites such as Trypanosoma and Leishmania. The wide diversity of processes regulated by SIR2 proteins makes them targets worthy of exploitation in anti-parasitic therapies. PMID:22906508

Increased iron supplied through Fet3p results in replicative life span extension of Saccharomyces cerevisiae under conditions requiring respiratory metabolism.

PubMed

Botta, Gabriela; Turn, Christina S; Quintyne, Nicholas J; Kirchman, Paul A

2011-10-01

We have previously shown that copper supplementation extends the replicative life span of Saccharomyces cerevisiae when grown under conditions forcing cells to respire. We now show that copper's effect on life span is through Fet3p, a copper containing enzyme responsible for high affinity transport of iron into yeast cells. Life span extensions can also be obtained by supplementing the growth medium with 1mM ferric chloride. Extension by high iron levels is still dependent on the presence of Fet3p. Life span extension by iron or copper requires growth on media containing glycerol as the sole carbon source, which forces yeast to respire. Yeast grown on glucose containing media supplemented with iron show no extension of life span. The iron associated with cells grown in media supplemented with copper or iron is 1.4-1.8 times that of cells grown without copper or iron supplementation. As with copper supplementation, iron supplementation partially rescues the life span of superoxide dismutase mutants. Cells grown with copper supplementation display decreased production of superoxide as measured by dihydroethidium staining. Copyright © 2011 Elsevier Inc. All rights reserved.

Computer Modeling of the Earliest Cellular Structures and Functions

NASA Technical Reports Server (NTRS)

Pohorille, Andrew; Chipot, Christophe; Schweighofer, Karl

2000-01-01

In the absence of extinct or extant record of protocells (the earliest ancestors of contemporary cells). the most direct way to test our understanding of the origin of cellular life is to construct laboratory models of protocells. Such efforts are currently underway in the NASA Astrobiology Program. They are accompanied by computational studies aimed at explaining self-organization of simple molecules into ordered structures and developing designs for molecules that perform proto-cellular functions. Many of these functions, such as import of nutrients, capture and storage of energy. and response to changes in the environment are carried out by proteins bound to membrane< We will discuss a series of large-scale, molecular-level computer simulations which demonstrate (a) how small proteins (peptides) organize themselves into ordered structures at water-membrane interfaces and insert into membranes, (b) how these peptides aggregate to form membrane-spanning structures (eg. channels), and (c) by what mechanisms such aggregates perform essential proto-cellular functions, such as proton transport of protons across cell walls, a key step in cellular bioenergetics. The simulations were performed using the molecular dynamics method, in which Newton's equations of motion for each item in the system are solved iteratively. The problems of interest required simulations on multi-nanosecond time scales, which corresponded to 10(exp 6)-10(exp 8) time steps.

How long will my mouse live? Machine learning approaches for prediction of mouse life span.

PubMed

Swindell, William R; Harper, James M; Miller, Richard A

2008-09-01

Prediction of individual life span based on characteristics evaluated at middle-age represents a challenging objective for aging research. In this study, we used machine learning algorithms to construct models that predict life span in a stock of genetically heterogeneous mice. Life-span prediction accuracy of 22 algorithms was evaluated using a cross-validation approach, in which models were trained and tested with distinct subsets of data. Using a combination of body weight and T-cell subset measures evaluated before 2 years of age, we show that the life-span quartile to which an individual mouse belongs can be predicted with an accuracy of 35.3% (+/-0.10%). This result provides a new benchmark for the development of life-span-predictive models, but improvement can be expected through identification of new predictor variables and development of computational approaches. Future work in this direction can provide tools for aging research and will shed light on associations between phenotypic traits and longevity.

Exploratory and problem-solving consumer behavior across the life span.

PubMed

Lesser, J A; Kunkel, S R

1991-09-01

Different cognitive functioning, social, and personality changes appear to occur systematically during the adult life span. This article synthesizes research on life span changes in order to develop age-specific models of shopping behavior. The models are tested within a naturalistic field study of shoppers.

Maternal caloric restriction partially rescues the deleterious effects of advanced maternal age on offspring

PubMed Central

Gribble, Kristin E; Jarvis, George; Bock, Martha; Mark Welch, David B

2014-01-01

While many studies have focused on the detrimental effects of advanced maternal age and harmful prenatal environments on progeny, little is known about the role of beneficial non-Mendelian maternal inheritance on aging. Here, we report the effects of maternal age and maternal caloric restriction (CR) on the life span and health span of offspring for a clonal culture of the monogonont rotifer Brachionus manjavacas. Mothers on regimens of chronic CR (CCR) or intermittent fasting (IF) had increased life span compared with mothers fed ad libitum (AL). With increasing maternal age, life span and fecundity of female offspring of AL-fed mothers decreased significantly and life span of male offspring was unchanged, whereas body size of both male and female offspring increased. Maternal CR partially rescued these effects, increasing the mean life span of AL-fed female offspring but not male offspring and increasing the fecundity of AL-fed female offspring compared with offspring of mothers of the same age. Both maternal CR regimens decreased male offspring body size, but only maternal IF decreased body size of female offspring, whereas maternal CCR caused a slight increase. Understanding the genetic and biochemical basis of these different maternal effects on aging may guide effective interventions to improve health span and life span. PMID:24661622

Developmental Regulation across the Life Span: Toward a New Synthesis

ERIC Educational Resources Information Center

Haase, Claudia M.; Heckhausen, Jutta; Wrosch, Carsten

2013-01-01

How can individuals regulate their own development to live happy, healthy, and productive lives? Major theories of developmental regulation across the life span have been proposed (e.g., dual-process model of assimilation and accommodation; motivational theory of life-span development; model of selection, optimization, and compensation), but they…

A Motivational Theory of Life-Span Development

ERIC Educational Resources Information Center

Heckhausen, Jutta; Wrosch, Carsten; Schulz, Richard

2010-01-01

This article had four goals. First, the authors identified a set of general challenges and questions that a life-span theory of development should address. Second, they presented a comprehensive account of their Motivational Theory of Life-Span Development. They integrated the model of optimization in primary and secondary control and the…

Increasing cell culture population doublings for long-term growth of finite life span human cell cultures

DOEpatents

Stampfer, Martha R.; Garbe, James C.

2016-06-28

Cell culture media formulations for culturing human epithelial cells are herein described. Also described are methods of increasing population doublings in a cell culture of finite life span human epithelial cells and prolonging the life span of human cell cultures. Using the cell culture media disclosed alone and in combination with addition to the cell culture of a compound associated with anti-stress activity achieves extended growth of pre-stasis cells and increased population doublings and life span in human epithelial cell cultures.

Increasing cell culture population doublings for long-term growth of finite life span human cell cultures

DOEpatents

Stampfer, Martha R; Garbe, James C

2015-02-24

Cell culture media formulations for culturing human epithelial cells are herein described. Also described are methods of increasing population doublings in a cell culture of finite life span human epithelial cells and prolonging the life span of human cell cultures. Using the cell culture media disclosed alone and in combination with addition to the cell culture of a compound associated with anti-stress activity achieves extended growth of pre-stasis cells and increased population doublings and life span in human epithelial cell cultures.

Sexual Conflict, Life Span, and Aging

PubMed Central

Adler, Margo I.; Bonduriansky, Russell

2014-01-01

The potential for sexual conflict to influence the evolution of life span and aging has been recognized for more than a decade, and recent work also suggests that variation in life span and aging can influence sexually antagonistic coevolution. However, empirical exploration of these ideas is only beginning. Here, we provide an overview of the ideas and evidence linking inter- and intralocus sexual conflicts with life span and aging. We aim to clarify the conceptual basis of this research program, examine the current state of knowledge, and suggest key questions for further investigation. PMID:24938876

Lifelong alpha-tocopherol supplementation increases the median life span of C57BL/6 mice in the cold but has only minor effects on oxidative damage.

PubMed

Selman, Colin; McLaren, Jane S; Mayer, Claus; Duncan, Jackie S; Collins, Andrew R; Duthie, Garry G; Redman, Paula; Speakman, John R

2008-02-01

The effects of dietary antioxidant supplementation on oxidative stress and life span are confused. We maintained C57BL/6 mice at 7 +/- 2 degrees C and supplemented their diet with alpha-tocopherol from 4 months of age. Supplementation significantly increased (p = 0.042) median life span by 15% (785 days, n = 44) relative to unsupplemented controls (682 days, n = 43) and also increased maximum life span (oldest 10%, p = 0.028). No sex or sex by treatment interaction effects were observed on life span, with treatment having no effect on resting or daily metabolic rate. Lymphocyte and hepatocyte oxidative DNA damage and hepatic lipid peroxidation were unaffected by supplementation, but hepatic oxidative DNA damage increased with age. Using a cDNA macroarray, genes associated with xenobiotic metabolism were significantly upregulated in the livers of female mice at 6 months of age (2 months supplementation). At 22 months of age (18 months supplementation) this response had largely abated, but various genes linked to the p21 signaling pathway were upregulated at this time. We suggest that alpha-tocopherol may initially be metabolized as a xenobiotic, potentially explaining why previous studies observe a life span extension generally when lifelong supplementation is initiated early in life. The absence of any significant effect on oxidative damage suggests that the life span extension observed was not mediated via any antioxidant properties of alpha-tocopherol. We propose that the life span extension observed following alpha-tocopherol supplementation may be mediated via upregulation of cytochrome p450 genes after 2 months of supplementation and/or upregulation of p21 signaling genes after 18 months of supplementation. However, these signaling pathways now require further investigation to establish their exact role in life span extension following alpha-tocopherol supplementation.

A gene involved in control of human cellular senescence on human chromosome 1q

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

Hensler, P.J.; Pereira-Smith, O.M.; Annab, L.A.

1994-04-01

Normal cells in culture exhibit limited division potential and have been used as a model for cellular senescence. In contrast, tumor-derived or carcinogen- or virus-transformed cells are capable of indefinite division. Fusion of normal human diploid fibroblasts with immortal human cells yielded hybrids having limited life spans, indicating that cellular senescence was dominant. Fusions of various immortal human cell lines with each other led to the identification of four complementation groups for indefinite division. The purpose of this study was to determine whether human chromosome 1 could complement the recessive immortal defect of human cell lines assigned to one ofmore » the four complementation groups. Using microcell fusion, the authors introduced a single normal human chromosome 1 into immortal human cell lines representing the complementation groups and determined that it caused loss of proliferative potential of an osteosarcoma-derived cell line (TE85), a cytomegalovirus-transformed lung fibroblast cell line (CMV-Mj-HEL-1), and a Ki-ras[sup +]-transformed derivative of TE85 (143B TK[sup [minus

Erythrocyte and blood antibacterial defense.

PubMed

Minasyan, Hayk

2014-06-01

It is an axiom that blood cellular immunity is provided by leukocytes. As to erythrocytes, it is generally accepted that their main function is respiration. Our research provides objective video and photo evidence regarding erythrocyte bactericidal function. Phase-contrast immersion vital microscopy of the blood of patients with bacteremia was performed, and the process of bacteria entrapping and killing by erythrocytes was shot by means of video camera. Video evidence demonstrates that human erythrocytes take active part in blood bactericidal action and can repeatedly engulf and kill bacteria of different species and size. Erythrocytes are extremely important integral part of human blood cellular immunity. a) are more numerous; b) are able to entrap and kill microorganisms repeatedly without being injured; c) are more resistant to infection and better withstand the attacks of pathogens; d) have longer life span and are produced faster; e) are inauspicious media for proliferation of microbes and do not support replication of chlamidiae, mycoplasmas, rickettsiae, viruses, etc.; and f) are more effective and uncompromised bacterial killers. Blood cellular immunity theory and traditional view regarding the function of erythrocytes in human blood should be revised.

Blade life span, structural investment, and nutrient allocation in giant kelp.

PubMed

Rodriguez, Gabriel E; Reed, Daniel C; Holbrook, Sally J

2016-10-01

The turnover of plant biomass largely determines the amount of energy flowing through an ecosystem and understanding the processes that regulate turnover has been of interest to ecologists for decades. Leaf life span theory has proven useful in explaining patterns of leaf turnover in relation to resource availability, but the predictions of this theory have not been tested for macroalgae. We measured blade life span, size, thickness, nitrogen content, pigment content, and maximum photosynthetic rate (P max) in the giant kelp (Macrocystis pyrifera) along a strong resource (light) gradient to test whether the predictions of leaf life span theory applied to this alga. We found that shorter blade life spans and larger blade areas were associated with increased light availability. In addition, nitrogen and P max decreased with blade age, and their decrease was greater in shorter lived blades. These observations are generally consistent with patterns observed for higher plants and the prevailing theory of leaf life span. By contrast, variation observed in pigments of giant kelp was inconsistent with that predicted by leaf life span theory, as blades growing in the most heavily shaded portion of the forest had the lowest chlorophyll content. This result may reflect the dual role of macroalgal blades in carbon fixation and nutrient absorption and the ability of giant kelp to modify blade physiology to optimize the acquisition of light and nutrients. Thus, the marine environment may place demands on resource acquisition and allocation that have not been previously considered with respect to leaf life span optimization.

78. VIEW SHOWING PLACEMENT OF LIFE SPAN SHOE ON PIER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

78. VIEW SHOWING PLACEMENT OF LIFE SPAN SHOE ON PIER 6, LOOKING NORTH, March 5, 1935 - Sacramento River Bridge, Spanning Sacramento River at California State Highway 275, Sacramento, Sacramento County, CA

Ordinary Stoichiometry of Extraordinary Microbes

NASA Astrophysics Data System (ADS)

Neveu, M.; Poret-Peterson, A. T.; Anbar, A. D.; Elser, J. J.

2013-12-01

Life on Earth seems to be composed of the same chemical elements in relatively conserved stoichiometric proportions. However, this observation is largely based on observations of biota from habitats spanning a moderate range of temperature and chemical composition (e.g., temperate lakes, forests, grasslands, oceanic phytoplankton). Whether this stoichiometry is conserved in settings that differ radically from such "normal" planetary settings may provide insight into the habitability of environments with radically different stoichiometries, and into possible stoichiometries for putative life beyond Earth. Here we report the first measurements of elemental stoichiometries of microbial extremophiles from hot springs of Yellowstone National Park (YNP). These phototrophic and chemotrophic microbes were collected in locations spanning large ranges of temperature (ambient to boiling) and pH (1 to 9). Microbial biomass was carefully extracted from hot spring sediment substrata following a procedure adapted from [1], which conserves cellular elemental abundances [2]. Their C and N contents were determined by Elemental Analysis Isotope Ratio Mass Spectrometry, and their P and trace element (Mg, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Mo, and non-biogenic Al and Ti) contents were measured by Inductively Coupled Plasma Mass Spectrometry. Residual mineral contamination was an issue in some samples with low measured C and N; we eliminated these from our results. Even in the remaining samples, contamination sometimes prevented accurate determinations of cellular Mg, Ca, Mn, and Fe abundances; however, the cellular Ni, Cu, Zn, and Mo contents were several-fold above contamination level. Although hot spring water and sediment elemental abundances varied by orders of magnitude, the data showed that the extremophiles have a major and trace element stoichiometry similar to those previously measured in "normal" microbial biomass [3-6]. For example, biomass C:N:P ratios resembled those commonly observed in temperate lakes (e.g., C:P ratios of 260 to 1600 and N:P ratios of 35 to 200) while cellular C:Fe ratios were of a similar magnitude to those of marine phytoplankton. Exceptions were Al and Ti, much higher than previously measured, likely because of contamination from residual sediment. Moreover, the low phosphorus contents (high C:P and N:P ratios) are suggestive of limited P supply. Chemotrophs and phototrophs had similar elemental compositions to one another, although Mg, Mn, Ni, and Zn abundances were higher and nearly constant in phototrophs, due to their importance in phototrophic metabolism. Despite the tremendous physical and chemical diversity of YNP environments, the stoichiometry of life in these settings is surprisingly ordinary. Thus, our study supports the view that the biological stoichiometry of life is heavily constrained by the elemental composition of core biomolecules, and that even life in extreme environments must operate within these constraints. In the frame of life detection in exotic locales, these results suggest a general elemental biosignature for life as we know it. References: [1] Amalfitano and Fazi. 2008. J. Microbiol. Meth. 75:237 [2] Neveu et al. L&O: Meth., in review [3] Ho et al. 2003. J. Phycol. 39:1145 [4] Nuester et al. 2012. Front. Microbiol. 3:150 [5] Sterner and Elser. 2002. Ecological Stoichiometry. Princeton U. Press [6] Twining et al. 2011. Deep-Sea Res. II 58:325

Learning From Leaders: Life-span Trends in Olympians and Supercentenarians

PubMed Central

Berthelot, Geoffroy; Marck, Adrien; Noirez, Philippe; Latouche, Aurélien; Toussaint, Jean-François

2015-01-01

Life-span trends progression has worldwide practical implications as it may affect the sustainability of modern societies. We aimed to describe the secular life-span trends of populations with a propensity to live longer—Olympians and supercentenarians—under two hypotheses: an ongoing life-span extension versus a biologic “probabilistic barrier” limiting further progression. In a study of life-span densities (total number of life durations per birth date), we analyzed 19,012 Olympians and 1,205 supercentenarians deceased between 1900 and 2013. Among most Olympians, we observed a trend toward increased life duration. This trend, however, decelerates at advanced ages leveling off with the upper values with a perennial gap between Olympians and supercentenarians during the whole observation period. Similar tendencies are observed among supercentenarians, and over the last years, a plateau attests to a stable longevity pattern among the longest-lived humans. The common trends between Olympians and supercentenarians indicate similar mortality pressures over both populations that increase with age, scenario better explained by a biologic “barrier” forecast. PMID:25143003

What Prolongs a Butterfly's Life?: Trade-Offs between Dormancy, Fecundity and Body Size

PubMed Central

Haeler, Elena; Fiedler, Konrad; Grill, Andrea

2014-01-01

In butterflies, life span often increases only at the expense of fecundity. Prolonged life span, on the other hand, provides more opportunities for oviposition. Here, we studied the association between life span and summer dormancy in two closely related species of Palearctic Meadow Brown butterflies, the endemic Maniola nurag and the widespread M. jurtina, from two climatic provenances, a Mediterranean and a Central European site, and tested the relationships between longevity, body size and fecundity. We experimentally induced summer dormancy and hence prolonged the butterflies’ life in order to study the effects of such a prolonged life. We were able to modulate longevity only in Mediterranean females by rearing them under summer photoperiodic conditions (light 16 h : dark 8 h), thereby more than doubling their natural life span, to up to 246 days. Central European individuals kept their natural average live span under all treatments, as did Mediterranean individuals under autumn treatment (light 11: dark 13). Body size only had a significant effect in the smaller species, M. nurag, where it affected the duration of dormancy and lifetime fecundity. In the larger species, M. jurtina, a prolonged adult life span did, surprisingly, not convey any fecundity loss. In M. nurag, which generally deposited fewer eggs, extended life had a fecundity cost. We conclude that Mediterranen M. jurtina butterflies have an extraordinary plasticity in aging which allows them to extend life span in response to adverse environmental conditions and relieve the time limitation on egg-laying while maintaining egg production at equal levels. PMID:25390334

Teaching the Psychology of Aging: A Life-Span Perspective.

ERIC Educational Resources Information Center

Seltzer, Mildred M.

There is a vast body of literature devoted to an examination of life-span development. Several authors have described the characteristics of the life-span approach and have distinguished it from more traditional forms of psychology. Emphasis has been placed on the multidirectional and multidimensional nature of development and change, as well as…

Qualitative Exploration of Acculturation and Life-Span Issues of Elderly Asian Americans

ERIC Educational Resources Information Center

Lee, Jee Hyang; Heo, Nanseol; Lu, Junfei; Portman, Tarrell Awe Agahe

2013-01-01

Awareness of aging issues across diverse populations begins the journey toward counselors becoming culturally competent across client life spans. Understanding the life-span experiences of cultural groups is important for helping professionals. The purpose of this research was to gain insight into the qualitative experiences of Asian American…

Amino acid sources in the adult diet do not affect life span and fecundity in the fruit-feeding butterfly Bicyclus anynana.

PubMed

Molleman, Freerk; Ding, Jimin; Wang, Jane-Ling; Brakefield, Paul M; Carey, James R; Zwaan, Bas J

2008-08-01

1. In tropical forests, the adults of many butterfly species feed on fruits rather than nectar from flowers and have long life spans. Rotting fruit and nectar differ from each other in many respects, including sources of amino acids and microbial life. If amino acids in the adult diet can be used for reproduction, this may have facilitated the evolution of extended life spans in this guild.2. This issue was addressed by investigating effects of banana, yeast, and amino acids in the adult diet of the fruit-feeding butterfly Bicyclus anynana (Lepidoptera) on longevity and female reproductive output in two experiments.3. Results showed that in the fruit-feeding butterfly B. anynana: (i) banana juice, but not sliced banana or added amino acids extend life span compared with a sugar solution of similar composition; (ii) compared with this sugar solution, other cohorts (banana juice-amino acid enriched) did not have significantly higher reproductive outputs; (iii) yeast does not represent a valuable source of nutrients; (iv) caloric restriction may cause decreased life span and rate of reproduction; and (v) increased rates of reproduction have a life span cost.

Maternal caloric restriction partially rescues the deleterious effects of advanced maternal age on offspring.

PubMed

Gribble, Kristin E; Jarvis, George; Bock, Martha; Mark Welch, David B

2014-08-01

While many studies have focused on the detrimental effects of advanced maternal age and harmful prenatal environments on progeny, little is known about the role of beneficial non-Mendelian maternal inheritance on aging. Here, we report the effects of maternal age and maternal caloric restriction (CR) on the life span and health span of offspring for a clonal culture of the monogonont rotifer Brachionus manjavacas. Mothers on regimens of chronic CR (CCR) or intermittent fasting (IF) had increased life span compared with mothers fed ad libitum (AL). With increasing maternal age, life span and fecundity of female offspring of AL-fed mothers decreased significantly and life span of male offspring was unchanged, whereas body size of both male and female offspring increased. Maternal CR partially rescued these effects, increasing the mean life span of AL-fed female offspring but not male offspring and increasing the fecundity of AL-fed female offspring compared with offspring of mothers of the same age. Both maternal CR regimens decreased male offspring body size, but only maternal IF decreased body size of female offspring, whereas maternal CCR caused a slight increase. Understanding the genetic and biochemical basis of these different maternal effects on aging may guide effective interventions to improve health span and life span. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Mechanisms underlying caloric restriction and life span regulation: implications for vascular aging

PubMed Central

Ungvari, Zoltan; Parrado-Fernandez, Cristina; Csiszar, Anna; de Cabo, Rafael

2008-01-01

This review focuses on the emerging evidence that attenuation of the production of reactive oxygen species (ROS) and inhibition of inflammatory pathways play a central role in the anti-aging cardiovascular effects of caloric restriction (CR). Particular emphasis is placed on the potential role of the plasma membrane redox system in CR-induced pathways responsible for sensing oxidative stress and increasing cellular oxidative stress resistance. We propose that CR increases bioavailability of NO, decreases vascular ROS generation, activates the Nrf2/ARE pathway inducing ROS detoxification systems, exerts anti-inflammatory effects and, thereby, suppresses initiation/progression of vascular disease that accompany aging. PMID:18340017

From rapalogs to anti-aging formula

PubMed Central

Blagosklonny, Mikhail V.

2017-01-01

Inhibitors of mTOR, including clinically available rapalogs such as rapamycin (Sirolimus) and Everolimus, are gerosuppressants, which suppress cellular senescence. Rapamycin slows aging and extends life span in a variety of species from worm to mammals. Rapalogs can prevent age-related diseases, including cancer, atherosclerosis, obesity, neurodegeneration and retinopathy and potentially rejuvenate stem cells, immunity and metabolism. Here, I further suggest how rapamycin can be combined with metformin, inhibitors of angiotensin II signaling (Losartan, Lisinopril), statins (simvastatin, atorvastatin), propranolol, aspirin and a PDE5 inhibitor. Rational combinations of these drugs with physical exercise and an anti-aging diet (Koschei formula) can maximize their anti-aging effects and decrease side effects. PMID:28548953

Sexual conflict, life span, and aging.

PubMed

Adler, Margo I; Bonduriansky, Russell

2014-06-17

The potential for sexual conflict to influence the evolution of life span and aging has been recognized for more than a decade, and recent work also suggests that variation in life span and aging can influence sexually antagonistic coevolution. However, empirical exploration of these ideas is only beginning. Here, we provide an overview of the ideas and evidence linking inter- and intralocus sexual conflicts with life span and aging. We aim to clarify the conceptual basis of this research program, examine the current state of knowledge, and suggest key questions for further investigation. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Defining wild-type life span in Caenorhabditis elegans.

PubMed

Gems, D; Riddle, D L

2000-05-01

The nematode Caenorhabditis elegans reproduces predominantly as a self-fertilizing hermaphrodite, and this drives laboratory populations to be homozygous at all genetic loci. Passaging of stocks can lead to fixation of spontaneous mutations, especially when the latter do not result in a selective disadvantage under laboratory conditions. Life span may be such a trait, since a comparison of six wild-type N2 lines derived from a common ancestor (but maintained separately in several laboratories) revealed four variants with median adult life spans ranging from 12.0 +/- 0.8 to 17.0 +/- 0.6 days at 20 degrees C. Fertility was also reduced in the two shortest-lived strains. We determined which life span most closely corresponds to that of the authentic wild type by two means. Firstly, N2 hermaphrodites were compared with seven C. elegans wild isolates. The latter were found to resemble only the longest-lived N2 strain. Comparison of male life spans of six lines also revealed additional strain variation. Secondly, life spans of F1 progeny issuing from crosses between N2 variants showed that short life spans were recessive, indicating that they result from loss-of-function mutations. We infer that the longest-lived N2 variant best resembles the original N2 isolate. This is the N2 male stock currently distributed by the Caenorhabditis Genetics Center.

Health Span-Extending Activity of Human Amniotic Membrane- and Adipose Tissue-Derived Stem Cells in F344 Rats

PubMed Central

Kim, Dajeong; Kyung, Jangbeen; Park, Dongsun; Choi, Ehn-Kyoung; Kim, Kwang Sei; Shin, Kyungha; Lee, Hangyoung; Shin, Il Seob; Kang, Sung Keun

2015-01-01

Aging brings about the progressive decline in cognitive function and physical activity, along with losses of stem cell population and function. Although transplantation of muscle-derived stem/progenitor cells extended the health span and life span of progeria mice, such effects in normal animals were not confirmed. Human amniotic membrane-derived mesenchymal stem cells (AMMSCs) or adipose tissue-derived mesenchymal stem cells (ADMSCs) (1 × 106 cells per rat) were intravenously transplanted to 10-month-old male F344 rats once a month throughout their lives. Transplantation of AMMSCs and ADMSCs improved cognitive and physical functions of naturally aging rats, extending life span by 23.4% and 31.3%, respectively. The stem cell therapy increased the concentration of acetylcholine and recovered neurotrophic factors in the brain and muscles, leading to restoration of microtubule-associated protein 2, cholinergic and dopaminergic nervous systems, microvessels, muscle mass, and antioxidative capacity. The results indicate that repeated transplantation of AMMSCs and ADMSCs elongate both health span and life span, which could be a starting point for antiaging or rejuvenation effects of allogeneic or autologous stem cells with minimum immune rejection. Significance This study demonstrates that repeated treatment with stem cells in normal animals has antiaging potential, extending health span and life span. Because antiaging and prolonged life span are issues currently of interest, these results are significant for readers and investigators. PMID:26315571

The Rate of Source Memory Decline across the Adult Life Span

ERIC Educational Resources Information Center

Cansino, Selene; Estrada-Manilla, Cinthya; Hernandez-Ramos, Evelia; Martinez-Galindo, Joyce Graciela; Torres-Trejo, Frine; Gomez-Fernandez, Tania; Ayala-Hernandez, Mariana; Osorio, David; Cedillo-Tinoco, Melisa; Garces-Flores, Lissete; Gomez-Melgarejo, Sandra; Beltran-Palacios, Karla; Guadalupe Garcia-Lazaro, Haydee; Garcia-Gutierrez, Fabiola; Cadena-Arenas, Yadira; Fernandez-Apan, Luisa; Bartschi, Andrea; Resendiz-Vera, Julieta; Rodriguez-Ortiz, Maria Dolores

2013-01-01

Previous studies have suggested that the ability to remember contextual information related to specific episodic experiences declines with advancing age; however, the exact moment in the adult life span when this deficit begins is still controversial. Source memory for spatial information was tested in a life span sample of 1,500 adults between…

Reduced Neuronal Transcription of Escargot, the Drosophila Gene Encoding a Snail-Type Transcription Factor, Promotes Longevity

PubMed Central

Symonenko, Alexander V.; Roshina, Natalia V.; Krementsova, Anna V.; Pasyukova, Elena G.

2018-01-01

In recent years, several genes involved in complex neuron specification networks have been shown to control life span. However, information on these genes is scattered, and studies to discover new neuronal genes and gene cascades contributing to life span control are needed, especially because of the recognized role of the nervous system in governing homeostasis, aging, and longevity. Previously, we demonstrated that several genes that encode RNA polymerase II transcription factors and that are involved in the development of the nervous system affect life span in Drosophila melanogaster. Among other genes, escargot (esg) was demonstrated to be causally associated with an increase in the life span of male flies. Here, we present new data on the role of esg in life span control. We show that esg affects the life spans of both mated and unmated males and females to varying degrees. By analyzing the survival and locomotion of the esg mutants, we demonstrate that esg is involved in the control of aging. We show that increased longevity is caused by decreased esg transcription. In particular, we demonstrate that esg knockdown in the nervous system increased life span, directly establishing the involvement of the neuronal esg function in life span control. Our data invite attention to the mechanisms regulating the esg transcription rate, which is changed by insertions of DNA fragments of different sizes downstream of the structural part of the gene, indicating the direction of further research. Our data agree with the previously made suggestion that alterations in gene expression during development might affect adult lifespan, due to epigenetic patterns inherited in cell lineages or predetermined during the development of the structural and functional properties of the nervous system. PMID:29760717

Experimental evolution reveals antagonistic pleiotropy in reproductive timing but not life span in Caenorhabditis elegans.

PubMed

Anderson, Jennifer L; Reynolds, Rose M; Morran, Levi T; Tolman-Thompson, Julie; Phillips, Patrick C

2011-12-01

Many mutations that dramatically extend life span in model organisms come with substantial fitness costs. Although these genetic manipulations provide valuable insight into molecular modulators of life span, it is currently unclear whether life-span extension is unavoidably linked to fitness costs. To examine this relationship, we evolved a genetically heterogeneous population of Caenorhabditis elegans for 47 generations, selecting for early fecundity. We asked whether an increase in early fecundity would necessitate a decrease in longevity or late fecundity (antagonistic pleiotropy). Caenorhabditis elegans experimentally evolved for increased early reproduction and decreased late reproduction but suffered no total fitness or life-span costs. Given that antagonistic pleiotropy among these traits has been previously demonstrated in some cases, we conclude that the genetic constraint is not absolute, that is, it is possible to uncouple longevity from early fecundity using genetic variation segregating within and among natural populations.

Herbal Supplement Extends Life Span Under Some Environmental Conditions and Boosts Stress Resistance

PubMed Central

Villeponteau, Bryant; Matsagas, Kennedy; Nobles, Amber C.; Rizza, Cristina; Horwitz, Marc; Benford, Gregory; Mockett, Robin J.

2015-01-01

Genetic studies indicate that aging is modulated by a great number of genetic pathways. We have used Drosophila longevity and stress assays to test a multipath intervention strategy. To carry out this strategy, we supplemented the flies with herbal extracts (SC100) that are predicted to modulate the expression of many genes involved in aging and stress resistance, such as mTOR, NOS, NF-KappaB, and VEGF. When flies were housed in large cages with SC100 added, daily mortality rates of both male and female flies were greatly diminished in mid to late life. Surprisingly, SC100 also stabilized midlife mortality rate increases so as to extend the maximum life span substantially beyond the limits previously reported for D. melanogaster. Under these conditions, SC100 also promoted robust resistance to partial starvation stress and to heat stress. Fertility was the same initially in both treated and control flies, but it became significantly higher in treated flies at older ages as the fertility of control flies declined. Mean and maximum life spans of flies in vials at the same test site were also extended by SC100, but the life spans were short in absolute terms. In contrast, at an independent test site where stress was minimized, the flies exhibited much longer mean life spans, but the survival curves became highly rectangular and the effects of SC100 on both mean and maximum life spans declined greatly or were abolished. The data indicate that SC100 is a novel herbal mix with striking effects on enhancing Drosophila stress resistance and life span in some environments, while minimizing mid to late life mortality rates. They also show that the environment and other factors can have transformative effects on both the length and distribution of survivorship, and on the ability of SC100 to extend the life span. PMID:25879540

The effect of aging on brain barriers and the consequences for Alzheimer's disease development.

PubMed

Gorlé, Nina; Van Cauwenberghe, Caroline; Libert, Claude; Vandenbroucke, Roosmarijn E

2016-08-01

Life expectancy has increased in most developed countries, which has led to an increase in the proportion of elderly people in the world's population. However, this increase in life expectancy is not accompanied by a lengthening of the health span since aging is characterized with progressive deterioration in cellular and organ functions. The brain is particularly vulnerable to disease, and this is reflected in the onset of age-related neurodegenerative diseases such as Alzheimer's disease. Research shows that dysfunction of two barriers in the central nervous system (CNS), the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB), plays an important role in the progression of these neurodegenerative diseases. The BBB is formed by the endothelial cells of the blood capillaries, whereas the BCSFB is formed by the epithelial cells of the choroid plexus (CP), both of which are affected during aging. Here, we give an overview of how these barriers undergo changes during aging and in Alzheimer's disease, thereby disturbing brain homeostasis. Studying these changes is needed in order to gain a better understanding of the mechanisms of aging at the brain barriers, which might lead to the development of new therapies to lengthen the health span (including mental health) and reduce the chances of developing Alzheimer's disease.

Idh2 deficiency accelerates renal dysfunction in aged mice.

PubMed

Lee, Su Jeong; Cha, Hanvit; Lee, Seoyoon; Kim, Hyunjin; Ku, Hyeong Jun; Kim, Sung Hwan; Park, Jung Hyun; Lee, Jin Hyup; Park, Kwon Moo; Park, Jeen-Woo

2017-11-04

The free radical or oxidative stress theory of aging postulates that senescence is due to an accumulation of cellular oxidative damage, caused largely by reactive oxygen species (ROS) that are produced as by-products of normal metabolic processes in mitochondria. The oxidative stress may arise as a result of either increased ROS production or decreased ability to detoxify ROS. The availability of the mitochondrial NADPH pool is critical for the maintenance of the mitochondrial antioxidant system. The major enzyme responsible for generating mitochondrial NADPH is mitochondrial NADP + -dependent isocitrate dehydrogenase (IDH2). Depletion of IDH2 in mice (idh2 -/- ) shortens life span and accelerates the degeneration of multiple age-sensitive traits, such as hair grayness, skin pathology, and eye pathology. Among the various internal organs tested in this study, IDH2 depletion-induced acceleration of senescence was uniquely observed in the kidney. Renal function and structure were greatly deteriorated in 24-month-old idh2 -/- mice compared with wild-type. In addition, disruption of redox status, which promotes oxidative damage and apoptosis, was more pronounced in idh2 -/- mice. These data support a significant role for increased oxidative stress as a result of compromised mitochondrial antioxidant defenses in modulating life span in mice, and thus support the oxidative stress theory of aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Restriction on an energy-dense diet improves markers of metabolic health and cellular aging in mice through decreasing hepatic mTOR activity.

PubMed

Schloesser, Anke; Campbell, Graeme; Glüer, Claus-Christian; Rimbach, Gerald; Huebbe, Patricia

2015-02-01

Dietary restriction (DR) on a normal low-fat diet improves metabolic health and may prolong life span. However, it is still uncertain whether restriction of an energy-dense, high-fat diet would also be beneficial and mitigate age-related processes. In the present study, we determined biomarkers of metabolic health, energy metabolism, and cellular aging in obesity-prone mice subjected to 30% DR on a high-fat diet for 6 months. Dietary-restricted mice had significantly lower body weights, less adipose tissue, lower energy expenditure, and altered substrate oxidation compared to their ad libitum-fed counterparts. Hepatic major urinary proteins (Mup) expression, which is linked to glucose and energy metabolism, and biomarkers of metabolic health, including insulin, glucose, cholesterol, and leptin/adiponectin ratio, were likewise reduced in high-fat, dietary-restricted mice. Hallmarks of cellular senescence such as Lamp2a and Hsc70 that mediate chaperone-mediated autophagy were induced and mechanistic target of rapamycin (mTOR) signaling mitigated upon high-fat DR. In contrast to DR applied in low-fat diets, anti-oxidant gene expression, proteasome activity, as well as 5'-adenosine monophosphate-activated protein kinase (AMPK) activation were not changed, suggesting that high-fat DR may attenuate some processes associated with cellular aging without the induction of cellular stress response or energy deprivation.

Teen Perceptions of Cellular Phones as a Communication Tool

ERIC Educational Resources Information Center

Jonas, Denise D.

2011-01-01

The excitement and interest in innovative technologies has spanned centuries. However, the invention of the cellular phone has surpassed previous technology interests, and changed the way we communicate today. Teens make up the fastest growing market of current cellular phone users. Consequently, the purpose of this study was to determine teen…

Learning From Leaders: Life-span Trends in Olympians and Supercentenarians.

PubMed

Antero-Jacquemin, Juliana da Silva; Berthelot, Geoffroy; Marck, Adrien; Noirez, Philippe; Latouche, Aurélien; Toussaint, Jean-François

2015-08-01

Life-span trends progression has worldwide practical implications as it may affect the sustainability of modern societies. We aimed to describe the secular life-span trends of populations with a propensity to live longer-Olympians and supercentenarians-under two hypotheses: an ongoing life-span extension versus a biologic "probabilistic barrier" limiting further progression. In a study of life-span densities (total number of life durations per birth date), we analyzed 19,012 Olympians and 1,205 supercentenarians deceased between 1900 and 2013. Among most Olympians, we observed a trend toward increased life duration. This trend, however, decelerates at advanced ages leveling off with the upper values with a perennial gap between Olympians and supercentenarians during the whole observation period. Similar tendencies are observed among supercentenarians, and over the last years, a plateau attests to a stable longevity pattern among the longest-lived humans. The common trends between Olympians and supercentenarians indicate similar mortality pressures over both populations that increase with age, scenario better explained by a biologic "barrier" forecast. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America.

The cost of the muse: poets die young.

PubMed

Kaufman, James C

2003-11-01

Although several investigations have found that poets tend to die younger than other types of writers, these studies often do not take into account variables of gender and culture. This study examines 1,987 deceased writers from four different cultures: American, Chinese, Turkish, and Eastern European. Both male and female poets had the shortest life spans of all four types of writers (fiction writers, poets, playwrights, and non-fiction writers), and poets had the shortest life spans in three of the four cultures (and the second shortest life span among Eastern European writers). Possible reasons for the poet's shorter life span are then discussed.

Individual differences in personality change across the adult life span.

PubMed

Schwaba, Ted; Bleidorn, Wiebke

2018-06-01

A precise and comprehensive description of personality continuity and change across the life span is the bedrock upon which theories of personality development are built. Little research has quantified the degree to which individuals deviate from mean-level developmental trends. In this study, we addressed this gap by examining individual differences in personality trait change across the life span. Data came from a nationally representative sample of 9,636 Dutch participants who provided Big Five self-reports at five assessment waves across 7 years. We divided our sample into 14 age groups (ages 16-84 at initial measurement) and estimated latent growth curve models to describe individual differences in personality change across the study period for each trait and age group. Across the adult life span, individual differences in personality change were small but significant until old age. For Openness, Conscientiousness, Extraversion, and Agreeableness, individual differences in change were most pronounced in emerging adulthood and decreased throughout midlife and old age. For Emotional Stability, individual differences in change were relatively consistent across the life span. These results inform theories of life span development and provide future directions for research on the causes and conditions of personality change. © 2017 Wiley Periodicals, Inc.

Effect of Ala-Glu-Asp-Gly peptide on life span and development of spontaneous tumors in female rats exposed to different illumination regimes.

PubMed

Vinogradova, I A; Bukalev, A V; Zabezhinski, M A; Semenchenko, A V; Khavinson, V Kh; Anisimov, V N

2007-12-01

The effects of Ala-Glu-Asp-Gly peptide (Epithalon) on the life span and development of spontaneous tumors were studied in female rats exposed to standard, natural for North-Western Russia, and constant illumination. The mean life span of animals exposed to constant or natural illumination decreased by 13.5 and 25.5%, the maximum by 9 and 7 months, respectively, and spontaneous tumors developed much more rapidly than in animals living under conditions of the standard light regimen. Epithalon (0.1 microg daily 5 times a week from the age of 4 months) did not change the life span of rats living under conditions of standard day/night regimen, while in rats exposed to the natural and constant light it promoted prolongation of the maximum life span by 95 and 24 days, respectively. Epithalon prolonged the mean life span of the last 10% of rats exposed to natural and constant illumination, treated with Epithalon, by 137 and 43 days, respectively. This peptide exhibited virtually no effect on the development of spontaneous tumors in rats exposed to standard and constant illumination, but significantly inhibited their development in rats exposed to natural light.

Life Span Evolution in Eusocial Workers—A Theoretical Approach to Understanding the Effects of Extrinsic Mortality in a Hierarchical System

PubMed Central

Kramer, Boris H.; Schaible, Ralf

2013-01-01

While the extraordinary life span of queens and division of labor in eusocial societies have been well studied, it is less clear which selective forces act on the short life span of workers. The disparity of life span between the queen and the workers is linked to a basic issue in sociobiology: How are the resources in a colony allocated between colony maintenance and reproduction? Resources for somatic maintenance of the colony can either be invested into quality or quantity of workers. Here, we present a theoretical optimization model that uses a hierarchical trade-off within insect colonies and extrinsic mortality to explain how different aging phenotypes could have evolved to keep resources secure in the colony. The model points to the significance of two factors. First, any investment that would generate a longer intrinsic life span for workers is lost if the individual dies from external causes while foraging. As a consequence, risky environments favor the evolution of workers with a shorter life span. Second, shorter-lived workers require less investment than long-lived ones, allowing the colony to allocate these resources to sexual reproduction or colony growth. PMID:23596527

Cranberry interacts with dietary macronutrients to promote healthy aging in Drosophila.

PubMed

Wang, Cecilia; Yolitz, Jason; Alberico, Thomas; Laslo, Mara; Sun, Yaning; Wheeler, Charles T; Sun, Xiaoping; Zou, Sige

2014-08-01

Botanicals possess numerous bioactivities, and some promote healthy aging. Dietary macronutrients are major determinants of life span. The interaction between botanicals and macronutrients that modulates life span is not well understood. Here, we investigated the effect of a cranberry-containing botanical on life span and the influence of macronutrients on the longevity-related effect of cranberry in Drosophila. Flies were supplemented with cranberry on three dietary conditions: standard, high sugar-low protein, and low sugar-high protein diets. We found that cranberry slightly extended life span in males fed with the low sugar-high protein diet but not with other diets. Cranberry extended life span in females fed with the standard diet and more prominently the high sugar-low protein diet but not with the low sugar-high protein diet. Life-span extension was associated with increased reproduction and higher expression of oxidative stress and heat shock response genes. Moreover, cranberry improved survival of sod1 knockdown and dfoxo mutant flies but did not increase wild-type fly's resistance to acute oxidative stress. Cranberry slightly extended life span in flies fed with a high-fat diet. These findings suggest that cranberry promotes healthy aging by increasing stress responsiveness. Our study reveals an interaction of cranberry with dietary macronutrients and stresses the importance of considering diet composition in designing interventions for promoting healthy aging. Published by Oxford University Press on behalf of the Gerontological Society of America 2013.

Health Span-Extending Activity of Human Amniotic Membrane- and Adipose Tissue-Derived Stem Cells in F344 Rats.

PubMed

Kim, Dajeong; Kyung, Jangbeen; Park, Dongsun; Choi, Ehn-Kyoung; Kim, Kwang Sei; Shin, Kyungha; Lee, Hangyoung; Shin, Il Seob; Kang, Sung Keun; Ra, Jeong Chan; Kim, Yun-Bae

2015-10-01

Aging brings about the progressive decline in cognitive function and physical activity, along with losses of stem cell population and function. Although transplantation of muscle-derived stem/progenitor cells extended the health span and life span of progeria mice, such effects in normal animals were not confirmed. Human amniotic membrane-derived mesenchymal stem cells (AMMSCs) or adipose tissue-derived mesenchymal stem cells (ADMSCs) (1×10(6) cells per rat) were intravenously transplanted to 10-month-old male F344 rats once a month throughout their lives. Transplantation of AMMSCs and ADMSCs improved cognitive and physical functions of naturally aging rats, extending life span by 23.4% and 31.3%, respectively. The stem cell therapy increased the concentration of acetylcholine and recovered neurotrophic factors in the brain and muscles, leading to restoration of microtubule-associated protein 2, cholinergic and dopaminergic nervous systems, microvessels, muscle mass, and antioxidative capacity. The results indicate that repeated transplantation of AMMSCs and ADMSCs elongate both health span and life span, which could be a starting point for antiaging or rejuvenation effects of allogeneic or autologous stem cells with minimum immune rejection. This study demonstrates that repeated treatment with stem cells in normal animals has antiaging potential, extending health span and life span. Because antiaging and prolonged life span are issues currently of interest, these results are significant for readers and investigators. ©AlphaMed Press.

Dietary restriction in two rotifer species: the effect of the length of food deprivation on life span and reproduction.

PubMed

Weithoff, Guntram

2007-08-01

According to resource allocation theory, animals face a trade off between the allocation of resources into reproduction and into individual growth/maintenance. This trade off is reinforced when food conditions decline. It is well established in biological research that many animals increase their life span when food is in suboptimal supply for growth and/or reproduction. Such a situation of reduced food availability is called dietary restriction. An increase in life span under dietary restricted conditions is seen as a strategy to tolerate periods of food shortage so that the animals can start reproduction again when food is in greater supply. In this study, the effect of dietary restriction on life span and reproduction in two rotifer species, Cephalodella sp. and Elosa worallii, was investigated using life table experiments. The food concentration under dietary restricted conditions was below the threshold for population growth. It was (1) tested whether the rotifers start reproduction again after food replenishment, and (2) estimated whether the time scale of dietary restricted conditions is relevant for the persistence of a population in the field. Only E. worallii responded to dietary restriction with an increase in life span at the expense of reproduction. After replenishment of food, E. worallii started to reproduce again within 1 day. With an increase in the duration of dietary restricted conditions of up to 15 days, which is longer than the median life span of E. worallii under food saturation, the life span increased and the life time reproduction decreased. These results suggest that in a temporally (or spatially) variable environment, some rotifer populations can persist even during long periods of severe food deprivation.

Leaf life span and the mobility of "non-mobile" mineral nutrients - the case of boron in conifers

Treesearch

Pedro J. Aphalo; Anna W. Schoettle; Tarja Lehto

2002-01-01

Nutrient conservation is considered important for the adaptation of plants to infertile environments. The importance of leaf life spans in controlling mean residence time of nutrients in plants has usually been analyzed in relation to nutrients that can be retranslocated within the plant. Longer leaf life spans increase the mean residence time of all mineral...

The Development of Memory Efficiency and Value-Directed Remembering across the Life Span: A Cross-Sectional Study of Memory and Selectivity

ERIC Educational Resources Information Center

Castel, Alan D.; Humphreys, Kathryn L.; Lee, Steve S.; Galvan, Adriana; Balota, David A.; McCabe, David P.

2011-01-01

Although attentional control and memory change considerably across the life span, no research has examined how the ability to strategically remember important information (i.e., value-directed remembering) changes from childhood to old age. The present study examined this in different age groups across the life span (N = 320, 5-96 years old). A…

Connecting Life Span Development with the Sociology of the Life Course: A New Direction.

PubMed

Gilleard, Chris; Higgs, Paul

2016-04-01

The life course has become a topic of growing interest within the social sciences. Attempts to link this sub-discipline with life span developmental psychology have been called for but with little sign of success. In this paper, we seek to address three interlinked issues concerning the potential for a more productive interchange between life course sociology and life span psychology. The first is to try to account for the failure of these two sub-disciplines to achieve any deepening engagement with each other, despite the long-expressed desirability of that goal; the second is to draw attention to the scope for enriching the sociology of the life course through Erik Erikson's model of life span development; and the last is the potential for linking Eriksonian theory with current debates within mainstream sociology about the processes involved in 'individualisation' and 'self-reflexivity' as an alternative entry point to bring together these two fields of work.

Connecting Life Span Development with the Sociology of the Life Course: A New Direction

PubMed Central

Gilleard, Chris; Higgs, Paul

2015-01-01

The life course has become a topic of growing interest within the social sciences. Attempts to link this sub-discipline with life span developmental psychology have been called for but with little sign of success. In this paper, we seek to address three interlinked issues concerning the potential for a more productive interchange between life course sociology and life span psychology. The first is to try to account for the failure of these two sub-disciplines to achieve any deepening engagement with each other, despite the long-expressed desirability of that goal; the second is to draw attention to the scope for enriching the sociology of the life course through Erik Erikson’s model of life span development; and the last is the potential for linking Eriksonian theory with current debates within mainstream sociology about the processes involved in ‘individualisation’ and ‘self-reflexivity’ as an alternative entry point to bring together these two fields of work. PMID:27041774

Alteration of travel patterns with vision loss from glaucoma and macular degeneration.

PubMed

Curriero, Frank C; Pinchoff, Jessie; van Landingham, Suzanne W; Ferrucci, Luigi; Friedman, David S; Ramulu, Pradeep Y

2013-11-01

The distance patients can travel outside the home influences how much of the world they can sample and to what extent they can live independently. Recent technological advances have allowed travel outside the home to be directly measured in patients' real-world routines. To determine whether decreased visual acuity (VA) from age-related macular degeneration (AMD) and visual field (VF) loss from glaucoma are associated with restricted travel patterns in older adults. Cross-sectional study. Patients were recruited from an eye clinic, while travel patterns were recorded during their real-world routines using a cellular tracking device. Sixty-one control subjects with normal vision, 84 subjects with glaucoma with bilateral VF loss, and 65 subjects with AMD with bilateral or severe unilateral loss of VA had their location tracked every 15 minutes between 7 am and 11 pm for 7 days using a tracking device. Average daily excursion size (defined as maximum distance away from home) and average daily excursion span (defined as maximum span of travel) were defined for each individual. The effects of vision loss on travel patterns were evaluated after controlling for individual and geographic factors. In multivariable models comparing subjects with AMD and control subjects, average excursion size and span decreased by approximately one-quarter mile for each line of better-eye VA loss (P ≤ .03 for both). Similar but not statistically significant associations were observed between average daily excursion size and span for severity of better-eye VF loss in subjects with glaucoma and control subjects. Being married or living with someone and younger age were associated with more distant travel, while less-distant travel was noted for older individuals, African Americans, and those living in more densely populated regions. Age-related macular degeneration-related loss of VA, but not glaucoma-related loss of VF, is associated with restriction of travel to more nearby locations. This constriction of life space may impact quality of life and restrict access to services.

Decision-making heuristics and biases across the life span.

PubMed

Strough, Jonell; Karns, Tara E; Schlosnagle, Leo

2011-10-01

We outline a contextual and motivational model of judgment and decision-making (JDM) biases across the life span. Our model focuses on abilities and skills that correspond to deliberative, experiential, and affective decision-making processes. We review research that addresses links between JDM biases and these processes as represented by individual differences in specific abilities and skills (e.g., fluid and crystallized intelligence, executive functioning, emotion regulation, personality traits). We focus on two JDM biases-the sunk-cost fallacy (SCF) and the framing effect. We trace the developmental trajectory of each bias from preschool through middle childhood, adolescence, early adulthood, and later adulthood. We conclude that life-span developmental trajectories differ depending on the bias investigated. Existing research suggests relative stability in the framing effect across the life span and decreases in the SCF with age, including in later life. We highlight directions for future research on JDM biases across the life span, emphasizing the need for process-oriented research and research that increases our understanding of JDM biases in people's everyday lives. © 2011 New York Academy of Sciences.

Decision-making heuristics and biases across the life span

PubMed Central

Strough, JoNell; Karns, Tara E.; Schlosnagle, Leo

2013-01-01

We outline a contextual and motivational model of judgment and decision-making (JDM) biases across the life span. Our model focuses on abilities and skills that correspond to deliberative, experiential, and affective decision-making processes. We review research that addresses links between JDM biases and these processes as represented by individual differences in specific abilities and skills (e.g., fluid and crystallized intelligence, executive functioning, emotion regulation, personality traits). We focus on two JDM biases—the sunk-cost fallacy (SCF) and the framing effect. We trace the developmental trajectory of each bias from preschool through middle childhood, adolescence, early adulthood, and later adulthood. We conclude that life-span developmental trajectories differ depending on the bias investigated. Existing research suggests relative stability in the framing effect across the life span and decreases in the SCF with age, including in later life. We highlight directions for future research on JDM biases across the life span, emphasizing the need for process-oriented research and research that increases our understanding of JDM biases in people’s everyday lives. PMID:22023568

Autophagy-mediated longevity is modulated by lipoprotein biogenesis

PubMed Central

Seah, Nicole E.; de Magalhaes Filho, C. Daniel; Petrashen, Anna P.; Henderson, Hope R.; Laguer, Jade; Gonzalez, Julissa; Dillin, Andrew; Hansen, Malene; Lapierre, Louis R.

2016-01-01

ABSTRACT Autophagy-dependent longevity models in C. elegans display altered lipid storage profiles, but the contribution of lipid distribution to life-span extension is not fully understood. Here we report that lipoprotein production, autophagy and lysosomal lipolysis are linked to modulate life span in a conserved fashion. We find that overexpression of the yolk lipoprotein VIT/vitellogenin reduces the life span of long-lived animals by impairing the induction of autophagy-related and lysosomal genes necessary for longevity. Accordingly, reducing vitellogenesis increases life span via induction of autophagy and lysosomal lipolysis. Life-span extension due to reduced vitellogenesis or enhanced lysosomal lipolysis requires nuclear hormone receptors (NHRs) NHR-49 and NHR-80, highlighting novel roles for these NHRs in lysosomal lipid signaling. In dietary-restricted worms and mice, expression of VIT and hepatic APOB (apolipoprotein B), respectively, are significantly reduced, suggesting a conserved longevity mechanism. Altogether, our study demonstrates that lipoprotein biogenesis is an important mechanism that modulates aging by impairing autophagy and lysosomal lipolysis. PMID:26671266

Life span effects of Hypericum perforatum extracts on Caenorhabditis elegans under heat stress.

PubMed

Kılıçgün, Hasan; Göksen, Gülden

2012-10-01

The beneficial effects of antioxidants in plants are mainly extrapolated from in vitro studies or short-term dietary supplementation studies. Due to cost and duration, relatively little is known about whether dietary antioxidants are beneficial in whole animals' life span or not. To address this question, under heat stress (35°C), Hypericum perforatum was extracted with petroleum ether and the nematodes Caenorhabditis elegans exposed to three different extract concentrations (1mg/mL, 0.1mg/mL, 0.01mg/mL) of H. perforatum. We report that Hypericum perforatum extracts did not increase life span and slow aging related increase in C. elegans. Moreover, one fraction (1mg/mL) increased declines of C. elegans life span and thermotolerance. Given this mounting evidence for life span role of H. perforatum in the presence of heat stress in vivo, the question whether H. perforatum acts as a prooxidant or an antioxidant in vivo under heat stress arises.

Life span effects of Hypericum perforatum extracts on Caenorhabditis elegans under heat stress

PubMed Central

Kılıçgün, Hasan; Göksen, Gülden

2012-01-01

Background: The beneficial effects of antioxidants in plants are mainly extrapolated from in vitro studies or short-term dietary supplementation studies. Due to cost and duration, relatively little is known about whether dietary antioxidants are beneficial in whole animals’ life span or not. Materials and Methods: To address this question, under heat stress (35°C), Hypericum perforatum was extracted with petroleum ether and the nematodes Caenorhabditis elegans exposed to three different extract concentrations (1mg/mL, 0.1mg/mL, 0.01mg/mL) of H. perforatum. Results: We report that Hypericum perforatum extracts did not increase life span and slow aging related increase in C. elegans. Moreover, one fraction (1mg/mL) increased declines of C. elegans life span and thermotolerance. Conclusion: Given this mounting evidence for life span role of H. perforatum in the presence of heat stress in vivo, the question whether H. perforatum acts as a prooxidant or an antioxidant in vivo under heat stress arises. PMID:24082638

Paternal smoking habits affect the reproductive life span of daughters.

PubMed

Fukuda, Misao; Fukuda, Kiyomi; Shimizu, Takashi; Nobunaga, Miho; Andersen, Elisabeth Wreford; Byskov, Anne Grete; Andersen, Claus Yding

2011-06-30

The present study assessed whether the smoking habits of fathers around the time of conception affected the period in which daughters experienced menstrual cycles (i.e., the reproductive life span). The study revealed that the smoking habits of the farther shortened the daughters' reproductive life span compared with daughters whose fathers did not smoke. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Structural covariance networks across the life span, from 6 to 94 years of age.

PubMed

DuPre, Elizabeth; Spreng, R Nathan

2017-10-01

Structural covariance examines covariation of gray matter morphology between brain regions and across individuals. Despite significant interest in the influence of age on structural covariance patterns, no study to date has provided a complete life span perspective-bridging childhood with early, middle, and late adulthood-on the development of structural covariance networks. Here, we investigate the life span trajectories of structural covariance in six canonical neurocognitive networks: default, dorsal attention, frontoparietal control, somatomotor, ventral attention, and visual. By combining data from five open-access data sources, we examine the structural covariance trajectories of these networks from 6 to 94 years of age in a sample of 1,580 participants. Using partial least squares, we show that structural covariance patterns across the life span exhibit two significant, age-dependent trends. The first trend is a stable pattern whose integrity declines over the life span. The second trend is an inverted-U that differentiates young adulthood from other age groups. Hub regions, including posterior cingulate cortex and anterior insula, appear particularly influential in the expression of this second age-dependent trend. Overall, our results suggest that structural covariance provides a reliable definition of neurocognitive networks across the life span and reveal both shared and network-specific trajectories.

ω-6 Polyunsaturated fatty acids extend life span through the activation of autophagy

PubMed Central

O'Rourke, Eyleen J.; Kuballa, Petric; Xavier, Ramnik; Ruvkun, Gary

2013-01-01

Adaptation to nutrient scarcity depends on the activation of metabolic programs to efficiently use internal reserves of energy. Activation of these programs in abundant food regimens can extend life span. However, the common molecular and metabolic changes that promote adaptation to nutritional stress and extend life span are mostly unknown. Here we present a response to fasting, enrichment of ω-6 polyunsaturated fatty acids (PUFAs), which promotes starvation resistance and extends Caenorhabditis elegans life span. Upon fasting, C. elegans induces the expression of a lipase, which in turn leads to an enrichment of ω-6 PUFAs. Supplementing C. elegans culture media with these ω-6 PUFAs increases their resistance to starvation and extends their life span in conditions of food abundance. Supplementation of C. elegans or human epithelial cells with these ω-6 PUFAs activates autophagy, a cell recycling mechanism that promotes starvation survival and slows aging. Inactivation of C. elegans autophagy components reverses the increase in life span conferred by supplementing the C. elegans diet with these fasting-enriched ω-6 PUFAs. We propose that the salubrious effects of dietary supplementation with ω-3/6 PUFAs (fish oils) that have emerged from epidemiological studies in humans may be due to a similar activation of autophagic programs. PMID:23392608

Genes that regulate both development and longevity in Caenorhabditis elegans

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

Larsen, P.L.; Albert, P.S.; Riddle, D.L.

1995-04-01

The nematode Caenorhabditis elegans responds to conditions of overcrowding and limited food by arresting development as a dauer larva. Genetic analysis of mutations that alter dauer larva formation (daf mutations) is presented along with an updated genetic pathway for dauer vs. nondauer development. Mutations in the daf-2 and daf-23 genes double adult life span, whereas mutations in four other dauer-constitutive genes positioned in a separate branch of this pathway (daf-1, daf-4, daf-7 and daf-8) do not. The increased life spans are suppressed completely by a daf-16 mutation and partially in a daf-2; daf-18 double mutant. A genetic pathway for determinationmore » of adult life span is presented based on the same strains and growth conditions used to characterize Daf phenotypes. Both dauer larva formation and adult life span are affected in daf-2; daf-12 double mutants in an allele-specific manner. Mutations in daf-12 do not extend adult life span, but certain combinations of daf-2 and daf-12 mutant alleles nearly quadruple it. This synergistic effect, which does not equivalently extend the fertile period, is the largest genetic extension of life span yet observed in a metazoan. 47 refs., 7 figs., 5 tabs.« less

Structural covariance networks across the life span, from 6 to 94 years of age

PubMed Central

DuPre, Elizabeth; Spreng, R. Nathan

2017-01-01

Structural covariance examines covariation of gray matter morphology between brain regions and across individuals. Despite significant interest in the influence of age on structural covariance patterns, no study to date has provided a complete life span perspective—bridging childhood with early, middle, and late adulthood—on the development of structural covariance networks. Here, we investigate the life span trajectories of structural covariance in six canonical neurocognitive networks: default, dorsal attention, frontoparietal control, somatomotor, ventral attention, and visual. By combining data from five open-access data sources, we examine the structural covariance trajectories of these networks from 6 to 94 years of age in a sample of 1,580 participants. Using partial least squares, we show that structural covariance patterns across the life span exhibit two significant, age-dependent trends. The first trend is a stable pattern whose integrity declines over the life span. The second trend is an inverted-U that differentiates young adulthood from other age groups. Hub regions, including posterior cingulate cortex and anterior insula, appear particularly influential in the expression of this second age-dependent trend. Overall, our results suggest that structural covariance provides a reliable definition of neurocognitive networks across the life span and reveal both shared and network-specific trajectories. PMID:29855624

Metabotypes with properly functioning mitochondria and anti-inflammation predict extended productive life span in dairy cows

PubMed Central

Huber, K.; Dänicke, S.; Rehage, J.; Sauerwein, H.; Otto, W.; Rolle-Kampczyk, U.; von Bergen, M.

2016-01-01

The failure to adapt metabolism to the homeorhetic demands of lactation is considered as a main factor in reducing the productive life span of dairy cows. The so far defined markers of production performance and metabolic health in dairy cows do not predict the length of productive life span satisfyingly. This study aimed to identify novel pathways and biomarkers related to productive life in dairy cows by means of (targeted) metabolomics. In a longitudinal study from 42 days before up to 100 days after parturition, we identified metabolites such as long-chain acylcarnitines and biogenic amines associated with extended productive life spans. These metabolites are mainly secreted by the liver and depend on the functionality of hepatic mitochondria. The concentrations of biogenic amines and some acylcarnitines differed already before the onset of lactation thus indicating their predictive potential for continuation or early ending of productive life. PMID:27089826

Metabotypes with properly functioning mitochondria and anti-inflammation predict extended productive life span in dairy cows.

PubMed

Huber, K; Dänicke, S; Rehage, J; Sauerwein, H; Otto, W; Rolle-Kampczyk, U; von Bergen, M

2016-04-19

The failure to adapt metabolism to the homeorhetic demands of lactation is considered as a main factor in reducing the productive life span of dairy cows. The so far defined markers of production performance and metabolic health in dairy cows do not predict the length of productive life span satisfyingly. This study aimed to identify novel pathways and biomarkers related to productive life in dairy cows by means of (targeted) metabolomics. In a longitudinal study from 42 days before up to 100 days after parturition, we identified metabolites such as long-chain acylcarnitines and biogenic amines associated with extended productive life spans. These metabolites are mainly secreted by the liver and depend on the functionality of hepatic mitochondria. The concentrations of biogenic amines and some acylcarnitines differed already before the onset of lactation thus indicating their predictive potential for continuation or early ending of productive life.

Molecular control of steady-state dendritic cell maturation and immune homeostasis.

PubMed

Hammer, Gianna Elena; Ma, Averil

2013-01-01

Dendritic cells (DCs) are specialized sentinels responsible for coordinating adaptive immunity. This function is dependent upon coupled sensitivity to environmental signs of inflammation and infection to cellular maturation-the programmed alteration of DC phenotype and function to enhance immune cell activation. Although DCs are thus well equipped to respond to pathogens, maturation triggers are not unique to infection. Given that immune cells are exquisitely sensitive to the biological functions of DCs, we now appreciate that multiple layers of suppression are required to restrict the environmental sensitivity, cellular maturation, and even life span of DCs to prevent aberrant immune activation during the steady state. At the same time, steady-state DCs are not quiescent but rather perform key functions that support homeostasis of numerous cell types. Here we review these functions and molecular mechanisms of suppression that control steady-state DC maturation. Corruption of these steady-state operatives has diverse immunological consequences and pinpoints DCs as potent drivers of autoimmune and inflammatory disease.

Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network.

PubMed

McConnell, Michael J; Moran, John V; Abyzov, Alexej; Akbarian, Schahram; Bae, Taejeong; Cortes-Ciriano, Isidro; Erwin, Jennifer A; Fasching, Liana; Flasch, Diane A; Freed, Donald; Ganz, Javier; Jaffe, Andrew E; Kwan, Kenneth Y; Kwon, Minseok; Lodato, Michael A; Mills, Ryan E; Paquola, Apua C M; Rodin, Rachel E; Rosenbluh, Chaggai; Sestan, Nenad; Sherman, Maxwell A; Shin, Joo Heon; Song, Saera; Straub, Richard E; Thorpe, Jeremy; Weinberger, Daniel R; Urban, Alexander E; Zhou, Bo; Gage, Fred H; Lehner, Thomas; Senthil, Geetha; Walsh, Christopher A; Chess, Andrew; Courchesne, Eric; Gleeson, Joseph G; Kidd, Jeffrey M; Park, Peter J; Pevsner, Jonathan; Vaccarino, Flora M

2017-04-28

Neuropsychiatric disorders have a complex genetic architecture. Human genetic population-based studies have identified numerous heritable sequence and structural genomic variants associated with susceptibility to neuropsychiatric disease. However, these germline variants do not fully account for disease risk. During brain development, progenitor cells undergo billions of cell divisions to generate the ~80 billion neurons in the brain. The failure to accurately repair DNA damage arising during replication, transcription, and cellular metabolism amid this dramatic cellular expansion can lead to somatic mutations. Somatic mutations that alter subsets of neuronal transcriptomes and proteomes can, in turn, affect cell proliferation and survival and lead to neurodevelopmental disorders. The long life span of individual neurons and the direct relationship between neural circuits and behavior suggest that somatic mutations in small populations of neurons can significantly affect individual neurodevelopment. The Brain Somatic Mosaicism Network has been founded to study somatic mosaicism both in neurotypical human brains and in the context of complex neuropsychiatric disorders. Copyright © 2017, American Association for the Advancement of Science.

Potential Mechanisms of Action of Dietary Phytochemicals for Cancer Prevention by Targeting Cellular Signaling Transduction Pathways.

PubMed

Chen, Hongyu; Liu, Rui Hai

2018-04-04

Cancer is a severe health problem that significantly undermines life span and quality. Dietary approach helps provide preventive, nontoxic, and economical strategies against cancer. Increased intake of fruits, vegetables, and whole grains are linked to reduced risk of cancer and other chronic diseases. The anticancer activities of plant-based foods are related to the actions of phytochemicals. One potential mechanism of action of anticancer phytochemicals is that they regulate cellular signal transduction pathways and hence affects cancer cell behaviors such as proliferation, apoptosis, and invasion. Recent publications have reported phytochemicals to have anticancer activities through targeting a wide variety of cell signaling pathways at different levels, such as transcriptional or post-transcriptional regulation, protein activation and intercellular messaging. In this review, we discuss major groups of phytochemicals and their regulation on cell signaling transduction against carcinogenesis via key participators, such as Nrf2, CYP450, MAPK, Akt, JAK/STAT, Wnt/β-catenin, p53, NF-κB, and cancer-related miRNAs.

Erythrocyte and blood antibacterial defense

PubMed Central

2014-01-01

It is an axiom that blood cellular immunity is provided by leukocytes. As to erythrocytes, it is generally accepted that their main function is respiration. Our research provides objective video and photo evidence regarding erythrocyte bactericidal function. Phase-contrast immersion vital microscopy of the blood of patients with bacteremia was performed, and the process of bacteria entrapping and killing by erythrocytes was shot by means of video camera. Video evidence demonstrates that human erythrocytes take active part in blood bactericidal action and can repeatedly engulf and kill bacteria of different species and size. Erythrocytes are extremely important integral part of human blood cellular immunity. Compared with phagocytic leukocytes, the erythrocytes: a) are more numerous; b) are able to entrap and kill microorganisms repeatedly without being injured; c) are more resistant to infection and better withstand the attacks of pathogens; d) have longer life span and are produced faster; e) are inauspicious media for proliferation of microbes and do not support replication of chlamidiae, mycoplasmas, rickettsiae, viruses, etc.; and f) are more effective and uncompromised bacterial killers. Blood cellular immunity theory and traditional view regarding the function of erythrocytes in human blood should be revised. PMID:24883200

Trehalose extends longevity in the nematode Caenorhabditis elegans.

PubMed

Honda, Yoko; Tanaka, Masashi; Honda, Shuji

2010-08-01

Trehalose is a disaccharide of glucose found in diverse organisms and is suggested to act as a stress protectant against heat, cold, desiccation, anoxia, and oxidation. Here, we demonstrate that treatment of Caenorhabditis elegans with trehalose starting from the young-adult stage extended the mean life span by over 30% without any side effects. Surprisingly, trehalose treatment starting even from the old-adult stage shortly thereafter retarded the age-associated decline in survivorship and extended the remaining life span by 60%. Demographic analyses of age-specific mortality rates revealed that trehalose extended the life span by lowering age-independent vulnerability. Moreover, trehalose increased the reproductive span and retarded the age-associated decrease in pharyngeal-pumping rate and the accumulation of lipofuscin autofluorescence. Trehalose also enhanced thermotolerance and reduced polyglutamine aggregation. These results suggest that trehalose suppressed aging by counteracting internal or external stresses that disrupt protein homeostasis. On the other hand, the life span-extending effect of trehalose was abolished in long-lived insulin/IGF-1-like receptor (daf-2) mutants. RNA interference-mediated inactivation of the trehalose-biosynthesis genes trehalose-6-phosphate synthase-1 (tps-1) and tps-2, which are known to be up-regulated in daf-2 mutants, decreased the daf-2 life span. These findings indicate that a reduction in insulin/IGF-1-like signaling extends life span, at least in part, through the aging-suppressor function of trehalose. Trehalose may be a lead compound for potential nutraceutical intervention of the aging process.

Aging in the colonial chordate, Botryllus schlosseri.

PubMed

Munday, Roma; Rodriguez, Delany; Di Maio, Alessandro; Kassmer, Susannah; Braden, Brian; Taketa, Daryl A; Langenbacher, Adam; De Tomaso, Anthony

2015-01-30

What mechanisms underlie aging? One theory, the wear-and-tear model, attributes aging to progressive deterioration in the molecular and cellular machinery which eventually lead to death through the disruption of physiological homeostasis. The second suggests that life span is genetically programmed, and aging may be derived from intrinsic processes which enforce a non-random, terminal time interval for the survivability of the organism. We are studying an organism that demonstrates both properties: the colonial ascidian, Botryllus schlosseri. Botryllus is a member of the Tunicata, the sister group to the vertebrates, and has a number of life history traits which make it an excellent model for studies on aging. First, Botryllus has a colonial life history, and grows by a process of asexual reproduction during which entire bodies, including all somatic and germline lineages, regenerate every week, resulting in a colony of genetically identical individuals. Second, previous studies of lifespan in genetically distinct Botryllus lineages suggest that a direct, heritable basis underlying mortality exists that is unlinked to reproductive effort and other life history traits. Here we will review recent efforts to take advantage of the unique life history traits of B. schlosseri and develop it into a robust model for aging research.

Aging in the colonial chordate, Botryllus schlosseri

PubMed Central

Munday, Roma; Rodriguez, Delany; Di Maio, Alessandro; Kassmer, Susannah; Braden, Brian; Taketa, Daryl A.; Langenbacher, Adam; De Tomaso, Anthony

2015-01-01

What mechanisms underlie aging? One theory, the wear-and-tear model, attributes aging to progressive deterioration in the molecular and cellular machinery which eventually lead to death through the disruption of physiological homeostasis. The second suggests that life span is genetically programmed, and aging may be derived from intrinsic processes which enforce a non-random, terminal time interval for the survivability of the organism. We are studying an organism that demonstrates both properties: the colonial ascidian, Botryllus schlosseri. Botryllus is a member of the Tunicata, the sister group to the vertebrates, and has a number of life history traits which make it an excellent model for studies on aging. First, Botryllus has a colonial life history, and grows by a process of asexual reproduction during which entire bodies, including all somatic and germline lineages, regenerate every week, resulting in a colony of genetically identical individuals. Second, previous studies of lifespan in genetically distinct Botryllus lineages suggest that a direct, heritable basis underlying mortality exists that is unlinked to reproductive effort and other life history traits. Here we will review recent efforts to take advantage of the unique life history traits of B. schlosseri and develop it into a robust model for aging research. PMID:26136620

The zebrafish as a gerontology model in nervous system aging, disease, and repair.

PubMed

Van Houcke, Jessie; De Groef, Lies; Dekeyster, Eline; Moons, Lieve

2015-11-01

Considering the increasing number of elderly in the world's population today, developing effective treatments for age-related pathologies is one of the biggest challenges in modern medical research. Age-related neurodegeneration, in particular, significantly impacts important sensory, motor, and cognitive functions, seriously constraining life quality of many patients. Although our understanding of the causal mechanisms of aging has greatly improved in recent years, animal model systems still have much to tell us about this complex process. Zebrafish (Danio rerio) have gained enormous popularity for this research topic over the past decade, since their life span is relatively short but, like humans, they are still subject to gradual aging. In addition, the extensive characterization of its well-conserved molecular and cellular physiology makes the zebrafish an excellent model to unravel the underlying mechanisms of aging, disease, and repair. This review provides a comprehensive overview of the progress made in zebrafish gerontology, with special emphasis on nervous system aging. We review the evidence that classic hallmarks of aging can also be recognized within this small vertebrate, both at the molecular and cellular level. Moreover, we illustrate the high level of similarity with age-associated human pathologies through a survey of the functional deficits that arise as zebrafish age. Copyright © 2015 Elsevier B.V. All rights reserved.

Divergent evolution of life span associated with mitochondrial DNA evolution.

PubMed

Stojković, Biljana; Sayadi, Ahmed; Đorđević, Mirko; Jović, Jelena; Savković, Uroš; Arnqvist, Göran

2017-01-01

Mitochondria play a key role in ageing. The pursuit of genes that regulate variation in life span and ageing have shown that several nuclear-encoded mitochondrial genes are important. However, the role of mitochondrial encoded genes (mtDNA) is more controversial and our appreciation of the role of mtDNA for the evolution of life span is limited. We use replicated lines of seed beetles that have been artificially selected for long or short life for >190 generations, now showing dramatic phenotypic differences, to test for a possible role of mtDNA in the divergent evolution of ageing and life span. We show that these divergent selection regimes led to the evolution of significantly different mtDNA haplotype frequencies. Selection for a long life and late reproduction generated positive selection for one specific haplotype, which was fixed in most such lines. In contrast, selection for reproduction early in life led to both positive selection as well as negative frequency-dependent selection on two different haplotypes, which were both present in all such lines. Our findings suggest that the evolution of life span was in part mediated by mtDNA, providing support for the emerging general tenet that adaptive evolution of life-history syndromes may involve mtDNA. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Working memory and inhibitory control across the life span: Intrusion errors in the Reading Span Test.

PubMed

Robert, Christelle; Borella, Erika; Fagot, Delphine; Lecerf, Thierry; de Ribaupierre, Anik

2009-04-01

The aim of this study was to examine to what extent inhibitory control and working memory capacity are related across the life span. Intrusion errors committed by children and younger and older adults were investigated in two versions of the Reading Span Test. In Experiment 1, a mixed Reading Span Test with items of various list lengths was administered. Older adults and children recalled fewer correct words and produced more intrusions than did young adults. Also, age-related differences were found in the type of intrusions committed. In Experiment 2, an adaptive Reading Span Test was administered, in which the list length of items was adapted to each individual's working memory capacity. Age groups differed neither on correct recall nor on the rate of intrusions, but they differed on the type of intrusions. Altogether, these findings indicate that the availability of attentional resources influences the efficiency of inhibition across the life span.

Influence of resveratrol on oxidative stress resistance and life span in Caenorhabditis elegans.

PubMed

Chen, Wei; Rezaizadehnajafi, Leila; Wink, Michael

2013-05-01

Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a polyphenol from red wine, has been reported to be beneficial in cases of ageing-related cardiovascular and neurodegenerative diseases owing to its property to reduce oxidative stress. Previous studies on the longevity promoting effect of resveratrol have been partly inconclusive, therefore we set out to investigate whether resveratrol at least promoted longevity in Caenorhabditis elegans under acute oxidative stress conditions. C. elegans was cultured under standard conditions with or without resveratrol. After exposure to juglone-induced acute oxidative stress, the survival rate and hsp-16.2::GFP expression were measured. The influence of resveratrol on life span was recorded also under oxidative stress induced by high glucose concentrations in the growth medium. No extension of the normal life span of C. elegans was observed either in liquid or solid growth media containing different concentrations of resveratrol. However, resveratrol alleviated juglone-induced lethal oxidative stress, and significantly prolonged the life span of C. elegans under conditions of acute oxidative damage and oxidative stress caused by high concentrations of glucose. Resveratrol, as an antioxidant, ameliorated oxidative stress in vivo but did not extend the life span of C. elegans under normal conditions. However, resveratrol did extend life span under conditions of oxidative stress. © 2013 The Authors. JPP © 2013 Royal Pharmaceutical Society.

Sustained Attention Across the Life Span in a Sample of 10,000: Dissociating Ability and Strategy.

PubMed

Fortenbaugh, Francesca C; DeGutis, Joseph; Germine, Laura; Wilmer, Jeremy B; Grosso, Mallory; Russo, Kathryn; Esterman, Michael

2015-09-01

Normal and abnormal differences in sustained visual attention have long been of interest to scientists, educators, and clinicians. Still lacking, however, is a clear understanding of how sustained visual attention varies across the broad sweep of the human life span. In the present study, we filled this gap in two ways. First, using an unprecedentedly large 10,430-person sample, we modeled age-related differences with substantially greater precision than have prior efforts. Second, using the recently developed gradual-onset continuous performance test (gradCPT), we parsed sustained-attention performance over the life span into its ability and strategy components. We found that after the age of 15 years, the strategy and ability trajectories saliently diverge. Strategy becomes monotonically more conservative with age, whereas ability peaks in the early 40s and is followed by a gradual decline in older adults. These observed life-span trajectories for sustained attention are distinct from results of other life-span studies focusing on fluid and crystallized intelligence. © The Author(s) 2015.

SIRT6 stabilizes DNA-dependent Protein Kinase at chromatin for DNA double-strand break repair

PubMed Central

McCord, Ronald A.; Michishita, Eriko; Hong, Tao; Berber, Elisabeth; Boxer, Lisa D.; Kusumoto, Rika; Guan, Shenheng; Shi, Xiaobing; Gozani, Or; Burlingame, Alma L.; Bohr, Vilhelm A.; Chua, Katrin F.

2009-01-01

The Sir2 chromatin regulatory factor links maintenance of genomic stability to life span extension in yeast. The mammalian Sir2 family member SIRT6 has been proposed to have analogous functions, because SIRT6-deficiency leads to shortened life span and an aging-like degenerative phenotype in mice, and SIRT6 knockout cells exhibit genomic instability and DNA damage hypersensitivity. However, the molecular mechanisms underlying these defects are not fully understood. Here, we show that SIRT6 forms a macromolecular complex with the DNA double-strand break (DSB) repair factor DNA-PK (DNA-dependent protein kinase) and promotes DNA DSB repair. In response to DSBs, SIRT6 associates dynamically with chromatin and is necessary for an acute decrease in global cellular acetylation levels on histone H3 Lysine 9. Moreover, SIRT6 is required for mobilization of the DNA-PK catalytic subunit (DNA-PKcs) to chromatin in response to DNA damage and stabilizes DNA-PKcs at chromatin adjacent to an induced site-specific DSB. Abrogation of these SIRT6 activities leads to impaired resolution of DSBs. Together, these findings elucidate a mechanism whereby regulation of dynamic interaction of a DNA repair factor with chromatin impacts on the efficiency of repair, and establish a link between chromatin regulation, DNA repair, and a mammalian Sir2 factor. PMID:20157594

Role of metabolic rate and DNA-repair in Drosophila aging Implications for the mitochondrial mutation theory of aging

NASA Technical Reports Server (NTRS)

Miquel, J.; Binnard, R.; Fleming, J. E.

1983-01-01

The notion that injury to mitochondrial DNA is a cause of intrinsic aging was tested by correlating the different respiration rates of several wild strains of Drosophila melanogaster with the life-spans. Respiration rate and aging in a mutant of D. melanogaster deficient in postreplication repair were also investigated. In agreement with the rate of living theory, there was an inverse relation between oxygen consumption and median life-span in flies having normal DNA repair. The mutant showed an abnormally low life-span as compared to the controls and also exhibited significant deficiency in mating fitness and a depressed metabolic rate. Therefore, the short life-span of the mutant may be due to the congenital condition rather than to accelerated aging.

Understanding retirement: the promise of life-span developmental frameworks.

PubMed

Löckenhoff, Corinna E

2012-09-01

The impending retirement of large population cohorts creates a pressing need for practical interventions to optimize outcomes at the individual and societal level. This necessitates comprehensive theoretical models that acknowledge the multi-layered nature of the retirement process and shed light on the dynamic mechanisms that drive longitudinal patterns of adjustment. The present commentary highlights ways in which contemporary life-span developmental frameworks can inform retirement research, drawing on the specific examples of Bronfenbrenner's Ecological Model, Baltes and Baltes Selective Optimization with Compensation Framework, Schulz and Heckhausen's Motivational Theory of Life-Span Development, and Carstensen's Socioemotional Selectivity Theory. Ultimately, a life-span developmental perspective on retirement offers not only new interpretations of known phenomena but may also help to identify novel directions for future research as well as promising pathways for interventions.

Electromagnetic field therapy delays cellular senescence and death by enhancement of the heat shock response.

PubMed

Perez, Felipe P; Zhou, Ximing; Morisaki, Jorge; Jurivich, Donald

2008-04-01

Hormesis may result when mild repetitive stress increases cellular defense against diverse injuries. This process may also extend in vitro cellular proliferative life span as well as delay and reverse some of the age-dependent changes in both replicative and non-replicative cells. This study evaluated the potential hormetic effect of non-thermal repetitive electromagnetic field shock (REMFS) and its impact on cellular aging and mortality in primary human T lymphocytes and fibroblast cell lines. Unlike previous reports employing electromagnetic radiation, this study used a long wave length, low energy, and non-thermal REMFS (50MHz/0.5W) for various therapeutic regimens. The primary outcomes examined were age-dependent morphological changes in cells over time, cellular death prevention, and stimulation of the heat shock response. REMFS achieved several biological effects that modified the aging process. REMFS extended the total number of population doublings of mouse fibroblasts and contributed to youthful morphology of cells near their replicative lifespan. REMFS also enhanced cellular defenses of human T cells as reflected in lower cell mortality when compared to non-treated T cells. To determine the mechanism of REMFS-induced effects, analysis of the cellular heat shock response revealed Hsp90 release from the heat shock transcription factor (HSF1). Furthermore, REMFS increased HSF1 phosphorylation, enhanced HSF1-DNA binding, and improved Hsp70 expression relative to non-REMFS-treated cells. These results show that non-thermal REMFS activates an anti-aging hormetic effect as well as reduces cell mortality during lethal stress. Because the REMFS configuration employed in this study can potentially be applied to whole body therapy, prospects for translating these data into clinical interventions for Alzheimer's disease and other degenerative conditions with aging are discussed.

Adaptive prolonged postreproductive life span in killer whales.

PubMed

Foster, Emma A; Franks, Daniel W; Mazzi, Sonia; Darden, Safi K; Balcomb, Ken C; Ford, John K B; Croft, Darren P

2012-09-14

Prolonged life after reproduction is difficult to explain evolutionarily unless it arises as a physiological side effect of increased longevity or it benefits related individuals (i.e., increases inclusive fitness). There is little evidence that postreproductive life spans are adaptive in nonhuman animals. By using multigenerational records for two killer whale (Orcinus orca) populations in which females can live for decades after their final parturition, we show that postreproductive mothers increase the survival of offspring, particularly their older male offspring. This finding may explain why female killer whales have evolved the longest postreproductive life span of all nonhuman animals.

Life and Self Meaning: The Process of Their Creation.

ERIC Educational Resources Information Center

Weenolsen, Patricia

Research has not addressed issues of life meaning in a life-span developmental framework. The Loss and Transcendence paradigm was developed as a humanistic-existential approach to life-span development which has as its central theme the concept that individuals are in a continuous process of creating their lives and their selves. To explore loss…

Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice.

PubMed

Strong, Randy; Miller, Richard A; Astle, Clinton M; Baur, Joseph A; de Cabo, Rafael; Fernandez, Elizabeth; Guo, Wen; Javors, Martin; Kirkland, James L; Nelson, James F; Sinclair, David A; Teter, Bruce; Williams, David; Zaveri, Nurulain; Nadon, Nancy L; Harrison, David E

2013-01-01

The National Institute on Aging Interventions Testing Program (ITP) was established to evaluate agents that are hypothesized to increase life span and/or health span in genetically heterogeneous mice. Each compound is tested in parallel at three test sites. It is the goal of the ITP to publish all results, negative or positive. We report here on the results of lifelong treatment of mice, beginning at 4 months of age, with each of five agents, that is, green tea extract (GTE), curcumin, oxaloacetic acid, medium-chain triglyceride oil, and resveratrol, on the life span of genetically heterogeneous mice. Each agent was administered beginning at 4 months of age. None of these five agents had a statistically significant effect on life span of male or female mice, by log-rank test, at the concentrations tested, although a secondary analysis suggested that GTE might diminish the risk of midlife deaths in females only.

Evaluation of Resveratrol, Green Tea Extract, Curcumin, Oxaloacetic Acid, and Medium-Chain Triglyceride Oil on Life Span of Genetically Heterogeneous Mice

PubMed Central

Miller, Richard A.; Astle, Clinton M.; Baur, Joseph A.; de Cabo, Rafael; Fernandez, Elizabeth; Guo, Wen; Javors, Martin; Kirkland, James L.; Nelson, James F.; Sinclair, David A.; Teter, Bruce; Williams, David; Zaveri, Nurulain; Nadon, Nancy L.; Harrison, David E.

2013-01-01

The National Institute on Aging Interventions Testing Program (ITP) was established to evaluate agents that are hypothesized to increase life span and/or health span in genetically heterogeneous mice. Each compound is tested in parallel at three test sites. It is the goal of the ITP to publish all results, negative or positive. We report here on the results of lifelong treatment of mice, beginning at 4 months of age, with each of five agents, that is, green tea extract (GTE), curcumin, oxaloacetic acid, medium-chain triglyceride oil, and resveratrol, on the life span of genetically heterogeneous mice. Each agent was administered beginning at 4 months of age. None of these five agents had a statistically significant effect on life span of male or female mice, by log-rank test, at the concentrations tested, although a secondary analysis suggested that GTE might diminish the risk of midlife deaths in females only. PMID:22451473

A Holistic Model for Wellness and Prevention over the Life Span.

ERIC Educational Resources Information Center

Witmer, J. Melvin; Sweeney, Thomas J.

1992-01-01

Presents integrated paradigm for wellness and prevention over the life span for purpose of theory building, research, clinical application, education, advocacy, and consciousness raising. Model described includes 11 characteristics desirable for optimal health and functioning. Notes characteristics are expressed through five life tasks of…

Explanatory style across the life span: evidence for stability over 52 years.

PubMed

Burns, M O; Seligman, M E

1989-03-01

Analyzed explanatory style across the life span. 30 Ss whose average age was 72 responded to questions about their current life and provided diaries or letters written in their youth, an average of 52 years earlier. A blind content analysis of explanatory style derived from these 2 sources revealed that explanatory style for negative events was stable throughout adult life (r = .54, p less than .002). In contrast, there appeared to be no stability of explanatory style for positive events between the same 2 time periods. These results suggest that explanatory style for negative events may persist across the life span and may constitute an enduring risk factor for depression, low achievement, and physical illness.

The Cost of Uncertain Life Span*

PubMed Central

Edwards, Ryan D.

2012-01-01

A considerable amount of uncertainty surrounds the length of human life. The standard deviation in adult life span is about 15 years in the U.S., and theory and evidence suggest it is costly. I calibrate a utility-theoretic model of preferences over length of life and show that one fewer year in standard deviation is worth about half a mean life year. Differences in the standard deviation exacerbate cross-sectional differences in life expectancy between the U.S. and other industrialized countries, between rich and poor countries, and among poor countries. Accounting for the cost of life-span variance also appears to amplify recently discovered patterns of convergence in world average human well-being. This is partly for methodological reasons and partly because unconditional variance in human length of life, primarily the component due to infant mortality, has exhibited even more convergence than life expectancy. PMID:22368324

Life-Span Developmental Psychology: Non-Normative Life Events. A Review of the Seventh West Virginia University Life-Span Developmental Psychology Conference.

ERIC Educational Resources Information Center

Richardson, Gale A.; Kwiatkowski, Bonnie M.

1981-01-01

Topics covered in this conference included parenting, terminal illness, the birth of severely disabled children, rape and family violence, separation and divorce, and hospitalization, and dealt with a wide range of methodologies and age periods. (Author/RH)

Sex differences in life span: Females homozygous for the X chromosome do not suffer the shorter life span predicted by the unguarded X hypothesis.

PubMed

Brengdahl, Martin; Kimber, Christopher M; Maguire-Baxter, Jack; Friberg, Urban

2018-03-01

Life span differs between the sexes in many species. Three hypotheses to explain this interesting pattern have been proposed, involving different drivers: sexual selection, asymmetrical inheritance of cytoplasmic genomes, and hemizygosity of the X(Z) chromosome (the unguarded X hypothesis). Of these, the unguarded X has received the least experimental attention. This hypothesis suggests that the heterogametic sex suffers a shortened life span because recessive deleterious alleles on its single X(Z) chromosome are expressed unconditionally. In Drosophila melanogaster, the X chromosome is unusually large (∼20% of the genome), providing a powerful model for evaluating theories involving the X. Here, we test the unguarded X hypothesis by forcing D. melanogaster females from a laboratory population to express recessive X-linked alleles to the same degree as males, using females exclusively made homozygous for the X chromosome. We find no evidence for reduced life span or egg-to-adult viability due to X homozygozity. In contrast, males and females homozygous for an autosome both suffer similar, significant reductions in those traits. The logic of the unguarded X hypothesis is indisputable, but our results suggest that the degree to which recessive deleterious X-linked alleles depress performance in the heterogametic sex appears too small to explain general sex differences in life span. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

The Impact of Life Stages on Parent-Child Relationships: A Comparative Look at Japanese & American University Students

ERIC Educational Resources Information Center

Takei, Yoshimitsu; Honda, Tokio; Shieh, Sheau-Hue

2007-01-01

Adolescence is often considered a period in a person's life when important physiological and emotional changes occur. When discussing adolescence, however, it should not be forgotten that it is just another stage in one's life span between birth and death. By adopting a life-span perspective, researchers are more likely to consider contextual…

Identity, prudential concern, and extended lives.

PubMed

Glannon, Walter

2002-06-01

Recent advances in human genetics suggest that it may become possible to genetically manipulate telomerase and embryonic stem cells to alter the mechanisms of aging and extend the human life span. But a life span significantly longer than the present norm would be undesirable because it would severely weaken the connections between past- and future-oriented mental states and turn the psychological grounds for personal identity and prudential concern for our future selves. In addition, the collective effects of longer lives might lower the quality of life for all people. These two problems provide reasons against genetic manipulation of cells to alter the length of the human life span.

Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans

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

Abegglen, Lisa M.; Caulin, Aleah F.; Chan, Ashley

Here, evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). Design, Setting, and Participants A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n=644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro inmore » the laboratory for DNA damage response. The study included African and Asian elephants (n=8), patients with LFS (n=10), and age-matched human controls (n=11). Human samples were collected at the University of Utah between June 2014 and July 2015. Exposures Ionizing radiation and doxorubicin. Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95% CI, 0%-5%]; African wild dog, 8% [95% CI, 0%-16%]; lion, 2% [95% CI, 0%-7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95% CI, 3.14%-6.49%), compared with humans, who have 11% to 25% cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction. In response to DNA damage, elephant lymphocytes underwent p53-mediated apoptosis at higher rates than human lymphocytes proportional to TP53 status (ionizing radiation exposure: patients with LFS, 2.71% [95% CI, 1.93%-3.48%] vs human controls, 7.17% [95% CI, 5.91%-8.44%] vs elephants, 14.64% [95% CI, 10.91%-18.37%]; P<.001; doxorubicin exposure: human controls, 8.10% [95% CI, 6.55%-9.66%] vs elephants, 24.77% [95% CI, 23.0%-26.53%]; P<.001). Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53. Compared with human cells, elephant cells demonstrated increased apoptotic response following DNA damage. These findings, if replicated, could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression.« less

Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans

DOE PAGES

Abegglen, Lisa M.; Caulin, Aleah F.; Chan, Ashley; ...

2015-10-08

Here, evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). Design, Setting, and Participants A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n=644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro inmore » the laboratory for DNA damage response. The study included African and Asian elephants (n=8), patients with LFS (n=10), and age-matched human controls (n=11). Human samples were collected at the University of Utah between June 2014 and July 2015. Exposures Ionizing radiation and doxorubicin. Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95% CI, 0%-5%]; African wild dog, 8% [95% CI, 0%-16%]; lion, 2% [95% CI, 0%-7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95% CI, 3.14%-6.49%), compared with humans, who have 11% to 25% cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction. In response to DNA damage, elephant lymphocytes underwent p53-mediated apoptosis at higher rates than human lymphocytes proportional to TP53 status (ionizing radiation exposure: patients with LFS, 2.71% [95% CI, 1.93%-3.48%] vs human controls, 7.17% [95% CI, 5.91%-8.44%] vs elephants, 14.64% [95% CI, 10.91%-18.37%]; P<.001; doxorubicin exposure: human controls, 8.10% [95% CI, 6.55%-9.66%] vs elephants, 24.77% [95% CI, 23.0%-26.53%]; P<.001). Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53. Compared with human cells, elephant cells demonstrated increased apoptotic response following DNA damage. These findings, if replicated, could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression.« less

Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans.

PubMed

Abegglen, Lisa M; Caulin, Aleah F; Chan, Ashley; Lee, Kristy; Robinson, Rosann; Campbell, Michael S; Kiso, Wendy K; Schmitt, Dennis L; Waddell, Peter J; Bhaskara, Srividya; Jensen, Shane T; Maley, Carlo C; Schiffman, Joshua D

2015-11-03

Evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n = 644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro in the laboratory for DNA damage response. The study included African and Asian elephants (n = 8), patients with LFS (n = 10), and age-matched human controls (n = 11). Human samples were collected at the University of Utah between June 2014 and July 2015. Ionizing radiation and doxorubicin. Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95% CI, 0%-5%]; African wild dog, 8% [95% CI, 0%-16%]; lion, 2% [95% CI, 0%-7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95% CI, 3.14%-6.49%), compared with humans, who have 11% to 25% cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction. In response to DNA damage, elephant lymphocytes underwent p53-mediated apoptosis at higher rates than human lymphocytes proportional to TP53 status (ionizing radiation exposure: patients with LFS, 2.71% [95% CI, 1.93%-3.48%] vs human controls, 7.17% [95% CI, 5.91%-8.44%] vs elephants, 14.64% [95% CI, 10.91%-18.37%]; P < .001; doxorubicin exposure: human controls, 8.10% [95% CI, 6.55%-9.66%] vs elephants, 24.77% [95% CI, 23.0%-26.53%]; P < .001). Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53. Compared with human cells, elephant cells demonstrated increased apoptotic response following DNA damage. These findings, if replicated, could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression.

Life-Span Extension in Mice by Preweaning Food Restriction and by Methionine Restriction in Middle Age

PubMed Central

Sun, Liou; Sadighi Akha, Amir A.; Miller, Richard A.

2009-01-01

Life span can be extended in rodents by restricting food availability (caloric restriction [CR]) or by providing food low in methionine (Meth-R). Here, we show that a period of food restriction limited to the first 20 days of life, via a 50% enlargement of litter size, shows extended median and maximal life span relative to mice from normal sized litters and that a Meth-R diet initiated at 12 months of age also significantly increases longevity. Furthermore, mice exposed to a CR diet show changes in liver messenger RNA patterns, in phosphorylation of Erk, Jnk2, and p38 kinases, and in phosphorylation of mammalian target of rapamycin and its substrate 4EBP1, HE-binding protein 1 that are not observed in liver from age-matched Meth-R mice. These results introduce new protocols that can increase maximal life span and suggest that the spectrum of metabolic changes induced by low-calorie and low-methionine diets may differ in instructive ways. PMID:19414512

The Writing Process: Effects of Life-Span Development on Imaging.

ERIC Educational Resources Information Center

Shock, Diane Hahn

A qualitative study focused on incubation and illumination within the act of writing to determine if life-span development affects image production during these creative, cognitive acts. Sixteen subjects of both sexes from four age groups represented major developmental stages in the life cycle. The research design provided two 90-minute sessions…

Personal Goals and Well-Being: How Do Young People Navigate Their Lives?

ERIC Educational Resources Information Center

Salmela-Aro, Katariina

2010-01-01

This chapter examines development through different life transitions, such as educational transitions and transition to parenthood during adolescence to adulthood in the context of the life-span model of personal goals. According to the life-span model of motivation, four key mechanisms--channeling, choice, co-regulation, and compensation--play a…

A CRTCal link between energy and life span.

PubMed

Brunet, Anne

2011-04-06

Cutting down calories prolongs life, but how this works remains largely unknown. A recent study in Nature (Mair et al., 2011) shows that life span extension triggered by the energy-sensing protein kinase AMPK is mediated by an evolutionarily conserved transcriptional circuit involving CRTC-1 and CREB. Copyright © 2011 Elsevier Inc. All rights reserved.

Visual Search Across the Life Span

ERIC Educational Resources Information Center

Hommel, Bernhard; Li, Karen Z. H.; Li, Shu-Chen

2004-01-01

Gains and losses in visual search were studied across the life span in a representative sample of 298 individuals from 6 to 89 years of age. Participants searched for single-feature and conjunction targets of high or low eccentricity. Search was substantially slowed early and late in life, age gradients were more pronounced in conjunction than in…

Improvement/Maintenance and Reorientation as Central Features of Coping with Major Life Change and Loss: Contributions of Three Life-Span Theories

ERIC Educational Resources Information Center

Boerner, Kathrin; Jopp, Daniela

2007-01-01

This article focuses on the common and unique contributions of three major life-span theories in addressing improvement/maintenance and reorientation, which represent central processes of coping with major life change and loss. For this purpose, we review and compare the dual-process model of assimilative and accommodative coping, the model of…

The Theory of Relativity: A Metatheory for Development?

ERIC Educational Resources Information Center

Sinnott, Jan Dynda

1981-01-01

Reviews relativity theory in physics to derive a relativistic metatheory applicable to life span developmental psychology. The discussion points out ways in which relativistic thinking might enhance understanding of life span development and epistemology. (Author/DB)

The primacy of primary control is a human universal: a reply to Gould's (1999) critique of the life-span theory of control.

PubMed

Heckhausen, J; Schulz, R

1999-07-01

This reply to S. J. Gould's (1999) critique of J. Heckhausen and R. Schulz's (1995) life-span theory of control addresses four issues: (1) the universal claim that primary control holds functional primacy over secondary control, (2) the status of secondary control as a confederate to primary control, (3) empirical evidence and paradigms for investigating universality and cultural variations, and (4) the capacity of the human control system to manage both gains and losses in control throughout the life span and aging-related decline in particular. Theoretical perspectives and empirical evidence from evolutionary, comparative, developmental, and cultural psychology are presented to support the authors' view that primary control striving holds functional primacy throughout the life span and across cultural and historical settings. Recommendations for empirically investigating the variations in the way primary control striving is expressed in different cultures are outlined.

Reproductive adaptation in Drosophila exposed to oxygen-enriched atmospheres

NASA Technical Reports Server (NTRS)

Kloek, G.; Winkle, L.

1979-01-01

Ten successive generations of a Drosophila melanogaster population were exposed to an atmospheric mix of 50% oxygen/50% nitrogen at standard pressure. This atmospheric mix has been shown to be toxic to this species and causes significantly shortened life span. By the fifth generation, survivorship and life span for the first 25-30 days were identical to control populations and total life span was shorter by only a few days. Egg-laying rates were stable in the experimental populations but below those of the controls. Hatching success was identical between experimental and control populations. Even though the egg-laying rates were lower in 50% oxygen, it was concluded that the population had adapted and could maintain a stable population in these conditions. The near-normal life spans, normal hatching rates, and overall population stability, exhibited following five generations of adaptation, were considered sufficient to allow continued reproduction in spite of a reduced egg-laying rate.

Life-span extension by a metacaspase in the yeast Saccharomyces cerevisiae.

PubMed

Hill, Sandra Malmgren; Hao, Xinxin; Liu, Beidong; Nyström, Thomas

2014-06-20

Single-cell species harbor ancestral structural homologs of caspase proteases, although the evolutionary benefit of such apoptosis-related proteins in unicellular organisms is unclear. Here, we found that the yeast metacaspase Mca1 is recruited to the insoluble protein deposit (IPOD) and juxtanuclear quality-control compartment (JUNQ) during aging and proteostatic stress. Elevating MCA1 expression counteracted accumulation of unfolded proteins and aggregates and extended life span in a heat shock protein Hsp104 disaggregase- and proteasome-dependent manner. Consistent with a role in protein quality control, genetic interaction analysis revealed that MCA1 buffers against deficiencies in the Hsp40 chaperone YDJ1 in a caspase cysteine-dependent manner. Life-span extension and aggregate management by Mca1 was only partly dependent on its conserved catalytic cysteine, which suggests that Mca1 harbors both caspase-dependent and independent functions related to life-span control. Copyright © 2014, American Association for the Advancement of Science.

Reproductive adaptation in Drosophila exposed to oxygen-enriched atmospheres.

PubMed

Kloek, G; Winkle, L

1979-04-01

Ten successive generations of a Drosophila melanogaster population were exposed to an atmospheric mix of 50% oxygen/50% nitrogen at standard pressure. This atmospheric mix has been shown to be toxic to this species and causes significantly shortened life span. By the fifth generation, survivorship and life span for the first 25-30 days were identical to control populations and total life span was shorter by only a few days. Egg-laying rates were stable in the experimental populations but below those of the controls. Hatching success was identical between experimental and control populations. Even though the egg-laying rates were lower in 50% oxygen, it was concluded that the population had adapted and could maintain a stable population in these conditions. The near-normal life spans, normal hatching rates, and overall population stability, exhibited following five generations of adaptation, were considered sufficient to allow continued reproduction in spite of a reduced egg-laying rate.

Gadd45 proteins: Relevance to aging, longevity and age-related pathologies

PubMed Central

Moskalev, Alexey A.; Smit-McBride, Zeljka; Shaposhnikov, Mikhail V.; Plyusnina, Ekaterina N.; Zhavoronkov, Alex; Budovsky, Arie; Tacutu, Robi; Fraifeld, Vadim E.

2013-01-01

The Gadd45 proteins have been intensively studied, in view of their important role in key cellular processes. Indeed, the Gadd45 proteins stand at the crossroad of the cell fates by controlling the balance between cell (DNA) repair, eliminating (apoptosis) or preventing the expansion of potentially dangerous cells (cell cycle arrest, cellular senescence), and maintaining the stem cell pool. However, the biogerontological aspects have not thus far received sufficient attention. Here we analyzed the pathways and modes of action by which Gadd45 members are involved in aging, longevity and age-related diseases. Because of their pleiotropic action, a decreased inducibility of Gadd45 members may have far-reaching consequences including genome instability, accumulation of DNA damage, and disorders in cellular homeostasis – all of which may eventually contribute to the aging process and age-related disorders (promotion of tumorigenesis, immune disorders, insulin resistance and reduced responsiveness to stress). Most recently, the dGadd45 gene has been identified as a longevity regulator in Drosophila. Although further wide-scale research is warranted, it is becoming increasingly clear that Gadd45s are highly relevant to aging, age-related diseases (ARDs) and to the control of life span, suggesting them as potential therapeutic targets in ARDs and pro-longevity interventions. PMID:21986581

EnLightenment: High resolution smartphone microscopy as an educational and public engagement platform.

PubMed

Wicks, Laura C; Cairns, Gemma S; Melnyk, Jacob; Bryce, Scott; Duncan, Rory R; Dalgarno, Paul A

2017-01-01

We developed a simple, cost-effective smartphone microscopy platform for use in educational and public engagement programs. We demonstrated its effectiveness, and potential for citizen science through a national imaging initiative, EnLightenment . The cost effectiveness of the instrument allowed for the program to deliver over 500 microscopes to more than 100 secondary schools throughout Scotland, targeting 1000's of 12-14 year olds. Through careful, quantified, selection of a high power, low-cost objective lens, our smartphone microscope has an imaging resolution of microns, with a working distance of 3 mm. It is therefore capable of imaging single cells and sub-cellular features, and retains usability for young children. The microscopes were designed in kit form and provided an interdisciplinary educational tool. By providing full lesson plans and support material, we developed a framework to explore optical design, microscope performance, engineering challenges on construction and real-world applications in life sciences, biological imaging, marine biology, art, and technology. A national online imaging competition framed EnLightenment ; with over 500 high quality images submitted of diverse content, spanning multiple disciplines. With examples of cellular and sub-cellular features clearly identifiable in some submissions, we show how young public can use these instruments for research-level imaging applications, and the potential of the instrument for citizen science programs.

Role of Metalloproteases in Vaccinia Virus Epitope Processing for Transporter Associated with Antigen Processing (TAP)-independent Human Leukocyte Antigen (HLA)-B7 Class I Antigen Presentation*

PubMed Central

Lorente, Elena; García, Ruth; Mir, Carmen; Barriga, Alejandro; Lemonnier, François A.; Ramos, Manuel; López, Daniel

2012-01-01

The transporter associated with antigen processing (TAP) translocates the viral proteolytic peptides generated by the proteasome and other proteases in the cytosol to the endoplasmic reticulum lumen. There, they complex with nascent human leukocyte antigen (HLA) class I molecules, which are subsequently recognized by the CD8+ lymphocyte cellular response. However, individuals with nonfunctional TAP complexes or tumor or infected cells with blocked TAP molecules are able to present HLA class I ligands generated by TAP-independent processing pathways. Herein, using a TAP-independent polyclonal vaccinia virus-polyspecific CD8+ T cell line, two conserved vaccinia-derived TAP-independent HLA-B*0702 epitopes were identified. The presentation of these epitopes in normal cells occurs via complex antigen-processing pathways involving the proteasome and/or different subsets of metalloproteinases (amino-, carboxy-, and endoproteases), which were blocked in infected cells with specific chemical inhibitors. These data support the hypothesis that the abundant cellular proteolytic systems contribute to the supply of peptides recognized by the antiviral cellular immune response, thereby facilitating immunosurveillance. These data may explain why TAP-deficient individuals live normal life spans without any increased susceptibility to viral infections. PMID:22298786

Does Dietary Restriction Reduce Life Span in Male Fruit-feeding Butterflies?

PubMed Central

Molleman, Freerk; Ding, Jimin; Boggs, Carol L.; Carey, James R.; Arlet, Małgorzata E.

2009-01-01

Male life history and resource allocation is not frequently studied in aging and life span research. Here we verify that males of long-lived fruit-feeding butterfly species have reduced longevity on restricted diets (Beck 2007 Oecologia), in contrast to the common finding of longevity extension in dietary restriction experiments in Drosophila and some other organisms. Males of some of the most long-lived species of fruit-feeding butterflies were collected from Kibale Forest, Uganda, and kept on diets of either sugar or mashed banana. Seven out of eight species had non-significantly longer life spans on mashed banana diets. Data analysis using a time-varying Cox-model with species as covariate showed that males had reduced survival on the sugar diet during the first 35 days of captive life, but the effect was absent or reversed at more advanced ages. These results challenge the generality of dietary restriction as a way to extend life span in animals. We argue that such studies on males are promising tools for better understanding life history evolution and aging because males display a wider variety of tactics for obtaining reproductive success than females. PMID:19580860

Nutritional Control of Chronological Aging and Heterochromatin in Saccharomyces cerevisiae.

PubMed

McCleary, David F; Rine, Jasper

2017-03-01

Calorie restriction extends life span in organisms as diverse as yeast and mammals through incompletely understood mechanisms.The role of NAD + -dependent deacetylases known as Sirtuins in this process, particularly in the yeast Saccharomyces cerevisiae , is controversial. We measured chronological life span of wild-type and sir2 Δ strains over a higher glucose range than typically used for studying yeast calorie restriction. sir2 Δ extended life span in high glucose complete minimal medium and had little effect in low glucose medium, revealing a partial role for Sir2 in the calorie-restriction response under these conditions. Experiments performed on cells grown in rich medium with a newly developed genetic strategy revealed that sir2 Δ shortened life span in low glucose while having little effect in high glucose, again revealing a partial role for Sir2 In complete minimal media, Sir2 shortened life span as glucose levels increased; whereas in rich media, Sir2 extended life span as glucose levels decreased. Using a genetic strategy to measure the strength of gene silencing at HML , we determined increasing glucose stabilized Sir2-based silencing during growth on complete minimal media. Conversely, increasing glucose destabilized Sir-based silencing during growth on rich media, specifically during late cell divisions. In rich medium, silencing was far less stable in high glucose than in low glucose during stationary phase. Therefore, Sir2 was involved in a response to nutrient cues including glucose that regulates chronological aging, possibly through Sir2-dependent modification of chromatin or deacetylation of a nonhistone protein. Copyright © 2017 by the Genetics Society of America.

Therapeutic Potential and Cellular Mechanisms of Panax Notoginseng on Prevention of Aging and Cell Senescence-Associated Diseases

PubMed Central

Zhao, Haiping; Han, Ziping; Li, Guangwen; Zhang, Sijia; Luo, Yumin

2017-01-01

Owing to a dramatic increase in average life expectancy, most countries in the world are rapidly entering an aging society. Therefore, extending health span with pharmacological agents targeting aging-related pathological changes, are now in the spotlight of gerosciences. Panax notoginseng (Burk.) F. H. Chen, a species of the genus Panax, has been called the "Miracle Root for the Preservation of Life," and has long been used as a Chinese herb with magical medicinal value. Panax notoginseng has been extensively employed in China to treat microcirculatory disturbances, inflammation, trauma, internal and external bleeding due to injury, and as a tonic. In recent years, with the deepening of the research pharmacologically, many new functions have been discovered. This review will introduce its pharmacological function on lifespan extension, anti-vascular aging, anti-brain aging, and anti-cancer properties, aiming to lay the ground for fully elucidating the potential mechanisms of Panax notoginseng’s anti-aging effect to promote its clinical application. PMID:29344413

Immunoblot analysis of cellular expression of Bcl-2 family proteins, Bcl-2, Bax, Bcl-X and Mcl-1, in human peripheral blood and lymphoid tissues.

PubMed

Ohta, K; Iwai, K; Kasahara, Y; Taniguchi, N; Krajewski, S; Reed, J C; Miyawaki, T

1995-11-01

The ability of Bcl-2 to inhibit apoptotic cell death is well established. Several homologues of the bcl-2 gene, such as bax, bcl-x or mcl-1, have recently been identified. Like Bcl-2, both Bcl-XL and Mcl-1 appear to function as repressors of apoptotic cell death, whereas Bax facilitates it, indicating possible interactions among them in the control of cellular survival. To investigate the in vivo role of expression of bcl-2 gene family products, immunoblot analysis using corresponding specific antisera was performed for peripheral blood cells and some lymphoid tissues in humans. We demonstrated that all Bcl-2 family proteins were expressed at various levels in hematolymphoid cell subpopulations isolated from peripheral blood, tonsil, spleen and thymus. Lymphoid expression of Bcl-2 family proteins tended to increase following activation, but declined with time in culture. Loss of Bcl-2 in cultured lymphoid cells was especially marked. Sole expression of Bax, but not other members of the Bcl-2 family, was observed on neutrophils, seemingly reflecting their shortest life-span among blood leukocytes. The results support the notion that a balance of expression of Bcl-2 family proteins may regulate the life and death of hematolymphoid cells at different stages of cell differentiation and activation.

Relationships of leaf dark respiration to leaf nitrogen, specific leaf area and leaf life-span: a test across biomes and functional groups.

PubMed

Reich, Peter B; Walters, Michael B; Ellsworth, David S; Vose, James M; Volin, John C; Gresham, Charles; Bowman, William D

1998-05-01

Based on prior evidence of coordinated multiple leaf trait scaling, we hypothesized that variation among species in leaf dark respiration rate (R d ) should scale with variation in traits such as leaf nitrogen (N), leaf life-span, specific leaf area (SLA), and net photosynthetic capacity (A max ). However, it is not known whether such scaling, if it exists, is similar among disparate biomes and plant functional types. We tested this idea by examining the interspecific relationships between R d measured at a standard temperature and leaf life-span, N, SLA and A max for 69 species from four functional groups (forbs, broad-leafed trees and shrubs, and needle-leafed conifers) in six biomes traversing the Americas: alpine tundra/subalpine forest, Colorado; cold temperate forest/grassland, Wisconsin; cool temperate forest, North Carolina; desert/shrubland, New Mexico; subtropical forest, South Carolina; and tropical rain forest, Amazonas, Venezuela. Area-based R d was positively related to area-based leaf N within functional groups and for all species pooled, but not when comparing among species within any site. At all sites, mass-based R d (R d-mass ) decreased sharply with increasing leaf life-span and was positively related to SLA and mass-based A max and leaf N (leaf N mass ). These intra-biome relationships were similar in shape and slope among sites, where in each case we compared species belonging to different plant functional groups. Significant R d-mass -N mass relationships were observed in all functional groups (pooled across sites), but the relationships differed, with higher R d at any given leaf N in functional groups (such as forbs) with higher SLA and shorter leaf life-span. Regardless of biome or functional group, R d-mass was well predicted by all combinations of leaf life-span, N mass and/or SLA (r 2 ≥ 0.79, P < 0.0001). At any given SLA, R d-mass rises with increasing N mass and/or decreasing leaf life-span; and at any level of N mass , R d-mass rises with increasing SLA and/or decreasing leaf life-span. The relationships between R d and leaf traits observed in this study support the idea of a global set of predictable interrelationships between key leaf morphological, chemical and metabolic traits.

Identification of senescence-associated genes in human bone marrow mesenchymal stem cells

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

Ryu, Eunsook; Hong, Su; Kang, Jaeku

2008-07-04

Human bone marrow mesenchymal stem cells (hBMMSCs) are multipotent stem cells that can differentiate into several specialized cell types, including bone, cartilage, and fat cells. The proliferative capacity of hBMMSCs paves the way for the development of regenerative medicine and tissue engineering. However, long-term in vitro culture of hBMMSCs leads to a reduced life span of the cells due to senescence, which leads eventually to growth arrest. To investigate the molecular mechanism behind the cellular senescence of hBMMSCs, microarray analysis was used to compare the expression profiles of early passage hBMMSCs, late passage hBMMSCs and hBMMSCs ectopically expressing human telomerasemore » reverse transcriptase (hTERT). Using an intersection analysis of 3892 differentially expressed genes (DEGs) out of 27,171 total genes analyzed, we identified 338 senescence-related DEGs. GO term categorization and pathway network analysis revealed that the identified genes are strongly related to known senescence pathways and mechanisms. The genes identified using this approach will facilitate future studies of the mechanisms underlying the cellular senescence of hBMMSCs.« less

A novel vaccine containing EphA2 epitope and LIGHT plasmid induces robust cellular immunity against glioma U251 cells.

PubMed

Chen, Hongjie; Yuan, Bangqing; Zheng, Zhaocong; Liu, Zheng; Wang, Shousen; Liu, Yong

2011-01-01

EphA2 is a receptor tyrosine kinase and can be acted as an attractive antigen for glioma vaccines. In addition, LIGHT plays an important role on enhancing T cell proliferation and cytokine production. To improve the CTL mediated immune response against glioma cells, we prepared the novel vaccine containing EphA2(883-891) peptide (TLADFDPRV) and LIGHT plasmid and utilized it to immunize the HLA-A2 transgenic HHD mice. In addition, trimera mice were immunized with the novel vaccine to elicit the antitumor immune response. The results demonstrated that the novel vaccine could induce robust cellular immunity against glioma U251 cells without lysing autologous lymphocytes. Moreover, the novel vaccine could significantly inhibit the tumor growth and prolong the life span of tumor bearing mice. These findings suggested that the novel vaccine containing EphA2 epitope and LIGHT plasmid could induce anti-tumor immunity against U251 cells expressing EphA2, and provided a promising strategy for glioma immunotherapy. Copyright © 2011 Elsevier Inc. All rights reserved.

Murine models of atrophy, cachexia, and sarcopenia in skeletal muscle

PubMed Central

Romanick, Mark; Brown-Borg, Holly M.

2013-01-01

With the extension of life span over the past several decades, the age-related loss of muscle mass and strength that characterizes sarcopenia is becoming more evident and thus, has a more significant impact on society. To determine ways to intervene and delay, or even arrest the physical frailty and dependence that accompany sarcopenia, it is necessary to identify those biochemical pathways that define this process. Animal models that mimic one or more of the physiological pathways involved with this phenomenon are very beneficial in providing an understanding of the cellular processes at work in sarcopenia. The ability to influence pathways through genetic manipulation gives insight into cellular responses and their impact on the physical expression of sarcopenia. This review evaluates several murine models that have the potential to elucidate biochemical processes integral to sarcopenia. Identifying animal models that reflect sarcopenia or its component pathways will enable researchers to better understand those pathways that contribute to age-related skeletal muscle mass loss, and in turn, develop interventions that will prevent, retard, arrest, or reverse this phenomenon. PMID:23523469

Deep-brain magnetic stimulation promotes adult hippocampal neurogenesis and alleviates stress-related behaviors in mouse models for neuropsychiatric disorders

PubMed Central

2014-01-01

Background Repetitive Transcranial Magnetic Stimulation (rTMS)/ Deep-brain Magnetic Stimulation (DMS) is an effective therapy for various neuropsychiatric disorders including major depression disorder. The molecular and cellular mechanisms underlying the impacts of rTMS/DMS on the brain are not yet fully understood. Results Here we studied the effects of deep-brain magnetic stimulation to brain on the molecular and cellular level. We examined the adult hippocampal neurogenesis and hippocampal synaptic plasticity of rodent under stress conditions with deep-brain magnetic stimulation treatment. We found that DMS promotes adult hippocampal neurogenesis significantly and facilitates the development of adult new-born neurons. Remarkably, DMS exerts anti-depression effects in the learned helplessness mouse model and rescues hippocampal long-term plasticity impaired by restraint stress in rats. Moreover, DMS alleviates the stress response in a mouse model for Rett syndrome and prolongs the life span of these animals dramatically. Conclusions Deep-brain magnetic stimulation greatly facilitates adult hippocampal neurogenesis and maturation, also alleviates depression and stress-related responses in animal models. PMID:24512669

Adaptation in Living Systems

NASA Astrophysics Data System (ADS)

Tu, Yuhai; Rappel, Wouter-Jan

2018-03-01

Adaptation refers to the biological phenomenon where living systems change their internal states in response to changes in their environments in order to maintain certain key functions critical for their survival and fitness. Adaptation is one of the most ubiquitous and arguably one of the most fundamental properties of living systems. It occurs throughout all biological scales, from adaptation of populations of species over evolutionary time to adaptation of a single cell to different environmental stresses during its life span. In this article, we review some of the recent progress made in understanding molecular mechanisms of cellular-level adaptation. We take the minimalist (or the physicist) approach and study the simplest systems that exhibit generic adaptive behaviors, namely chemotaxis in bacterium cells (Escherichia coli) and eukaryotic cells (Dictyostelium). We focus on understanding the basic biochemical interaction networks that are responsible for adaptation dynamics. By combining theoretical modeling with quantitative experimentation, we demonstrate universal features in adaptation as well as important differences in different cellular systems. Future work in extending the modeling framework to study adaptation in more complex systems such as sensory neurons is also discussed.

The importance of adult life-span perspective in explaining variations in political ideology.

PubMed

Sedek, Grzegorz; Kossowska, Malgorzata; Rydzewska, Klara

2014-06-01

As a comment on Hibbing et al.'s paper, we discuss the evolution of political and social views from more liberal to more conservative over the span of adulthood. We show that Hibbing et al.'s theoretical model creates a false prediction from this developmental perspective, as increased conservatism in the adult life-span trajectory is accompanied by the avoidance of negative bias.

Life-span extension by dietary restriction is mediated by NLP-7 signaling and coelomocyte endocytosis in C. elegans.

PubMed

Park, Sang-Kyu; Link, Christopher D; Johnson, Thomas E

2010-02-01

Recent studies have shown that the rate of aging can be modulated by diverse interventions. Dietary restriction is the most widely used intervention to promote longevity; however, the mechanisms underlying the effect of dietary restriction remain elusive. In a previous study, we identified two novel genes, nlp-7 and cup-4, required for normal longevity in Caenorhabditis elegans. nlp-7 is one of a set of neuropeptide-like protein genes; cup-4 encodes an ion-channel involved in endocytosis by coelomocytes. Here, we assess whether nlp-7 and cup-4 mediate longevity increases by dietary restriction. RNAi of nlp-7 or cup-4 significantly reduces the life span of the eat-2 mutant, a genetic model of dietary restriction, but has no effect on the life span of long-lived mutants resulting from reduced insulin/IGF-1 signaling or dysfunction of the mitochondrial electron transport chain. The life-span extension observed in wild-type N2 worms by dietary restriction using bacterial dilution is prevented significantly in nlp-7 and cup-4 mutants. RNAi knockdown of genes encoding candidate receptors of NLP-7 and genes involved in endocytosis by coelomocytes also specifically shorten the life span of the eat-2 mutant. We conclude that two novel pathways, NLP-7 signaling and endocytosis by coelomocytes, are required for life extension under dietary restriction in C. elegans.

The control processes and subjective well-being of Chinese teachers: evidence of convergence with and divergence from the key propositions of the motivational theory of life-span development

PubMed Central

Wong, Wan-chi; Li, Yin; Sun, Xiaoyan; Xu, Huanu

2014-01-01

An analytical review of the motivational theory of life-span development reveals that this theory has undergone a series of elegant theoretical integrations. Its claim to universality nonetheless brings forth unresolved controversies. With the purpose of scrutinizing the key propositions of this theory, an empirical study was designed to examine the control processes and subjective well-being of Chinese teachers (N = 637). The OPS-Scales (Optimization in Primary and Secondary Control Scales) for the Domain of Teaching were constructed to assess patterns of control processes. Three facets of subjective well-being were investigated with the Positive and Negative Affect Schedule, the Life Satisfaction Scale, and the Subjective Vitality Scale. The results revealed certain aspects of alignment with and certain divergences from the key propositions of the motivational theory of life-span development. Neither “primacy of primary control” nor “primacy of secondary control” was clearly supported. Notably, using different criteria for subjective well-being yielded different subtypes of primary and secondary control as predictors. The hypothesized life-span trajectories of primary and secondary control received limited support. To advance the theory in this area, we recommend incorporating Lakatos' ideas about sophisticated falsification by specifying the hard core of the motivational theory of life-span development and articulating new auxiliary hypotheses. PMID:24904483

Foraging across the life span: is there a reduction in exploration with aging?

PubMed Central

Mata, Rui; Wilke, Andreas; Czienskowski, Uwe

2013-01-01

Does foraging change across the life span, and in particular, with aging? We report data from two foraging tasks used to investigate age differences in search in external environments as well as internal search in memory. Overall, the evidence suggests that foraging behavior may undergo significant changes across the life span across internal and external search. In particular, we find evidence of a trend toward reduced exploration with increased age. We discuss these findings in light of theories that postulate a link between aging and reductions in novelty seeking and exploratory behavior. PMID:23616741

Molecular genetic approaches to the study of cellular senescence.

PubMed

Goletz, T J; Smith, J R; Pereira-Smith, O M

1994-01-01

Cellular senescence is an inability of cells to synthesize DNA and divide, which results in a terminal loss of proliferation despite the maintenance of basic metabolic processes. Senescence has been proposed as a model for the study of aging at the cellular level, and the basis for this model system and its features have been summarized. Although strong experimental evidence exists to support the hypothesis that cellular senescence is a dominant active process, the mechanisms responsible for this phenomenon remain a mystery. Investigators have taken several approaches to gain a better understanding of senescence. Several groups have documented the differences between young and senescent cells, and others have identified changes that occur during the course of a cell's in vitro life span. Using molecular and biochemical approaches, important changes in gene expression and function of cell-cycle-associated products have been identified. The active production of an inhibitor of DNA synthesis has been demonstrated. This may represent the final step in a cascade of events governing senescence. The study of immortal cells which have escaped senescence has also provided useful information, particularly with regard to the genes governing the senescence program. These studies have identified four complementation groups for indefinite division, which suggests that there are at least four genes or gene pathways in the senescence program. Through the use of microcell-mediated chromosome transfer, chromosomes encoding senescence genes have been identified; efforts to clone these genes are ongoing.(ABSTRACT TRUNCATED AT 250 WORDS)

Peroxiredoxin 5 confers protection against oxidative stress and apoptosis and also promotes longevity in Drosophila

PubMed Central

Radyuk, Svetlana N.; Michalak, Katarzyna; Klichko, Vladimir I.; Benes, Judith; Rebrin, Igor; Sohal, Rajindar S.; Orr, William C.

2010-01-01

Peroxiredoxin 5 is a distinct isoform of the peroxiredoxin gene family. The antioxidative and anti-apoptotic functions of peroxiredoxin 5 have been extensively demonstrated in cell culture experiments. In the present paper, we provide the first functional analysis of peroxiredoxin 5 in a multicellular organism, Drosophila melanogaster. Similar to its mammalian, yeast or human counterparts, dPrx5 (Drosophila peroxiredoxin 5) is expressed in several cellular compartments, including the cytosol, nucleus and the mitochondrion. Global overexpression of dPrx5 in flies increased resistance to oxidative stress and extended their life span by up to 30% under normal conditions. The dprx5−/− null flies were comparatively more susceptible to oxidative stress, had higher incidence of apoptosis, and a shortened life span. TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) analysis revealed that the dprx5−/− null mutant had discernible tissue-specific apoptotic patterns, similar to those observed in control flies exposed to paraquat. In addition, apoptosis was particularly notable in oenocytes. During development the dPrx5 levels co-varied with ecdysone pulses, suggesting inter-relationship between ecdystreroids and dPrx5 expression. The importance of dPrx5 for development was further underscored by the embryonic lethal phenotype of progeny derived from the dprx5−/− null mutant. Results from the present study suggest that the antioxidant and anti-apoptotic activities of dPrx5 play a critical role in development and aging of the fly. PMID:19128239

Oxidative stress and the evolution of sex differences in life span and ageing in the decorated cricket, Gryllodes sigillatus.

PubMed

Archer, Catharine R; Sakaluk, Scott K; Selman, Colin; Royle, Nick J; Hunt, John

2013-03-01

The Free Radical Theory of Ageing (FRTA) predicts that oxidative stress, induced when levels of reactive oxygen species exceed the capacity of antioxidant defenses, causes ageing. Recently, it has also been argued that oxidative damage may mediate important life-history trade-offs. Here, we use inbred lines of the decorated cricket, Gryllodes sigillatus, to estimate the genetic (co)variance between age-dependent reproductive effort, life span, ageing, oxidative damage, and total antioxidant capacity within and between the sexes. The FRTA predicts that oxidative damage should accumulate with age and negatively correlate with life span. We find that protein oxidation is greater in the shorter lived sex (females) and negatively genetically correlated with life span in both sexes. However, oxidative damage did not accumulate with age in either sex. Previously we have shown antagonistic pleiotropy between the genes for early-life reproductive effort and ageing rate in both sexes, although this was stronger in females. In females, we find that elevated fecundity early in life is associated with greater protein oxidation later in life, which is in turn positively correlated with the rate of ageing. Our results provide mixed support for the FRTA but suggest that oxidative stress may mediate sex-specific life-history strategies in G. sigillatus. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Corrigendum: Childhood Adversity, Self-Esteem, and Diurnal Cortisol Profiles Across the Life Span.

PubMed

2018-01-01

Original article: Zilioli, S., Slatcher, R. B., Chi, P., Li, X., Zhao, J., & Zhao, G. (2016). Childhood adversity, self-esteem, and diurnal cortisol profiles across the life span. Psychological Science, 27, 1249-1265. doi:10.1177/0956797616658287.

Sibling Communication Functions across the Life-Span.

ERIC Educational Resources Information Center

Myers, Scott A.; Smith, Ronda L.; Sonnier, Michelle F.

An investigation examined whether perceived use of sibling functional communication skills differed across the life-span. Participants were recruited through university students enrolled in an introductory communication course at a southern university. All students received extra credit for recruiting two participants. Potential participants were…

Royal Darwinian Demons: Enforced Changes in Reproductive Efforts Do Not Affect the Life Expectancy of Ant Queens.

PubMed

Schrempf, Alexandra; Giehr, Julia; Röhrl, Ramona; Steigleder, Sarah; Heinze, Jürgen

2017-04-01

One of the central tenets of life-history theory is that organisms cannot simultaneously maximize all fitness components. This results in the fundamental trade-off between reproduction and life span known from numerous animals, including humans. Social insects are a well-known exception to this rule: reproductive queens outlive nonreproductive workers. Here, we take a step forward and show that under identical social and environmental conditions the fecundity-longevity trade-off is absent also within the queen caste. A change in reproduction did not alter life expectancy, and even a strong enforced increase in reproductive efforts did not reduce residual life span. Generally, egg-laying rate and life span were positively correlated. Queens of perennial social insects thus seem to maximize at the same time two fitness parameters that are normally negatively correlated. Even though they are not immortal, they best approach a hypothetical "Darwinian demon" in the animal kingdom.

Heart rate reduction and longevity in mice.

PubMed

Gent, Sabine; Kleinbongard, Petra; Dammann, Philip; Neuhäuser, Markus; Heusch, Gerd

2015-03-01

Heart rate correlates inversely with life span across all species, including humans. In patients with cardiovascular disease, higher heart rate is associated with increased mortality, and such patients benefit from pharmacological heart rate reduction. However, cause-and-effect relationships between heart rate and longevity, notably in healthy individuals, are not established. We therefore prospectively studied the effects of a life-long pharmacological heart rate reduction on longevity in mice. We hypothesized, that the total number of cardiac cycles is constant, and that a 15% heart rate reduction might translate into a 15% increase in life span. C57BL6/J mice received either placebo or ivabradine at a dose of 50 mg/kg/day in drinking water from 12 weeks to death. Heart rate and body weight were monitored. Autopsy was performed on all non-autolytic cadavers, and parenchymal organs were evaluated macroscopically. Ivabradine reduced heart rate by 14% (median, interquartile range 12-15%) throughout life, and median life span was increased by 6.2% (p = 0.01). Body weight and macroscopic findings were not different between placebo and ivabradine. Life span was not increased to the same extent as heart rate was reduced, but nevertheless significantly prolonged by 6.2%.

A cost–benefit analysis of acclimation to low irradiance in tropical rainforest tree seedlings: leaf life span and payback time for leaf deployment

PubMed Central

Coste, Sabrina; Roggy, Jean-Christophe; Schimann, Heidy; Epron, Daniel; Dreyer, Erwin

2011-01-01

The maintenance in the long run of a positive carbon balance under very low irradiance is a prerequisite for survival of tree seedlings below the canopy or in small gaps in a tropical rainforest. To provide a quantitative basis for this assumption, experiments were carried out to determine whether construction cost (CC) and payback time for leaves and support structures, as well as leaf life span (i) differ among species and (ii) display an irradiance-elicited plasticity. Experiments were also conducted to determine whether leaf life span correlates to CC and payback time and is close to the optimal longevity derived from an optimization model. Saplings from 13 tropical tree species were grown under three levels of irradiance. Specific-CC was computed, as well as CC scaled to leaf area at the metamer level. Photosynthesis was recorded over the leaf life span. Payback time was derived from CC and a simple photosynthesis model. Specific-CC displayed only little interspecific variability and irradiance-elicited plasticity, in contrast to CC scaled to leaf area. Leaf life span ranged from 4 months to >26 months among species, and was longest in seedlings grown under lowest irradiance. It was always much longer than payback time, even under the lowest irradiance. Leaves were shed when their photosynthesis had reached very low values, in contrast to what was predicted by an optimality model. The species ranking for the different traits was stable across irradiance treatments. The two pioneer species always displayed the smallest CC, leaf life span, and payback time. All species displayed a similar large irradiance-elicited plasticity. PMID:21511904

Evolutionary and mechanistic theories of aging.

PubMed

Hughes, Kimberly A; Reynolds, Rose M

2005-01-01

Senescence (aging) is defined as a decline in performance and fitness with advancing age. Senescence is a nearly universal feature of multicellular organisms, and understanding why it occurs is a long-standing problem in biology. Here we present a concise review of both evolutionary and mechanistic theories of aging. We describe the development of the general evolutionary theory, along with the mutation accumulation, antagonistic pleiotropy, and disposable soma versions of the evolutionary model. The review of the mechanistic theories focuses on the oxidative stress resistance, cellular signaling, and dietary control mechanisms of life span extension. We close with a discussion of how an approach that makes use of both evolutionary and molecular analyses can address a critical question: Which of the mechanisms that can cause variation in aging actually do cause variation in natural populations?

Dietary restriction decreases coenzyme Q and ubiquinol potentially via changes in gene expression in the model organism C. elegans.

PubMed

Fischer, Alexandra; Klapper, Maja; Onur, Simone; Menke, Thomas; Niklowitz, Petra; Döring, Frank

2015-05-06

Dietary restriction (DR) is a robust intervention that extends both health span and life span in many organisms. Ubiquinol and ubiquinone represent the reduced and oxidized forms of coenzyme Q (CoQ). CoQ plays a central role in energy metabolism and functions in several cellular processes including gene expression. Here we used the model organism Caenorhabditis elegans to determine level and redox state of CoQ and expression of genes in response to DR. We found that DR down-regulates the steady-state expression levels of several evolutionary conserved genes (i.e. coq-1) that encode key enzymes of the mevalonate and CoQ-synthesizing pathways. In line with this, DR decreases the levels of total CoQ and ubiquinol. This CoQ-reducing effect of DR is obvious in adult worms but not in L4 larvae and is also evident in the eat-2 mutant, a genetic model of DR. In conclusion, we propose that DR reduces the level of CoQ and ubiquinol via gene expression in the model organism C. elegans. © 2015 International Union of Biochemistry and Molecular Biology.

KIRA1 and ORESARA1 terminate flower receptivity by promoting cell death in the stigma of Arabidopsis.

PubMed

Gao, Zhen; Daneva, Anna; Salanenka, Yuliya; Van Durme, Matthias; Huysmans, Marlies; Lin, Zongcheng; De Winter, Freya; Vanneste, Steffen; Karimi, Mansour; Van de Velde, Jan; Vandepoele, Klaas; Van de Walle, Davy; Dewettinck, Koen; Lambrecht, Bart N; Nowack, Moritz K

2018-05-28

Flowers have a species-specific functional life span that determines the time window in which pollination, fertilization and seed set can occur. The stigma tissue plays a key role in flower receptivity by intercepting pollen and initiating pollen tube growth toward the ovary. In this article, we show that a developmentally controlled cell death programme terminates the functional life span of stigma cells in Arabidopsis. We identified the leaf senescence regulator ORESARA1 (also known as ANAC092) and the previously uncharacterized KIRA1 (also known as ANAC074) as partially redundant transcription factors that modulate stigma longevity by controlling the expression of programmed cell death-associated genes. KIRA1 expression is sufficient to induce cell death and terminate floral receptivity, whereas lack of both KIRA1 and ORESARA1 substantially increases stigma life span. Surprisingly, the extension of stigma longevity is accompanied by only a moderate extension of flower receptivity, suggesting that additional processes participate in the control of the flower's receptive life span.

Getting together: Social contact frequency across the life span.

PubMed

Sander, Julia; Schupp, Jürgen; Richter, David

2017-08-01

Frequent social interactions are strongly linked to positive affect, longevity, and good health. Although there has been extensive research on changes in the size of social networks over time, little attention has been given to the development of contact frequency across the life span. In this cohort-sequential longitudinal study, we examined intraindividual changes in the frequency of social contact with family and nonfamily members, and potential moderators of these changes. The data come from the 1998, 2003, 2008, and 2013 waves of the German Socio-Economic Panel (SOEP) study (N = 36,716; age range: 17-85 years). Using latent growth curve analysis, we found that the frequency of in-person contact with family members remained relatively stable across the life span. In contrast, the frequency of visits to and from nonfamily members (neighbors, friends, and acquaintances) declined following a cubic trajectory and dropped below the frequency of family visits when respondents were in their mid-30s. Relationship status and gender had a slight effect on both of these relationship trajectories. Subjective current health status and employment status influenced the life span trajectory of nonfamily social contact only. Changes of residence and the birth of a child, both of which constitute major turning points in the life course, did not affect the life span trajectory of either family or nonfamily in-person contact. The findings are discussed here in the context of earlier findings and in relation to socioemotional selectivity and social convoy theory and the evolutionary life history approach. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Effect of habitat preference on frond life span in three Cyathea tree ferns

NASA Astrophysics Data System (ADS)

Chiu, Tzu Yun; Wang, Hsiang Hua; Lun Kuo, Yao; Kume, Tomonori

2013-04-01

It has been reported that plants living in various geographical areas had different physiological forms, as factors of microenvironment have strong impacts on physiological characters. However, the physiological characters of fronds have been scarcely reported in ferns. In this study, we investigated physiological differences in response to the habitat preference in the three tree ferns in northeast Taiwan, Cyathea lepifera, C. spinulosa, and C. podophylla, prefer to open site, edge of forest, and interior forest, respectively. The canopy openness above the individuals of C. lepifera, C. spinulosa and C. podophylla were 29.2 ± 14.10 , 7.0 ± 3.07 and 5.0 ± 2.24 %, respectively. Among three species, C. podophylla had the longest frond life span (13.0 ± 4.12 months) than the two others (C. lepifera (6.8 ± 1.29 months) and C. spinulosa (7.3 ±1.35 months). Our result supported the general patterns that shade intolerant species have a shorter leaf life span than shade tolerant species. The maximum net CO2 assimilation of C. lepifera, C. spinulosa and C. podophylla were 11.46 ± 1.34, 8.27 ± 0.69, and 6.34 ± 0.54 μmol CO2 m-2 s-1, respectively. As well, C. lepifera had the highest photosynthetic light saturation point (LSP), while C. podophylla had the lowest LSP among these three tree ferns. These suggested that C. lepifera could be more efficient for capturing and utilizing light resources under the larger canopy openness condition than the other two species. We also found that frond C : N ratio were positively correlated with frond life span among species. C. podophylla, with the longest frond life span, had the highest frond C : N ratio (22.17 ± 1.95), which was followed by C. spinulosa (18.58 ± 1.37) and C. lepifera (18.68 ± 2.63) with shorter frond life span. The results were consistent to the theory that the fronds and leaves of shade intolerant species have high photosynthetic abilities with low C : N ratio. Key words: Canopy openness, frond life span, tree fern, Cyathea, frond C : N ratio

Post-dauer life span of Caenorhabditis elegans dauer larvae can be modified by X-irradiation.

PubMed

Onodera, Akira; Yanase, Sumino; Ishii, Takamasa; Yasuda, Kayo; Miyazawa, Masaki; Hartman, Philip S; Ishii, Naoaki

2010-01-01

The time spent as a dauer larva does not affect adult life span in Caenorhabditis elegans, as if aging is suspended in this quiescent developmental stage. We now report that modest doses X-irradiation of dauer larvae increased their post-dauer longevity. Post-irradiation incubation of young dauer larvae did not modify this beneficial effect of radiation. Conversely, holding dauer larvae prior to irradiation rendered them refractory to this X-radiation-induced response. We present a model to explain these results. These experiments demonstrate that dauer larvae provide an excellent opportunity to study mechanisms by which X irradiation can extend life span.

Spontaneous locomotor activity and life span. A test of the rate of living theory in Drosophila melanogaster.

PubMed

Lints, F A; Le Bourg, E; Lints, C V

1984-01-01

The spontaneous locomotor activity and life span of approximately 600 individuals of both sexes and of three widely different genotypes of Drosophila melanogaster have been measured. Neither at the individual nor at the populational level could a significant correlation between spontaneous locomotor activity and life span be found. The results are discussed in relation with Pearl's [The rate of living, London University Press, London 1928] rate of living theory. That theory has been tested in relation with environmental temperature, oxygen consumption and activity. It is shown that the theory has received no definite confirmation until now.

Feminist Developmental Theory: Implications for Counseling.

ERIC Educational Resources Information Center

Wastell, Colin A.

1996-01-01

Discusses the importance of counseling guided by a life-span development model. Emphasizes that one popular theory should be modified by taking into account a broader understanding of life-span development in terms of commonalities and differences in male and female development. Examines implications with borderline personality disorder and…

Target of Rapamycin Signaling Regulates Metabolism, Growth, and Life Span in Arabidopsis[W][OA

PubMed Central

Ren, Maozhi; Venglat, Prakash; Qiu, Shuqing; Feng, Li; Cao, Yongguo; Wang, Edwin; Xiang, Daoquan; Wang, Jinghe; Alexander, Danny; Chalivendra, Subbaiah; Logan, David; Mattoo, Autar; Selvaraj, Gopalan; Datla, Raju

2012-01-01

Target of Rapamycin (TOR) is a major nutrition and energy sensor that regulates growth and life span in yeast and animals. In plants, growth and life span are intertwined not only with nutrient acquisition from the soil and nutrition generation via photosynthesis but also with their unique modes of development and differentiation. How TOR functions in these processes has not yet been determined. To gain further insights, rapamycin-sensitive transgenic Arabidopsis thaliana lines (BP12) expressing yeast FK506 Binding Protein12 were developed. Inhibition of TOR in BP12 plants by rapamycin resulted in slower overall root, leaf, and shoot growth and development leading to poor nutrient uptake and light energy utilization. Experimental limitation of nutrient availability and light energy supply in wild-type Arabidopsis produced phenotypes observed with TOR knockdown plants, indicating a link between TOR signaling and nutrition/light energy status. Genetic and physiological studies together with RNA sequencing and metabolite analysis of TOR-suppressed lines revealed that TOR regulates development and life span in Arabidopsis by restructuring cell growth, carbon and nitrogen metabolism, gene expression, and rRNA and protein synthesis. Gain- and loss-of-function Ribosomal Protein S6 (RPS6) mutants additionally show that TOR function involves RPS6-mediated nutrition and light-dependent growth and life span in Arabidopsis. PMID:23275579

Yeast MRX deletions have short chronological life span and more triacylglycerols.

PubMed

Kanagavijayan, Dhanabalan; Rajasekharan, Ram; Srinivasan, Malathi

2016-02-01

Saccharomyces cerevisiae is an excellent model organism for lipid research. Here, we have used yeast haploid RAdiation Damage (RAD) deletion strains to study life span and lipid storage patterns. RAD genes are mainly involved in DNA repair mechanism and hence, their deletions have resulted in shorter life span. Viable RAD mutants were screened for non-polar lipid content, and some of the mutants showed significantly high amounts of triacylglycerol (TAG) and steryl ester, besides short chronological life span. Among these, RAD50, MRE11 and XRS2 form a complex, MRX that is involved in homologous recombination that showed an increase in the amount of TAG. Microarray data of single MRX deletions revealed that besides DNA damage signature genes, lipid metabolism genes are also differentially expressed. Lipid biosynthetic genes (LPP1, SLC1) were upregulated and lipid hydrolytic gene (TGL3) was downregulated. We observed that rad50Δ, mre11Δ, xrs2Δ and mrxΔ strains have high number of lipid droplets (LDs) with fragmented mitochondria. These mutants have a short chronological life span compared to wild type. Aged wild-type cells also accumulated TAG with LDs of ∼2.0 μm in diameter. These results suggest that TAG accumulation and big size LDs could be possible markers for premature or normal aging. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Like cognitive function, decision making across the life span shows profound age-related changes.

PubMed

Tymula, Agnieszka; Rosenberg Belmaker, Lior A; Ruderman, Lital; Glimcher, Paul W; Levy, Ifat

2013-10-15

It has long been known that human cognitive function improves through young adulthood and then declines across the later life span. Here we examined how decision-making function changes across the life span by measuring risk and ambiguity attitudes in the gain and loss domains, as well as choice consistency, in an urban cohort ranging in age from 12 to 90 y. We identified several important age-related patterns in decision making under uncertainty: First, we found that healthy elders between the ages of 65 and 90 were strikingly inconsistent in their choices compared with younger subjects. Just as elders show profound declines in cognitive function, they also show profound declines in choice rationality compared with their younger peers. Second, we found that the widely documented phenomenon of ambiguity aversion is specific to the gain domain and does not occur in the loss domain, except for a slight effect in older adults. Finally, extending an earlier report by our group, we found that risk attitudes across the life span show an inverted U-shaped function; both elders and adolescents are more risk-averse than their midlife counterparts. Taken together, these characterizations of decision-making function across the life span in this urban cohort strengthen the conclusions of previous reports suggesting a profound impact of aging on cognitive function in this domain.

View of central lift span truss web of Tensaw River ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View of central lift span truss web of Tensaw River Bridge, showing support girders for life house, looking east - Tensaw River Lift Bridge, Spanning Tensaw River at U.S. Highway 90, Mobile, Mobile County, AL

FACT SHEET: EPA ISSUES UPDATED CANCER GUIDELINES AND SUPPLEMENTAL GUIDANCE ON RISKS FROM EARLY-LIFE EXPOSURE

EPA Science Inventory

March 29, 2005

FACT SHEET: Women's Spirituality across the Life Span: Implications for Counseling

ERIC Educational Resources Information Center

Briggs, Michele Kielty; Dixon, Andrea L.

2013-01-01

Women's spirituality has unique characteristics that are often ignored within the spirituality literature. The authors review the literature on women's spirituality to reveal the major themes women have identified as relevant to their spiritual journeys across the life span. Implications for counseling and ideas for practice are included after…

Spatial Abilities across the Adult Life Span

ERIC Educational Resources Information Center

Borella, Erika; Meneghetti, Chiara; Ronconi, Lucia; De Beni, Rossana

2014-01-01

The study investigates age-related effects across the adult life span on spatial abilities (testing subabilities based on a distinction between spatial visualization, mental rotation, and perspective taking) and spatial self-assessments. The sample consisted of 454 participants (223 women and 231 men) from 20 to 91 years of age. Results showed…

Sensorimotor Synchronization across the Life Span

ERIC Educational Resources Information Center

Drewing, Knut; Aschersleben, Gisa; Li, Shu-Chen

2006-01-01

The present study investigates the contribution of general processing resources as well as other more specific factors to the life-span development of sensorimotor synchronization and its component processes. Within a synchronization tapping paradigm, a group of 286 participants, 6 to 88 years of age, were asked to synchronize finger taps with…

Sex-Role Inconstancy, Biology, and Successful Aging: A Dialectical Model

ERIC Educational Resources Information Center

Sinnott, Jan Dynda

1977-01-01

This paper examines sex-role inconstancy from a life-span point of view. New environmental realities and an increasing life-span may make traditional sex roles less functional in old age. Evidence is presented for more successful aging in persons manifesting convergent sex-role behavior. (Author)

Redesign of a Life Span Development Course Using Fink's Taxonomy

ERIC Educational Resources Information Center

Fallahi, Carolyn R.

2008-01-01

This study compared a traditional lecture-based life span development course to the same course redesigned using Fink's (2003) taxonomy of significant learning. The goals, activities, and feedback within the course corresponded to Fink's 6 taxa (knowledge, application, integration, human dimension, caring, learning how to learn). Undergraduates in…

Neuromodulation of Behavioral and Cognitive Development across the Life Span

ERIC Educational Resources Information Center

Li, Shu-Chen

2012-01-01

Among other mechanisms, behavioral and cognitive development entail, on the one hand, contextual scaffolding and, on the other hand, neuromodulation of adaptive neurocognitive representations across the life span. Key brain networks underlying cognition, emotion, and motivation are innervated by major transmitter systems (e.g., the catecholamines…

Vitamins and aging: pathways to NAD+ synthesis.

PubMed

Denu, John M

2007-05-04

Recent genetic evidence reveals additional salvage pathways for NAD(+) synthesis. In this issue, Belenky et al. (2007) report that nicotinamide riboside, a new NAD(+) precursor, regulates Sir2 deacetylase activity and life span in yeast. The ability of nicotinamide riboside to enhance life span does not depend on calorie restriction.

Large-brained frogs mature later and live longer.

PubMed

Yu, Xin; Zhong, Mao Jun; Li, Da Yong; Jin, Long; Liao, Wen Bo; Kotrschal, Alexander

2018-05-01

Brain sizes vary substantially across vertebrate taxa, yet, the evolution of brain size appears tightly linked to the evolution of life histories. For example, larger brained species generally live longer than smaller brained species. A larger brain requires more time to grow and develop at a cost of exceeded gestation period and delayed weaning age. The cost of slower development may be compensated by better homeostasis control and increased cognitive abilities, both of which should increase survival probabilities and hence life span. To date, this relationship between life span and brain size seems well established in homoeothermic animals, especially in mammals. Whether this pattern occurs also in other clades of vertebrates remains enigmatic. Here, we undertake the first comparative test of the relationship between life span and brain size in an ectothermic vertebrate group, the anuran amphibians. After controlling for the effects of shared ancestry and body size, we find a positive correlation between brain size, age at sexual maturation, and life span across 40 species of frogs. Moreover, we also find that the ventral brain regions, including the olfactory bulbs, are larger in long-lived species. Our results indicate that the relationship between life history and brain evolution follows a general pattern across vertebrate clades. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

Lactobacillus salivarius strain FDB89 induced longevity in Caenorhabditis elegans by dietary restriction.

PubMed

Zhao, Yang; Zhao, Liang; Zheng, Xiaonan; Fu, Tianjiao; Guo, Huiyuan; Ren, Fazheng

2013-04-01

In this study, we utilized the nematode Caenorhabditis elegans to assess potential life-expanding effect of Lactobacillus salivarius strain FDB89 (FDB89) isolated from feces of centenarians in Bama County (Guangxi, China). This study showed that feeding FDB89 extended the mean life span in C. elegans by up to 11.9% compared to that of control nematodes. The reduced reproductive capacities, pharyngeal pumping rate, growth, and increased superoxide dismutase (SOD) activity and XTT reduction capacity were also observed in FDB89 feeding worms. To probe the anti-aging mechanism further, we incorporated a food gradient feeding assay and assayed the life span of eat-2 mutant. The results demonstrated that the maximal life span of C. elegans fed on FDB89 was achieved at the concentration of 1.0 mg bacterial cells/plate, which was 10-fold greater than that of C. elegans fed on E. coli OP50 (0.1 mg bacterial cells/plate). However, feeding FDB89 could not further extend the life span of eat-2 mutant. These results indicated that FDB89 modulated the longevity of C. elegans in a dietary restriction-dependent manner and expanded the understanding of anti-aging effect of probiotics.

EnLightenment: High resolution smartphone microscopy as an educational and public engagement platform

PubMed Central

Wicks, Laura C.; Cairns, Gemma S.; Melnyk, Jacob; Bryce, Scott; Duncan, Rory R.; Dalgarno, Paul A.

2018-01-01

We developed a simple, cost-effective smartphone microscopy platform for use in educational and public engagement programs. We demonstrated its effectiveness, and potential for citizen science through a national imaging initiative, EnLightenment. The cost effectiveness of the instrument allowed for the program to deliver over 500 microscopes to more than 100 secondary schools throughout Scotland, targeting 1000’s of 12-14 year olds. Through careful, quantified, selection of a high power, low-cost objective lens, our smartphone microscope has an imaging resolution of microns, with a working distance of 3 mm. It is therefore capable of imaging single cells and sub-cellular features, and retains usability for young children. The microscopes were designed in kit form and provided an interdisciplinary educational tool. By providing full lesson plans and support material, we developed a framework to explore optical design, microscope performance, engineering challenges on construction and real-world applications in life sciences, biological imaging, marine biology, art, and technology. A national online imaging competition framed EnLightenment ; with over 500 high quality images submitted of diverse content, spanning multiple disciplines. With examples of cellular and sub-cellular features clearly identifiable in some submissions, we show how young public can use these instruments for research-level imaging applications, and the potential of the instrument for citizen science programs. PMID:29623296

Adaptive immune responses to booster vaccination against yellow fever virus are much reduced compared to those after primary vaccination.

PubMed

Kongsgaard, Michael; Bassi, Maria R; Rasmussen, Michael; Skjødt, Karsten; Thybo, Søren; Gabriel, Mette; Hansen, Morten Bagge; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup; Buus, Soren; Stryhn, Anette

2017-04-06

Outbreaks of Yellow Fever occur regularly in endemic areas of Africa and South America frequently leading to mass vaccination campaigns straining the availability of the attenuated Yellow Fever vaccine, YF-17D. The WHO has recently decided to discontinue regular booster-vaccinations since a single vaccination is deemed to confer life-long immune protection. Here, we have examined humoral (neutralizing antibody) and cellular (CD8 and CD4 T cell) immune responses in primary and booster vaccinees (the latter spanning 8 to 36 years after primary vaccination). After primary vaccination, we observed strong cellular immune responses with T cell activation peaking ≈2 weeks and subsiding to background levels ≈ 4 weeks post-vaccination. The number of antigen-specific CD8+ T cells declined over the following years. In >90% of vaccinees, in vitro expandable T cells could still be detected >10 years post-vaccination. Although most vaccinees responded to a booster vaccination, both the humoral and cellular immune responses observed following booster vaccination were strikingly reduced compared to primary responses. This suggests that pre-existing immunity efficiently controls booster inoculums of YF-17D. In a situation with epidemic outbreaks, one could argue that a more efficient use of a limited supply of the vaccine would be to focus on primary vaccinations.

Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans

PubMed Central

Abegglen, Lisa M.; Caulin, Aleah F.; Chan, Ashley; Lee, Kristy; Robinson, Rosann; Campbell, Michael S.; Kiso, Wendy K.; Schmitt, Dennis L.; Waddell, Peter J; Bhaskara, Srividya; Jensen, Shane T.; Maley, Carlo C.; Schiffman, Joshua D.

2016-01-01

IMPORTANCE Evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. OBJECTIVE To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). DESIGN, SETTING, AND PARTICIPANTS A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n = 644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro in the laboratory for DNA damage response. The study included African and Asian elephants (n = 8), patients with LFS (n = 10), and age-matched human controls (n = 11). Human samples were collected at the University of Utah between June 2014 and July 2015. EXPOSURES Ionizing radiation and doxorubicin. MAIN OUTCOMES AND MEASURES Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. RESULTS Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95%CI, 0%–5%]; African wild dog, 8%[95%CI, 0%–16%]; lion, 2%[95%CI, 0% –7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95%CI, 3.14%–6.49%), compared with humans, who have 11% to 25%cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction. In response to DNA damage, elephant lymphocytes underwent p53-mediated apoptosis at higher rates than human lymphocytes proportional to TP53 status (ionizing radiation exposure: patients with LFS, 2.71% [95%CI, 1.93%–3.48%] vs human controls, 7.17%[95%CI, 5.91%–8.44%] vs elephants, 14.64%[95%CI, 10.91%–18.37%]; P < .001; doxorubicin exposure: human controls, 8.10% [95%CI, 6.55%–9.66%] vs elephants, 24.77%[95%CI, 23.0%–26.53%]; P < .001). CONCLUSIONS AND RELEVANCE Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53. Compared with human cells, elephant cells demonstrated increased apoptotic response following DNA damage. These findings, if replicated, could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression. PMID:26447779

Friendship in childhood and adulthood: lessons across the life span.

PubMed

Sherman, A M; de Vries, B; Lansford, J E

2000-01-01

Friendship occupies an important place in the growing body of literature in child development and gerontological research. As such, it may be useful for researchers from both fields to consider what can be learned from work carried out in each tradition. Therefore, we present a selected review of topics in friendship research across the life span. Through discussion of the value of friendship, the development of friendship, challenges to friendship, the gendered nature of friendship, and the connection between friends and family, points of commonality and contrast are identified. We conclude by presenting possible avenues for future investigation for researchers interested in friendship at any point in the life span.

Weight concern across the life-span: relationship to self-esteem and feminist identity.

PubMed

Tiggemann, M; Stevens, C

1999-07-01

The aim of this study was to investigate the correlates of weight concern across the life-span. Questionnaires assessing weight concern, self-esteem, and feminist attitudes were completed in their homes by 180 women aged between 18 and 60 years. It was found that there was a negative relationship between weight concern and self-esteem for 30 to 49-year-old women, but not for younger or older women. A similar pattern held for feminist attitudes. Among 30 to 49-year-old women, a strong feminist orientation related to a lesser concern with weight. It was concluded that the meaning and experience of body weight and size change across the life-span.

Age Stereotypes and Self-Views Revisited: Patterns of Internalization and Projection Processes Across the Life Span.

PubMed

Kornadt, Anna E; Voss, Peggy; Rothermund, Klaus

2017-07-01

We investigated processes of age stereotype internalization into the self and projection of self-views onto age stereotypes from a life-span perspective, taking age-related differences in the relevance of life domains into account. Age stereotypes and self-views in eight life domains were assessed in a sample of N = 593 persons aged 30-80 years (T1) at two time points that were separated by a 4-year time interval. We estimated cross-lagged projection and internalization effects in multigroup structural equation models. Internalization and projection effects were contingent on age group and life domain: Internalization effects were strongest in the young and middle-aged groups and emerged in the domains family, personality, work, and leisure. Projection effects in different domains were most pronounced for older participants. Our findings suggest that the internalization of age stereotypes is triggered by domain-specific expectations of impending age-related changes and transitions during certain phases of the life span. Projection processes, however, seem to occur in response to changes that have already been experienced by the individual. Our study demonstrates the dynamic interrelation of age stereotypes and self-views across the life course and highlights the importance of a differentiated, life-span perspective for the understanding of these mechanisms. © 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.

Attachment and the Processing of Social Information across the Life Span: Theory and Evidence

ERIC Educational Resources Information Center

Dykas, Matthew J.; Cassidy, Jude

2011-01-01

Researchers have used J. Bowlby's (1969/1982, 1973, 1980, 1988) attachment theory frequently as a basis for examining whether experiences in close personal relationships relate to the processing of social information across childhood, adolescence, and adulthood. We present an integrative life-span-encompassing theoretical model to explain the…

Effects of a Short Strategy Training on Metacognitive Monitoring across the Life-Span

ERIC Educational Resources Information Center

von der Linden, Nicole; Löffler, Elisabeth; Schneider, Wolfgang

2015-01-01

The present study was conducted to explore the potential positive influence of a short strategy training on metacognitive monitoring competencies covering a life-span approach. Participants of four age groups (3rd-grade children, adolescents, younger and older adults) concluded a paired-associate learning task. Additionally, they gave delayed…

Psychopathology in Williams Syndrome: The Effect of Individual Differences across the Life Span

ERIC Educational Resources Information Center

Dodd, Helen F.; Porter, Melanie A.

2009-01-01

This research aimed to comprehensively explore psychopathology in Williams syndrome (WS) across the life span and evaluate the relationship between psychopathology and age category (child or adult), gender, and cognitive ability. The parents of 50 participants with WS, ages 6-50 years, were interviewed using the Schedule for Affective Disorders…

Influence of Domain Knowledge on Monitoring Performance across the Life Span

ERIC Educational Resources Information Center

Löffler, Elisabeth; von der Linden, Nicole; Schneider, Wolfgang

2016-01-01

Two studies were conducted to investigate effects of domain knowledge on metacognitive monitoring across the life span in materials of different complexity. Participants from 4 age groups (3rd-grade children, adolescents, younger and older adults) were compared using an expert-novice paradigm. In Study 1, soccer experts' and novices'…

Reading through the Life Span: Individual Differences in Psycholinguistic Effects

ERIC Educational Resources Information Center

Davies, Rob A. I.; Arnell, Ruth; Birchenough, Julia M. H.; Grimmond, Debbie; Houlson, Sam

2017-01-01

The effects of psycholinguistic variables are critical to the evaluation of theories about the cognitive reading system. However, reading research has tended to focus on the impact of key variables on average performance. We report the first investigation examining variation in psycholinguistic effects across the life span, from childhood into old…

Getting Together: Social Contact Frequency across the Life Span

ERIC Educational Resources Information Center

Sander, Julia; Schupp, Jürgen; Richter, David

2017-01-01

Frequent social interactions are strongly linked to positive affect, longevity, and good health. Although there has been extensive research on changes in the size of social networks over time, little attention has been given to the development of contact frequency across the life span. In this cohort-sequential longitudinal study, we examined…

Thermoregulatory, Cardiovascular, and Metabolic Responses to Mild Caloric Restriction in the Brown Norway Rat

EPA Science Inventory

Caloric restriction (CR) has been demonstrated to prolong the life span of a variety of species. CR-induced reduction in core temperature (Tc) is considered a key mechanism responsible for prolonging life span in rodents; however, little is known on the regulation of CR-induced h...

Assistive Device Use in Visually Impaired Older Adults: Role of Control Beliefs

ERIC Educational Resources Information Center

Becker, Stefanie; Wahl, Hans-Werner; Schilling, Oliver; Burmedi, David

2005-01-01

Purpose: We investigate whether psychological control, conceptually framed within the life-span theory of control by Heckhausen and Schulz, drives assistive device use in visually impaired elders. In particular, we expect the two primary control modes differentiated in the life-span theory of control (i.e., selective primary and compensatory…

Body Image across the Life Span in Adult Women: The Role of Self-Objectification.

ERIC Educational Resources Information Center

Tiggemann, Marika; Lynch, Jessica E.

2001-01-01

Investigated body image across life span in cross-section of women ages 20-84 years. Found that although body dissatisfaction remained stable, self-objectification, habitual body monitoring, appearance anxiety, and disordered eating all significantly decreased with age. Self- objectification mediated the relationship between age and disordered…

Dopa decarboxylase (Ddc) affects variation in Drosophila longevity.

PubMed

De Luca, Maria; Roshina, Nataliya V; Geiger-Thornsberry, Gretchen L; Lyman, Richard F; Pasyukova, Elena G; Mackay, Trudy F C

2003-08-01

Mutational analyses in model organisms have shown that genes affecting metabolism and stress resistance regulate life span, but the genes responsible for variation in longevity in natural populations are largely unidentified. Previously, we mapped quantitative trait loci (QTLs) affecting variation in longevity between two Drosophila melanogaster strains. Here, we show that the longevity QTL in the 36E;38B cytogenetic interval on chromosome 2 contains multiple closely linked QTLs, including the Dopa decarboxylase (Ddc) locus. Complementation tests to mutations show that Ddc is a positional candidate gene for life span in these strains. Linkage disequilibrium (LD) mapping in a sample of 173 alleles from a single population shows that three common molecular polymorphisms in Ddc account for 15.5% of the genetic contribution to variance in life span from chromosome 2. The polymorphisms are in strong LD, and the effects of the haplotypes on longevity suggest that the polymorphisms are maintained by balancing selection. DDC catalyzes the final step in the synthesis of the neurotransmitters, dopamine and serotonin. Thus, these data implicate variation in the synthesis of bioamines as a factor contributing to natural variation in individual life span.

The development of memory efficiency and value-directed remembering across the life span: a cross-sectional study of memory and selectivity.

PubMed

Castel, Alan D; Humphreys, Kathryn L; Lee, Steve S; Galván, Adriana; Balota, David A; McCabe, David P

2011-11-01

Although attentional control and memory change considerably across the life span, no research has examined how the ability to strategically remember important information (i.e., value-directed remembering) changes from childhood to old age. The present study examined this in different age groups across the life span (N = 320, 5-96 years old). A selectivity task was used in which participants were asked to study and recall items worth different point values in order to maximize their point score. This procedure allowed for measures of memory quantity/capacity (number of words recalled) and memory efficiency/selectivity (the recall of high-value items relative to low-value items). Age-related differences were found for memory capacity, as young adults recalled more words than the other groups. However, in terms of selectivity, younger and older adults were more selective than adolescents and children. The dissociation between these measures across the life span illustrates important age-related differences in terms of memory capacity and the ability to selectively remember high-value information.

Evidence for a relationship between longevity of mammalian species and life spans of normal fibroblasts in vitro and erythrocytes in vivo

PubMed Central

Röhme, Dan

1981-01-01

The replicative life spans of mammalian fibroblasts in vitro were studied in a number of cell cultures representing eight species. Emphasis was placed on determining the population doubling level at which phase III (a period of decrease in the rate of proliferation) and chromosomal alterations occur. All the cell cultures studied went through a growth crisis, a period of apparent growth cessation lasting for at least 2 weeks. In most cultures, the crisis represented the end of their replicative capacities, but in some cultures cell proliferation was resumed after the crisis. A predominantly diploid chromosome constitution (more than 75%) was demonstrated prior to the growth crisis. In cultures in which cell proliferation was resumed after the crisis, a nondiploid constitution prevailed in all cases except the rat (with 90% or more diploid cells all the time). The growth crisis occurred at population doubling levels that were characteristic for the species and was shown to be related to the species' maximal life span by a strict power law, being proportional to the square root of the maximal life span. Based on data in the literature, the same relationship was also valid for the lifespans of circulating mammalian erythrocytes in vivo. These results may indicate the prevalence of a common functional basis regulating the life span of fibroblasts and erythrocytes and thus operating in replicative as well as postmitotic cells in vitro and in vivo. PMID:6946449

Dietary Interventions to Extend Life Span and Health Span Based on Calorie Restriction

PubMed Central

Minor, Robin K.; Allard, Joanne S.; Younts, Caitlin M.; Ward, Theresa M.

2010-01-01

The societal impact of obesity, diabetes, and other metabolic disorders continues to rise despite increasing evidence of their negative long-term consequences on health span, longevity, and aging. Unfortunately, dietary management and exercise frequently fail as remedies, underscoring the need for the development of alternative interventions to successfully treat metabolic disorders and enhance life span and health span. Using calorie restriction (CR)—which is well known to improve both health and longevity in controlled studies—as their benchmark, gerontologists are coming closer to identifying dietary and pharmacological therapies that may be applicable to aging humans. This review covers some of the more promising interventions targeted to affect pathways implicated in the aging process as well as variations on classical CR that may be better suited to human adaptation. PMID:20371545

Towards a perceptive understanding of size in cellular biology.

PubMed

Zoppè, Monica

2017-06-29

Cells are minute-typically too small to be seen by the human eye. Even so, the cellular world encompasses a range of scales, from roughly a tenth of a nanometer (10 -10 m) to a millimeter (10 -3 m) or larger, spanning seven orders of magnitude or more. Because they are so far from our experience, it is difficult for us to envision such scales. To help our imagination grasp such dimensions, I propose the adoption of a 'perceptive scale' that can facilitate a more direct experience of cellular sizes. From this, as I argue below, will stem a new perception also of biological shape, cellular space and dynamic processes.

S-nitrosylation drives cell senescence and aging in mammals by controlling mitochondrial dynamics and mitophagy.

PubMed

Rizza, Salvatore; Cardaci, Simone; Montagna, Costanza; Di Giacomo, Giuseppina; De Zio, Daniela; Bordi, Matteo; Maiani, Emiliano; Campello, Silvia; Borreca, Antonella; Puca, Annibale A; Stamler, Jonathan S; Cecconi, Francesco; Filomeni, Giuseppe

2018-04-10

S -nitrosylation, a prototypic redox-based posttranslational modification, is frequently dysregulated in disease. S -nitrosoglutathione reductase (GSNOR) regulates protein S -nitrosylation by functioning as a protein denitrosylase. Deficiency of GSNOR results in tumorigenesis and disrupts cellular homeostasis broadly, including metabolic, cardiovascular, and immune function. Here, we demonstrate that GSNOR expression decreases in primary cells undergoing senescence, as well as in mice and humans during their life span. In stark contrast, exceptionally long-lived individuals maintain GSNOR levels. We also show that GSNOR deficiency promotes mitochondrial nitrosative stress, including excessive S -nitrosylation of Drp1 and Parkin, thereby impairing mitochondrial dynamics and mitophagy. Our findings implicate GSNOR in mammalian longevity, suggest a molecular link between protein S -nitrosylation and mitochondria quality control in aging, and provide a redox-based perspective on aging with direct therapeutic implications.

Atomic Detail Visualization of Photosynthetic Membranes with GPU-Accelerated Ray Tracing

PubMed Central

Vandivort, Kirby L.; Barragan, Angela; Singharoy, Abhishek; Teo, Ivan; Ribeiro, João V.; Isralewitz, Barry; Liu, Bo; Goh, Boon Chong; Phillips, James C.; MacGregor-Chatwin, Craig; Johnson, Matthew P.; Kourkoutis, Lena F.; Hunter, C. Neil

2016-01-01

The cellular process responsible for providing energy for most life on Earth, namely photosynthetic light-harvesting, requires the cooperation of hundreds of proteins across an organelle, involving length and time scales spanning several orders of magnitude over quantum and classical regimes. Simulation and visualization of this fundamental energy conversion process pose many unique methodological and computational challenges. We present, in two accompanying movies, light-harvesting in the photosynthetic apparatus found in purple bacteria, the so-called chromatophore. The movies are the culmination of three decades of modeling efforts, featuring the collaboration of theoretical, experimental, and computational scientists. We describe the techniques that were used to build, simulate, analyze, and visualize the structures shown in the movies, and we highlight cases where scientific needs spurred the development of new parallel algorithms that efficiently harness GPU accelerators and petascale computers. PMID:27274603

Independently evolved virulence effectors converge onto hubs in a plant immune system network.

PubMed

Mukhtar, M Shahid; Carvunis, Anne-Ruxandra; Dreze, Matija; Epple, Petra; Steinbrenner, Jens; Moore, Jonathan; Tasan, Murat; Galli, Mary; Hao, Tong; Nishimura, Marc T; Pevzner, Samuel J; Donovan, Susan E; Ghamsari, Lila; Santhanam, Balaji; Romero, Viviana; Poulin, Matthew M; Gebreab, Fana; Gutierrez, Bryan J; Tam, Stanley; Monachello, Dario; Boxem, Mike; Harbort, Christopher J; McDonald, Nathan; Gai, Lantian; Chen, Huaming; He, Yijian; Vandenhaute, Jean; Roth, Frederick P; Hill, David E; Ecker, Joseph R; Vidal, Marc; Beynon, Jim; Braun, Pascal; Dangl, Jeffery L

2011-07-29

Plants generate effective responses to infection by recognizing both conserved and variable pathogen-encoded molecules. Pathogens deploy virulence effector proteins into host cells, where they interact physically with host proteins to modulate defense. We generated an interaction network of plant-pathogen effectors from two pathogens spanning the eukaryote-eubacteria divergence, three classes of Arabidopsis immune system proteins, and ~8000 other Arabidopsis proteins. We noted convergence of effectors onto highly interconnected host proteins and indirect, rather than direct, connections between effectors and plant immune receptors. We demonstrated plant immune system functions for 15 of 17 tested host proteins that interact with effectors from both pathogens. Thus, pathogens from different kingdoms deploy independently evolved virulence proteins that interact with a limited set of highly connected cellular hubs to facilitate their diverse life-cycle strategies.

Site-Specific Antioxidative Therapy for Prevention of Atherosclerosis and Cardiovascular Disease

PubMed Central

Otani, Hajime

2013-01-01

Oxidative stress has been implicated in pathophysiology of aging and age-associated disease. Antioxidative medicine has become a practice for prevention of atherosclerosis. However, limited success in preventing cardiovascular disease (CVD) in individuals with atherosclerosis using general antioxidants has prompted us to develop a novel antioxidative strategy to prevent atherosclerosis. Reducing visceral adipose tissue by calorie restriction (CR) and regular endurance exercise represents a causative therapy for ameliorating oxidative stress. Some of the recently emerging drugs used for the treatment of CVD may be assigned as site-specific antioxidants. CR and exercise mimetic agents are the choice for individuals who are difficult to continue CR and exercise. Better understanding of molecular and cellular biology of redox signaling will pave the way for more effective antioxidative medicine for prevention of CVD and prolongation of healthy life span. PMID:23738041

Proteostasis and REDOX state in the heart

PubMed Central

Christians, Elisabeth S.

2012-01-01

Force-generating contractile cells of the myocardium must achieve and maintain their primary function as an efficient mechanical pump over the life span of the organism. Because only half of the cardiomyocytes can be replaced during the entire human life span, the maintenance strategy elicited by cardiac cells relies on uninterrupted renewal of their components, including proteins whose specialized functions constitute this complex and sophisticated contractile apparatus. Thus cardiac proteins are continuously synthesized and degraded to ensure proteome homeostasis, also termed “proteostasis.” Once synthesized, proteins undergo additional folding, posttranslational modifications, and trafficking and/or become involved in protein-protein or protein-DNA interactions to exert their functions. This includes key transient interactions of cardiac proteins with molecular chaperones, which assist with quality control at multiple levels to prevent misfolding or to facilitate degradation. Importantly, cardiac proteome maintenance depends on the cellular environment and, in particular, the reduction-oxidation (REDOX) state, which is significantly different among cardiac organelles (e.g., mitochondria and endoplasmic reticulum). Taking into account the high metabolic activity for oxygen consumption and ATP production by mitochondria, it is a challenge for cardiac cells to maintain the REDOX state while preventing either excessive oxidative or reductive stress. A perturbed REDOX environment can affect protein handling and conformation (e.g., disulfide bonds), disrupt key structure-function relationships, and trigger a pathogenic cascade of protein aggregation, decreased cell survival, and increased organ dysfunction. This review covers current knowledge regarding the general domain of REDOX state and protein folding, specifically in cardiomyocytes under normal-healthy conditions and during disease states associated with morbidity and mortality in humans. PMID:22003057

Genome and Epigenome Editing in Mechanistic Studies of Human Aging and Aging-Related Disease.

PubMed

Lau, Cia-Hin; Suh, Yousin

2017-01-01

The recent advent of genome and epigenome editing technologies has provided a new paradigm in which the landscape of the human genome and epigenome can be precisely manipulated in their native context. Genome and epigenome editing technologies can be applied to many aspects of aging research and offer the potential to develop novel therapeutics against age-related diseases. Here, we discuss the latest technological advances in the CRISPR-based genome and epigenome editing toolbox, and provide insight into how these synthetic biology tools could facilitate aging research by establishing in vitro cell and in vivo animal models to dissect genetic and epigenetic mechanisms underlying aging and age-related diseases. We discuss recent developments in the field with the aims to precisely modulate gene expression and dynamic epigenetic landscapes in a spatial and temporal manner in cellular and animal models, by complementing the CRISPR-based editing capability with conditional genetic manipulation tools including chemically inducible expression systems, optogenetics, logic gate genetic circuits, tissue-specific promoters, and the serotype-specific adeno-associated virus. We also discuss how the combined use of genome and epigenome editing tools permits investigators to uncover novel molecular pathways involved in the pathophysiology and etiology conferred by risk variants associated with aging and aging-related disease. A better understanding of the genetic and epigenetic regulatory mechanisms underlying human aging and age-related disease will significantly contribute to the developments of new therapeutic interventions for extending health span and life span, ultimately improving the quality of life in the elderly populations. © 2016 S. Karger AG, Basel.

Proteostasis and REDOX state in the heart.

PubMed

Christians, Elisabeth S; Benjamin, Ivor J

2012-01-01

Force-generating contractile cells of the myocardium must achieve and maintain their primary function as an efficient mechanical pump over the life span of the organism. Because only half of the cardiomyocytes can be replaced during the entire human life span, the maintenance strategy elicited by cardiac cells relies on uninterrupted renewal of their components, including proteins whose specialized functions constitute this complex and sophisticated contractile apparatus. Thus cardiac proteins are continuously synthesized and degraded to ensure proteome homeostasis, also termed "proteostasis." Once synthesized, proteins undergo additional folding, posttranslational modifications, and trafficking and/or become involved in protein-protein or protein-DNA interactions to exert their functions. This includes key transient interactions of cardiac proteins with molecular chaperones, which assist with quality control at multiple levels to prevent misfolding or to facilitate degradation. Importantly, cardiac proteome maintenance depends on the cellular environment and, in particular, the reduction-oxidation (REDOX) state, which is significantly different among cardiac organelles (e.g., mitochondria and endoplasmic reticulum). Taking into account the high metabolic activity for oxygen consumption and ATP production by mitochondria, it is a challenge for cardiac cells to maintain the REDOX state while preventing either excessive oxidative or reductive stress. A perturbed REDOX environment can affect protein handling and conformation (e.g., disulfide bonds), disrupt key structure-function relationships, and trigger a pathogenic cascade of protein aggregation, decreased cell survival, and increased organ dysfunction. This review covers current knowledge regarding the general domain of REDOX state and protein folding, specifically in cardiomyocytes under normal-healthy conditions and during disease states associated with morbidity and mortality in humans.

Pervasive gene expression responses to a fluctuating diet in Drosophila melanogaster: The importance of measuring multiple traits to decouple potential mediators of life span and reproduction.

PubMed

Zandveld, Jelle; van den Heuvel, Joost; Mulder, Maarten; Brakefield, Paul M; Kirkwood, Thomas B L; Shanley, Daryl P; Zwaan, Bas J

2017-11-01

Phenotypic plasticity is an important concept in life-history evolution, and most organisms, including Drosophila melanogaster, show a plastic life-history response to diet. However, little is known about how these life-history responses are mediated. In this study, we compared adult female flies fed an alternating diet (yoyo flies) with flies fed a constant low (CL) or high (CH) diet and tested how whole genome expression was affected by these diet regimes and how the transcriptional responses related to different life-history traits. We showed that flies were able to respond quickly to diet fluctuations throughout life span by drastically changing their transcription. Importantly, by measuring the response of multiple life-history traits we were able to decouple groups of genes associated with life span or reproduction, life-history traits that often covary with a diet change. A coexpression network analysis uncovered which genes underpin the separate and shared regulation of these life-history traits. Our study provides essential insights to help unravel the genetic architecture mediating life-history responses to diet, and it shows that the flies' whole genome transcription response is highly plastic. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Age Differences and Educational Attainment across the Life Span on Three Generations of Wechsler Adult Scales

ERIC Educational Resources Information Center

Kaufman, A. S.; Salthouse, T. A.; Scheiber, C.; Chen, H.

2016-01-01

Patterns of maintenance of ability across the life span have been documented on tests of knowledge ("Gc"), as have patterns of steady decline on measures of reasoning ("Gf/Gv"), working memory ("Gsm"), and speed ("Gs"). Whether these patterns occur at the same rate for adults from different educational…

Age Differences in Five Personality Domains across the Life Span

ERIC Educational Resources Information Center

Allemand, Mathias; Zimprich, Daniel; Hendriks, A. A. Jolijn

2008-01-01

The present study addresses the issue of age differences in 5 personality domains across the life span in a cross-sectional study. In contrast to most previous studies, the present study follows a methodologically more rigorous approach to warrant that age-related differences in personality structure and mean level can be meaningfully compared. It…

Developmental Change in Proactive Interference across the Life Span: Evidence from Two Working Memory Tasks

ERIC Educational Resources Information Center

Loosli, Sandra V.; Rahm, Benjamin; Unterrainer, Josef M.; Weiller, Cornelius; Kaller, Christoph P.

2014-01-01

Working memory (WM) as the ability to temporarily maintain and manipulate various kinds of information is known to be affected by proactive interference (PI) from previously relevant contents, but studies on developmental changes in the susceptibility to PI are scarce. In the present study, we investigated life span development of item-specific…

Life-Span Issues in the Fair and Non-Discriminatory Evaluation of Workers.

ERIC Educational Resources Information Center

Alexander, Ralph A.; Barrett, Gerald V.

Until recently, older workers have not been recognized as a group requiring special attention in the area of fair employment practices. Thus, progress has been slow towards the development of valid and reliable indices of performance which are applicable across the life span. Research shows that many measures of employee evaluation provide no…

Essentialist Reasoning and Knowledge Effects on Biological Reasoning in Young Children

ERIC Educational Resources Information Center

Herrmann, Patricia A.; French, Jason A.; DeHart, Ganie B.; Rosengren, Karl S.

2013-01-01

Biological kinds undergo a variety of changes during their life span, and these changes vary in degree by organism. Understanding that an organism, such as a caterpillar, maintains category identity over its life span despite dramatic changes is a key concept in biological reasoning. At present, we know little about the developmental trajectory of…

Cell longevity and sustained primary growth in palm stems.

PubMed

Tomlinson, P Barry; Huggett, Brett A

2012-12-01

Longevity, or organismal life span, is determined largely by the period over which constituent cells can function metabolically. Plants, with modular organization (the ability continually to develop new organs and tissues) differ from animals, with unitary organization (a fixed body plan), and this difference is reflected in their respective life spans, potentially much longer in plants than animals. We draw attention to the observation that palm trees, as a group of monocotyledons without secondary growth comparable to that of lignophytes (plants with secondary growth from a bifacial cambium), retain by means of sustained primary growth living cells in their trunks throughout their organismal life span. Does this make palms the longest-lived trees because they can grow as individuals for several centuries? No conventional lignophyte retains living metabolically active differentiated cell types in its trunk for this length of time, even though the tree as a whole can exist for millennia. Does this contrast also imply that the long-lived cells in a palm trunk have exceptional properties, which allows this seeming immortality? We document the long-life of many tall palm species and their inherent long-lived stem cell properties, comparing such plants to conventional trees. We provide a summary of aspects of cell age and life span in animals and plants. Cell replacement is a feature of animal function, whereas conventional trees rely on active growth centers (meristems) to sustain organismal development. However, the long persistence of living cells in palm trunks is seen not as evidence for unique metabolic processes that sustain longevity, but is a consequence of unique constructional features. This conclusion suggests that the life span of plant cells is not necessarily genetically determined.

From menarche to menopause: the fertile life span of celiac women.

PubMed

Santonicola, Antonella; Iovino, Paola; Cappello, Carmelina; Capone, Pietro; Andreozzi, Paolo; Ciacci, Carolina

2011-10-01

We evaluated menopause-associated disorders and fertile life span in women with celiac disease (CD) under untreated conditions and after long-term treatment with a gluten-free diet. The participants were 33 women with CD after menopause (untreated CD group), 25 celiac women consuming a gluten-free diet at least 10 years before menopause (treated CD group), and 45 healthy volunteers (control group). The Menopause Rating Scale questionnaire was used to gather information on menopause-associated disorders. The International Physical Activity Questionnaire was used to acquire information on physical activity. Untreated celiac women had a shorter duration of fertile life span than did the control women because of an older age of menarche and a younger age of menopause (P < 0.01). The scores for hot flushes, muscle/joint problems, and irritability were higher in untreated celiac women than in the control women (higher by 49.4%, 121.4%, and 58.6%, respectively; P < 0.05). In comparison with untreated CD, long-lasting treatment of CD was not associated with a significant difference in the duration of fertile life span, but was only associated with a significant reduction in muscle/joint problems (a reduction of 47.1%; P < 0.05). Late menarche and early menopause causes a shorter fertile period in untreated celiac women compared with control women. A gluten-free diet that started at least 10 years before menopause prolongs the fertile life span of celiac women. The perception of intensity of hot flushes and irritability is more severe in untreated celiac women than in controls. Low physical exercise and/or poorer quality of life frequently reported by untreated celiac women might be the cause of reduced discomfort tolerance, thus increasing the subjective perception of menopausal symptoms.

Extreme longevity in a deep-sea vestimentiferan tubeworm and its implications for the evolution of life history strategies

NASA Astrophysics Data System (ADS)

Durkin, Alanna; Fisher, Charles R.; Cordes, Erik E.

2017-08-01

The deep sea is home to many species that have longer life spans than their shallow-water counterparts. This trend is primarily related to the decline in metabolic rates with temperature as depth increases. However, at bathyal depths, the cold-seep vestimentiferan tubeworm species Lamellibrachia luymesi and Seepiophila jonesi reach extremely old ages beyond what is predicted by the simple scaling of life span with body size and temperature. Here, we use individual-based models based on in situ growth rates to show that another species of cold-seep tubeworm found in the Gulf of Mexico, Escarpia laminata, also has an extraordinarily long life span, regularly achieving ages of 100-200 years with some individuals older than 300 years. The distribution of results from individual simulations as well as whole population simulations involving mortality and recruitment rates support these age estimates. The low 0.67% mortality rate measurements from collected populations of E. laminata are similar to mortality rates in L. luymesi and S. jonesi and play a role in evolution of the long life span of cold-seep tubeworms. These results support longevity theory, which states that in the absence of extrinsic mortality threats, natural selection will select for individuals that senesce slower and reproduce continually into their old age.

Pomegranate Juice Enhances Healthy Lifespan in Drosophila melanogaster: An Exploratory Study

PubMed Central

Balasubramani, Subramani Paranthaman; Mohan, Jayaram; Chatterjee, Arunita; Patnaik, Esha; Kukkupuni, Subrahmanya Kumar; Nongthomba, Upendra; Venkatasubramanian, Padmavathy

2014-01-01

Exploring innovative ways to ensure healthy aging of populations is a pre-requisite to contain rising healthcare costs. Scientific research into the principles and practices of traditional medicines can provide new insights and simple solutions to lead a healthy life. Rasayana is a dedicated branch of Ayurveda (an Indian medicine) that deals with methods to increase vitality and delay aging through the use of diet, herbal supplements, and other lifestyle practices. The life-span and health-span enhancing actions of the fruits of pomegranate (Punica granatum L.), a well-known Rasayana, were tested on Drosophila melanogaster (fruitfly) model. Supplementation of standard corn meal with 10% (v/v) pomegranate juice (PJ) extended the life-span of male and female flies by 18 and 8%, respectively. When male and female flies were mixed and reared together, there was 19% increase in the longevity of PJ fed flies, as assessed by MSD, the median survival day (24.8). MSD for control and resveratrol (RV) groups was at 20.8 and 23.1 days, respectively. A two-fold enhancement in fecundity, improved resistance to oxidative stress (H2O2 and paraquat induced) and to Candida albicans infection were observed in PJ fed flies. Further, the flies in the PJ fed group were physically active over an extended period of time, as assessed by the climbing assay. PJ thus outperformed both control and RV groups in the life-span and health-span parameters tested. This study provides the scope to explore the potential of PJ as a nutraceutical to improve health span and lifespan in human beings. PMID:25566518

Health span approximates life span among many supercentenarians: compression of morbidity at the approximate limit of life span.

PubMed

Andersen, Stacy L; Sebastiani, Paola; Dworkis, Daniel A; Feldman, Lori; Perls, Thomas T

2012-04-01

We analyze the relationship between age of survival, morbidity, and disability among centenarians (age 100-104 years), semisupercentenarians (age 105-109 years), and supercentenarians (age 110-119 years). One hundred and four supercentenarians, 430 semisupercentenarians, 884 centenarians, 343 nonagenarians, and 436 controls were prospectively followed for an average of 3 years (range 0-13 years). The older the age group, generally, the later the onset of diseases, such as cancer, cardiovascular disease, dementia, and stroke, as well as of cognitive and functional decline. The hazard ratios for these individual diseases became progressively less with older and older age, and the relative period of time spent with disease was lower with increasing age group. We observed a progressive delay in the age of onset of physical and cognitive function impairment, age-related diseases, and overall morbidity with increasing age. As the limit of human life span was effectively approached with supercentenarians, compression of morbidity was generally observed.

Health Span Approximates Life Span Among Many Supercentenarians: Compression of Morbidity at the Approximate Limit of Life Span

PubMed Central

Andersen, Stacy L.; Sebastiani, Paola; Dworkis, Daniel A.; Feldman, Lori

2012-01-01

We analyze the relationship between age of survival, morbidity, and disability among centenarians (age 100–104 years), semisupercentenarians (age 105–109 years), and supercentenarians (age 110–119 years). One hundred and four supercentenarians, 430 semisupercentenarians, 884 centenarians, 343 nonagenarians, and 436 controls were prospectively followed for an average of 3 years (range 0–13 years). The older the age group, generally, the later the onset of diseases, such as cancer, cardiovascular disease, dementia, and stroke, as well as of cognitive and functional decline. The hazard ratios for these individual diseases became progressively less with older and older age, and the relative period of time spent with disease was lower with increasing age group. We observed a progressive delay in the age of onset of physical and cognitive function impairment, age-related diseases, and overall morbidity with increasing age. As the limit of human life span was effectively approached with supercentenarians, compression of morbidity was generally observed. PMID:22219514

Epigenetic linkage of aging, cancer and nutrition

PubMed Central

Daniel, Michael; Tollefsbol, Trygve O.

2015-01-01

Epigenetic mechanisms play a pivotal role in the expression of genes and can be influenced by both the quality and quantity of diet. Dietary compounds such as sulforaphane (SFN) found in cruciferous vegetables and epigallocatechin-3-gallate (EGCG) in green tea exhibit the ability to affect various epigenetic mechanisms such as DNA methyltransferase (DNMT) inhibition, histone modifications via histone deacetylase (HDAC), histone acetyltransferase (HAT) inhibition, or noncoding RNA expression. Regulation of these epigenetic mechanisms has been shown to have notable influences on the formation and progression of various neoplasms. We have shown that an epigenetic diet can influence both cellular longevity and carcinogenesis through the modulation of certain key genes that encode telomerase and p16. Caloric restriction (CR) can also play a crucial role in aging and cancer. Reductions in caloric intake have been shown to increase both the life- and health-span in a variety of animal models. Moreover, restriction of glucose has been demonstrated to decrease the incidence of age-related diseases such as cancer and diabetes. A diet rich in compounds such as genistein, SFN and EGCG can positively modulate the epigenome and lead to many health benefits. Also, reducing the quantity of calories and glucose in the diet can confer an increased health-span, including reduced cancer incidence. PMID:25568452

Psychosocial stressors and the short life spans of legendary jazz musicians.

PubMed

Patalano, F

2000-04-01

Mean age at death of 168 legendary jazz musicians and 100 renowned classical musicians were compared to examine whether psychosocial stressors such as severe substance abuse, haphazard working conditions, lack of acceptance of jazz as an art form in the United States, marital and family discord, and a vagabond life style may have contributed to shortened life spans for the jazz musicians. Analysis indicated that the jazz musicians died at an earlier age (57.2 yr.) than the classical musicians (73.3 yr.).

Changes in Acoustic Characteristics of the Voice across the Life Span: Measures from Individuals 4-93 Years of Age

ERIC Educational Resources Information Center

Stathopoulos, Elaine T.; Huber, Jessica E.; Sussman, Joan E.

2011-01-01

Purpose: The purpose of the present investigation was to examine acoustic voice changes across the life span. Previous voice production investigations used small numbers of participants, had limited age ranges, and produced contradictory results. Method: Voice recordings were made from 192 male and female participants 4-93 years of age. Acoustic…

Modeling Life-Span Growth Curves of Cognition Using Longitudinal Data with Multiple Samples and Changing Scales of Measurement

ERIC Educational Resources Information Center

McArdle, John J.; Grimm, Kevin J.; Hamagami, Fumiaki; Bowles, Ryan P.; Meredith, William

2009-01-01

The authors use multiple-sample longitudinal data from different test batteries to examine propositions about changes in constructs over the life span. The data come from 3 classic studies on intellectual abilities in which, in combination, 441 persons were repeatedly measured as many as 16 times over 70 years. They measured cognitive constructs…

The Use of Digital Technologies across the Adult Life Span in Distance Education

ERIC Educational Resources Information Center

Jelfs, Anne; Richardson, John T. E.

2013-01-01

In June 2010, a survey was carried out to explore access to digital technology, attitudes to digital technology and approaches to studying across the adult life span in students taking courses with the UK Open University. In total, 7000 people were surveyed, of whom more than 4000 responded. Nearly all these students had access to a computer and…

Auditory Environment across the Life Span of Cochlear Implant Users: Insights from Data Logging

ERIC Educational Resources Information Center

Busch, Tobias; Vanpoucke, Filiep; van Wieringen, Astrid

2017-01-01

Purpose: We describe the natural auditory environment of people with cochlear implants (CIs), how it changes across the life span, and how it varies between individuals. Method: We performed a retrospective cross-sectional analysis of Cochlear Nucleus 6 CI sound-processor data logs. The logs were obtained from 1,501 people with CIs (ages 0-96…

The Development of Attentional Networks: Cross-Sectional Findings from a Life Span Sample

ERIC Educational Resources Information Center

Waszak, Florian; Li, Shu-Chen; Hommel, Bernhard

2010-01-01

Using a population-based sample of 263 individuals ranging from 6 to 89 years of age, we investigated the gains and losses in the abilities to (a) use exogenous cues to shift attention covertly and (b) ignore conflicting information across the life span. The participants' ability to shift visual attention was tested by a typical Posner-type…

Life-Span Development of Visual Working Memory: When Is Feature Binding Difficult?

ERIC Educational Resources Information Center

Cowan, Nelson; Naveh-Benjamin, Moshe; Kilb, Angela; Saults, J. Scott

2006-01-01

We asked whether the ability to keep in working memory the binding between a visual object and its spatial location changes with development across the life span more than memory for item information. Paired arrays of colored squares were identical or differed in the color of one square, and in the latter case, the changed color was unique on…

Gains and Losses in Creative Personality as Perceived by Adults across the Life Span

ERIC Educational Resources Information Center

Hui, Anna N. N.; Yeung, Dannii Y.; Sue-Chan, Christina; Chan, Kara; Hui, Desmond C. K.; Cheng, Sheung-Tak

2014-01-01

In this study, we used a life span model to study the subjective perception of creative personality (CP) in emerging, young, middle-aged, and older Hong Kong Chinese adults. We also asked participants to estimate the approximate age by which people develop and lose CP across adulthood. We expected an interesting interplay between internalized age…

Extending the Human Life Span: An Exploratory Study of Pro- and Anti-Longevity Attitudes

ERIC Educational Resources Information Center

Kogan, Nathan; Tucker, Jennifer; Porter, Matthew

2011-01-01

Successful efforts by biologists to substantially increase the life span of non-human animals has raised the possibility of extrapolation to humans, which in turn has given rise to bioethical argumentation, pro and con. The present study converts these arguments into pro- and anti-longevity items on a questionnaire and examines the structure and…

Attitudes Toward Death Across the Life Span.

ERIC Educational Resources Information Center

Maiden, Robert; Walker, Gail

To understand the change and development of people's attitudes toward death over the life span, a 62-item attitude questionnaire on death and dying was administered to 90 adults. Participants included five females and five males in each of nine age categories: 18-20, 20-24, 25-29, 30-34, 35-39, 40-49, 50-59, 60-64, and 65 or older. Participants…

Life-Span Differences in the Uses and Gratifications of Tablets: Implications for Older Adults

PubMed Central

Magsamen-Conrad, Kate; Dowd, John; Abuljadail, Mohammad; Alsulaiman, Saud; Shareefi, Adnan

2015-01-01

This study extends Uses and Gratifications theory by examining the uses and gratifications of a new technological device, the tablet computer, and investigating the differential uses and gratifications of tablet computers across the life-span. First, we utilized a six-week tablet training intervention to adapt and extend existing measures to the tablet as a technological device. Next, we used paper-based and online surveys (N=847), we confirmed four main uses of tablets: 1) Information Seeking, 2) Relationship Maintenance, 3) Style, 4) Amusement and Killing time, and added one additional use category 5) Organization. We discovered differences among the five main uses of tablets across the life-span, with older adults using tablets the least overall. Builders, Boomers, GenX and GenY all reported the highest means for information seeking. Finally, we used a structural equation model to examine how uses and gratifications predicts hours of tablet use. The study provides limitations and suggestions for future research and marketers. In particular, this study offers insight to the relevancy of theory as it applies to particular information and communication technologies and consideration of how different periods in the life-span affect tablet motivations. PMID:26113769

Life-Span Differences in the Uses and Gratifications of Tablets: Implications for Older Adults.

PubMed

Magsamen-Conrad, Kate; Dowd, John; Abuljadail, Mohammad; Alsulaiman, Saud; Shareefi, Adnan

2015-11-01

This study extends Uses and Gratifications theory by examining the uses and gratifications of a new technological device, the tablet computer, and investigating the differential uses and gratifications of tablet computers across the life-span. First, we utilized a six-week tablet training intervention to adapt and extend existing measures to the tablet as a technological device. Next, we used paper-based and online surveys ( N =847), we confirmed four main uses of tablets: 1) Information Seeking, 2) Relationship Maintenance, 3) Style, 4) Amusement and Killing time, and added one additional use category 5) Organization. We discovered differences among the five main uses of tablets across the life-span, with older adults using tablets the least overall. Builders, Boomers, GenX and GenY all reported the highest means for information seeking. Finally, we used a structural equation model to examine how uses and gratifications predicts hours of tablet use. The study provides limitations and suggestions for future research and marketers. In particular, this study offers insight to the relevancy of theory as it applies to particular information and communication technologies and consideration of how different periods in the life-span affect tablet motivations.

Growth and Decay in Life-Like Cellular Automata

NASA Astrophysics Data System (ADS)

Eppstein, David

Since the study of life began, many have asked: is it unique in the universe, or are there other interesting forms of life elsewhere? Before we can answer that question, we should ask others: What makes life special? If we happen across another system with life-like behavior, how would we be able to recognize it? We are speaking, of course, of the mathematical systems of cellular automata, of the fascinating patterns that have been discovered and engineered in Conway's Game of Life, and of the possible existence of other cellular automaton rules with equally complex behavior to that of Life.

Life-span perspective of personality in dementia.

PubMed

Kolanowski, A M; Whall, A L

1996-01-01

To propose an alternative view of personality change in dementia by presenting existing evidence for the continuity of personality. As the population continues to age, dementing illnesses will account for a greater proportion of morbidity and mortality; the care of these people will have a significant effect on the health care system. Life-span perspective of personality continuity. SCOPE METHOD: Review of current literature on personality in dementia using Medline, 1980-1994; CINAHL, 1990-1994; and Psych Lit., 1980-1994. Although there are systematic shifts in personality with dementia, individuals tend to maintain their unique pattern of premorbid personality traits. The personalities of dementia patients seem to reflect adaptive patterns that served them in the past. Use of a life-span perspective can enhance individualized care for demented patients and advance theory development.

Demography of Genotypes: Failure of the Limited Life-Span Paradigm in Drosophila melanogaster

NASA Astrophysics Data System (ADS)

Curtsinger, James W.; Fukui, Hidenori H.; Townsend, David R.; Vaupel, James W.

1992-10-01

Experimental systems that are amenable to genetic manipulation can be used to address fundamental questions about genetic and nongenetic determinants of longevity. Analysis of large cohorts of ten genotypes of Drosophila melanogaster raised under conditions that favored extended survival has revealed variation between genotypes in both the slope and location of age-specific mortality curves. More detailed examination of a single genotype showed that the mortality trajectory was best fit by a two-stage Gompertz model, with no age-specific increase in mortality rates beyond 30 days after emergence. These results are contrary to the limited life-span paradigm, which postulates well-defined, genotype-specific limits on life-span and brief periods of intense and rapidly accelerating mortality rates at the oldest ages.

A unique life history among tetrapods: An annual chameleon living mostly as an egg

PubMed Central

Karsten, Kristopher B.; Andriamandimbiarisoa, Laza N.; Fox, Stanley F.; Raxworthy, Christopher J.

2008-01-01

The ≈28,300 species of tetrapods (four-limbed vertebrates) almost exclusively have perennial life spans. Here, we report the discovery of a remarkable annual tetrapod from the arid southwest of Madagascar: the chameleon Furcifer labordi, with a posthatching life span of just 4–5 months. At the start of the active season (November), an age cohort of hatchlings emerges; larger juveniles or adults are not present. These hatchlings grow rapidly, reach sexual maturity in less than 2 months, and reproduce in January–February. After reproduction, senescence appears, and the active season concludes with population-wide adult death. Consequently, during the dry season, the entire population is represented by developing eggs that incubate for 8–9 months before synchronously hatching at the onset of the following rainy season. Remarkably, this chameleon spends more of its short annual life cycle inside the egg than outside of it. Our review of tetrapod longevity (>1,700 species) finds no others with such a short life span. These findings suggest that the notorious rapid death of chameleons in captivity may, for some species, actually represent the natural adult life span. Consequently, a new appraisal may be warranted concerning the viability of chameleon breeding programs, which could have special significance for species of conservation concern. Additionally, because F. labordi is closely related to other perennial species, this chameleon group may prove also to be especially well suited for comparative studies that focus on life history evolution and the ecological, genetic, and/or hormonal determinants of aging, longevity, and senescence. PMID:18591659

A unique life history among tetrapods: an annual chameleon living mostly as an egg.

PubMed

Karsten, Kristopher B; Andriamandimbiarisoa, Laza N; Fox, Stanley F; Raxworthy, Christopher J

2008-07-01

The approximately 28,300 species of tetrapods (four-limbed vertebrates) almost exclusively have perennial life spans. Here, we report the discovery of a remarkable annual tetrapod from the arid southwest of Madagascar: the chameleon Furcifer labordi, with a posthatching life span of just 4-5 months. At the start of the active season (November), an age cohort of hatchlings emerges; larger juveniles or adults are not present. These hatchlings grow rapidly, reach sexual maturity in less than 2 months, and reproduce in January-February. After reproduction, senescence appears, and the active season concludes with population-wide adult death. Consequently, during the dry season, the entire population is represented by developing eggs that incubate for 8-9 months before synchronously hatching at the onset of the following rainy season. Remarkably, this chameleon spends more of its short annual life cycle inside the egg than outside of it. Our review of tetrapod longevity (>1,700 species) finds no others with such a short life span. These findings suggest that the notorious rapid death of chameleons in captivity may, for some species, actually represent the natural adult life span. Consequently, a new appraisal may be warranted concerning the viability of chameleon breeding programs, which could have special significance for species of conservation concern. Additionally, because F. labordi is closely related to other perennial species, this chameleon group may prove also to be especially well suited for comparative studies that focus on life history evolution and the ecological, genetic, and/or hormonal determinants of aging, longevity, and senescence.

Drosophila melanogaster as a model system of aluminum toxicity and aging.

PubMed

Kijak, Ewelina; Rosato, Ezio; Knapczyk, Katarzyna; Pyza, Elżbieta

2014-04-01

The aim of this study was to investigate the toxic effects of aluminum (Al) on the model organism-Drosophila melanogaster. The study is especially concerned with the effects of aluminum on the fruit fly's development, life span, and circadian rhythm in rest and activity. Flies were exposed to aluminum in concentrations from 40 to 280 mg/kg in rearing media or the flies were raised on control medium. Moreover, the life span of insects exposed to aluminum containing 40, 120, or 240 mg/kg of Al in the medium, only during their larval development, during the whole life cycle and only in their adult life was tested. To check if aluminum and aging cause changes in D. melanogaster behavior, the locomotor activity of flies at different ages was recorded. Results showed that aluminum is toxic in concentrations above 160 mg/kg in the rearing medium. Depending on Al concentration and time of exposure, the life span of the flies was shortened. At intermediate concentrations (120 mg/kg), however, Al had a stimulating effect on males increasing their life span and level of locomotor activity. At higher concentration the aluminum exposure increased or decreased the level of locomotor activity of D. melanogaster depending on age of flies. In addition, in the oldest insects reared on aluminum supplemented media and in mid-aged flies reared on the highest concentration of Al the daily rhythm of activity was disrupted. © 2013 Institute of Zoology, Chinese Academy of Sciences.

Quantifying the Structure of Free Association Networks across the Life Span

ERIC Educational Resources Information Center

Dubossarsky, Haim; De Deyne, Simon; Hills, Thomas T.

2017-01-01

We investigate how the mental lexicon changes over the life span using free association data from over 8,000 individuals, ranging from 10 to 84 years of age, with more than 400 cue words per age group. Using network analysis, with words as nodes and edges defined by the strength of shared associations, we find that associative networks evolve in a…

Self-Esteem Development across the Life Span: A Longitudinal Study with a Large Sample from Germany

ERIC Educational Resources Information Center

Orth, Ulrich; Maes, Jürgen; Schmitt, Manfred

2015-01-01

The authors examined the development of self-esteem across the life span. Data came from a German longitudinal study with 3 assessments across 4 years of a sample of 2,509 individuals ages 14 to 89 years. The self-esteem measure used showed strong measurement invariance across assessments and birth cohorts. Latent growth curve analyses indicated…

Delayed accumulation of intestinal coliform bacteria enhances life span and stress resistance in Caenorhabditis elegans fed respiratory deficient E. coli.

PubMed

Gomez, Fernando; Monsalve, Gabriela C; Tse, Vincent; Saiki, Ryoichi; Weng, Emily; Lee, Laura; Srinivasan, Chandra; Frand, Alison R; Clarke, Catherine F

2012-12-20

Studies with the nematode model Caenorhabditis elegans have identified conserved biochemical pathways that act to modulate life span. Life span can also be influenced by the composition of the intestinal microbiome, and C. elegans life span can be dramatically influenced by its diet of Escherichia coli. Although C. elegans is typically fed the standard OP50 strain of E. coli, nematodes fed E. coli strains rendered respiratory deficient, either due to a lack coenzyme Q or the absence of ATP synthase, show significant life span extension. Here we explore the mechanisms accounting for the enhanced nematode life span in response to these diets. The intestinal load of E. coli was monitored by determination of worm-associated colony forming units (cfu/worm or coliform counts) as a function of age. The presence of GFP-expressing E. coli in the worm intestine was also monitored by fluorescence microscopy. Worms fed the standard OP50 E. coli strain have high cfu and GFP-labeled bacteria in their guts at the L4 larval stage, and show saturated coliform counts by day five of adulthood. In contrast, nematodes fed diets of respiratory deficient E. coli lacking coenzyme Q lived significantly longer and failed to accumulate bacteria within the lumen at early ages. Animals fed bacteria deficient in complex V showed intermediate coliform numbers and were not quite as long-lived. The results indicate that respiratory deficient Q-less E. coli are effectively degraded in the early adult worm, either at the pharynx or within the intestine, and do not accumulate in the intestinal tract until day ten of adulthood. The findings of this study suggest that the nematodes fed the respiratory deficient E. coli diet live longer because the delay in bacterial colonization of the gut subjects the worms to less stress compared to worms fed the OP50 E. coli diet. This work suggests that bacterial respiration can act as a virulence factor, influencing the ability of bacteria to colonize and subsequently harm the animal host. Respiratory deficient bacteria may pose a useful model for probing probiotic relationships within the gut microbiome in higher organisms.

Causes and consequences of variation in conifer leaf life-span

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

Reich, P.B.; Koike, T.; Gower, S.T.

1995-07-01

Species with mutually supporting traits, such as high N{sub mass}, SLA, and A{sub mass}, and short leaf life-span, tend to inhabit either generally resource-rich environments or spatial and/or temporal microhabitats that are resource-rich in otherwise more limited habitats (e.g., {open_quotes}precipitation{close_quotes} ephemerals in warm deserts or spring ephemerals in the understory of temperate deciduous forests). In contrast, species with long leaf life-span often support foliage with low SLA, N{sub mass}, and A{sub mass}, and often grow in low-temperature limited, dry, and/or nutrient-poor environments. The contrast between evergreen and deciduous species, and the implications that emerge from such comparisons, can be consideredmore » a paradigm of modern ecological theory. However, based on the results of Reich et al. (1992) and Gower et al. (1993), coniferous species with foliage that persists for 9-10 years are likely to assimilate and allocate carbon and nutrients differently than other evergreen conifers that retain foliage for 2-3 years. Thus, attempts to contrast ecophysiological or ecosystem characteristics of evergreen versus deciduous life forms may be misleading, and pronounced differences among evergreen conifers may be ignored. Clearly, the deciduous-evergreen contrast, although useful in several ways, should be viewed from the broader perspective of a gradient in leaf life-span.« less

Atomic detail visualization of photosynthetic membranes with GPU-accelerated ray tracing

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

Stone, John E.; Sener, Melih; Vandivort, Kirby L.

The cellular process responsible for providing energy for most life on Earth, namely, photosynthetic light-harvesting, requires the cooperation of hundreds of proteins across an organelle, involving length and time scales spanning several orders of magnitude over quantum and classical regimes. Simulation and visualization of this fundamental energy conversion process pose many unique methodological and computational challenges. In this paper, we present, in two accompanying movies, light-harvesting in the photosynthetic apparatus found in purple bacteria, the so-called chromatophore. The movies are the culmination of three decades of modeling efforts, featuring the collaboration of theoretical, experimental, and computational scientists. Finally, we describemore » the techniques that were used to build, simulate, analyze, and visualize the structures shown in the movies, and we highlight cases where scientific needs spurred the development of new parallel algorithms that efficiently harness GPU accelerators and petascale computers.« less

Atomic detail visualization of photosynthetic membranes with GPU-accelerated ray tracing

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

Stone, John E.; Sener, Melih; Vandivort, Kirby L.

The cellular process responsible for providing energy for most life on Earth, namely, photosynthetic light-harvesting, requires the cooperation of hundreds of proteins across an organelle, involving length and time scales spanning several orders of magnitude over quantum and classical regimes. Simulation and visualization of this fundamental energy conversion process pose many unique methodological and computational challenges. We present, in two accompanying movies, light-harvesting in the photosynthetic apparatus found in purple bacteria, the so-called chromatophore. The movies are the culmination of three decades of modeling efforts, featuring the collaboration of theoretical, experimental, and computational scientists. We describe the techniques that weremore » used to build, simulate, analyze, and visualize the structures shown in the movies, and we highlight cases where scientific needs spurred the development of new parallel algorithms that efficiently harness GPU accelerators and petascale computers.« less

Atomic detail visualization of photosynthetic membranes with GPU-accelerated ray tracing

DOE PAGES

Stone, John E.; Sener, Melih; Vandivort, Kirby L.; ...

2015-12-12

The cellular process responsible for providing energy for most life on Earth, namely, photosynthetic light-harvesting, requires the cooperation of hundreds of proteins across an organelle, involving length and time scales spanning several orders of magnitude over quantum and classical regimes. Simulation and visualization of this fundamental energy conversion process pose many unique methodological and computational challenges. In this paper, we present, in two accompanying movies, light-harvesting in the photosynthetic apparatus found in purple bacteria, the so-called chromatophore. The movies are the culmination of three decades of modeling efforts, featuring the collaboration of theoretical, experimental, and computational scientists. Finally, we describemore » the techniques that were used to build, simulate, analyze, and visualize the structures shown in the movies, and we highlight cases where scientific needs spurred the development of new parallel algorithms that efficiently harness GPU accelerators and petascale computers.« less

Neuronal control of energy homeostasis

PubMed Central

Gao, Qian; Horvath, Tamas L.

2013-01-01

Neuronal control of body energy homeostasis is the key mechanism by which animals and humans regulate their long-term energy balance. Various hypothalamic neuronal circuits (which include the hypothalamic melanocortin, midbrain dopamine reward and caudal brainstem autonomic feeding systems) control energy intake and expenditure to maintain body weight within a narrow range for long periods of a life span. Numerous peripheral metabolic hormones and nutrients target these structures providing feedback signals that modify the default “settings” of neuronal activity to accomplish this balance. A number of molecular genetic tools for manipulating individual components of brain energy homeostatic machineries, in combination with anatomical, electrophysiological, pharmacological and behavioral techniques, have been developed, which provide a means for elucidating the complex molecular and cellular mechanisms of feeding behavior and metabolism. This review will highlight some of these advancements and focus on the neuronal circuitries of energy homeostasis. PMID:18061579

NF-κB Essential Modulator (NEMO) Is Critical for Thyroid Function.

PubMed

Reale, Carla; Iervolino, Anna; Scudiero, Ivan; Ferravante, Angela; D'Andrea, Luca Egildo; Mazzone, Pellegrino; Zotti, Tiziana; Leonardi, Antonio; Roberto, Luca; Zannini, Mariastella; de Cristofaro, Tiziana; Shanmugakonar, Muralitharan; Capasso, Giovambattista; Pasparakis, Manolis; Vito, Pasquale; Stilo, Romania

2016-03-11

The I-κB kinase (IKK) subunit NEMO/IKKγ (NEMO) is an adapter molecule that is critical for canonical activation of NF-κB, a pleiotropic transcription factor controlling immunity, differentiation, cell growth, tumorigenesis, and apoptosis. To explore the functional role of canonical NF-κB signaling in thyroid gland differentiation and function, we have generated a murine strain bearing a genetic deletion of the NEMO locus in thyroid. Here we show that thyrocyte-specific NEMO knock-out mice gradually develop hypothyroidism after birth, which leads to reduced body weight and shortened life span. Histological and molecular analysis indicate that absence of NEMO in thyrocytes results in a dramatic loss of the thyroid gland cellularity, associated with down-regulation of thyroid differentiation markers and ongoing apoptosis. Thus, NEMO-dependent signaling is essential for normal thyroid physiology. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Osteoporosis and alzheimer pathology: Role of cellular stress response and hormetic redox signaling in aging and bone remodeling

PubMed Central

Cornelius, Carolin; Koverech, Guido; Crupi, Rosalia; Di Paola, Rosanna; Koverech, Angela; Lodato, Francesca; Scuto, Maria; Salinaro, Angela T.; Cuzzocrea, Salvatore; Calabrese, Edward J.; Calabrese, Vittorio

2014-01-01

Alzheimer’s disease (AD) and osteoporosis are multifactorial progressive degenerative disorders. Increasing evidence shows that osteoporosis and hip fracture are common complication observed in AD patients, although the mechanisms underlying this association remain poorly understood. Reactive oxygen species (ROS) are emerging as intracellular redox signaling molecules involved in the regulation of bone metabolism, including receptor activator of nuclear factor-κB ligand-dependent osteoclast differentiation, but they also have cytotoxic effects that include lipoperoxidation and oxidative damage to proteins and DNA. ROS generation, which is implicated in the regulation of cellular stress response mechanisms, is an integrated, highly regulated, process under control of redox sensitive genes coding for redox proteins called vitagenes. Vitagenes, encoding for proteins such as heat shock proteins (Hsps) Hsp32, Hsp70, the thioredoxin, and the sirtuin protein, represent a systems controlling a complex network of intracellular signaling pathways relevant to life span and involved in the preservation of cellular homeostasis under stress conditions. Consistently, nutritional anti-oxidants have demonstrated their neuroprotective potential through a hormetic-dependent activation of vitagenes. The biological relevance of dose–response affects those strategies pointing to the optimal dosing to patients in the treatment of numerous diseases. Thus, the heat shock response has become an important hormetic target for novel cytoprotective strategies focusing on the pharmacological development of compounds capable of modulating stress response mechanisms. Here we discuss possible signaling mechanisms involved in the activation of vitagenes which, relevant to bone remodeling and through enhancement of cellular stress resistance provide a rationale to limit the deleterious consequences associated to homeostasis disruption with consequent impact on the aging process. PMID:24959146

Oxidative Damage and Cellular Defense Mechanisms in Sea Urchin Models of Aging

PubMed Central

Du, Colin; Anderson, Arielle; Lortie, Mae; Parsons, Rachel; Bodnar, Andrea

2013-01-01

The free radical or oxidative stress theory of aging proposes that the accumulation of oxidative cellular damage is a major contributor to the aging process and a key determinant of species longevity. This study investigates the oxidative stress theory in a novel model for aging research, the sea urchin. Sea urchins present a unique model for the study of aging due to the existence of species with tremendously different natural life spans including some species with extraordinary longevity and negligible senescence. Cellular oxidative damage, antioxidant capacity and proteasome enzyme activities were measured in the tissues of three sea urchin species: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus and Strongylocentrotus purpuratus which has an intermediate lifespan. Levels of protein carbonyls and 4-hydroxynonenal (HNE) measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) measured in cell-free coelomic fluid showed no general increase with age. The fluorescent age-pigment lipofuscin measured in muscle, nerve and esophagus, increased with age however it appeared to be predominantly extracellular. Antioxidant mechanisms (total antioxidant capacity, superoxide dismutase) and proteasome enzyme activities were maintained with age. In some instances, levels of oxidative damage were lower and antioxidant activity higher in cells or tissues of the long-lived species compared to the short-lived species, however further studies are required to determine the relationship between oxidative damage and longevity in these animals. Consistent with the predictions of the oxidative stress theory of aging, the results suggest that negligible senescence is accompanied by a lack of accumulation of cellular oxidative damage with age and maintenance of antioxidant capacity and proteasome enzyme activities may be important mechanisms to mitigate damage. PMID:23707327

Coping with cyclic oxygen availability: evolutionary aspects.

PubMed

Flück, Martin; Webster, Keith A; Graham, Jeffrey; Giomi, Folco; Gerlach, Frank; Schmitz, Anke

2007-10-01

Both the gradual rise in atmospheric oxygen over the Proterozoic Eon as well as episodic fluctuations in oxygen over several million-year time spans during the Phanerozoic Era, have arguably exerted strong selective forces on cellular and organismic respiratory specialization and evolution. The rise in atmospheric oxygen, some 2 billion years after the origin of life, dramatically altered cell biology and set the stage for the appearance of multicelluar life forms in the Vendian (Ediacaran) Period of the Neoproterozoic Era. Over much of the Paleozoic, the level of oxygen in the atmosphere was near the present atmospheric level (21%). In the Late Paleozoic, however, there were extended times during which the level of atmospheric oxygen was either markedly lower or markedly higher than 21%. That these Paleozoic shifts in atmospheric oxygen affected the biota is suggested by the correlations between: (1) Reduced oxygen and the occurrences of extinctions, a lowered biodiversity and shifts in phyletic succession, and (2) During hyperoxia, the corresponding occurrence of phenomena such as arthropod gigantism, the origin of insect flight, and the evolution of vertebrate terrestriality. Basic similarities in features of adaptation to hyopoxia, manifest in living organisms at levels ranging from genetic and cellular to physiological and behavioral, suggest the common and early origin of a suite of adaptive mechanisms responsive to fluctuations in ambient oxygen. Comparative integrative approaches addressing the molecular bases of phenotypic adjustments to cyclic oxygen fluctuation provide broad insight into the incremental steps leading to the early evolution of homeostatic respiratory mechanisms and to the specialization of organismic respiratory function.

Ageing in a eusocial insect: molecular and physiological characteristics of life span plasticity in the honey bee

PubMed Central

Münch, D.; Amdam, G. V.; Wolschin, F.

2008-01-01

Summary Commonly held views assume that ageing, or senescence, represents an inevitable, passive, and random decline in function that is strongly linked to chronological age. In recent years, genetic intervention of life span regulating pathways, for example, in Drosophila as well as case studies in non-classical animal models, have provided compelling evidence to challenge these views. Rather than comprehensively revisiting studies on the established genetic model systems of ageing, we here focus on an alternative model organism with a wild type (unselected genotype) characterized by a unique diversity in longevity – the honey bee. Honey bee (Apis mellifera) life span varies from a few weeks to more than 2 years. This plasticity is largely controlled by environmental factors. Thereby, although individuals are closely related genetically, distinct life histories can emerge as a function of social environmental change. Another remarkable feature of the honey bee is the occurrence of reverted behavioural ontogeny in the worker (female helper) caste. This behavioural peculiarity is associated with alterations in somatic maintenance functions that are indicative of reverted senescence. Thus, although intraspecific variation in organismal life span is not uncommon, the honey bee holds great promise for gaining insights into regulatory pathways that can shape the time-course of ageing by delaying, halting or even reversing processes of senescence. These aspects provide the setting of our review. We will highlight comparative findings from Drosophila melanogaster and Caenorhabditis elegans in particular, and focus on knowledge spanning from molecular- to behavioural-senescence to elucidate how the honey bee can contribute to novel insights into regulatory mechanisms that underlie plasticity and robustness or irreversibility in ageing. PMID:18728759

Ageing in a eusocial insect: molecular and physiological characteristics of life span plasticity in the honey bee.

PubMed

Münch, D; Amdam, G V; Wolschin, F

2008-01-01

Commonly held views assume that ageing, or senescence, represents an inevitable, passive, and random decline in function that is strongly linked to chronological age. In recent years, genetic intervention of life span regulating pathways, for example, in Drosophila as well as case studies in non-classical animal models, have provided compelling evidence to challenge these views.Rather than comprehensively revisiting studies on the established genetic model systems of ageing, we here focus on an alternative model organism with a wild type (unselected genotype) characterized by a unique diversity in longevity - the honey bee.Honey bee (Apis mellifera) life span varies from a few weeks to more than 2 years. This plasticity is largely controlled by environmental factors. Thereby, although individuals are closely related genetically, distinct life histories can emerge as a function of social environmental change.Another remarkable feature of the honey bee is the occurrence of reverted behavioural ontogeny in the worker (female helper) caste. This behavioural peculiarity is associated with alterations in somatic maintenance functions that are indicative of reverted senescence. Thus, although intraspecific variation in organismal life span is not uncommon, the honey bee holds great promise for gaining insights into regulatory pathways that can shape the time-course of ageing by delaying, halting or even reversing processes of senescence. These aspects provide the setting of our review.We will highlight comparative findings from Drosophila melanogaster and Caenorhabditis elegans in particular, and focus on knowledge spanning from molecular- to behavioural-senescence to elucidate how the honey bee can contribute to novel insights into regulatory mechanisms that underlie plasticity and robustness or irreversibility in ageing.

Differential longitudinal changes in cortical thickness, surface area and volume across the adult life span: regions of accelerating and decelerating change.

PubMed

Storsve, Andreas B; Fjell, Anders M; Tamnes, Christian K; Westlye, Lars T; Overbye, Knut; Aasland, Hilde W; Walhovd, Kristine B

2014-06-18

Human cortical thickness and surface area are genetically independent, emerge through different neurobiological events during development, and are sensitive to different clinical conditions. However, the relationship between changes in the two over time is unknown. Additionally, longitudinal studies have almost invariably been restricted to older adults, precluding the delineation of adult life span trajectories of change in cortical structure. In this longitudinal study, we investigated changes in cortical thickness, surface area, and volume after an average interval of 3.6 years in 207 well screened healthy adults aged 23-87 years. We hypothesized that the relationships among metrics are dynamic across the life span, that the primary contributor to cortical volume reductions in aging is cortical thinning, and that magnitude of change varies with age and region. Changes over time were seen in cortical area (mean annual percentage change [APC], -0.19), thickness (APC, -0.35), and volume (APC, -0.51) in most regions. Volume changes were primarily explained by changes in thickness rather than area. A negative relationship between change in thickness and surface area was found across several regions, where more thinning was associated with less decrease in area, and vice versa. Accelerating changes with increasing age was seen in temporal and occipital cortices. In contrast, decelerating changes were seen in prefrontal and anterior cingulate cortices. In conclusion, a dynamic relationship between cortical thickness and surface area changes exists throughout the adult life span. The mixture of accelerating and decelerating changes further demonstrates the importance of studying these metrics across the entire adult life span. Copyright © 2014 the authors 0270-6474/14/348488-11$15.00/0.

Inducible knockdown of pregnancy-associated plasma protein-A gene expression in adult female mice extends life span.

PubMed

Bale, Laurie K; West, Sally A; Conover, Cheryl A

2017-08-01

Pregnancy-associated plasma protein-A (PAPP-A) knockout (KO) mice, generated through homologous recombination in embryonic stem cells, have a significantly increased lifespan compared to wild-type littermates. However, it is unknown whether this longevity advantage would pertain to PAPP-A gene deletion in adult animals. In the present study, we used tamoxifen (Tam)-inducible Cre recombinase-mediated excision of the floxed PAPP-A (fPAPP-A) gene in mice at 5 months of age. fPAPP-A mice, which were either positive (pos) or negative (neg) for Tam-Cre, received Tam treatment with quarterly boosters. Only female mice could be used with this experimental design. fPAPP-A/neg and fPAPP-A/pos mice had similar weights at the start of the experiment and showed equivalent weight gain. We found that fPAPP-A/pos mice had a significant extension of life span (P = 0.005). The median life span was increased by 21% for fPAPP-A/pos compared to fPAPP-A/neg mice. Analysis of mortality in life span quartiles indicated that the proportion of deaths of fPAPP-A/pos mice were lower than fPAPP-A/neg mice at young adult ages (P = 0.002 for 601-800 days) and higher than fPAPP-A/neg mice at older ages (P = 0.004 for >1000 days). Thus, survival curves and age-specific mortality indicate that female mice with knockdown of PAPP-A gene expression as adults have an extended healthy life span. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Dietary supplementation with Lovaza and krill oil shortens the life span of long-lived F1 mice.

PubMed

Spindler, Stephen R; Mote, Patricia L; Flegal, James M

2014-06-01

Marine oils rich in ω-3 polyunsaturated fatty acids have been recommended as a preventive treatment for patients at risk for cardiovascular diseases. These oils also are the third most consumed dietary supplement in the USA. However, evidence for their health benefits is equivocal. We tested the daily, isocaloric administration of krill oil (1.17 g oil/kg diet) and Lovaza (Omacor; 4.40 g/kg diet), a pharmaceutical grade fish oil, beginning at 12 months of age, on the life span and mortality-related pathologies of long-lived, male, B6C3F1 mice. The oils were incorporated into the chemically defined American Institute of Nutrition (AIN)-93 M diet. An equivalent volume of soybean oil was removed. Krill oil was 3 % and Lovaza 11 % of the oil in the diets. When their effects were analyzed together, the marine oils significantly shortened life span by 6.6 % (P = 0.0321; log-rank test) relative to controls. Individually, Lovaza and krill oil non-significantly shortened median life span by 9.8 and 4.7 %, respectively. Lovaza increased the number of enlarged seminal vesicles (7.1-fold). Lovaza and krill oil significantly increased lung tumors (4.1- and 8.2-fold) and hemorrhagic diathesis (3.9- and 3.1-fold). Analysis of serum from treated mice found that Lovaza slightly increased blood urea nitrogen, while krill oil modestly increased bilirubin, triglycerides, and blood glucose levels. Taken together, the results do not support the idea that the consumption of isolated ω-3 fatty acid-rich oils will increase the life span or health of initially healthy individuals.

A Modelling Study for Predicting Life of Downhole Tubes Considering Service Environmental Parameters and Stress

PubMed Central

Zhao, Tianliang; Liu, Zhiyong; Du, Cuiwei; Hu, Jianpeng; Li, Xiaogang

2016-01-01

A modelling effort was made to try to predict the life of downhole tubes or casings, synthetically considering the effect of service influencing factors on corrosion rate. Based on the discussed corrosion mechanism and corrosion processes of downhole tubes, a mathematic model was established. For downhole tubes, the influencing factors are environmental parameters and stress, which vary with service duration. Stress and the environmental parameters including water content, partial pressure of H2S and CO2, pH value, total pressure and temperature, were considered to be time-dependent. Based on the model, life-span of an L80 downhole tube in oilfield Halfaya, an oilfield in Iraq, was predicted. The results show that life-span of the L80 downhole tube in Halfaya is 247 months (approximately 20 years) under initial stress of 0.1 yield strength and 641 months (approximately 53 years) under no initial stress, which indicates that an initial stress of 0.1 yield strength will reduce the life-span by more than half. PMID:28773872

[Effects of sub-micro emulsion composition on cellular disposition of incorporated lipophilic drug].

PubMed

Sun, Xiao-Yi; Xiang, Zhi-Qiang; Wu, Shuo; Lv, Yuan-Yuan; Liang, Wen-Quan

2013-09-01

To investigate the effects of sub-micro emulsion composition on cellular uptake and disposition of incorporated lipophilic drug. Sub-micro emulsions containing 10 % oil, 1.2 % lecithin and 2.25 % glycerol were prepared, and the fluorescent agent coumarin 6 was used as a model drug. The effects of oil types, co-surfactants and cationic lipid on uptake and elimination kinetics of 6-coumarin in HeLa cells were studied. The uptake mechanism of sub-micro emulsions was further investigated. Oil type and Tweens had no influence on the cellular uptake. Modifications of surfactants with Span series increased the cellular influx, among which Span 20 with hydrophilic-lipophilic balance (HLB) value of 8.6 was the best enhancer. The intracellular drug level reached up to (46.09 ± 1.98)ng/μg protein which had significant difference with control group [(38.54 ± 0.34)ng/μg protein]. The positively charged emulsions significantly increased the uptake rate constant and elimination rate constant which were 4 times and 1.5 times of those in anionic groups, respectively. The uptake enhancement was also observed in cationic emulsions, cellular concentrations at plateau were (42.73 ± 0.84)ng/μg protein, which was about 3 times of that in anionic emulsions [(15.71 ± 0.74)ng/μg protein], when extracellular drug concentration kept at 100 ng/ml. Cationic emulsions delivered the payload mainly by direct drug transfer to contacted cells, while the negative ones depended on both drug passive diffusion and clathrin-mediated endocytosis of drug containing oil droplets which accounted for 20% of the intracellular drug. Interfacial characteristic of sub-micro emulsions such as co-surfactants HLB as well as zeta potentials can influence lipophilic drug both in cellular uptake and elimination.

Food-derived sensory cues modulate longevity via distinct neuroendocrine insulin-like peptides

PubMed Central

Artan, Murat; Jeong, Dae-Eun; Lee, Dongyeop; Kim, Young-Il; Son, Heehwa G.; Husain, Zahabiya; Kim, Jinmahn; Altintas, Ozlem; Kim, Kyuhyung; Alcedo, Joy; Lee, Seung-Jae V.

2016-01-01

Environmental fluctuations influence organismal aging by affecting various regulatory systems. One such system involves sensory neurons, which affect life span in many species. However, how sensory neurons coordinate organismal aging in response to changes in environmental signals remains elusive. Here, we found that a subset of sensory neurons shortens Caenorhabditis elegans’ life span by differentially regulating the expression of a specific insulin-like peptide (ILP), INS-6. Notably, treatment with food-derived cues or optogenetic activation of sensory neurons significantly increases ins-6 expression and decreases life span. INS-6 in turn relays the longevity signals to nonneuronal tissues by decreasing the activity of the transcription factor DAF-16/FOXO. Together, our study delineates a mechanism through which environmental sensory cues regulate aging rates by modulating the activities of specific sensory neurons and ILPs. PMID:27125673

Deletion of Brca2 exon 27 causes hypersensitivity to DNA crosslinks, chromosomal instability, and reduced life span in mice

NASA Technical Reports Server (NTRS)

Donoho, Greg; Brenneman, Mark A.; Cui, Tracy X.; Donoviel, Dorit; Vogel, Hannes; Goodwin, Edwin H.; Chen, David J.; Hasty, Paul

2003-01-01

The Brca2 tumor-suppressor gene contributes to genomic stability, at least in part by a role in homologous recombinational repair. BRCA2 protein is presumed to function in homologous recombination through interactions with RAD51. Both exons 11 and 27 of Brca2 code for domains that interact with RAD51; exon 11 encodes eight BRC motifs, whereas exon 27 encodes a single, distinct interaction domain. Deletion of all RAD51-interacting domains causes embryonic lethality in mice. A less severe phenotype is seen with BRAC2 truncations that preserve some, but not all, of the BRC motifs. These mice can survive beyond weaning, but are runted and infertile, and die very young from cancer. Cells from such mice show hypersensitivity to some genotoxic agents and chromosomal instability. Here, we have analyzed mice and cells with a deletion of only the RAD51-interacting region encoded by exon 27. Mice homozygous for this mutation (called brca2(lex1)) have a shorter life span than that of control littermates, possibly because of early onsets of cancer and sepsis. No other phenotype was observed in these animals; therefore, the brca2(lex1) mutation is less severe than truncations that delete some BRC motifs. However, at the cellular level, the brca2(lex1) mutation causes reduced viability, hypersensitivity to the DNA interstrand crosslinking agent mitomycin C, and gross chromosomal instability, much like more severe truncations. Thus, the extreme carboxy-terminal region encoded by exon 27 is important for BRCA2 function, probably because it is required for a fully functional interaction between BRCA2 and RAD51. Copyright 2003 Wiley-Liss, Inc.

Neuronal Cbl Controls Biosynthesis of Insulin-Like Peptides in Drosophila melanogaster

PubMed Central

Yu, Yue; Sun, Ying; He, Shengqi; Yan, Cheng; Rui, Liangyou; Li, Wenjun

2012-01-01

The Cbl family proteins function as both E3 ubiquitin ligases and adaptor proteins to regulate various cellular signaling events, including the insulin/insulin-like growth factor 1 (IGF1) and epidermal growth factor (EGF) pathways. These pathways play essential roles in growth, development, metabolism, and survival. Here we show that in Drosophila melanogaster, Drosophila Cbl (dCbl) regulates longevity and carbohydrate metabolism through downregulating the production of Drosophila insulin-like peptides (dILPs) in the brain. We found that dCbl was highly expressed in the brain and knockdown of the expression of dCbl specifically in neurons by RNA interference increased sensitivity to oxidative stress or starvation, decreased carbohydrate levels, and shortened life span. Insulin-producing neuron-specific knockdown of dCbl resulted in similar phenotypes. dCbl deficiency in either the brain or insulin-producing cells upregulated the expression of dilp genes, resulting in elevated activation of the dILP pathway, including phosphorylation of Drosophila Akt and Drosophila extracellular signal-regulated kinase (dERK). Genetic interaction analyses revealed that blocking Drosophila epidermal growth factor receptor (dEGFR)-dERK signaling in pan-neurons or insulin-producing cells by overexpressing a dominant-negative form of dEGFR abolished the effect of dCbl deficiency on the upregulation of dilp genes. Furthermore, knockdown of c-Cbl in INS-1 cells, a rat β-cell line, also increased insulin biosynthesis and glucose-stimulated secretion in an ERK-dependent manner. Collectively, these results suggest that neuronal dCbl regulates life span, stress responses, and metabolism by suppressing dILP production and the EGFR-ERK pathway mediates the dCbl action. Cbl suppression of insulin biosynthesis is evolutionarily conserved, raising the possibility that Cbl may similarly exert its physiological actions through regulating insulin production in β cells. PMID:22778134

Two copies of mthmg1, encoding a novel mitochondrial HMG-like protein, delay accumulation of mitochondrial DNA deletions in Podospora anserina.

PubMed

Dequard-Chablat, Michelle; Allandt, Cynthia

2002-08-01

In the filamentous fungus Podospora anserina, two degenerative processes which result in growth arrest are associated with mitochondrial genome (mitochondrial DNA [mtDNA]) instability. Senescence is correlated with mtDNA rearrangements and amplification of specific regions (senDNAs). Premature death syndrome is characterized by the accumulation of specific mtDNA deletions. This accumulation is due to indirect effects of the AS1-4 mutation, which alters a cytosolic ribosomal protein gene. The mthmg1 gene has been identified as a double-copy suppressor of premature death. It greatly delays premature death and the accumulation of deletions when it is present in two copies in an ASI-4 context. The duplication of mthmg1 has no significant effect on the wild-type life span or on senDNA patterns. In anAS1+ context, deletion of the mthmg1 gene alters germination, growth, and fertility and reduces the life span. The deltamthmg1 senescent strains display a particular senDNA pattern. This deletion is lethal in an AS1-4 context. According to its physical properties (very basic protein with putative mitochondrial targeting sequence and HMG-type DNA-binding domains) and the cellular localization of an mtHMG1-green fluorescent protein fusion, mtHMG1 appears to be a mitochondrial protein possibly associated with mtDNA. It is noteworthy that it is the first example of a protein combining the two DNA-binding domains, AT-hook motif and HMG-1 boxes. It may be involved in the stability and/or transmission of the mitochondrial genome. To date, no structural homologues have been found in other organisms. However, mtHMG1 displays functional similarities with the Saccharomyces cerevisiae mitochondrial HMG-box protein Abf2.

Reconstructing life history of hominids and humans.

PubMed

Crews, Douglas E; Gerber, Linda M

2003-06-01

Aspects of life history, such as processes and timing of development, age at maturation, and life span are consistently associated with one another across the animal kingdom. Species that develop rapidly tend to mature and reproduce early, have many offspring, and exhibit shorter life spans (r-selection) than those that develop slowly, have extended periods of premature growth, mature later in life, reproduce later and less frequently, have few offspring and/or single births, and exhibit extended life spans (K-selection). In general, primates are among the most K-selected of species. A suite of highly derived life history traits characterizes humans. Among these are physically immature neonates, slowed somatic development both in utero and post-natally, late attainment of reproductive maturity and first birth, and extended post-mature survival. Exactly when, why, and through what types of evolutionary interactions this suite arose is currently the subject of much conjecture and debate. Humankind's biocultural adaptations have helped to structure human life history evolution in unique ways not seen in other animal species. Among all species, life history traits may respond rapidly to alterations in selective pressures through hormonal processes. Selective pressures on life history likely varied widely among hominids and humans over their evolutionary history. This suggests that current patterns of human growth, development, maturation, reproduction, and post-mature survival may be of recent genesis, rather then long-standing adaptations. Thus, life history patterns observed among contemporary human and chimpanzee populations may provide little insight to those that existed earlier in hominid/human evolution.

Studying the replicative life span of yeast cells.

PubMed

Sinclair, David A

2013-01-01

The budding yeast Saccharomyces cerevisiae is a useful model for elucidating the pathways that control life span and the influence of environmental factors, such as calorie restriction (CR). For 75 years, CR has been studied for its ability to delay diseases of aging in mammals, from cancer to cardiovascular disease (McCay et al., Nutr Rev 33:241-243, 1975). In many other species, reducing calorie intake extends life span, including unicellular organisms (Jiang et al., FASEB J 14:2135-2137, 2000; Lin et al., Science 289:2126-2128, 2000), invertebrates (Rogina and Helfand, Proc Natl Acad Sci U S A 101:15998-16003, 2004), and rodents (Martín-Montalvo et al., Oncogene 30:505-520, 2011). Here we describe how to calorically restrict yeast cells, the methods used to determine the replicative life span (RLS) of budding yeast cells, how to selectively kill daughter cells using the mother enrichment program (MEP), how to measure recombination frequency at the rDNA locus, how to isolate large quantities of old cells, and how to analyze the circular forms of DNA known as extrachromosomal rDNA circles (ERCs), a cause of aging in S. cerevisiae (Petes, Cell 19:765-774, 1980; Sinclair and Guarente, Cell 91:1033-1042, 1997; Defossez et al., Mol Cell 3:447-455, 1999).

Fragmentation, Fusion, and Genetic Homogeneity in a Calcareous Sponge (Porifera, Calcarea).

PubMed

Padua, André; Leocorny, Pedro; Custódio, Márcio Reis; Klautau, Michelle

2016-06-01

Sessile marine invertebrates living on hard substrata usually present strategies such as size variations, longer life spans, fragmentation and fusion to occupy and compete for space. Calcareous sponges are usually small and short-lived, and some species are known to undergo frequent fragmentation and fusion events. However, whether fusion occurs only between genetically identical individuals remains unclear. We investigated the occurrence of chimaeras in the calcareous sponge Clathrina aurea by following the dynamics of fragmentation and fusion of 66 individuals in the field for up to 18 months and determined size variations and the life span of each individual. Microsatellites were used to determine whether fusion events occur among genetically different individuals. Growth and shrinkage of individuals were frequently observed, showing that size cannot be associated with age in C. aurea. The life span of the species ranged from 1 to 16 months (mean: 4.7 months). Short life spans and variable growth rates have been observed in other species of the class Calcarea. Fragmentation and fusion events were observed, but fusion events always occurred between genetically identical individuals, as has been suggested by graft experiments in adult Demospongiae and other Calcarea. These results suggest that at least C. aurea adults may have some mechanism to avoid chimaerism. © 2016 Wiley Periodicals, Inc.

Intermittent Administration of Rapamycin Extends the Life Span of Female C57BL/6J Mice.

PubMed

Arriola Apelo, Sebastian I; Pumper, Cassidy P; Baar, Emma L; Cummings, Nicole E; Lamming, Dudley W

2016-07-01

Inhibition of the mTOR (mechanistic target of rapamycin) signaling pathway by the FDA-approved drug rapamycin promotes life span in numerous model organisms and delays age-related disease in mice. However, the utilization of rapamycin as a therapy for age-related diseases will likely prove challenging due to the serious metabolic and immunological side effects of rapamycin in humans. We recently identified an intermittent rapamycin treatment regimen-2mg/kg administered every 5 days-with a reduced impact on glucose homeostasis and the immune system as compared with chronic treatment; however, the ability of this regimen to extend life span has not been determined. Here, we report for the first time that an intermittent rapamycin treatment regimen starting as late as 20 months of age can extend the life span of female C57BL/6J mice. Our work demonstrates that the anti-aging potential of rapamycin is separable from many of its negative side effects and suggests that carefully designed dosing regimens may permit the safer use of rapamycin and its analogs for the treatment of age-related diseases in humans. © The Author 2016. 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.

GENOMIC BASIS OF AGING AND LIFE HISTORY EVOLUTION IN DROSOPHILA MELANOGASTER

PubMed Central

Remolina, Silvia C.; Chang, Peter L.; Leips, Jeff; Nuzhdin, Sergey V.; Hughes, Kimberly A.

2015-01-01

Natural diversity in aging and other life history patterns is a hallmark of organismal variation. Related species, populations, and individuals within populations show genetically based variation in life span and other aspects of age-related performance. Population differences are especially informative because these differences can be large relative to within-population variation and because they occur in organisms with otherwise similar genomes. We used experimental evolution to produce populations divergent for life span and late-age fertility and then used deep genome sequencing to detect sequence variants with nucleotide-level resolution. Several genes and genome regions showed strong signatures of selection, and the same regions were implicated in independent comparisons, suggesting that the same alleles were selected in replicate lines. Genes related to oogenesis, immunity, and protein degradation were implicated as important modifiers of late-life performance. Expression profiling and functional annotation narrowed the list of strong candidate genes to 38, most of which are novel candidates for regulating aging. Life span and early-age fecundity were negatively correlated among populations; therefore the alleles we identified also are candidate regulators of a major life-history trade-off. More generally, we argue that hitchhiking mapping can be a powerful tool for uncovering the molecular bases of quantitative genetic variation. PMID:23106705

3D Printing Variable Stiffness Foams Using Viscous Thread Instability

NASA Astrophysics Data System (ADS)

Lipton, Jeffrey I.; Lipson, Hod

2016-08-01

Additive manufacturing of cellular structures has numerous applications ranging from fabrication of biological scaffolds and medical implants, to mechanical weight reduction and control over mechanical properties. Various additive manufacturing processes have been used to produce open regular cellular structures limited only by the resolution of the printer. These efforts have focused on printing explicitly designed cells or explicitly planning offsets between strands. Here we describe a technique for producing cellular structures implicitly by inducing viscous thread instability when extruding material. This process allows us to produce complex cellular structures at a scale that is finer than the native resolution of the printer. We demonstrate tunable effective elastic modulus and density that span two orders of magnitude. Fine grained cellular structures allow for fabrication of foams for use in a wide range of fields ranging from bioengineering, to robotics to food printing.

A Semi-quantum Version of the Game of Life

NASA Astrophysics Data System (ADS)

Flitney, Adrian P.; Abbott, Derek

The following sections are included: * Background and Motivation * Classical cellular automata * Conway's game of life * Quantum cellular automata * Semi-quantum Life * The idea * A first model * A semi-quantum model * Discussion * Summary * References

Shorter Life Span of Microorganisms and Plants as a Consequence of Shielded Magnetic Environment

NASA Astrophysics Data System (ADS)

Dobrota, C.; Piso, I. M.; Bathory, D.

The geomagnetic field is an essential environmental factor for life and health on this planet. In order to survey how magnetic fields affect the life span and the nitrogenase (an iron-sulphur enzyme) activity of Azotobacter chroococcum as well as the life span, the main organic synthesis and the water balance of plants (22 species), the biological tests were incubated under shielded magnetic field and also in normal geo-magnetic environment. The shielding level was about 10-6 of the terrestrial magnetic field.Life cycles of all organisms require the co-ordinated control of a complex set of interlocked physiological processes and metabolic pathways. Such processes are likely to be regulated by a large number of genes. Our researches suggest that the main point in biological structures, which seems to be affected by the low magnetic environment, is the water molecule. Magnetic field induces a molecular alignment. Under shielded conditions, unstructured water molecules with fewer hydrogen bonds, which are producing a more reactive environment, are occurring. As compared to control, the life span of both microorganisms and plants was shorter in shielded environment. A higher nitrogenase affinity for the substrate was recorded in normal geo-magnetic field compared to low magnetic field. The synthesis of carbohydrates, lipids, proteins and enzymes was modified under experimental conditions. The stomatal conductance was higher between 158 and 300% in shielded environment indicating an important water loss from the plant cells.Our results support the idea that the shielded magnetic environment induces different reactions depending on the time of exposure and on the main metabolic pathways of the cells.

Methods for Stem Cell Production and Therapy

NASA Technical Reports Server (NTRS)

Valluri, Jagan V. (Inventor); Claudio, Pier Paolo (Inventor)

2015-01-01

The present invention relates to methods for rapidly expanding a stem cell population with or without culture supplements in simulated microgravity conditions. The present invention relates to methods for rapidly increasing the life span of stem cell populations without culture supplements in simulated microgravity conditions. The present invention also relates to methods for increasing the sensitivity of cancer stem cells to chemotherapeutic agents by culturing the cancer stem cells under microgravity conditions and in the presence of omega-3 fatty acids. The methods of the present invention can also be used to proliferate cancer cells by culturing them in the presence of omega-3 fatty acids. The present invention also relates to methods for testing the sensitivity of cancer cells and cancer stem cells to chemotherapeutic agents by culturing the cancer cells and cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce tissue for use in transplantation by culturing stem cells or cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce cellular factors and growth factors by culturing stem cells or cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce cellular factors and growth factors to promote differentiation of cancer stem cells under microgravity conditions.

Functional RNA elements in the dengue virus genome.

PubMed

Gebhard, Leopoldo G; Filomatori, Claudia V; Gamarnik, Andrea V

2011-09-01

Dengue virus (DENV) genome amplification is a process that involves the viral RNA, cellular and viral proteins, and a complex architecture of cellular membranes. The viral RNA is not a passive template during this process; it plays an active role providing RNA signals that act as promoters, enhancers and/or silencers of the replication process. RNA elements that modulate RNA replication were found at the 5' and 3' UTRs and within the viral coding sequence. The promoter for DENV RNA synthesis is a large stem loop structure located at the 5' end of the genome. This structure specifically interacts with the viral polymerase NS5 and promotes RNA synthesis at the 3' end of a circularized genome. The circular conformation of the viral genome is mediated by long range RNA-RNA interactions that span thousands of nucleotides. Recent studies have provided new information about the requirement of alternative, mutually exclusive, structures in the viral RNA, highlighting the idea that the viral genome is flexible and exists in different conformations. In this article, we describe elements in the promoter SLA and other RNA signals involved in NS5 polymerase binding and activity, and provide new ideas of how dynamic secondary and tertiary structures of the viral RNA participate in the viral life cycle.

Mitochondrial-Nuclear Epistasis: Implications for Human Aging and Longevity

PubMed Central

Tranah, Gregory

2010-01-01

There is substantial evidence that mitochondria are involved in the aging process. Mitochondrial function requires the coordinated expression of hundreds of nuclear genes and a few dozen mitochondrial genes, many of which have been associated with either extended or shortened life span. Impaired mitochondrial function resulting from mtDNA and nuclear DNA variation is likely to contribute to an imbalance in cellular energy homeostasis, increased vulnerability to oxidative stress, and an increased rate of cellular senescence and aging. The complex genetic architecture of mitochondria suggests that there may be an equally complex set of gene interactions (epistases) involving genetic variation in the nuclear and mitochondrial genomes. Results from Drosophila suggest that the effects of mtDNA haplotypes on longevity vary among different nuclear allelic backgrounds, which could account for the inconsistent associations that have been observed between mitochondrial DNA (mtDNA) haplogroups and survival in humans. A diversity of pathways may influence the way mitochondria and nuclear – mitochondrial interactions modulate longevity, including: oxidative phosphorylation; mitochondrial uncoupling; antioxidant defenses; mitochondrial fission and fusion; and sirtuin regulation of mitochondrial genes. We hypothesize that aging and longevity, as complex traits having a significant genetic component, are likely to be controlled by nuclear gene variants interacting with both inherited and somatic mtDNA variability. PMID:20601194

AUTEN-67, an autophagy-enhancing drug candidate with potent antiaging and neuroprotective effects.

PubMed

Papp, Diána; Kovács, Tibor; Billes, Viktor; Varga, Máté; Tarnóci, Anna; Hackler, László; Puskás, László G; Liliom, Hanna; Tárnok, Krisztián; Schlett, Katalin; Borsy, Adrienn; Pádár, Zsolt; Kovács, Attila L; Hegedűs, Krisztina; Juhász, Gábor; Komlós, Marcell; Erdős, Attila; Gulyás, Balázs; Vellai, Tibor

2016-01-01

Autophagy is a major molecular mechanism that eliminates cellular damage in eukaryotic organisms. Basal levels of autophagy are required for maintaining cellular homeostasis and functioning. Defects in the autophagic process are implicated in the development of various age-dependent pathologies including cancer and neurodegenerative diseases, as well as in accelerated aging. Genetic activation of autophagy has been shown to retard the accumulation of damaged cytoplasmic constituents, delay the incidence of age-dependent diseases, and extend life span in genetic models. This implies that autophagy serves as a therapeutic target in treating such pathologies. Although several autophagy-inducing chemical agents have been identified, the majority of them operate upstream of the core autophagic process, thereby exerting undesired side effects. Here, we screened a small-molecule library for specific inhibitors of MTMR14, a myotubularin-related phosphatase antagonizing the formation of autophagic membrane structures, and isolated AUTEN-67 (autophagy enhancer-67) that significantly increases autophagic flux in cell lines and in vivo models. AUTEN-67 promotes longevity and protects neurons from undergoing stress-induced cell death. It also restores nesting behavior in a murine model of Alzheimer disease, without apparent side effects. Thus, AUTEN-67 is a potent drug candidate for treating autophagy-related diseases.

Potential large animal models for gene therapy of human genetic diseases of immune and blood cell systems.

PubMed

Bauer, Thomas R; Adler, Rima L; Hickstein, Dennis D

2009-01-01

Genetic mutations involving the cellular components of the hematopoietic system--red blood cells, white blood cells, and platelets--manifest clinically as anemia, infection, and bleeding. Although gene targeting has recapitulated many of these diseases in mice, these murine homologues are limited as translational models by their small size and brief life span as well as the fact that mutations induced by gene targeting do not always faithfully reflect the clinical manifestations of such mutations in humans. Many of these limitations can be overcome by identifying large animals with genetic diseases of the hematopoietic system corresponding to their human disease counterparts. In this article, we describe human diseases of the cellular components of the hematopoietic system that have counterparts in large animal species, in most cases carrying mutations in the same gene (CD18 in leukocyte adhesion deficiency) or genes in interacting proteins (DNA cross-link repair 1C protein and protein kinase, DNA-activated catalytic polypeptide in radiation-sensitive severe combined immunodeficiency). Furthermore, we describe the potential of these animal models to serve as disease-specific preclinical models for testing the efficacy and safety of clinical interventions such as hematopoietic stem cell transplantation or gene therapy before their use in humans with the corresponding disease.

Establishment of immortal multipotent rat salivary progenitor cell line toward salivary gland regeneration.

PubMed

Yaniv, Adi; Neumann, Yoav; David, Ran; Stiubea-Cohen, Raluca; Orbach, Yoav; Lang, Stephan; Rotter, Nicole; Dvir-Ginzberg, Mona; Aframian, Doron J; Palmon, Aaron

2011-01-01

Adult salivary gland stem cells are promising candidates for cell therapy and tissue regeneration in cases of irreversible damage to salivary glands in head and neck cancer patients undergoing irradiation therapy. At present, the major restriction in handling such cells is their relatively limited life span during in vitro cultivation, resulting in an inadequate experimental platform to explore the salivary gland-originated stem cells as candidates for future clinical application in therapy. We established a spontaneous immortal integrin α6β1-expressing cell line of adult salivary progenitor cells from rats (rat salivary clone [RSC]) and investigated their ability to sustain cellular properties. This line was able to propagate for more than 400 doublings without loss of differentiation potential. RSC could differentiate in vitro to both acinar- and ductal-like structures and could be further manipulated upon culturing on a 3D scaffolds with different media supplements. Moreover, RSC expressed salivary-specific mRNAs and proteins as well as epithelial stem cell markers, and upon differentiation process their expression was changed. These results suggest RSC as a good model for further studies exploring cellular senescence, differentiation, and in vitro tissue engineering features as a crucial step toward reengineering irradiation-impaired salivary glands.

A tribute to Dr. Gordon Hisashi Sato (December 24, 1927-March 31, 2017).

PubMed

Sato, J Denry; Okamoto, Tetsuji; Barnes, David; Hayashi, Jun; Serrero, Ginette; McKeehan, Wallace L

2018-03-01

Gordon H. Sato, an innovator in mammalian tissue culture and integrated cellular physiology, passed away in 2017. In tribute to Dr. Sato, In Vitro Cellular and Developmental Biology-Animal presents a collection of invited remembrances from six colleagues whose associations with Dr. Sato spanned more than 40 years. Dr. Sato was a past president of the Tissue Culture Association (now the Society for In Vitro Biology), editor-in-chief of In Vitro Cellular and Developmental Biology (1987-1991), and the recipient of the lifetime achievement award from the Society for In Vitro Biology (2002). He was elected to the US National Academy of Sciences in 1984.

Life-span development of self-esteem and its effects on important life outcomes.

PubMed

Orth, Ulrich; Robins, Richard W; Widaman, Keith F

2012-06-01

We examined the life-span development of self-esteem and tested whether self-esteem influences the development of important life outcomes, including relationship satisfaction, job satisfaction, occupational status, salary, positive and negative affect, depression, and physical health. Data came from the Longitudinal Study of Generations. Analyses were based on 5 assessments across a 12-year period of a sample of 1,824 individuals ages 16 to 97 years. First, growth curve analyses indicated that self-esteem increases from adolescence to middle adulthood, reaches a peak at about age 50 years, and then decreases in old age. Second, cross-lagged regression analyses indicated that self-esteem is best modeled as a cause rather than a consequence of life outcomes. Third, growth curve analyses, with self-esteem as a time-varying covariate, suggested that self-esteem has medium-sized effects on life-span trajectories of affect and depression, small to medium-sized effects on trajectories of relationship and job satisfaction, a very small effect on the trajectory of health, and no effect on the trajectory of occupational status. These findings replicated across 4 generations of participants--children, parents, grandparents, and their great-grandparents. Together, the results suggest that self-esteem has a significant prospective impact on real-world life experiences and that high and low self-esteem are not mere epiphenomena of success and failure in important life domains. 2012 APA, all rights reserved

Nup100 regulates Saccharomyces cerevisiae replicative life span by mediating the nuclear export of specific tRNAs

PubMed Central

Lord, Christopher L.; Ospovat, Ophir; Wente, Susan R.

2017-01-01

Nuclear pore complexes (NPCs), which are composed of nucleoporins (Nups) and regulate transport between the nucleus and cytoplasm, significantly impact the replicative life span (RLS) of Saccharomyces cerevisiae. We previously reported that deletion of the nonessential gene NUP100 increases RLS, although the molecular basis for this effect was unknown. In this study, we find that nuclear tRNA accumulation contributes to increased longevity in nup100Δ cells. Fluorescence in situ hybridization (FISH) experiments demonstrate that several specific tRNAs accumulate in the nuclei of nup100Δ mutants. Protein levels of the transcription factor Gcn4 are increased when NUP100 is deleted, and GCN4 is required for the elevated life spans of nup100Δ mutants, similar to other previously described tRNA export and ribosomal mutants. Northern blots indicate that tRNA splicing and aminoacylation are not significantly affected in nup100Δ cells, suggesting that Nup100 is largely required for nuclear export of mature, processed tRNAs. Distinct tRNAs accumulate in the nuclei of nup100Δ and msn5Δ mutants, while Los1-GFP nucleocytoplasmic shuttling is unaffected by Nup100. Thus, we conclude that Nup100 regulates tRNA export in a manner distinct from Los1 or Msn5. Together, these experiments reveal a novel Nup100 role in the tRNA life cycle that impacts the S. cerevisiae life span. PMID:27932586

Relationships of leaf dark respiration to leaf nitrogen, specific leaf area and leaf life-span: a test across biomes and functional groups

Treesearch

Peter B. Reich; Michael B. Walters; David S. Ellsworth; [and others; [Editor’s note: James M.. Vose is the SRS co-author for this publication.

1998-01-01

Based on prior evidence of coordinated multiple leaf trait scaling, the authors hypothesized that variation among species in leaf dark respiration rate (Rd) should scale with variation in traits such as leaf nitrogen (N), leaf life-span, specific leaf area (SLA), and net photosynthetic capacity (Amax). However, it is not known whether such scaling, if it exists, is...

[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.

Spatial abilities across the adult life span.

PubMed

Borella, Erika; Meneghetti, Chiara; Ronconi, Lucia; De Beni, Rossana

2014-02-01

The study investigates age-related effects across the adult life span on spatial abilities (testing subabilities based on a distinction between spatial visualization, mental rotation, and perspective taking) and spatial self-assessments. The sample consisted of 454 participants (223 women and 231 men) from 20 to 91 years of age. Results showed nonlinear age-related effects for spatial visualization and perspective taking but linear effects for mental rotation; few or no age-related effects were found for spatial self-assessments. Working memory accounted for only a small proportion of the variance in all spatial tasks and had no effect on spatial self-assessments. Overall, our findings suggest that the influence of age on spatial skills across the adult life span is considerable, but the effects of age change as a function of the spatial task considered, and the effect on spatial self-assessment is more marginal.

Food-derived sensory cues modulate longevity via distinct neuroendocrine insulin-like peptides.

PubMed

Artan, Murat; Jeong, Dae-Eun; Lee, Dongyeop; Kim, Young-Il; Son, Heehwa G; Husain, Zahabiya; Kim, Jinmahn; Altintas, Ozlem; Kim, Kyuhyung; Alcedo, Joy; Lee, Seung-Jae V

2016-05-01

Environmental fluctuations influence organismal aging by affecting various regulatory systems. One such system involves sensory neurons, which affect life span in many species. However, how sensory neurons coordinate organismal aging in response to changes in environmental signals remains elusive. Here, we found that a subset of sensory neurons shortens Caenorhabditis elegans' life span by differentially regulating the expression of a specific insulin-like peptide (ILP), INS-6. Notably, treatment with food-derived cues or optogenetic activation of sensory neurons significantly increases ins-6 expression and decreases life span. INS-6 in turn relays the longevity signals to nonneuronal tissues by decreasing the activity of the transcription factor DAF-16/FOXO. Together, our study delineates a mechanism through which environmental sensory cues regulate aging rates by modulating the activities of specific sensory neurons and ILPs. © 2016 Artan et al.; Published by Cold Spring Harbor Laboratory Press.

Caenorhabditis elegans as Model System in Pharmacology and Toxicology: Effects of Flavonoids on Redox-Sensitive Signalling Pathways and Ageing

PubMed Central

Koch, Karoline; Havermann, Susannah; Büchter, Christian

2014-01-01

Flavonoids are secondary plant compounds that mediate diverse biological activities, for example, by scavenging free radicals and modulating intracellular signalling pathways. It has been shown in various studies that distinct flavonoid compounds enhance stress resistance and even prolong the life span of organisms. In the last years the model organism C. elegans has gained increasing importance in pharmacological and toxicological sciences due to the availability of various genetically modified nematode strains, the simplicity of modulating genes by RNAi, and the relatively short life span. Several studies have been performed demonstrating that secondary plant compounds influence ageing, stress resistance, and distinct signalling pathways in the nematode. Here we present an overview of the modulating effects of different flavonoids on oxidative stress, redox-sensitive signalling pathways, and life span in C. elegans introducing the usability of this model system for pharmacological and toxicological research. PMID:24895670

Basic traits predict the prevalence of personality disorder across the life span: the example of psychopathy.

PubMed

Vachon, David D; Lynam, Donald R; Widiger, Thomas A; Miller, Joshua D; McCrae, Robert R; Costa, Paul T

2013-05-01

Personality disorders (PDs) may be better understood in terms of dimensions of general personality functioning rather than as discrete categorical conditions. Personality-trait descriptions of PDs are robust across methods and settings, and PD assessments based on trait measures show good construct validity. The study reported here extends research showing that basic traits (e.g., impulsiveness, warmth, straightforwardness, modesty, and deliberation) can re-create the epidemiological characteristics associated with PDs. Specifically, we used normative changes in absolute trait levels to simulate age-related differences in the prevalence of psychopathy in a forensic setting. Results demonstrated that trait information predicts the rate of decline for psychopathy over the life span; discriminates the decline of psychopathy from that of a similar disorder, antisocial PD; and accurately predicts the differential decline of subfactors of psychopathy. These findings suggest that basic traits provide a parsimonious account of PD prevalence across the life span.

daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans.

PubMed

Lin, K; Dorman, J B; Rodan, A; Kenyon, C

1997-11-14

The wild-type Caenorhabditis elegans nematode ages rapidly, undergoing development, senescence, and death in less than 3 weeks. In contrast, mutants with reduced activity of the gene daf-2, a homolog of the insulin and insulin-like growth factor receptors, age more slowly than normal and live more than twice as long. These mutants are active and fully fertile and have normal metabolic rates. The life-span extension caused by daf-2 mutations requires the activity of the gene daf-16. daf-16 appears to play a unique role in life-span regulation and encodes a member of the hepatocyte nuclear factor 3 (HNF-3)/forkhead family of transcriptional regulators. In humans, insulin down-regulates the expression of certain genes by antagonizing the activity of HNF-3, raising the possibility that aspects of this regulatory system have been conserved.

A congruent phylogenomic signal places eukaryotes within the Archaea.

PubMed

Williams, Tom A; Foster, Peter G; Nye, Tom M W; Cox, Cymon J; Embley, T Martin

2012-12-22

Determining the relationships among the major groups of cellular life is important for understanding the evolution of biological diversity, but is difficult given the enormous time spans involved. In the textbook 'three domains' tree based on informational genes, eukaryotes and Archaea share a common ancestor to the exclusion of Bacteria. However, some phylogenetic analyses of the same data have placed eukaryotes within the Archaea, as the nearest relatives of different archaeal lineages. We compared the support for these competing hypotheses using sophisticated phylogenetic methods and an improved sampling of archaeal biodiversity. We also employed both new and existing tests of phylogenetic congruence to explore the level of uncertainty and conflict in the data. Our analyses suggested that much of the observed incongruence is weakly supported or associated with poorly fitting evolutionary models. All of our phylogenetic analyses, whether on small subunit and large subunit ribosomal RNA or concatenated protein-coding genes, recovered a monophyletic group containing eukaryotes and the TACK archaeal superphylum comprising the Thaumarchaeota, Aigarchaeota, Crenarchaeota and Korarchaeota. Hence, while our results provide no support for the iconic three-domain tree of life, they are consistent with an extended eocyte hypothesis whereby vital components of the eukaryotic nuclear lineage originated from within the archaeal radiation.

Smaller Fleas: Viruses of Microorganisms

PubMed Central

Hyman, Paul; Abedon, Stephen T.

2012-01-01

Life forms can be roughly differentiated into those that are microscopic versus those that are not as well as those that are multicellular and those that, instead, are unicellular. Cellular organisms seem generally able to host viruses, and this propensity carries over to those that are both microscopic and less than truly multicellular. These viruses of microorganisms, or VoMs, in fact exist as the world's most abundant somewhat autonomous genetic entities and include the viruses of domain Bacteria (bacteriophages), the viruses of domain Archaea (archaeal viruses), the viruses of protists, the viruses of microscopic fungi such as yeasts (mycoviruses), and even the viruses of other viruses (satellite viruses). In this paper we provide an introduction to the concept of viruses of microorganisms, a.k.a., viruses of microbes. We provide broad discussion particularly of VoM diversity. VoM diversity currently spans, in total, at least three-dozen virus families. This is roughly ten families per category—bacterial, archaeal, fungal, and protist—with some virus families infecting more than one of these microorganism major taxa. Such estimations, however, will vary with further discovery and taxon assignment and also are dependent upon what forms of life one includes among microorganisms. PMID:24278736

Partner preferences across the life span: online dating by older adults.

PubMed

Alterovitz, Sheyna Sears-Roberts; Mendelsohn, Gerald A

2009-06-01

Stereotypes of older adults as withdrawn or asexual fail to recognize that romantic relationships in later life are increasingly common. The authors analyzed 600 Internet personal ads from 4 age groups: 20-34, 40-54, 60-74, and 75+ years. Predictions from evolutionary theory held true in later life, when reproduction is no longer a concern. Across the life span, men sought physical attractiveness and offered status-related information more than women; women were more selective than men and sought status more than men. With age, men desired women increasingly younger than themselves, whereas women desired older men until ages 75 and over, when they sought men younger than themselves. (c) 2009 APA, all rights reserved.

Balancing Life Roles to Achieve Career Happiness and Life Satisfaction.

ERIC Educational Resources Information Center

Peronne, Kristin Marie

2000-01-01

A study guided by Super's Life Span, Life Space approach included a survey of 119 women and 66 men about sacrifices made in life and work roles to achieve balance and satisfaction. Differences in sacrifices and satisfaction were related to the combination of life roles they occupied. (SK)

Nutritional deficiency, immunologic function, and disease.

PubMed Central

Good, R. A.; Fernandes, G.; Yunis, E. J.; Cooper, W. C.; Jose, D. C.; Kramer, T. R.; Hansen, M. A.

1976-01-01

Several experiments conducted by our group over a period of 6 years have shown that nutritional stress, especially protein and/or calorie deprivation, leads to many, often dramatic, changes in the immune responses of mice, rats, and guinea pigs. Chronic protein deprivation (CPD) has been shown to create an enhancing effect on the cell-mediated immune responses of these animals. Humoral responses under CPD conditions were most often found to be depressed, but sometimes were unaffected, depending on the nature of the antigen employed. Chronic protein deprivation, consistent with the pattern just mentioned, improved tumor immunity by depressing production of B-cell blocking factors, and, in at least one instance, resistance to development of mammary adenocarcinoma in C3H mice was associated with evidence of increased numbers of T suppressor cells. Profound nutritional deficits (less than 5% protein per total daily food intake) depressed both cellular and humoral immunity. Early, though temporary, protein deprivation caused a long-term depression of both cellular and humoral immunity also, with the humoral component being the first to recover. Manipulation of protein and calories was found to have a profound effect on certain autoimmune conditions. Diets high in fat and low in protein favored reproduction but shortened the life of NZB mice, whereas diets high in protein and low in fat inhibited development of autoimmunity and prolonged life. Chronic moderate protein restriction permitted NZB mice to maintain their normally waning immunologic functions much longer than mice fed a normal protein intake. Further, the low-protein diet was associated with a delay in development of manifestations of autoimmunity. Decreasing dietary calories by a reduction of fats, carbohydrates, and proteins more than doubled the average life span of (NZB X NZW)F1 mice, a strain prone to early death from autoimmune disease. Histopathologic studies using immunofluorescent microscopy revealed that the development of the renal lesions caused by the deposition of antigen-antibody complexes, which is so characteristic of these mice, was markedly delayed. PMID:8988

Life span and reproductive cost explain interspecific variation in the optimal onset of reproduction.

PubMed

Mourocq, Emeline; Bize, Pierre; Bouwhuis, Sandra; Bradley, Russell; Charmantier, Anne; de la Cruz, Carlos; Drobniak, Szymon M; Espie, Richard H M; Herényi, Márton; Hötker, Hermann; Krüger, Oliver; Marzluff, John; Møller, Anders P; Nakagawa, Shinichi; Phillips, Richard A; Radford, Andrew N; Roulin, Alexandre; Török, János; Valencia, Juliana; van de Pol, Martijn; Warkentin, Ian G; Winney, Isabel S; Wood, Andrew G; Griesser, Michael

2016-02-01

Fitness can be profoundly influenced by the age at first reproduction (AFR), but to date the AFR-fitness relationship only has been investigated intraspecifically. Here, we investigated the relationship between AFR and average lifetime reproductive success (LRS) across 34 bird species. We assessed differences in the deviation of the Optimal AFR (i.e., the species-specific AFR associated with the highest LRS) from the age at sexual maturity, considering potential effects of life history as well as social and ecological factors. Most individuals adopted the species-specific Optimal AFR and both the mean and Optimal AFR of species correlated positively with life span. Interspecific deviations of the Optimal AFR were associated with indices reflecting a change in LRS or survival as a function of AFR: a delayed AFR was beneficial in species where early AFR was associated with a decrease in subsequent survival or reproductive output. Overall, our results suggest that a delayed onset of reproduction beyond maturity is an optimal strategy explained by a long life span and costs of early reproduction. By providing the first empirical confirmations of key predictions of life-history theory across species, this study contributes to a better understanding of life-history evolution. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

The resolution of ambiguity as the basis for life: A cellular bridge between Western reductionism and Eastern holism.

PubMed

Torday, John S; Miller, William B

2017-12-01

Boundary conditions enable cellular life through negentropy, chemiosmosis, and homeostasis as identifiable First Principles of Physiology. Self-referential awareness of status arises from this organized state to sustain homeostatic imperatives. Preferred homeostatic status is dependent upon the appraisal of information and its communication. However, among living entities, sources of information and their dissemination are always imprecise. Consequently, living systems exist within an innate state of ambiguity. It is presented that cellular life and evolutionary development are a self-organizing cellular response to uncertainty in iterative conformity with its basal initiating parameters. Viewing the life circumstance in this manner permits a reasoned unification between Western rational reductionism and Eastern holism. Copyright © 2017 Elsevier Ltd. All rights reserved.

3D Printing Variable Stiffness Foams Using Viscous Thread Instability

PubMed Central

Lipton, Jeffrey I.; Lipson, Hod

2016-01-01

Additive manufacturing of cellular structures has numerous applications ranging from fabrication of biological scaffolds and medical implants, to mechanical weight reduction and control over mechanical properties. Various additive manufacturing processes have been used to produce open regular cellular structures limited only by the resolution of the printer. These efforts have focused on printing explicitly designed cells or explicitly planning offsets between strands. Here we describe a technique for producing cellular structures implicitly by inducing viscous thread instability when extruding material. This process allows us to produce complex cellular structures at a scale that is finer than the native resolution of the printer. We demonstrate tunable effective elastic modulus and density that span two orders of magnitude. Fine grained cellular structures allow for fabrication of foams for use in a wide range of fields ranging from bioengineering, to robotics to food printing. PMID:27503148

Self-esteem development across the life span: a longitudinal study with a large sample from Germany.

PubMed

Orth, Ulrich; Maes, Jürgen; Schmitt, Manfred

2015-02-01

The authors examined the development of self-esteem across the life span. Data came from a German longitudinal study with 3 assessments across 4 years of a sample of 2,509 individuals ages 14 to 89 years. The self-esteem measure used showed strong measurement invariance across assessments and birth cohorts. Latent growth curve analyses indicated that self-esteem follows a quadratic trajectory across the life span, increasing during adolescence, young adulthood, and middle adulthood, reaching a peak at age 60 years, and then declining in old age. No cohort effects on average levels of self-esteem or on the shape of the trajectory were found. Moreover, the trajectory did not differ across gender, level of education, or for individuals who had lived continuously in West versus East Germany (i.e., the 2 parts of Germany that had been separate states from 1949 to 1990). However, the results suggested that employment status, household income, and satisfaction in the domains of work, relationships, and health contribute to a more positive life span trajectory of self-esteem. The findings have significant implications, because they call attention to developmental stages in which individuals may be vulnerable because of low self-esteem (such as adolescence and old age) and to factors that predict successful versus problematic developmental trajectories. PsycINFO Database Record (c) 2015 APA, all rights reserved.

The life span-prolonging effect of sirtuin-1 is mediated by autophagy.

PubMed

Morselli, Eugenia; Maiuri, Maria Chiara; Markaki, Maria; Megalou, Evgenia; Pasparaki, Angela; Palikaras, Konstantinos; Criollo, Alfredo; Galluzzi, Lorenzo; Malik, Shoaib Ahmad; Vitale, Ilio; Michaud, Mickael; Madeo, Frank; Tavernarakis, Nektarios; Kroemer, Guido

2010-01-01

The life span of various model organisms can be extended by caloric restriction as well as by autophagy-inducing pharmacological agents. Life span-prolonging effects have also been observed in yeast cells, nematodes and flies upon the overexpression of the deacetylase Sirtuin-1. Intrigued by these observations and by the established link between caloric restriction and Sirtuin-1 activation, we decided to investigate the putative implication of Sirtuin-1 in the response of human cancer cells and Caenorhabditis elegans to multiple triggers of autophagy. Our data indicate that the activation of Sirtuin-1 (by the pharmacological agent resveratrol and/or genetic means) per se ignites autophagy, and that Sirtuin-1 is required for the autophagic response to nutrient deprivation, in both human and nematode cells, but not for autophagy triggered by downstream signals such as the inhibition of mTOR or p53. Since the life spanextending effects of Sirtuin-1 activators are lost in autophagy-deficient C. elegans, our results suggest that caloric restriction and resveratrol extend longevity, at least in experimental settings, by activating autophagy.

Sites of Retroviral DNA Integration: From Basic Research to Clinical Applications

PubMed Central

Serrao, Erik; Engelman, Alan N.

2016-01-01

One of the most crucial steps in the life cycle of a retrovirus is the integration of the viral DNA (vDNA) copy of the RNA genome into the genome of an infected host cell. Integration provides for efficient viral gene expression as well as for the segregation of the viral genomes to daughter cells upon cell division. Some integrated viruses are not well expressed, and cells latently infected with HIV-1 can resist the action of potent antiretroviral drugs and remain dormant for decades. Intensive research has been dedicated to understanding the catalytic mechanism of integration, as well as the viral and cellular determinants that influence integration site distribution throughout the host genome. In this review we summarize the evolution of techniques that have been used to recover and map retroviral integration sites, from the early days that first indicated that integration could occur in multiple cellular DNA locations, to current technologies that map upwards of millions of unique integration sites from single in vitro integration reactions or cell culture infections. We further review important insights gained from the use of such mapping techniques, including the monitoring of cell clonal expansion in patients treated with retrovirus-based gene therapy vectors, or AIDS patients on suppressive antiretroviral therapy (ART). These insights span from integrase (IN) enzyme sequence preferences within target DNA (tDNA) at the sites of integration, to the roles of host cellular proteins in mediating global integration distribution, to the potential relationship between genomic location of vDNA integration site and retroviral latency. PMID:26508664

Resveratrol stimulates AMP kinase activity in neurons.

PubMed

Dasgupta, Biplab; Milbrandt, Jeffrey

2007-04-24

Resveratrol is a polyphenol produced by plants that has multiple beneficial activities similar to those associated with caloric restriction (CR), such as increased life span and delay in the onset of diseases associated with aging. CR improves neuronal health, and the global beneficial effects of CR have been postulated to be mediated by the nervous system. One key enzyme thought to be activated during CR is the AMP-activated kinase (AMPK), a sensor of cellular energy levels. AMPK is activated by increases in the cellular AMP:ATP ratio, whereupon it functions to help preserve cellular energy. In this regard, the regulation of dietary food intake by hypothalamic neurons is mediated by AMPK. The suppression of nonessential energy expenditure by activated AMPK along with the CR mimetic and neuroprotective properties of resveratrol led us to hypothesize that neuronal activation of AMPK could be an important component of resveratrol activity. Here, we show that resveratrol activated AMPK in Neuro2a cells and primary neurons in vitro as well as in the brain. Resveratrol and the AMPK-activating compound 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) promoted robust neurite outgrowth in Neuro2a cells, which was blocked by genetic and pharmacologic inhibition of AMPK. Resveratrol also stimulated mitochondrial biogenesis in an AMPK-dependent manner. Resveratrol-stimulated AMPK activity in neurons depended on LKB1 activity but did not require the NAD-dependent protein deacetylase SIRT1 during this time frame. These findings suggest that neuronal activation of AMPK by resveratrol could affect neuronal energy homeostasis and contribute to the neuroprotective effects of resveratrol.

Physical Performance Across the Adult Life Span: Correlates With Age and Physical Activity.

PubMed

Hall, Katherine S; Cohen, Harvey J; Pieper, Carl F; Fillenbaum, Gerda G; Kraus, William E; Huffman, Kim M; Cornish, Melissa A; Shiloh, Andrew; Flynn, Christy; Sloane, Richard; Newby, L Kristin; Morey, Miriam C

2017-04-01

A number of large-scale population studies have provided valuable information about physical performance in aged individuals; however, there is little information about trajectories of function and associations with age across the adult life span. We developed a mobility-focused physical performance screener designed to be appropriate for the adult life span. The physical performance battery includes measures of mobility, strength, endurance, and balance. Physical activity (PA) was assessed with accelerometry. We examined age-related trends in physical performance and PA, and the relationship between physical performance and PA across the age range (30-90+), by decade, in 775 participants enrolled in the study 2012-2014. Physical performance was worse with increasing age decade. Although men performed better than women across all ages, the decrement by age group was similar between genders. Worsening physical performance was observed as early as the fifth decade for chair stands and balance and in the sixth decade for gait speed and aerobic endurance. The number and strength of significant associations between physical performance and PA increased with greater age: the greatest number of significant associations was seen in the 60-79 age groups, with fewer reported in the 30-59 and 80-90+ age groups. More PA was associated with better physical function. These results emphasize the importance of a life span approach to studies of function and aging. This work points to the need for a physical performance screener that spans across adulthood as a clinical tool for identifying functional decline. © The Author 2016. 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.

Deficiency mapping of quantitative trait loci affecting longevity in Drosophila melanogaster.

PubMed Central

Pasyukova, E G; Vieira, C; Mackay, T F

2000-01-01

In a previous study, sex-specific quantitative trait loci (QTL) affecting adult longevity were mapped by linkage to polymorphic roo transposable element markers, in a population of recombinant inbred lines derived from the Oregon and 2b strains of Drosophila melanogaster. Two life span QTL were each located on chromosomes 2 and 3, within sections 33E-46C and 65D-85F on the cytological map, respectively. We used quantitative deficiency complementation mapping to further resolve the locations of life span QTL within these regions. The Oregon and 2b strains were each crossed to 47 deficiencies spanning cytological regions 32F-44E and 64C-76B, and quantitative failure of the QTL alleles to complement the deficiencies was assessed. We initially detected a minimum of five and four QTL in the chromosome 2 and 3 regions, respectively, illustrating that multiple linked factors contribute to each QTL detected by recombination mapping. The QTL locations inferred from deficiency mapping did not generally correspond to those of candidate genes affecting oxidative and thermal stress or glucose metabolism. The chromosome 2 QTL in the 35B-E region was further resolved to a minimum of three tightly linked QTL, containing six genetically defined loci, 24 genes, and predicted genes that are positional candidates corresponding to life span QTL. This region was also associated with quantitative variation in life span in a sample of 10 genotypes collected from nature. Quantitative deficiency complementation is an efficient method for fine-scale QTL mapping in Drosophila and can be further improved by controlling the background genotype of the strains to be tested. PMID:11063689

The Social Context of Managing Diabetes across the Life Span

PubMed Central

Wiebe, Deborah J.; Helgeson, Vicki; Berg, Cynthia A.

2016-01-01

Diabetes self-management is crucial to maintaining quality of life and preventing long-term complications, and occurs daily in the context of close interpersonal relationships. This article examines how social relationships are central to meeting the complex demands of managing type 1 and type 2 diabetes across the life span. The social context of diabetes management includes multiple resources, including family (parents, spouses), peers, romantic partners, and health care providers. We discuss how these social resources change across the life span, focusing on childhood and adolescence, emerging adulthood, and adulthood and aging. We review how diabetes both affects and is affected by key social relationships at each developmental period. Despite high variability in how the social context is conceptualized and measured across studies, findings converge on the characteristics of social relationships that facilitate or undermine diabetes management across the life span. These characteristics are consistent with both Interpersonal Theory and Self-Determination Theory, two organizing frameworks that we utilize to explore social behaviors that are related to diabetes management. Involvement and support from one’s social partners, particularly family members, is consistently associated with good diabetes outcomes when characterized by warmth, collaboration and acceptance. Under-involvement and interactions characterized by conflict and criticism are consistently associated with poor diabetes outcomes. Intrusive involvement that contains elements of social control may undermine diabetes management, particularly when it impinges on self-efficacy. Implications for future research directions and for interventions that promote the effective use of the social context to improve diabetes self-management are discussed. PMID:27690482

Nup100 regulates Saccharomyces cerevisiae replicative life span by mediating the nuclear export of specific tRNAs.

PubMed

Lord, Christopher L; Ospovat, Ophir; Wente, Susan R

2017-03-01

Nuclear pore complexes (NPCs), which are composed of nucleoporins (Nups) and regulate transport between the nucleus and cytoplasm, significantly impact the replicative life span (RLS) of Saccharomyces cerevisiae We previously reported that deletion of the nonessential gene NUP100 increases RLS, although the molecular basis for this effect was unknown. In this study, we find that nuclear tRNA accumulation contributes to increased longevity in nup100 Δ cells. Fluorescence in situ hybridization (FISH) experiments demonstrate that several specific tRNAs accumulate in the nuclei of nup100 Δ mutants. Protein levels of the transcription factor Gcn4 are increased when NUP100 is deleted, and GCN4 is required for the elevated life spans of nup100 Δ mutants, similar to other previously described tRNA export and ribosomal mutants. Northern blots indicate that tRNA splicing and aminoacylation are not significantly affected in nup100 Δ cells, suggesting that Nup100 is largely required for nuclear export of mature, processed tRNAs. Distinct tRNAs accumulate in the nuclei of nup100 Δ and msn5 Δ mutants, while Los1-GFP nucleocytoplasmic shuttling is unaffected by Nup100. Thus, we conclude that Nup100 regulates tRNA export in a manner distinct from Los1 or Msn5. Together, these experiments reveal a novel Nup100 role in the tRNA life cycle that impacts the S. cerevisiae life span. © 2017 Lord et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

The Impact of Recent Federal Administrative Rules on Army Dental Care. Volume 1. A Cost Analysis of Bloodborne Pathogens: A Report of Consultation

DTIC Science & Technology

1992-12-31

procedure codes 9973 and 9974), and the unit cost to the Fort Sam Houston DENTAC ($.79). Expenditures on dental handpieces were estimated using the guidance...life span after which it is due for replacement. The effects of steam sterilization on dental handpieces decreases their life span substantially... handpieces should be sterilized between patients. ADA 18 May, 1992. 12. Reddy, T.G. Director, Dental Services, US Army Health Services Command

Blood volume and red cell life span (M113), part C

NASA Technical Reports Server (NTRS)

Johnson, P. C., Jr.

1973-01-01

Prechamber, in-chamber, and postchamber blood samples taken from Skylab simulation crewmembers did not indicate significant shortening of the red cell life span during the mission. This does not suggest that the space simulation environment could not be associated with red cell enzyme changes. It does show that any changes in enzymes were not sufficiently great to significantly shorten red cell survival. There was no evidence of bone marrow erythropoetic suppression nor was there any evidence of increased red cell destruction.

Rapamycin: the cure for all that ails.

PubMed

Hasty, Paul

2010-02-01

Target of rapamycin (TOR) signaling stimulates cell growth by regulating protein synthesis in response to a variety of stimuli in a wide range of species and is inhibited by rapamycin, a naturally occurring antifungal compound produced by bacteria and discovered on Easter Island or in the local vernacular, Rapa Nui (rapamycin's namesake). Recently, rapamycin was shown to extend life span for mice, even when administered late in life, suggesting that inhibiting the mammalian TOR pathway may improve health span for people.

Relating Life-Span Research to the Development of Gifted and Talented Children. Abstracts of Selected Papers [from] The Annual Esther Katz Rosen Symposium on the Psychological Development of Gifted Children (3rd, Lawrence, Kansas, February 19-20, 1993).

ERIC Educational Resources Information Center

Kansas Univ., Lawrence.

This monograph presents abstracts of 29 papers that relate life-span research to the development of gifted and talented children. Sample topics include: attitudes about rural schools and programs for the gifted; social competence, self-esteem, and parent-child time and interaction in an advantaged subculture; helping families of gifted children…

Personality, self-rated health, and subjective age in a life-span sample: the moderating role of chronological age.

PubMed

Stephan, Yannick; Demulier, Virginie; Terracciano, Antonio

2012-12-01

The present study tested whether chronological age moderates the association between subjective age and self-rated health and personality in a community-dwelling life-span sample (N = 1,016; age range: 18-91 years). Self-rated health, extraversion, and openness to experience were associated with a younger subjective age at older ages. Conscientious individuals felt more mature early in life. Conscientiousness, neuroticism, and agreeableness were not related to subjective age at older ages. These findings suggest that with aging self-rated health and personality traits are increasingly important for subjective age. 2013 APA, all rights reserved

The Tölz Temporal Topography Study: mapping the visual field across the life span. Part II: cognitive factors shaping visual field maps.

PubMed

Poggel, Dorothe A; Treutwein, Bernhard; Calmanti, Claudia; Strasburger, Hans

2012-08-01

Part I described the topography of visual performance over the life span. Performance decline was explained only partly by deterioration of the optical apparatus. Part II therefore examines the influence of higher visual and cognitive functions. Visual field maps for 95 healthy observers of static perimetry, double-pulse resolution (DPR), reaction times, and contrast thresholds, were correlated with measures of visual attention (alertness, divided attention, spatial cueing), visual search, and the size of the attention focus. Correlations with the attentional variables were substantial, particularly for variables of temporal processing. DPR thresholds depended on the size of the attention focus. The extraction of cognitive variables from the correlations between topographical variables and participant age substantially reduced those correlations. There is a systematic top-down influence on the aging of visual functions, particularly of temporal variables, that largely explains performance decline and the change of the topography over the life span.

Effects of High Magneto-Gravitational Environment on Silkworm Embryogenesis

NASA Astrophysics Data System (ADS)

Tian, Zongcheng; Li, Muwang; Qian, Airong; Xu, Huiyun; Wang, Zhe; Di, Shengmeng; Yang, Pengfei; Hu, Lifang; Ding, Chong; Zhang, Wei; Luo, Mingzhi; Han, Jing; Gao, Xiang; Huang, Yongping; Shang, Peng

2010-04-01

The objective of this research was to observe whether silkworm embryos can survive in a high magneto-gravitational environment (HMGE) and what significant phenotype changes can be produced. The hatching rate, hatching time, life span, growth velocity and cocoon weight of silkworm were measured after silkworm embryos were exposed to HMGE (0 g, 12 T; 1 g, 16 T; and 2 g, 12 T) for a period of time. Compared with the control group, 0 g exposure resulted in a lower hatching rate and a shorter life span. Statistically insignificant morphological changes had been observed for larvae growth velocity, incidence of abnormal markings and weight of cocoons. These results suggest that the effect of HMGE on silkworm embryogenesis is not lethal. Bio-effects of silkworm embryogenesis at 0 g in a HMGE were similar with those of space flight. The hatching time, life span and hatching rates of silkworm may be potential phenotype markers related to exposure in a weightless environment.

Review of certain low-level ionizing radiation studies in mice and guinea pigs

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

Congdon, C.C.

1987-05-01

Starting in the early 1940s, Egon Lorenz and collaborators at the National Cancer Institute began an extended study of chronic low-level ionizing radiation effects in what was then the tolerance range for man. Observations on life span, body weight and radiation carcinogenesis, among others, were made in mice, guinea pigs and rabbits. At the then-permissible exposure level, 0.1 R** per 8-h day until natural death, experimental mice and guinea pigs had a slightly greater mean life span compared to control animals. In addition, there was marked weight gain during the growth phase in both species. Increased tumor incidence was alsomore » observed at the 0.1-R level in mice. The primary hypothesis for increased median life span has been rebound regenerative hyperplasia during the early part of the exposure; in the presence of continuing injury, there is physiological enhancement of defense mechanisms against intercurrent infection. The body weight gain has not been explained. 32 references.« less

Spermidine: a novel autophagy inducer and longevity elixir.

PubMed

Madeo, Frank; Eisenberg, Tobias; Büttner, Sabrina; Ruckenstuhl, Christoph; Kroemer, Guido

2010-01-01

Spermidine is a ubiquitous polycation that is synthesized from putrescine and serves as a precursor of spermine. Putrescine, spermidine and spermine all are polyamines that participate in multiple known and unknown biological processes. Exogenous supply of spermidine prolongs the life span of several model organisms including yeast (Saccharomyces cerevisiae), nematodes (Caenorhabditis elegans) and flies (Drosophila melanogaster) and significantly reduces age-related oxidative protein damage in mice, indicating that this agent may act as a universal anti-aging drug. Spermidine induces autophagy in cultured yeast and mammalian cells, as well as in nematodes and flies. Genetic inactivation of genes essential for autophagy abolishes the life span-prolonging effect of spermidine in yeast, nematodes and flies. These findings complement expanding evidence that autophagy mediates cytoprotection against a variety of noxious agents and can confer longevity when induced at the whole-organism level. We hypothesize that increased autophagic turnover of cytoplasmic organelles or long-lived proteins is involved in most if not all life span-prolonging therapies.

Conditional inhibition of autophagy genes in adult Drosophila impairs immunity without compromising longevity.

PubMed

Ren, Chunli; Finkel, Steven E; Tower, John

2009-03-01

Immune function declines with age in Drosophila and humans, and autophagy is implicated in immune function. In addition, autophagy genes are required for life span extension caused by reduced insulin/IGF1-like signaling and dietary restriction in Caenorhabditiselegans. To test if the autophagy pathway might be limiting for immunity and/or life span in adult Drosophila, the Geneswitch system was used to cause conditional inactivation of the autophagy genes Atg5, Atg7 and Atg12 by RNAi. Conditional inhibition of Atg genes in adult flies reduced lysotracker staining of adult tissues, and reduced resistance to injected Escherichia coli, as evidenced by increased bacterial titers and reduced fly survival. However, survival of uninjected flies was unaffected by Atg gene inactivation. The data indicate that Atg gene activity is required for normal immune function in adult flies, and suggest that neither autophagy nor immune function are limiting for adult life span under typical laboratory conditions.

Variation in Age and Size in Fennoscandian Three-Spined Sticklebacks (Gasterosteus aculeatus)

PubMed Central

DeFaveri, Jacquelin; Merilä, Juha

2013-01-01

Average age and maximum life span of breeding adult three-spined sticklebacks (Gasterosteus aculeatus) were determined in eight Fennoscandian localities with the aid of skeletochronology. The average age varied from 1.8 to 3.6 years, and maximum life span from three to six years depending on the locality. On average, fish from marine populations were significantly older than those from freshwater populations, but variation within habitat types was large. We also found significant differences in mean body size among different habitat types and populations, but only the population differences remained significant after accounting for variation due to age effects. These results show that generation length and longevity in three-spined sticklebacks can vary significantly from one locality to another, and that population differences in mean body size cannot be explained as a simple consequence of differences in population age structure. We also describe a nanistic population from northern Finland exhibiting long life span and small body size. PMID:24260496

Variation in age and size in Fennoscandian three-spined sticklebacks (Gasterosteus aculeatus).

PubMed

DeFaveri, Jacquelin; Merilä, Juha

2013-01-01

Average age and maximum life span of breeding adult three-spined sticklebacks (Gasterosteus aculeatus) were determined in eight Fennoscandian localities with the aid of skeletochronology. The average age varied from 1.8 to 3.6 years, and maximum life span from three to six years depending on the locality. On average, fish from marine populations were significantly older than those from freshwater populations, but variation within habitat types was large. We also found significant differences in mean body size among different habitat types and populations, but only the population differences remained significant after accounting for variation due to age effects. These results show that generation length and longevity in three-spined sticklebacks can vary significantly from one locality to another, and that population differences in mean body size cannot be explained as a simple consequence of differences in population age structure. We also describe a nanistic population from northern Finland exhibiting long life span and small body size.

All about Animal Life Cycles. Animal Life for Children. [Videotape].

ERIC Educational Resources Information Center

2000

While watching the development from tadpole to frog, caterpillar to butterfly, and pup to wolf, children learn about the life cycles of animals, the different stages of development, and the average life spans of a variety of creatures. This videotape correlates to the following National Science Education Standards for Life Science: characteristics…

Holistic life-span health outcomes among elite intercollegiate student-athletes.

PubMed

Sorenson, Shawn C; Romano, Russell; Scholefield, Robin M; Martin, Brandon E; Gordon, James E; Azen, Stanley P; Schroeder, E Todd; Salem, George J

2014-01-01

Competitive sports are recognized as having unique health benefits and risks, and the effect of sports on life-span health among elite athletes has received increasing attention. However, supporting scientific data are sparse and do not represent modern athletes. To assess holistic life-span health and health-related quality-of-life (HRQL) among current and former National Collegiate Athletic Association student-athletes (SAs). Cross-sectional study. A large Division I university. Population-based sample of 496 university students and alumni (age 17-84 years), including SAs and an age-matched and sex-matched nonathlete (NA) control group. Participants completed anonymous, self-report questionnaires. We measured the Short-Form 12 (SF-12) physical and mental component HRQL scores and cumulative lifetime experience and relative risk of treatment for joint, cardiopulmonary, and psychosocial health concerns. Older alumni (age 43+ years) SAs reported greater joint health concerns than NAs (larger joint summary scores; P = .04; Cohen d = 0.69; probability of clinically important difference [pCID] = 77%; treatment odds ratio [OR] = 14.0, 95% confidence interval [CI] = 1.6, 126). Joint health for current and younger alumni SAs was similar to that for NAs. Older alumni reported greater cardiopulmonary health concerns than younger alumni (summary score P < .001; d = 1.05; pCID = 85%; OR = 5.8, 95% CI = 2.0, 16) and current students (P < .001; d = 2.25; pCID >99.5%; OR = 7.1, 95% CI = 3.3, 15), but the risk was similar for SAs and NAs. Current SAs demonstrated evidence of better psychosocial health (summary score P = .006; d = -0.52; pCID = 40%) and mental component HRQL (P = .008; d = 0.50; pCID = 48%) versus NAs but similar psychosocial treatment odds (OR = 0.87, 95% CI = 0.39, 1.9). Psychosocial health and mental component HRQL were similar between alumni SAs and NAs. No differences were observed between SAs and NAs in physical component HRQL. The SAs demonstrated significant, clinically meaningful evidence of greater joint health concerns later in life, comparable cardiopulmonary health, and differences in life-span psychosocial health and HRQL profiles compared with NAs. These data provide timely evidence regarding a compelling public issue and highlight the need for further study of life-span health among modern athletes.

Holistic Life-Span Health Outcomes Among Elite Intercollegiate Student–Athletes

PubMed Central

Sorenson, Shawn C.; Romano, Russell; Scholefield, Robin M.; Martin, Brandon E.; Gordon, James E.; Azen, Stanley P.; Schroeder, E. Todd; Salem, George J.

2014-01-01

Context: Competitive sports are recognized as having unique health benefits and risks, and the effect of sports on life-span health among elite athletes has received increasing attention. However, supporting scientific data are sparse and do not represent modern athletes. Objective: To assess holistic life-span health and health-related quality-of-life (HRQL) among current and former National Collegiate Athletic Association student–athletes (SAs). Design: Cross-sectional study. Setting: A large Division I university. Patients or Other Participants: Population-based sample of 496 university students and alumni (age 17–84 years), including SAs and an age-matched and sex-matched nonathlete (NA) control group. Main Outcome Measure(s): Participants completed anonymous, self-report questionnaires. We measured the Short-Form 12 (SF-12) physical and mental component HRQL scores and cumulative lifetime experience and relative risk of treatment for joint, cardiopulmonary, and psychosocial health concerns. Results: Older alumni (age 43+ years) SAs reported greater joint health concerns than NAs (larger joint summary scores; P = .04; Cohen d = 0.69; probability of clinically important difference [pCID] = 77%; treatment odds ratio [OR] = 14.0, 95% confidence interval [CI] = 1.6, 126). Joint health for current and younger alumni SAs was similar to that for NAs. Older alumni reported greater cardiopulmonary health concerns than younger alumni (summary score P < .001; d = 1.05; pCID = 85%; OR = 5.8, 95% CI = 2.0, 16) and current students (P < .001; d = 2.25; pCID >99.5%; OR = 7.1, 95% CI = 3.3, 15), but the risk was similar for SAs and NAs. Current SAs demonstrated evidence of better psychosocial health (summary score P = .006; d = −0.52; pCID = 40%) and mental component HRQL (P = .008; d = 0.50; pCID = 48%) versus NAs but similar psychosocial treatment odds (OR = 0.87, 95% CI = 0.39, 1.9). Psychosocial health and mental component HRQL were similar between alumni SAs and NAs. No differences were observed between SAs and NAs in physical component HRQL. Conclusions: The SAs demonstrated significant, clinically meaningful evidence of greater joint health concerns later in life, comparable cardiopulmonary health, and differences in life-span psychosocial health and HRQL profiles compared with NAs. These data provide timely evidence regarding a compelling public issue and highlight the need for further study of life-span health among modern athletes. PMID:25117874

"Pull and push back" concepts of longevity and life span extension.

PubMed

Muradian, Khachik

2013-12-01

The negative relation between metabolism and life span is a fundamental gerontological discovery well documented in a variety of ontogenetic and phylogenetic models. But how the long-lived species and populations sustain lower metabolic rate and, in more general terms, what is the efficient way to decline the metabolism? The suggested 'pull and push back' hypothesis assumes that decreased Po2 (hypoxia) and/or increased [Formula: see text] (hypercapnia) may create preconditions for the declined metabolic and aging rates. However, wider implementation of such ideas is compromised because of little advances in modification of the metabolic rate. Artificial atmosphere with controlled [Formula: see text] and [Formula: see text] could be a promising approach because of the minimal external invasions and involvement of the backward and forward loops ensuring physiological self-regulation of the metabolic perturbations. General considerations and existing data indicate that manipulations of [Formula: see text] may be more efficient in life span extension than [Formula: see text]. Thus, maximum life span of mammals positively correlates with the blood [Formula: see text] and HCO3 (-) but not with [Formula: see text]. Yet, proportional decease of the body [Formula: see text] and increase of [Formula: see text] seems the most optimal regime ensuring lower losses of the energy equivalents. Furthermore, especially rewarding results could be expected when such changes are modeled without major external invasions using the animals' inner capacity to consume O2 and generate CO2, as it is typical for the extreme longevity.

Down regulation of miR-124 in both Werner syndrome DNA helicase mutant mice and mutant Caenorhabditis elegans wrn-1 reveals the importance of this microRNA in accelerated aging

PubMed Central

Dallaire, Alexandra; Garand, Chantal; Paquet, Eric R.; Mitchell, Sarah J.; de Cabo, Rafael; Simard, Martin J.

2012-01-01

Small non-coding microRNAs are believed to be involved in the mechanism of aging but nothing is known on the impact of microRNAs in the progeroid disorder Werner syndrome (WS). WS is a premature aging disorder caused by mutations in a RecQ-like DNA helicase. Mice lacking the helicase domain of the WRN ortholog exhibit many phenotypic features of WS, including a pro-oxidant status and a shorter mean life span. Caenorhabditis elegans (C. elegans) with a nonfunctional wrn-1 DNA helicase also exhibit a shorter life span. Thus, both models are relevant to study the expression of microRNAs involved in WS. In this study, we show that miR-124 expression is lost in the liver of Wrn helicase mutant mice. Interestingly, the expression of this conserved miR-124 in whole wrn-1 mutant worms is also significantly reduced. The loss of mir-124 in C. elegans increases reactive oxygen species formation and accumulation of the aging marker lipofuscin, reduces whole body ATP levels and results in a reduction in life span. Finally, supplementation of vitamin C normalizes the median life span of wrn-1 and mir-124 mutant worms. These results suggest that biological pathways involving WRN and miR-124 are conserved in the aging process across different species. PMID:23075628

Elevated CO2 and O3 effects on fine-root survivorship in ponderosa pine mesocosms.

PubMed

Phillips, Donald L; Johnson, Mark G; Tingey, David T; Storm, Marjorie J

2009-07-01

Atmospheric carbon dioxide (CO(2)) and ozone (O(3)) concentrations are rising, which may have opposing effects on tree C balance and allocation to fine roots. More information is needed on interactive CO(2) and O(3) effects on roots, particularly fine-root life span, a critical demographic parameter and determinant of soil C and N pools and cycling rates. We conducted a study in which ponderosa pine (Pinus ponderosa) seedlings were exposed to two levels of CO(2) and O(3) in sun-lit controlled-environment mesocosms for 3 years. Minirhizotrons were used to monitor individual fine roots in three soil horizons every 28 days. Proportional hazards regression was used to analyze effects of CO(2), O(3), diameter, depth, and season of root initiation on fine-root survivorship. More fine roots were produced in the elevated CO(2) treatment than in ambient CO(2). Elevated CO(2), increasing root diameter, and increasing root depth all significantly increased fine-root survivorship and median life span. Life span was slightly, but not significantly, lower in elevated O(3), and increased O(3) did not reduce the effect of elevated CO(2). Median life spans varied from 140 to 448 days depending on the season of root initiation. These results indicate the potential for elevated CO(2) to increase the number of fine roots and their residence time in the soil, which is also affected by root diameter, root depth, and phenology.

Loss of the clock protein PER2 shortens the erythrocyte life span in mice.

PubMed

Sun, Qi; Zhao, Yue; Yang, Yunxia; Yang, Xiao; Li, Minghui; Xu, Xi; Wen, Dan; Wang, Junsong; Zhang, Jianfa

2017-07-28

Cell proliferation and release from the bone marrow have been demonstrated to be controlled by circadian rhythms in both humans and mice. However, it is unclear whether local circadian clocks in the bone marrow influence physiological functions and life span of erythrocytes. Here, we report that loss of the clock gene Per2 significantly decreased erythrocyte life span. Mice deficient in Per2 were more susceptible to acute stresses in the erythrocytes, becoming severely anemic upon phenylhydrazine, osmotic, and H 2 O 2 challenges. 1 H NMR-based metabolomics analysis revealed that the Per2 depletion causes significant changes in metabolic profiles of erythrocytes, including increased lactate and decreased ATP levels compared with wild-type mice. The lower ATP levels were associated with hyperfunction of Na + /K + -ATPase activity in Per2 -null erythrocytes, and inhibition of Na + /K + -ATPase activity by ouabain efficiently rescued ATP levels. Per2 -null mice displayed increased levels of Na + /K + -ATPase α1 (ATP1A1) in the erythrocyte membrane, and transfection of Per2 cDNA into the erythroleukemic cell line TF-1 inhibited Atp1a1 expression. Furthermore, we observed that PER2 regulates Atp1a1 transcription through interacting with trans-acting transcription factor 1 (SP1). Our findings reveal that Per2 function in the bone marrow is required for the regulation of life span in circulating erythrocytes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Loss of Ubp3 increases silencing, decreases unequal recombination in rDNA, and shortens the replicative life span in Saccharomyces cerevisiae.

PubMed

Oling, David; Masoom, Rehan; Kvint, Kristian

2014-06-15

Ubp3 is a conserved ubiquitin protease that acts as an antisilencing factor in MAT and telomeric regions. Here we show that ubp3∆ mutants also display increased silencing in ribosomal DNA (rDNA). Consistent with this, RNA polymerase II occupancy is lower in cells lacking Ubp3 than in wild-type cells in all heterochromatic regions. Moreover, in a ubp3∆ mutant, unequal recombination in rDNA is highly suppressed. We present genetic evidence that this effect on rDNA recombination, but not silencing, is entirely dependent on the silencing factor Sir2. Further, ubp3∆ sir2∆ mutants age prematurely at the same rate as sir2∆ mutants. Thus our data suggest that recombination negatively influences replicative life span more so than silencing. However, in ubp3∆ mutants, recombination is not a prerequisite for aging, since cells lacking Ubp3 have a shorter life span than isogenic wild-type cells. We discuss the data in view of different models on how silencing and unequal recombination affect replicative life span and the role of Ubp3 in these processes. © 2014 Öling et al. 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).

Successful immortalization of mesenchymal progenitor cells derived from human placenta and the differentiation abilities of immortalized cells

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

Zhang Xiaohong; Soda, Yasushi; Takahashi, Kenji

2006-12-29

We reported previously that mesenchymal progenitor cells derived from chorionic villi of the human placenta could differentiate into osteoblasts, adipocytes, and chondrocytes under proper induction conditions and that these cells should be useful for allogeneic regenerative medicine, including cartilage tissue engineering. However, similar to human mesenchymal stem cells (hMSCs), though these placental cells can be isolated easily, they are difficult to study in detail because of their limited life span in vitro. To overcome this problem, we attempted to prolong the life span of human placenta-derived mesenchymal cells (hPDMCs) by modifying hTERT and Bmi-1, and investigated whether these modified hPDMCsmore » retained their differentiation capability and multipotency. Our results indicated that the combination of hTERT and Bmi-1 was highly efficient in prolonging the life span of hPDMCs with differentiation capability to osteogenic, adipogenic, and chondrogenic cells in vitro. Clonal cell lines with directional differentiation ability were established from the immortalized parental hPDMC/hTERT + Bmi-1. Interestingly, hPDMC/Bmi-1 showed extended proliferation after long-term growth arrest and telomerase was activated in the immortal hPDMC/Bmi-1 cells. However, the differentiation potential was lost in these cells. This study reports a method to extend the life span of hPDMCs with hTERT and Bmi-1 that should become a useful tool for the study of mesenchymal stem cells.« less

The challenges in moving from ageing to successful longevity.

PubMed

Kolovou, Genovefa; Barzilai, Nir; Caruso, Calogero; Sikora, Ewa; Capri, Miriam; Tzanetakou, Irene P; Bilianou, Helen; Avery, Peter; Katsiki, Niki; Panotopoulos, George; Franceschi, Claudio; Benetos, Athanase; Mikhailidis, Dimitri P

2014-01-01

During the last decades survival has significantly improved and centenarians are becoming a fast-growing group of the population. Human life span is mainly dependent on environmental and genetic factors. Favourable modifications of lifestyle factors (e.g. physical activity, diet and not smoking) and healthcare (e.g. effective vascular disease prevention) have also increased human life span. Genetic factors contribute to the variation of human life span by around 25%, which is believed to be more profound after 85 years of age. It is likely that multiple factors influence life span and we need answers to questions such as: 1) What does it take to reach 100?, 2) Do centenarians have better health during their lifespan compared with contemporaries who died at a younger age?, 3) Do centenarians have protective modifications of body composition, fat distribution and energy expenditure, maintain high physical and cognitive function, and sustained engagement in social and productive activities?, 4) Do centenarians have genes which contribute to longevity?, 5) Do centenarians benefit from epigenetic phenomena?, 6) Is it possible to influence the transgenerational epigenetic inheritance (epigenetic memory) which leads to longevity?, 7) Is the influence of nutrigenomics important for longevity?, 8) Do centenarians benefit more from drug treatment, particularly in primary prevention?, and, 9) Are there any potential goals for drug research? Many definitions of successful ageing have been proposed, but at present there is no consensus definition. Such definitions may need to differentiate between "Longevity Syndrome" and "Exceptional Longevity".

Development of the Life Story in Early Adolescence

ERIC Educational Resources Information Center

Steiner, Kristina L.; Pillemer, David B.

2018-01-01

Life span developmental psychology proposes that the ability to create a coherent life narrative does not develop until early adolescence. Using a novel methodology, 10-, 12-, and 14-year-old participants were asked to tell their life stories aloud to a researcher. Later, participants separated their transcribed narratives into self-identified…

Perceptions of Life Changes: An Alternate Measure of Aging through Time.

ERIC Educational Resources Information Center

Suggs, Patricia K.; Kivett, Vira R.

Retrospective strategies measuring perceived life changes over time can further the advancement of life span developmental research. Researchers have neglected the individual's perception of his/her life changes over time. This study attempts to determine discriminators of change over time as operationalized by perceptions of change. Subjects…

Study of the combined effects of smoking and inhalation of uranium ore dust, radon daughters and diesel oil exhaust fumes in hamsters and dogs. Final report

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

Cross, F.T.; Palmer, R.F.; Filipy, R.E.

1978-09-01

Exposure to particulates from uranium ore dust and diesel exhaust soot provoked inflammatory and proliferative responses in lungs. Also exposure to radon and radon daughters yielded increased occurrences of bronchiolar epithelial hyperplasia and metaplastic changes of alveolar epithelium. The data suggest that this cellular change is also a precursor of premalignant change in hamsters. The authors suggest an animal model other than the hamster based on two observations: (1) the Syrian golden hamster has been shown to be highly refractory to carcinoma induction; and (2) that when exposed to realistic levels of agents in life-span exposure regimens, the hamster doesmore » not develop lesions. Dog studies with cigarette smoke exposure showed mitigating effects on radon daughter induced respiratory tract cancer. Two reasons are suggested although no empirical evidence was gathered. A strict comparison of human and animal exposures and interpolative models are not possible at this time. (PCS)« less

Cancerous tumor: the high frequency of a rare event.

PubMed

Galam, S; Radomski, J P

2001-05-01

A simple model for cancer growth is presented using cellular automata. Cells diffuse randomly on a two-dimensional square lattice. Individual cells can turn cancerous at a very low rate. During each diffusive step, local fights may occur between healthy and cancerous cells. Associated outcomes depend on some biased local rules, which are independent of the overall cancerous cell density. The models unique ingredients are the frequency of local fights and the bias amplitude. While each isolated cancerous cell is eventually destroyed, an initial two-cell tumor cluster is found to have a nonzero probabilty to spread over the whole system. The associated phase diagram for survival or death is obtained as a function of both the rate of fight and the bias distribution. Within the model, although the occurrence of a killing cluster is a very rare event, it turns out to happen almost systematically over long periods of time, e.g., on the order of an adults life span. Thus, after some age, survival from tumorous cancer becomes random.

Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function.

PubMed

Jones, Natalie C; Lynn, Megan L; Gaudenz, Karin; Sakai, Daisuke; Aoto, Kazushi; Rey, Jean-Phillipe; Glynn, Earl F; Ellington, Lacey; Du, Chunying; Dixon, Jill; Dixon, Michael J; Trainor, Paul A

2008-02-01

Treacher Collins syndrome (TCS) is a congenital disorder of craniofacial development arising from mutations in TCOF1, which encodes the nucleolar phosphoprotein Treacle. Haploinsufficiency of Tcof1 perturbs mature ribosome biogenesis, resulting in stabilization of p53 and the cyclin G1-mediated cell-cycle arrest that underpins the specificity of neuroepithelial apoptosis and neural crest cell hypoplasia characteristic of TCS. Here we show that inhibition of p53 prevents cyclin G1-driven apoptotic elimination of neural crest cells while rescuing the craniofacial abnormalities associated with mutations in Tcof1 and extending life span. These improvements, however, occur independently of the effects on ribosome biogenesis; thus suggesting that it is p53-dependent neuroepithelial apoptosis that is the primary mechanism underlying the pathogenesis of TCS. Our work further implies that neuroepithelial and neural crest cells are particularly sensitive to cellular stress during embryogenesis and that suppression of p53 function provides an attractive avenue for possible clinical prevention of TCS craniofacial birth defects and possibly those of other neurocristopathies.

Space radiation health research, 1991-1992

NASA Technical Reports Server (NTRS)

Jablin, M. H. (Compiler); Brooks, C. (Compiler); Ferraro, G. (Compiler); Dickson, K. J. (Compiler); Powers, J. V. (Compiler); Wallace-Robinson, J. (Compiler); Zafren, B. (Compiler)

1993-01-01

The present volume is a collection of 227 abstracts of radiation research sponsored by the NASA Space Radiation Health Program for the period 1991-1992. Each abstract has been categorized within one of three discipline areas: Physics, Biology and Risk Assessment. Topic areas within each discipline have been assigned as follows: Physics - Atomic Physics, Theory, Cosmic Ray and Astrophysics, Experimental, Environments and Environmental Models, Solar Activity and Prediction, Experiments, Radiation Transport and Shielding, Theory and Model Development, Experimental Studies, and Instrumentation. Biology - Biology, Molecular Biology, Cellular Radiation Biology, Transformation, Mutation, Lethality, Survival, DNA Damage and Repair, Tissue, Organs, and Organisms, In Vivo/In Vitro Systems, Carcinogenesis and Life Shortening, Cataractogenesis, Genetics/Developmental, Radioprotectants, Plants, and Other Effects. Risk Assessment - Risk Assessment, Radiation Health and Epidemiology, Space Flight Radiation Health Physics, Inter- and Intraspecies Extrapolation and Radiation Limits and Standards. Section I contains refereed journals; Section II contains reports/meetings. Keywords and author indices are provided. A collection of abstracts spanning the period 1986-1990 was previously issued as NASA Technical Memorandum 4270.

Establishment and characterization of immortalized bovine endometrial epithelial cells

PubMed Central

Bai, Hanako; Sakurai, Toshihiro; Bai, Rulan; Yamakoshi, Sachiko; Aoki, Etsunari; Kuse, Mariko; Okuda, Kiyoshi; Imakawa, Kazuhiko

2014-01-01

Bovine primary uterine endometrial epithelial cells (EECs) are not ideal for long-term studies, because primary EECs lose hormone responsiveness quickly, and/or they tend to have a short life span. The aims of this study were to establish immortalized bovine EECs and to characterize these cells following long-term cultures. Immortalized bovine EECs were established by transfecting retroviral vectors encoding human papillomavirus (HPV) E6 and E7, and human telomerase reverse transcriptase (hTERT) genes. Established bovine immortalized EECs (imEECs) showed the same morphology as primary EECs, and could be grown without any apparent changes for over 60 passages. In addition, imEECs have maintained the features as EECs, exhibiting oxytocin (OT) and interferon tau (IFNT) responsiveness. Therefore, these imEECs, even after numbers of passages, could be used as an in vitro model to investigate cellular and molecular mechanisms, by which the uterine epithelium responds to IFNT stimulation, the event required for the maternal recognition of pregnancy in the bovine species. PMID:24735401

FoxO is a critical regulator of stem cell maintenance in immortal Hydra.

PubMed

Boehm, Anna-Marei; Khalturin, Konstantin; Anton-Erxleben, Friederike; Hemmrich, Georg; Klostermeier, Ulrich C; Lopez-Quintero, Javier A; Oberg, Hans-Heinrich; Puchert, Malte; Rosenstiel, Philip; Wittlieb, Jörg; Bosch, Thomas C G

2012-11-27

Hydra's unlimited life span has long attracted attention from natural scientists. The reason for that phenomenon is the indefinite self-renewal capacity of its stem cells. The underlying molecular mechanisms have yet to be explored. Here, by comparing the transcriptomes of Hydra's stem cells followed by functional analysis using transgenic polyps, we identified the transcription factor forkhead box O (FoxO) as one of the critical drivers of this continuous self-renewal. foxO overexpression increased interstitial stem cell and progenitor cell proliferation and activated stem cell genes in terminally differentiated somatic cells. foxO down-regulation led to an increase in the number of terminally differentiated cells, resulting in a drastically reduced population growth rate. In addition, it caused down-regulation of stem cell genes and antimicrobial peptide (AMP) expression. These findings contribute to a molecular understanding of Hydra's immortality, indicate an evolutionarily conserved role of FoxO in controlling longevity from Hydra to humans, and have implications for understanding cellular aging.

From Children to Adults: Motor Performance across the Life-Span

PubMed Central

Leversen, Jonas S. R.; Haga, Monika; Sigmundsson, Hermundur

2012-01-01

The life-span approach to development provides a theoretical framework to examine the general principles of life-long development. This study aims to investigate motor performance across the life span. It also aims to investigate if the correlations between motor tasks increase with aging. A cross-sectional design was used to describe the effects of aging on motor performance across age groups representing individuals from childhood to young adult to old age. Five different motor tasks were used to study changes in motor performance within 338 participants (7–79 yrs). Results showed that motor performance increases from childhood (7–9) to young adulthood (19–25) and decreases from young adulthood (19–25) to old age (66–80). These results are mirroring results from cognitive research. Correlation increased with increasing age between two fine motor tasks and two gross motor tasks. We suggest that the findings might be explained, in part, by the structural changes that have been reported to occur in the developing and aging brain and that the theory of Neural Darwinism can be used as a framework to explain why these changes occur. PMID:22719958

Inbreeding Depression and Male Survivorship in Drosophila: Implications for Senescence Theory

PubMed Central

Swindell, William R.; Bouzat, Juan L.

2006-01-01

The extent to which inbreeding depression affects longevity and patterns of survivorship is an important issue from several research perspectives, including evolutionary biology, conservation biology, and the genetic analysis of quantitative traits. However, few previous inbreeding depression studies have considered longevity as a focal life-history trait. We maintained laboratory populations of Drosophila melanogaster at census population sizes of 2 and 10 male-female pairs for up to 66 generations and performed repeated assays of male survivorship throughout this time period. On average, significant levels of inbreeding depression were observed for median life span and age-specific mortality. For age-specific mortality, the severity of inbreeding depression increased over the life span. We found that a baseline inbreeding load of 0.307 lethal equivalents per gamete affected age-specific mortality, and that this value increased at a rate of 0.046 per day of the life span. With respect to some survivorship parameters, the differentiation of lineages was nonlinear with respect to the inbreeding coefficient, which suggested that nonadditive genetic variation contributed to variation among lineages. These findings provide insights into the genetic basis of longevity as a quantitative trait and have implications regarding the mutation-accumulation evolutionary explanation of senescence. PMID:16204222

A Low Protein Diet Increases the Hypoxic Tolerance in Drosophila

PubMed Central

Vigne, Paul; Frelin, Christian

2006-01-01

Dietary restriction is well known to increase the life span of a variety of organisms from yeast to mammals, but the relationships between nutrition and the hypoxic tolerance have not yet been considered. Hypoxia is a major cause of cell death in myocardial infarction and stroke. Here we forced hypoxia-related death by exposing one-day-old male Drosophila to chronic hypoxia (5% O2) and analysed their survival. Chronic hypoxia reduced the average life span from 33.6 days to 6.3 days when flies were fed on a rich diet. A demographic analysis indicated that chronic hypoxia increased the slope of the mortality trajectory and not the short-term risk of death. Dietary restriction produced by food dilution, by yeast restriction, or by amino acid restriction partially reversed the deleterious action of hypoxia. It increased the life span of hypoxic flies up to seven days, which represented about 25% of the life time of an hypoxic fly. Maximum survival of hypoxic flies required only dietary sucrose, and it was insensitive to drugs such as rapamycin and resveratrol, which increase longevity of normoxic animals. The results thus uncover a new link between protein nutrition, nutrient signalling, and resistance to hypoxic stresses. PMID:17183686

Development of "material-specific" hemispheric specialization from beginning to end.

PubMed

Gingras, Benjamin; Braun, Claude M J

2018-07-01

Disparity of verbal and performance intelligence (VIQ, PIQ) on the Wechsler scales of intelligence is a conceptually cluttered and empirically weak measure of hemispheric specialization (HS). However, in the context of life span research, it is the only measure that can be exploited meta-analytically with the lesion method from prenatal life to late senescence. We assembled 1917 cases with a unilateral cortical focal brain lesion occurring at all ages and a post-lesion VIQ and PIQ. Lesion locus, volume and side were documented for each case, as well as age at lesion onset, age at first symptoms and age at the IQ test, presence/absence of epilepsy, lesion aetiology, gender, date of publication or of transfer of medical file. With and without covariate adjustment, HS was significant across the life span though its pattern changed. HS increased linearly and highly significantly until late senescence. Only in early adulthood did VIQ appear to vacate the right temporal lobe and occupy the left and PIQ vacate the left parietal lobe and occupy the right until late senescence. Biomaturational factors are more important in the ontogeny of material-specific HS over the whole life span than previously established.

Rapamycin Increases Mortality in db/db Mice, a Mouse Model of Type 2 Diabetes.

PubMed

Sataranatarajan, Kavithalakshmi; Ikeno, Yuji; Bokov, Alex; Feliers, Denis; Yalamanchili, Himabindu; Lee, Hak Joo; Mariappan, Meenalakshmi M; Tabatabai-Mir, Hooman; Diaz, Vivian; Prasad, Sanjay; Javors, Martin A; Ghosh Choudhury, Goutam; Hubbard, Gene B; Barnes, Jeffrey L; Richardson, Arlan; Kasinath, Balakuntalam S

2016-07-01

We examined the effect of rapamycin on the life span of a mouse model of type 2 diabetes, db/db mice. At 4 months of age, male and female C57BLKSJ-lepr (db/db) mice (db/db) were placed on either a control diet, lacking rapamycin or a diet containing rapamycin and maintained on these diets over their life span. Rapamycin was found to reduce the life span of the db/db mice. The median survival of male db/db mice fed the control and rapamycin diets was 349 and 302 days, respectively, and the median survival of female db/db mice fed the control and rapamycin diets was 487 and 411 days, respectively. Adjusting for gender differences, rapamycin increased the mortality risk 1.7-fold in both male and female db/db mice. End-of-life pathological data showed that suppurative inflammation was the main cause of death in the db/db mice, which is enhanced slightly by rapamycin treatment. © 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.

Staying young at heart: autophagy and adaptation to cardiac aging.

PubMed

Leon, Leonardo J; Gustafsson, Åsa B

2016-06-01

Aging is a predominant risk factor for developing cardiovascular disease. Therefore, the cellular processes that contribute to aging are attractive targets for therapeutic interventions that can delay or prevent the development of age-related diseases. Our understanding of the underlying mechanisms that contribute to the decline in cell and tissue functions with age has greatly advanced over the past decade. Classical hallmarks of aging cells include increased levels of reactive oxygen species, DNA damage, accumulation of dysfunctional organelles, oxidized proteins and lipids. These all contribute to a progressive decline in the normal physiological function of the cell and to the onset of age-related conditions. A major cause of the aging process is progressive loss of cellular quality control. Autophagy is an important quality control pathway and is necessary to maintain cardiac homeostasis and to adapt to stress. A reduction in autophagy has been observed in a number of aging models and there is compelling evidence that enhanced autophagy delays aging and extends life span. Enhancing autophagy counteracts age-associated accumulation of protein aggregates and damaged organelles in cells. In this review, we discuss the functional role of autophagy in maintaining homeostasis in the heart, and how a decline is associated with accelerated cardiac aging. We also evaluate therapeutic approaches being researched in an effort to maintain a healthy young heart. Copyright © 2015 Elsevier Ltd. All rights reserved.

What the Erythrocytic Nuclear Alteration Frequencies Could Tell Us about Genotoxicity and Macrophage Iron Storage?

PubMed

Gomes, Juliana M M; Ribeiro, Heder J; Procópio, Marcela S; Alvarenga, Betânia M; Castro, Antônio C S; Dutra, Walderez O; da Silva, José B B; Corrêa Junior, José D

2015-01-01

Erythrocytic nuclear alterations have been considered as an indicative of organism's exposure to genotoxic agents. Due to their close relationship among their frequencies and DNA damages, they are considered excellent markers of exposure in eukaryotes. However, poor data has been found in literature concerning their genesis, differential occurrence and their life span. In this study, we use markers of cell viability; genotoxicity and cellular turn over in order to shed light to these events. Tilapia and their blood were exposed to cadmium in acute exposure and in vitro assays. They were analyzed using flow cytometry for oxidative stress and membrane disruption, optical microscopy for erythrocytic nuclear alteration, graphite furnace atomic absorption spectrometry for cadmium content in aquaria water, blood and cytochemical and analytical electron microscopy techniques for the hemocateretic aspects. The results showed a close relationship among the total nuclear alterations and cadmium content in the total blood and melanomacrophage centres area, mismatching reactive oxygen species and membrane damages. Moreover, nuclear alterations frequencies (vacuolated, condensed and blebbed) showed to be associated to cadmium exposure whereas others (lobed and bud) were associated to depuration period. Decrease on nuclear alterations frequencies was also associated with hemosiderin increase inside spleen and head kidney macrophages mainly during depurative processes. These data disclosure in temporal fashion the main processes that drive the nuclear alterations frequencies and their relationship with some cellular and systemic biomarkers.

Cell transformation and mutability of different genetic loci in mammalian cells by metabolically activated carcinogenic polycylic hydrocarbons

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

Huberman, E.

1977-01-01

Treatment of experimental animals with chemical carcinogens, including some polycyclic hydrocarbons, can result in the formation of malignant tumors. The process whereby some chemicals induce malignancy is as yet unknown. However, in a model system using mammalian cells in culture, it was possible to show that the chemical carcinogens induce malignant transformation rather than select for pre-existing tumor cells. In the process of the in vitro cell transformation, the normal cells, which have an oriented pattern of cell growth, a limited life-span in vitro, and are not tumorigenic, are converted into cells that have a hereditary random pattern of cellmore » growth, the ability to grow continuously in culture, and the ability to form tumors in vivo. This stable heritable phenotype of the transformed cells is similar to that of cells derived from spontaneous or experimentally induced tumors. Such stable heritable phenotype changes may arise from alteration in gene expression due to a somatic mutation after interaction of the carcinogen with cellular DNA. In the present experiments we have shown that metabolically activated carcinogenic polycyclic hydrocarbons which have been shown to bind to cellular DNA induce somatic mutations at different genetic loci in mammalian cells and that there is a relationship between the degree of mutant induction and the degree of carcinogenicity of the different hydrocarbons tested.« less

The Lcn2-engineered HEK-293 cells show senescence under stressful condition

PubMed Central

Bahmani, Bahareh; Amiri, Fatemeh; Mohammadi Roushandeh, Amaneh; Bahadori, Marzie; Harati, Mozhgan Dehghan; Habibi Roudkenar, Mehryar

2015-01-01

Objective(s): Lipocalin2 (Lcn2) gene is highly expressed in response to various types of cellular stresses. The precise role of Lcn2 has not been fully understood yet. However, it plays a key role in controlling vital cellular processes such as proliferation, apoptosis and metabolism. Recently it was shown that Lcn2 decreases senescence and increases proliferation of mesenchymal stem cells (MSC) with finite life span under either normal or oxidative stress conditions. However, Lcn2 effects on immortal cell line with infinite proliferation are not defined completely. Materials and Materials and Methods: HEK-293 cells were transfected with recombinant pcDNA3.1 containing Lcn2 fragment (pcDNA3.1-Lcn2). Expression of lipocalin2 in transfected cells was evaluated by RT-PCR, real time RT-PCR, and ELISA. Different cell groups were treated with H2O2 and WST-1 assay was performed to determine their proliferation rate. Senescence was studied by β-galactosidase and gimsa staining methods as well as evaluation of the expression of senescence-related genes by real time RT-PCR. Results: Lcn2 increased cell proliferation under normal culture condition, while the proliferation slightly decreased under oxidative stress. This decrease was further found to be attributed to senescence. Conclusion: Our findings indicated that under harmful conditions, Lcn2 gene is responsible for the regulation of cell survival through senescence. PMID:26124931

Senescence of immortal human fibroblasts by the introduction of normal human chromosome 6

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

Sandhu, A.K.; Hubbard, K.; Kaur, G.P.

1994-06-07

In these studies the authors show that introduction of a normal human chromosome 6 or 6q can suppress the immortal phenotype of simian virus 40-transformed human fibroblasts (SV/HF). Normal human fibroblasts have a limited life span in culture. Immortal clones of SV/HF displayed nonrandom rearrangements in chromosome 6. Single human chromosomes present in mouse/human monochromosomal hybrids were introduced into SV/HF via microcell fusion and maintained by selection for a dominant selectable marker gpt, previously integrated into the human chromosome. Clones of SV/HF cells bearing chromosome 6 displayed limited potential for cell division and morphological characteristics of senescent cells. The lossmore » of chromosome 6 from the suppressed clones correlated with the reappearance of immortal clones. Introduced chromosome 6 in the senescing cells was distinguished from those of parental cells by analysis for DNA sequences specific for the donor chromosome. The results further show that suppression of immortal phenotype in SV/HF is specific to chromosome 6. Introduction of individual human chromosomes 2, 8, or 19 did not impart cellular senescence in SV/HF. In addition, introduction of chromosome 6 into human glioblastoma cells did not lead to senescence. Based upon these results the authors propose that at least one of the genes (SEN6) for cellular senescence in human fibroblasts is present on the long arm of chromosome 6.« less

What the Erythrocytic Nuclear Alteration Frequencies Could Tell Us about Genotoxicity and Macrophage Iron Storage?

PubMed Central

Gomes, Juliana M. M.; Ribeiro, Heder J.; Procópio, Marcela S.; Alvarenga, Betânia M.; Castro, Antônio C. S.; Dutra, Walderez O.; da Silva, José B. B.; Corrêa Junior, José D.

2015-01-01

Erythrocytic nuclear alterations have been considered as an indicative of organism’s exposure to genotoxic agents. Due to their close relationship among their frequencies and DNA damages, they are considered excellent markers of exposure in eukaryotes. However, poor data has been found in literature concerning their genesis, differential occurrence and their life span. In this study, we use markers of cell viability; genotoxicity and cellular turn over in order to shed light to these events. Tilapia and their blood were exposed to cadmium in acute exposure and in vitro assays. They were analyzed using flow cytometry for oxidative stress and membrane disruption, optical microscopy for erythrocytic nuclear alteration, graphite furnace atomic absorption spectrometry for cadmium content in aquaria water, blood and cytochemical and analytical electron microscopy techniques for the hemocateretic aspects. The results showed a close relationship among the total nuclear alterations and cadmium content in the total blood and melanomacrophage centres area, mismatching reactive oxygen species and membrane damages. Moreover, nuclear alterations frequencies (vacuolated, condensed and blebbed) showed to be associated to cadmium exposure whereas others (lobed and bud) were associated to depuration period. Decrease on nuclear alterations frequencies was also associated with hemosiderin increase inside spleen and head kidney macrophages mainly during depurative processes. These data disclosure in temporal fashion the main processes that drive the nuclear alterations frequencies and their relationship with some cellular and systemic biomarkers. PMID:26619141

Getting older isn’t all that bad: Better decisions and coping when facing ’sunk costs’

PubMed Central

de Bruin, Wändi Bruine; Strough, JoNell; Parker, Andrew M.

2014-01-01

Because people of all ages face decisions that affect their quality of life, decision-making competence is important across the life span. According to theories of rational decision making, one crucial decision skill involves the ability to discontinue failing commitments despite irrecoverable investments also referred to as ‘sunk costs.’ We find that older adults are better than younger adults at making decisions to discontinue such failing commitments especially when irrecoverable losses are large, as well as at coping with the associated irrecoverable losses. Our results are relevant to interventions that aim to promote better decision-making competence across the life span. PMID:25244483

Getting older isn't all that bad: better decisions and coping when facing "sunk costs".

PubMed

Bruine de Bruin, Wändi; Strough, JoNell; Parker, Andrew M

2014-09-01

Because people of all ages face decisions that affect their quality of life, decision-making competence is important across the life span. According to theories of rational decision making, one crucial decision skill involves the ability to discontinue failing commitments despite irrecoverable investments also referred to as "sunk costs." We find that older adults are better than younger adults at making decisions to discontinue such failing commitments especially when irrecoverable losses are large, as well as at coping with the associated irrecoverable losses. Our results are relevant to interventions that aim to promote better decision-making competence across the life span. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Social and demographic correlates of loneliness in late life.

PubMed

Revenson, T A; Johnson, J L

1984-02-01

Although loneliness is often viewed as a serious problem of old age, few studies have addressed either its measurement or prevalence among older populations. The present study analyzed survey data from newspaper questionnaires circulated in three North American cities (N = 2,026) in order to examine the prevalence of loneliness across the life-span and some of its correlates in late life. Loneliness decreased across the adult life-span, with respondents age 65 and older the least lonely; elders were also more satisfied with their social relationships. Neither gender nor living alone was related to loneliness for older people. The data also partially confirm the desolation hypothesis, suggesting that desolation, or the loss of an intimate attachment, rather than isolation per se is a major correlate of loneliness in late life. Further, recency of loss was strongly related to increased loneliness. Directions for future research and intervention are discussed.

Expert Panel Recommendations on Lower Urinary Tract Health of Women Across Their Life Span

PubMed Central

Losada, Liliana; Amundsen, Cindy L.; Ashton-Miller, James; Chai, Toby; Close, Clare; Damaser, Margot; DiSanto, Michael; Dmochowski, Roger; Fraser, Matthew O.; Kielb, Stephanie J.; Kuchel, George; Mueller, Elizabeth R.; Parker-Autry, Candace; Wolfe, Alan J.

2016-01-01

Abstract Urologic and kidney problems are common in women across their life span and affect their daily life, including physical activity, sexual relations, social life, and future health. Urological health in women is still understudied and the underlying mechanisms of female urological dysfunctions are not fully understood. The Society for Women's Health Research (SWHR®) recognized the need to have a roundtable discussion where researchers and clinicians would define the current state of knowledge, gaps, and recommendations for future research directions to transform women's urological health. This report summarizes the discussions, which focused on epidemiology, clinical presentation, basic science, prevention strategies, and efficacy of current therapies. Experts around the table agreed on a set of research, education, and policy recommendations that have the potential to dramatically increase awareness and improve women's urological health at all stages of life. PMID:27285829

A RabGAP Regulates Life-Cycle Duration via Trimeric G-protein Cascades in Dictyostelium discoideum

PubMed Central

Kuwayama, Hidekazu; Miyanaga, Yukihiro; Urushihara, Hideko; Ueda, Masahiro

2013-01-01

Background The life-cycle of cellular slime molds comprises chronobiologically regulated processes. During the growth phase, the amoeboid cells proliferate at a definite rate. Upon starvation, they synthesize cAMP as both first and second messengers in signalling pathways and form aggregates, migrating slugs, and fruiting bodies, consisting of spores and stalk cells, within 24 h. In Dictyostelium discoideum, because most growth-specific events cease during development, proliferative and heterochronic mutations are not considered to be interrelated and no genetic factor governing the entire life-cycle duration has ever been identified. Methodology/Principal Findings Using yeast 2-hybrid library screening, we isolated a Dictyostelium discoideum RabGAP, Dd Rbg-3, as a candidate molecule by which the Dictyostelium Gα2 subunit directs its effects. Rab GTPase-activating protein, RabGAP, acts as a negative regulator of Rab small GTPases, which orchestrate the intracellular membrane trafficking involved in cell proliferation. Deletion mutants of Dd rbg-3 exhibited an increased growth rate and a shortened developmental period, while an overexpression mutant demonstrated the opposite effects. We also show that Dd Rbg-3 interacts with 2 Gα subunits in an activity-dependent manner in vitro. Furthermore, both human and Caenorhabditis elegans rbg-3 homologs complemented the Dd rbg-3–deletion phenotype in D. discoideum, indicating that similar pathways may be generally conserved in multicellular organisms. Conclusions/Significance Our findings suggest that Dd Rbg-3 acts as a key element regulating the duration of D. discoideum life-span potentially via trimeric G-protein cascades. PMID:24349132

Coupled Phases and Combinatorial Selection in Fluctuating Hydrothermal Pools: A Scenario to Guide Experimental Approaches to the Origin of Cellular Life

PubMed Central

Damer, Bruce; Deamer, David

2015-01-01

Hydrothermal fields on the prebiotic Earth are candidate environments for biogenesis. We propose a model in which molecular systems driven by cycles of hydration and dehydration in such sites undergo chemical evolution in dehydrated films on mineral surfaces followed by encapsulation and combinatorial selection in a hydrated bulk phase. The dehydrated phase can consist of concentrated eutectic mixtures or multilamellar liquid crystalline matrices. Both conditions organize and concentrate potential monomers and thereby promote polymerization reactions that are driven by reduced water activity in the dehydrated phase. In the case of multilamellar lipid matrices, polymers that have been synthesized are captured in lipid vesicles upon rehydration to produce a variety of molecular systems. Each vesicle represents a protocell, an “experiment” in a natural version of combinatorial chemistry. Two kinds of selective processes can then occur. The first is a physical process in which relatively stable molecular systems will be preferentially selected. The second is a chemical process in which rare combinations of encapsulated polymers form systems capable of capturing energy and nutrients to undergo growth by catalyzed polymerization. Given continued cycling over extended time spans, such combinatorial processes will give rise to molecular systems having the fundamental properties of life. PMID:25780958

L-type Ca2+ channels in the heart: structure and regulation.

PubMed

Treinys, Rimantas; Jurevicius, Jonas

2008-01-01

This review analyzes the structure and regulation mechanisms of voltage-dependent L-type Ca(2+) channel in the heart. L-type Ca(2+) channels in the heart are composed of four different polypeptide subunits, and the pore-forming subunit alpha(1) is the most important part of the channel. In cardiac myocytes, Ca(2+) enter cell cytoplasm from extracellular space mainly through L-type Ca(2+) channels; these channels are very important system in heart Ca(2+) uptake regulation. L-type Ca(2+) channels are responsible for the activation of sarcoplasmic reticulum channels (RyR2) and force of muscle contraction generation in heart; hence, activity of the heart depends on L-type Ca(2+) channels. Phosphorylation of channel-forming subunits by different kinases is one of the most important ways to change the activity of L-type Ca(2+) channel. Additionally, the activity of L-type Ca(2+) channels depends on Ca(2+) concentration in cytoplasm. Ca(2+) current in cardiac cells can facilitate, and this process is regulated by phosphorylation of L-type Ca(2+) channels and intracellular Ca(2+) concentration. Disturbances in cellular Ca(2+) transport and regulation of L-type Ca(2+) channels are directly related to heart diseases, life quality, and life span.

Understanding mechanisms of autoimmunity through translational research in vitiligo

PubMed Central

Strassner, James P; Harris, John E

2016-01-01

Vitiligo is an autoimmune disease of the skin that leads to life-altering depigmentation and remains difficult to treat. However, clinical observations and translational studies over 30-40 years have led to the development of an insightful working model of disease pathogenesis: Genetic risk spanning both immune and melanocyte functions is pushed over a threshold by known and suspected environmental factors to initiate autoimmune T cell-mediated killing of melanocytes. While under cellular stress, melanocytes appear to signal innate immunity to activate T cells. Once the autoimmune T cell response is established, the IFN-γ-STAT1-CXCL10 signaling axis becomes the primary inflammatory pathway driving both progression and maintenance of vitiligo. This pathway is a tempting target for both existing and developing pharmaceuticals, but further detailing how melanocytes signal their own demise may also lead to new therapeutic targets. Research in vitiligo may be the future key to understand the pathogenesis of organ-specific autoimmunity, as vitiligo is common, reversible, progresses over the life of the individual, has been relatively well-defined, and is quite easy to study using translational and clinical approaches. What is revealed in these studies can lead to innovative treatments and also help elucidate the principles that underlie similar organ-specific autoimmune diseases, especially in cases where the target organ is less accessible. PMID:27764715

Facilitating Career Development through Super's Life Career Rainbow.

ERIC Educational Resources Information Center

Okocha, Aneneosa A.

Super's life-span life-space theory offers a developmental framework for career counseling. This paper provides a brief overview of Super's theory of Life Career Rainbow (LCR) segment. The LCR feature is useful for identifying the stage of a client's career development and in formulating goals for counseling. The assessment is accomplished by…

A virocentric perspective on the evolution of life

PubMed Central

Koonin, Eugene V.; Dolja, Valerian V.

2015-01-01

Viruses and/or virus-like selfish elements are associated with all cellular life forms and are the most abundant biological entities on Earth, with the number of virus particles in many environments exceeding the number of cells by one to two orders of magnitude. The genetic diversity of viruses is commensurately enormous and might substantially exceed the diversity of cellular organisms. Unlike cellular organisms with their uniform replication-expression scheme, viruses possess either RNA or DNA genomes and exploit all conceivable replication-expression strategies. Although viruses extensively exchange genes with their hosts, there exists a set of viral hallmark genes that are shared by extremely diverse groups of viruses to the exclusion of cellular life forms. Coevolution of viruses and host defense systems is a key aspect in the evolution of both viruses and cells, and viral genes are often recruited for cellular functions. Together with the fundamental inevitability of the emergence of genomic parasites in any evolving replicator system, these multiple lines of evidence reveal the central role of viruses in the entire evolution of life. PMID:23850169

Integrating Varieties of Life Course Concepts

PubMed Central

2012-01-01

A body of work referred to as the “life course” framework (also known as “life course theory,” the “life course paradigm,” and the “life course perspective”) has been increasingly used to motivate and justify the examination of the relationships among variables in social and behavioral science, particularly in the study of population health and aging. Yet, there is very little agreement on what some of these concepts mean, and there is hardly any agreement on what the “life course” is. This article focuses on the different ways in which the concept of “life course” is used in the contemporary study of aging and human development, particularly with regard to health and well-being. Clarification is given for how “life course” is distinguished from “life span” and “life cycle,” among other “life” words. This work reviews the conceptual literature on the life course, beginning with its formative years in the 1960s and 1970s, through to the present time. Detailed research of several literatures across disciplines revealed five different uses of the term “life course”: (a) life course as time or age, (b) life course as life stages, (c) life course as events, transitions, and trajectories, (d) life course as life-span human development, and (e) life course as early life influences (and their cumulation) on later adult outcomes. To the extent the concept of life course has a multiplicity of meanings that are at variance with one another, this is problematic, as communication is thereby hindered. On the other hand, to the extent the concept of life course involves a rich tapestry of different emphases, this is a good thing, and the diversity of meanings should be retained. This paper proposes a conceptual integration based in part on Riley’s age stratification model that resolves the various meanings of life course into one general framework. Coupled with a demographic conceptualization of the life course, this framework embeds the concept of “life course” within a broader perspective of life-span development. This framework is proposed as an integrated perspective for studying the causes and consequences of “life course events and transitions” and understanding the manner by which “life events” and the role transitions they signify influence the life-span development of outcomes of interest across stages of the life cycle. PMID:22399576

Evolution of monogamy, paternal investment, and female life history in Peromyscus.

PubMed

Jašarević, Eldin; Bailey, Drew H; Crossland, Janet P; Dawson, Wallace D; Szalai, Gabor; Ellersieck, Mark R; Rosenfeld, Cheryl S; Geary, David C

2013-02-01

The timing of reproductive development and associated trade-offs in quantity versus quality of offspring produced across the life span are well documented in a wide range of species. The relation of these aspects of maternal life history to monogamy and paternal investment in offspring is not well studied in mammals, due in part to the rarity of the latter. By using five large, captive-bred populations of Peromyscus species that range from promiscuous mating with little paternal investment (P. maniculatus bairdii) to social and genetic monogamy with substantial paternal investment (P. californicus insignis), we modeled the interaction between monogamy and female life history. Monogamy and high paternal investment were associated with smaller litter size, delayed maternal reproduction that extended over a longer reproductive life span, and larger, higher quality offspring. The results suggest monogamy and paternal investment can alter the evolution of female life-history trajectories in mammals. PsycINFO Database Record (c) 2013 APA, all rights reserved

Life-span Socioeconomic Trajectory, Nativity, and Cognitive Aging in Mexican Americans: The Sacramento Area Latino Study on Aging

PubMed Central

Zeki Al-Hazzouri, Adina; Aiello, Allison E.

2011-01-01

Objectives. Early life circumstances influence health across the life span. Migration and ethnicity may modify the lifetime trajectory of socioeconomic status (SES) and lead to heterogeneity in cognitive aging in later life. Methods. We examined the effects of both lifetime socioeconomic trajectory and cumulative disadvantage from childhood through adulthood on late life cognitive performance in a 9-year cohort of 1,789 Mexican Americans aged 60–100 years in 1998–1999. Results. Compared with those with low SES sustained over the life course, we found that those with more advantaged lifetime SES trajectories experienced fewer declines on a test of global cognitive function and a short-term verbal memory test. These associations are larger in first- and second-generation immigrant families. Discussion. Heterogeneity of cognitive aging among diverse race/ethnic groups may be influenced by intergenerational changes in SES, cultural norms, and behaviors and changes in health related to changes in the social and physical environment. PMID:21743044

Life-span socioeconomic trajectory, nativity, and cognitive aging in Mexican Americans: the Sacramento Area Latino Study on Aging.

PubMed

Haan, Mary N; Zeki Al-Hazzouri, Adina; Aiello, Allison E

2011-07-01

Early life circumstances influence health across the life span. Migration and ethnicity may modify the lifetime trajectory of socioeconomic status (SES) and lead to heterogeneity in cognitive aging in later life. We examined the effects of both lifetime socioeconomic trajectory and cumulative disadvantage from childhood through adulthood on late life cognitive performance in a 9-year cohort of 1,789 Mexican Americans aged 60-100 years in 1998-1999. Compared with those with low SES sustained over the life course, we found that those with more advantaged lifetime SES trajectories experienced fewer declines on a test of global cognitive function and a short-term verbal memory test. These associations are larger in first- and second-generation immigrant families. Heterogeneity of cognitive aging among diverse race/ethnic groups may be influenced by intergenerational changes in SES, cultural norms, and behaviors and changes in health related to changes in the social and physical environment.

Differential effects of LifeAct-GFP and actin-GFP on cell mechanics assessed using micropipette aspiration.

PubMed

Sliogeryte, Kristina; Thorpe, Stephen D; Wang, Zhao; Thompson, Clare L; Gavara, Nuria; Knight, Martin M

2016-01-25

The actin cytoskeleton forms a dynamic structure involved in many fundamental cellular processes including the control of cell morphology, migration and biomechanics. Recently LifeAct-GFP (green fluorescent protein) has been proposed for visualising actin structure and dynamics in live cells as an alternative to actin-GFP which has been shown to affect cell mechanics. Here we compare the two approaches in terms of their effect on cellular mechanical behaviour. Human mesenchymal stem cells (hMSCs) were analysed using micropipette aspiration and the effective cellular equilibrium and instantaneous moduli calculated using the standard linear solid model. We show that LifeAct-GFP provides clearer visualisation of F-actin organisation and dynamics. Furthermore, LifeAct-GFP does not alter effective cellular mechanical properties whereas actin-GFP expression causes an increase in the cell modulus. Interestingly, LifeAct-GFP expression did produce a small (~10%) increase in the percentage of cells exhibiting aspiration-induced membrane bleb formation, whilst actin-GFP expression reduced blebbing. Further studies examined the influence of LifeAct-GFP in other cell types, namely chondrogenically differentiated hMSCs and murine chondrocytes. LifeAct-GFP also had no effect on the moduli of these non-blebbing cells for which mechanical properties are largely dependent on the actin cortex. In conclusion we show that LifeAct-GFP enables clearer visualisation of actin organisation and dynamics without disruption of the biomechanical properties of either the whole cell or the actin cortex. Thus the study provides new evidence supporting the use of LifeAct-GFP rather than actin-GFP for live cell microscopy and the study of cellular mechanobiology. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

17. DETAIL OF SOUTH PORTAL, SHOWING "TREE OF LIFE" RAILING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

17. DETAIL OF SOUTH PORTAL, SHOWING "TREE OF LIFE" RAILING DETAIL AS WELL AS BUILDER'S PLATE. - Falls Bridge, Spanning Schuylkill River, connecting East & West River Drives, Philadelphia, Philadelphia County, PA

Life Satisfaction, Self-Esteem, and Subjective Age in Women across the Life Span

ERIC Educational Resources Information Center

Borzumato-Gainey, Christine; Kennedy, Alison; McCabe, Beth; Degges-White, Suzanne

2009-01-01

A study of 320 women, ages 21 to 69, explored the relations among relationship status, subjective age, self-esteem, and life satisfaction. Women in married or partnered relationships had higher levels of life satisfaction than did single women. Women in their 30s and 40s had significantly lower levels of life satisfaction than did other age…

Two-carbon metabolites, polyphenols and vitamins influence yeast chronological life span in winemaking conditions

PubMed Central

2012-01-01

Background Viability in a non dividing state is referred to as chronological life span (CLS). Most grape juice fermentation happens when Saccharomyces cerevisiae yeast cells have stopped dividing; therefore, CLS is an important factor toward winemaking success. Results We have studied both the physical and chemical determinants influencing yeast CLS. Low pH and heat shorten the maximum wine yeast life span, while hyperosmotic shock extends it. Ethanol plays an important negative role in aging under winemaking conditions, but additional metabolites produced by fermentative metabolism, such as acetaldehyde and acetate, have also a strong impact on longevity. Grape polyphenols quercetin and resveratrol have negative impacts on CLS under winemaking conditions, an unexpected behavior for these potential anti-oxidants. We observed that quercetin inhibits alcohol and aldehyde dehydrogenase activities, and that resveratrol performs a pro-oxidant role during grape juice fermentation. Vitamins nicotinic acid and nicotinamide are precursors of NAD+, and their addition reduces mean longevity during fermentation, suggesting a metabolic unbalance negative for CLS. Moreover, vitamin mix supplementation at the end of fermentation shortens CLS and enhances cell lysis, while amino acids increase life span. Conclusions Wine S. cerevisiae strains are able to sense changes in the environmental conditions and adapt their longevity to them. Yeast death is influenced by the conditions present at the end of wine fermentation, particularly by the concentration of two-carbon metabolites produced by the fermentative metabolism, such as ethanol, acetic acid and acetaldehyde, and also by the grape juice composition, particularly its vitamin content. PMID:22873488

Normative personality trait development in adulthood: A 6-year cohort-sequential growth model.

PubMed

Milojev, Petar; Sibley, Chris G

2017-03-01

The present study investigated patterns of normative change in personality traits across the adult life span (19 through 74 years of age). We examined change in extraversion, agreeableness, conscientiousness, neuroticism, openness to experience and honesty-humility using data from the first 6 annual waves of the New Zealand Attitudes and Values Study (N = 10,416; 61.1% female, average age = 49.46). We present a cohort-sequential latent growth model assessing patterns of mean-level change due to both aging and cohort effects. Extraversion decreased as people aged, with the most pronounced declines occurring in young adulthood, and then again in old age. Agreeableness, indexed with a measure focusing on empathy, decreased in young adulthood and remained relatively unchanged thereafter. Conscientiousness increased among young adults then leveled off and remained fairly consistent for the rest of the adult life span. Neuroticism and openness to experience decreased as people aged. However, the models suggest that these latter effects may also be partially due to cohort differences, as older people showed lower levels of neuroticism and openness to experience more generally. Honesty-humility showed a pronounced and consistent increase across the adult life span. These analyses of large-scale longitudinal national probability panel data indicate that different dimensions of personality follow distinct developmental processes throughout adulthood. Our findings also highlight the importance of young adulthood (up to about the age of 30) in personality trait development, as well as continuing change throughout the adult life span. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Dietary consumption of monosodium L-glutamate induces adaptive response and reduction in the life span of Drosophila melanogaster.

PubMed

Abolaji, Amos O; Olaiya, Charles O; Oluwadahunsi, Oluwagbenga J; Farombi, Ebenezer O

2017-04-01

Adaptive response is the ability of an organism to better counterattack stress-induced damage in response to a number of different cytotoxic agents. Monosodium L-glutamate (MSG), the sodium salt of amino acid glutamate, is commonly used as a food additive. We investigated the effects of MSG on the life span and antioxidant response in Drosophila melanogaster (D. melanogaster). Both genders (1 to 3 days old) of flies were fed with diet containing MSG (0.1, 0.5, and 2.5-g/kg diet) for 5 days to assess selected antioxidant and oxidative stress markers, while flies for longevity were fed for lifetime. Thereafter, the longevity assay, hydrogen peroxide (H 2 O 2 ), and reactive oxygen and nitrogen species levels were determined. Also, catalase, glutathione S-transferase and acetylcholinesterase activities, and total thiol content were evaluated in the flies. We found that MSG reduced the life span of the flies by up to 23% after continuous exposure. Also, MSG increased reactive oxygen and nitrogen species and H 2 O 2 generations and total thiol content as well as the activities of catalase and glutathione S-transferase in D. melanogaster (P < .05). In conclusion, consumption of MSG for 5 days by D. melanogaster induced adaptive response, but long-term exposure reduced life span of flies. This study may therefore have public health significance in humans, and thus, moderate consumption of MSG is advocated by the authors. Copyright © 2017 John Wiley & Sons, Ltd.

Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms.

PubMed

Patel, Sonal A; Chaudhari, Amol; Gupta, Richa; Velingkaar, Nikkhil; Kondratov, Roman V

2016-04-01

Calorie restriction (CR) increases longevity in many species by unknown mechanisms. The circadian clock was proposed as a potential mediator of CR. Deficiency of the core component of the circadian clock-transcriptional factor BMAL1 (brain and muscle ARNT [aryl hydrocarbon receptor nuclear translocator]-like protein 1)-results in accelerated aging. Here we investigated the role of BMAL1 in mechanisms of CR. The 30% CR diet increased the life span of wild-type (WT) mice by 20% compared to mice on anad libitum(AL) diet but failed to increase life span ofBmal1(-/-)mice. BMAL1 deficiency impaired CR-mediated changes in the plasma levels of IGF-1 and insulin. We detected a statistically significantly reduction of IGF-1 in CRvs.AL by 50 to 70% in WT mice at several daily time points tested, while inBmal1(-/-)the reduction was not significant. Insulin levels in WT were reduced by 5 to 9%, whileBmal1(-/-)induced it by 10 to 35% at all time points tested. CR up-regulated the daily average expression ofBmal1(by 150%) and its downstream target genesPeriods(by 470% forPer1and by 130% forPer2). We propose that BMAL1 is an important mediator of CR, and activation of BMAL1 might link CR mechanisms with biologic clocks.-Patel, S. A., Chaudhari, A., Gupta, R., Velingkaar, N., Kondratov, R. V. Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms. © FASEB.

Physical Activity Throughout the Adult Life Span and Domain-Specific Cognitive Function in Old Age: A Systematic Review of Cross-Sectional and Longitudinal Data.

PubMed

Engeroff, Tobias; Ingmann, Tobias; Banzer, Winfried

2018-06-01

A growing body of literature suggests that physical activity might alleviate the age-related neurodegeneration and decline of cognitive function. However, most of this evidence is based on data investigating the association of exercise interventions or current physical activity behavior with cognitive function in elderly subjects. We performed a systematic review and hypothesize that physical activity during the adult life span is connected with maintained domain-specific cognitive functions during late adulthood defined as age 60+ years. We performed a systematic literature search up to November 2017 in PubMed, Web of Science, and Google Scholar without language limitations for studies analyzing the association of leisure physical activity during the adult life span (age 18+ years) and domain-specific cognitive functions in older adults (age 60+ years). The literature review yielded 14,294 articles and after applying inclusion and exclusion criteria, nine cross-sectional and 14 longitudinal studies were included. Moderate- and vigorous-intensity leisure physical activity was associated with global cognitive function and specific cognitive domains including executive functions and memory but not attention or working memory. Most studies assessed mid- to late-adulthood physical activity, thus information concerning the influence of young adult life-span physical activity is currently lacking. Observational evidence that moderate- and vigorous-intensity leisure physical activity is beneficially associated with maintained cognitive functions during old age is accumulating. Further studies are necessary to confirm a causal link by assessing objective physical activity data and the decline of cognitive functions at multiple time points during old age.

DNA oxidative damage and life expectancy in houseflies.

PubMed Central

Agarwal, S; Sohal, R S

1994-01-01

The objective of this study was to explore the relationship between oxidative molecular damage and the aging process by determining whether such damage is associated with the rate of aging, using the adult housefly as the experimental organism. Because the somatic tissues in the housefly consist of long-lived postmitotic cells, it provides an excellent model system for studying cumulative age-related cellular alterations. Rate of aging in the housefly was manipulated by varying the rate of metabolism (physical activity). The concentration of 8-hydroxydeoxyguanosine (80HdG) was used as an indicator of DNA oxidation. Exposure of live flies to x-rays and hyperoxia elevated the level of 8OHdG. The level of 8OHdG in mitochondrial as well as total DNA increased with the age of flies. Mitochondrial DNA was 3 times more susceptible to age-related oxidative damage than nuclear DNA. A decrease in the level of physical activity of the flies was found to prolong the life-span and corresponding reduce the level of 8OHdG in both mitochondrial and total DNA. Under all conditions examined, mitochondrial DNA exhibited a higher level of oxidative damage than total DNA. The 8OHdG levels were found to be inversely associated with the life expectancy of houseflies. The pattern of age-associated accrural of 8OHdG was virtually identical to that of protein carbonyl content. Altoghether, results of this study support the hypothesis that oxidative molecular damage is a causal factor in senescence. PMID:7991627

Life-span development of visual working memory: when is feature binding difficult?

PubMed

Cowan, Nelson; Naveh-Benjamin, Moshe; Kilb, Angela; Saults, J Scott

2006-11-01

We asked whether the ability to keep in working memory the binding between a visual object and its spatial location changes with development across the life span more than memory for item information. Paired arrays of colored squares were identical or differed in the color of one square, and in the latter case, the changed color was unique on that trial (item change) or was duplicated elsewhere in the array (color-location binding change). Children (8-10 and 11-12 years old) and older adults (65-85 years old) showed deficits relative to young adults. These were only partly simulated by dividing attention in young adults. The older adults had an additional deficiency, specifically in binding information, which was evident only when item- and binding-change trials were mixed together. In that situation, the older adults often overlooked the more subtle, binding-type changes. Some working memory processes related to binding undergo life-span development in an inverted-U shape, whereas other, bias- and salience-related processes that influence the use of binding information seem to develop monotonically.

Taste bud cell dynamics during normal and sodium-restricted development.

PubMed

Hendricks, Susan J; Brunjes, Peter C; Hill, David L

2004-04-26

Taste bud volume increases over the postnatal period to match the number of neurons providing innervation. To clarify age-related changes in fungiform taste bud volume, the current study investigated developmental changes in taste bud cell number, proliferation rate, and life span. Taste bud growth can largely be accounted for by addition of cytokeratin-19-positive taste bud cells. Examination of taste bud cell kinetics with 3H-thymidine autoradiography revealed that cell life span and turnover periods were not altered during normal development but that cells were produced more rapidly in young rats, a prominent modification that could lead to increased taste bud size. By comparison, dietary sodium restriction instituted during pre- and postnatal development results in small taste buds at adulthood as a result of fewer cytokeratin-19-positive cells. The dietary manipulation also had profound influences on taste bud growth kinetics, including an increased latency for cells to enter the taste bud and longer life span and turnover periods. These studies provide fundamental, new information about taste bud development under normal conditions and after environmental manipulations that impact nerve/target matching. Copyright 2004 Wiley-Liss, Inc.

Lung glutathione reductase induction in aging catalase-depleted frogs correlates with early survival throughout the life span.

PubMed

Perez-Campo, R; Lopez-Torres, M; Rojas, C; Cadenas, S; Barja de Quiroga, G

1993-02-01

A comprehensive experimental study on free radical-related parameters was performed in the lung throughout the life span of 220 initially young or old frogs. No age related differences were found transversely or longitudinally for lung superoxide dismutase, catalase, Se-dependent and -independent glutathione peroxidases, glutathione reductase, GSH, GSSG, or GSSG/GSH ratio. Continuous catalase depletion with aminotriazole led to glutathione reductase induction in the lung after 14.5 months of experimentation. This was accompanied by a great increase in survival rate of treated animals in relation to controls (especially in the old group). After 26.5 months of experimentation, glutathione reductase induction was lost and GSSG/GSH values tended to increase. This was followed by a 3-month long period of acute decrease in survival rate of treated animals. It is suggested that a high antioxidant/prooxidant balance is of protective value against causes of early death and can possibly be used in the future (when appropriately controlled) to increase the number of healthy years of the normal life span.

DNA damage leads to progressive replicative decline but extends the life span of long-lived mutant animals.

PubMed

Lans, H; Lindvall, J M; Thijssen, K; Karambelas, A E; Cupac, D; Fensgård, O; Jansen, G; Hoeijmakers, J H J; Nilsen, H; Vermeulen, W

2013-12-01

Human-nucleotide-excision repair (NER) deficiency leads to different developmental and segmental progeroid symptoms of which the pathogenesis is only partially understood. To understand the biological impact of accumulating spontaneous DNA damage, we studied the phenotypic consequences of DNA-repair deficiency in Caenorhabditis elegans. We find that DNA damage accumulation does not decrease the adult life span of post-mitotic tissue. Surprisingly, loss of functional ERCC-1/XPF even further extends the life span of long-lived daf-2 mutants, likely through an adaptive activation of stress signaling. Contrariwise, NER deficiency leads to a striking transgenerational decline in replicative capacity and viability of proliferating cells. DNA damage accumulation induces severe, stochastic impairment of development and growth, which is most pronounced in NER mutants that are also impaired in their response to ionizing radiation and inter-strand crosslinks. These results suggest that multiple DNA-repair pathways can protect against replicative decline and indicate that there might be a direct link between the severity of symptoms and the level of DNA-repair deficiency in patients.

Age trends for failures of sustained attention.

PubMed

Carriere, Jonathan S A; Cheyne, J Allan; Solman, Grayden J F; Smilek, Daniel

2010-09-01

Recent research has revealed an age-related reduction in errors in a sustained attention task, suggesting that sustained attention abilities improve with age. Such results seem paradoxical in light of the well-documented age-related declines in cognitive performance. In the present study, performance on the sustained attention to response task (SART) was assessed in a supplemented archival sample of 638 individuals between 14 and 77 years old. SART errors and response speed appeared to decline in a linear fashion as a function of age throughout the age span studied. In contrast, other measures of sustained attention (reaction time coefficient of variation), anticipation, and omissions) showed a decrease early in life and then remained unchanged for the rest of the life span. Thus, sustained attention shows improvements with maturation in early adulthood but then does not change with aging in older adults. On the other hand, aging across the entire life span leads to a more strategic (i.e., slower) response style that reduces the overt and critical consequences (i.e., SART errors) of momentary task disengagement. (c) 2010 APA, all rights reserved.

Does telomere elongation lead to a longer lifespan if cancer is considered?

NASA Astrophysics Data System (ADS)

Masa, Michael; Cebrat, Stanisław; Stauffer, Dietrich

2006-05-01

As cell proliferation is limited due to the loss of telomere repeats in DNA of normal somatic cells during division, telomere attrition can possibly play an important role in determining the maximum life span of organisms as well as contribute to the process of biological ageing. With computer simulations of cell culture development in organisms, which consist of tissues of normal somatic cells with finite growth, we obtain an increase of life span and life expectancy for longer telomeric DNA in the zygote. By additionally considering a two-mutation model for carcinogenesis and indefinite proliferation by the activation of telomerase, we demonstrate that the risk of dying due to cancer can outweigh the positive effect of longer telomeres on the longevity.

The Effects of Role Congruence and Role Conflict on Work, Marital, and Life Satisfaction

ERIC Educational Resources Information Center

Perrone, Kristin M.; Webb, L. Kay; Blalock, Rachel H.

2005-01-01

The impact of role congruence and role conflict on work, marital, and life satisfaction was studied using Super's life-span, life-space theory. A conceptual model of relationships between these variables was proposed, and gender differences were examined. Participants were 35 male and 60 female college graduates who completed surveys by mail.…

Red blood cell dynamics: from cell deformation to ATP release.

PubMed

Wan, Jiandi; Forsyth, Alison M; Stone, Howard A

2011-10-01

The mechanisms of red blood cell (RBC) deformation under both static and dynamic, i.e., flow, conditions have been studied extensively since the mid 1960s. Deformation-induced biochemical reactions and possible signaling in RBCs, however, were proposed only fifteen years ago. Therefore, the fundamental relationship between RBC deformation and cellular signaling dynamics i.e., mechanotransduction, remains incompletely understood. Quantitative understanding of the mechanotransductive pathways in RBCs requires integrative studies of physical models of RBC deformation and cellular biochemical reactions. In this article we review the physical models of RBC deformation, spanning from continuum membrane mechanics to cellular skeleton dynamics under both static and flow conditions, and elaborate the mechanistic links involved in deformation-induced ATP release. This journal is © The Royal Society of Chemistry 2011

14 CFR 170.3 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... approach control service. Arrival means any aircraft arriving at an airport. Benefit-cost ratio means the... (i.e., ATCT) divided by the discounted life cycle costs. Ceiling means the vertical distance between... to aviation users over the life span of a facility or service. Life cycle costs means the value of...

14 CFR 170.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... approach control service. Arrival means any aircraft arriving at an airport. Benefit-cost ratio means the... (i.e., ATCT) divided by the discounted life cycle costs. Ceiling means the vertical distance between... to aviation users over the life span of a facility or service. Life cycle costs means the value of...

14 CFR 170.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... approach control service. Arrival means any aircraft arriving at an airport. Benefit-cost ratio means the... (i.e., ATCT) divided by the discounted life cycle costs. Ceiling means the vertical distance between... to aviation users over the life span of a facility or service. Life cycle costs means the value of...

14 CFR 170.3 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... approach control service. Arrival means any aircraft arriving at an airport. Benefit-cost ratio means the... (i.e., ATCT) divided by the discounted life cycle costs. Ceiling means the vertical distance between... to aviation users over the life span of a facility or service. Life cycle costs means the value of...

The Balancing Act of Adult Life. ERIC Digest.

ERIC Educational Resources Information Center

Kerka, Sandra

Life is more complex than ever for adults in the 21st century as a result of technological advances; the changing nature of work, workplaces, and working relationships; international economic competition; the changing demographics of workers, families, and communities; and longer life spans. Learning to cope with all these changing…

Distribution of the anther-smut pathogen Microbotryum on species of the Caryophyllaceae

PubMed Central

Hood, Michael E; Mena-Alí, Jorge I; Gibson, Amanda K; Oxelman, Bengt; Giraud, Tatiana; Yockteng, Roxana; Arroyo, Mary T K; Conti, Fabio; Pedersen, Amy B; Gladieux, Pierre; Antonovics, Janis

2010-01-01

Summary Understanding disease distributions is of fundamental and applied importance, yet few studies benefit from integrating broad sampling with ecological and phylogenetic data. Here, anther-smut disease, caused by the fungus Microbotryum, was assessed using herbarium specimens of Silene and allied genera of the Caryophyllaceae.A total of 42 000 herbarium specimens were examined, and plant geographical distributions and morphological and life history characteristics were tested as correlates of disease occurrence. Phylogenetic comparative methods were used to determine the association between disease and plant life-span.Disease was found on 391 herbarium specimens from 114 species and all continents with native Silene. Anther smut occurred exclusively on perennial plants, consistent with the pathogen requiring living hosts to overwinter. The disease was estimated to occur in 80% of perennial species of Silene and allied genera. The correlation between plant life-span and disease was highly significant while controlling for the plant phylogeny, but the disease was not correlated with differences in floral morphology.Using resources available in natural history collections, this study illustrates how disease distribution can be determined, not by restriction to a clade of susceptible hosts or to a limited geographical region, but by association with host life-span, a trait that has undergone frequent evolutionary transitions. PMID:20406409

Thrombokinetics in patients with rheumatoid arthritis treated with D-penicillamine.

PubMed Central

Thomas, D; Gallus, A S; Brooks, P M; Tampi, R; Geddes, R; Hill, W

1984-01-01

The mechanism of D-penicillamine induced thrombocytopenia in rheumatoid arthritis was investigated by measuring platelet life-span and platelet production rate in 2 groups of rheumatoid arthritis patients treated with 250-750 mg/day D-penicillamine, 14 with a normal platelet count and 9 with thrombocytopenia (platelet count 50-130 X 10(9)/1). Age matched control patients not treated with D-penicillamine included 14 with rheumatoid arthritis and 9 with osteoarthritis. The platelet life-span was normal, but platelet production rate was significantly reduced in the thrombocytopenic patients, suggesting that D-penicillamine causes thrombocytopenia through bone marrow suppression. PMID:6742902

[Immunogenicity of L5178Y cells modified by different reagents].

PubMed

Gómez-Estrada, H; López-de la Rosa, L M; Becerril-Meza, G; Arellano-Blanco, J; Fernández-Quintero, P

1977-01-01

Lymphoma L5178Y cells were treated with neuraminidase of Vibrio cholerae, potassium iodine, dithiotreitol (DTT), mercaptoethanol, glutaraldehyde, iodoacetamide, merthiolate, sodium periodate, urea, papaine, trypsine and EDTA, to increase immunoreaction in tumor cells. Mice were immunized with modified tumor cells every week for one month. Thereafter non modified tumor cells were transplanted to previously immunized mice. Only the immunization with neuraminidase-treated cells rejected the tumor. Although the immunization with cells treated with potassium iodine, DTT and mercaptoethanol did not reject tumor, prolonged significantly span of life. The other reactives had neither effect on tumor rejection nor on span of life.

Hard-Earned Wisdom: Exploratory Processing of Difficult Life Experience Is Positively Associated with Wisdom

ERIC Educational Resources Information Center

Weststrate, Nic M.; Glück, Judith

2017-01-01

Laypersons and experts believe that wisdom is cultivated through a diverse range of positive and negative life experiences. Yet, not all individuals with life experience are wise. We propose that one possible determinant of growth in wisdom from life experience is self-reflection. In a life span sample of adults (N = 94) ranging from 26 to 92…

What Is Life? What Was Life? What Will Life Be?

NASA Astrophysics Data System (ADS)

Deamer, D.

Our laboratory is exploring self-assembly processes and polymerization reactions of organic compounds in natural geothermal environments and related laboratory simulations. Although the physical environment that fostered primitive cellular life is still largely unconstrained, we can be reasonably confident that liquid water was required, together with a source of organic compounds and energy to drive polymerization reactions. There must also have been a process by which the compounds were sufficiently concentrated to undergo physical and chemical interactions. In earlier work we observed that macromolecules such as nucleic acids and proteins are readily encapsulated in membranous boundaries during wet-dry cycles such as those that would occur at the edges of geothermal springs or tide pools. The resulting structures are referred to as protocells, in that they exhibit certain properties of living cells and are models of the kinds of encapsulated macromolecular systems that would have led toward the first forms of cellular life. However, the assembly of protocells is markedly inhibited by conditions associated with extreme environments: High temperature, high salt concentrations, and low pH ranges. From a biophysical perspective, it follows that the most plausible planetary environment for the origin of cellular life would be an aqueous phase at moderate temperature ranges and low ionic strength, having a pH value near neutrality and divalent cations at submillimolar concentrations. This suggestion is in marked contrast to the view that life most likely began in a geothermal or marine environment, perhaps even the extreme environment of a hydrothermal vent. A more plausible site for the origin of cellular life would be fresh water pools maintained by rain falling on volcanic land masses resembling present-day Hawaii and Iceland. After the first cellular life was able to establish itself in a relatively benign environment, it would rapidly begin to adapt through Darwinian selection to more rigorous environments, including the extreme temperatures, salt concentrations and pH ranges that we now associate with the limits of life on the Earth.

Towards a Quantum Game of Life

NASA Astrophysics Data System (ADS)

Flitney, Adrian P.; Abbott, Derek

Cellular automata provide a means of obtaining complex behaviour from a simple array of cells and a deterministic transition function. They supply a method of computation that dispenses with the need for manipulation of individual cells and they are computationally universal. Classical cellular automata have proved of great interest to computer scientists but the construction of quantum cellular automata pose particular difficulties. We present a version of John Conway's famous two-dimensional classical cellular automata Life that has some quantum-like features, including interference effects. Some basic structures in the new automata are given and comparisons are made with Conway's game.

Royal Jelly-Mediated Prolongevity and Stress Resistance in Caenorhabditis elegans Is Possibly Modulated by the Interplays of DAF-16, SIR-2.1, HCF-1, and 14-3-3 Proteins.

PubMed

Wang, Xiaoxia; Cook, Lauren F; Grasso, Lindsay M; Cao, Min; Dong, Yuqing

2015-07-01

Recent studies suggest that royal jelly (RJ) and its related substances may have antiaging properties. However, the molecular mechanisms underlying the beneficial effects remain elusive. We report that the effects of RJ and enzyme-treated RJ (eRJ) on life span and health span in Caenorhabditis elegans (C elegans) are modulated by the sophisticated interplays of DAF-16, SIR-2.1, HCF-1, and 14-3-3 proteins. Dietary supplementation with RJ or eRJ increased C. elegans life span in a dose-dependent manner. The RJ and eRJ consumption increased the tolerance of C elegans to oxidative stress, ultraviolet irradiation, and heat shock stress. Our genetic analyses showed that RJ/eRJ-mediated life-span extension requires insulin/IGF-1 signaling and the activities of DAF-16, SIR-2.1, HCF-1, and FTT-2, a 14-3-3 protein. Earlier studies reported that DAF-16/FOXO, SIR-2.1/SIRT1, FTT-2, and HCF-1 have extensive interplays in worms and mammals. Our present findings suggest that RJ/eRJ-mediated promotion of longevity and stress resistance in C elegans is dependent on these conserved interplays. From an evolutionary point of view, this study not only provides new insights into the molecular mechanisms of RJ's action on health span promotion in C elegans, but also has imperative implications in using RJ/eRJ as nutraceuticals to delay aging and age-related disorders. © The Author 2014. 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.

VIV analysis of pipelines under complex span conditions

NASA Astrophysics Data System (ADS)

Wang, James; Steven Wang, F.; Duan, Gang; Jukes, Paul

2009-06-01

Spans occur when a pipeline is laid on a rough undulating seabed or when upheaval buckling occurs due to constrained thermal expansion. This not only results in static and dynamic loads on the flowline at span sections, but also generates vortex induced vibration (VIV), which can lead to fatigue issues. The phenomenon, if not predicted and controlled properly, will negatively affect pipeline integrity, leading to expensive remediation and intervention work. Span analysis can be complicated by: long span lengths, a large number of spans caused by a rough seabed, and multi-span interactions. In addition, the complexity can be more onerous and challenging when soil uncertainty, concrete degradation and unknown residual lay tension are considered in the analysis. This paper describes the latest developments and a ‘state-of-the-art’ finite element analysis program that has been developed to simulate the span response of a flowline under complex boundary and loading conditions. Both VIV and direct wave loading are captured in the analysis and the results are sequentially used for the ultimate limit state (ULS) check and fatigue life calculation.

Integrating the pace-of-life syndrome across species, sexes and individuals: covariation of life history and personality under pesticide exposure.

PubMed

Debecker, Sara; Sanmartín-Villar, Iago; de Guinea-Luengo, Miguel; Cordero-Rivera, Adolfo; Stoks, Robby

2016-05-01

The pace-of-life syndrome (POLS) hypothesis integrates covariation of life-history traits along a fast-slow continuum and covariation of behavioural traits along a proactive-reactive personality continuum. Few studies have investigated these predicted life-history/personality associations among species and between sexes. Furthermore, whether and how contaminants interfere with POLS patterns remains unexplored. We tested for covariation patterns in life history and in behaviour, and for life-history/personality covariation among species, among individuals within species and between sexes. Moreover, we investigated whether pesticide exposure affects covariation between life history and behaviour and whether species and sexes with a faster POLS strategy have a higher sensitivity to pesticides. We reared larvae of four species of Ischnura damselflies in a common garden experiment with an insecticide treatment (chlorpyrifos absent/present) in the final instar. We measured four life-history traits (larval growth rate during the pesticide treatment, larval development time, adult mass and life span) and two behavioural traits (larval feeding activity and boldness, each before and after the pesticide treatment). At the individual level, life-history traits and behavioural traits aligned along a fast-slow and a proactive-reactive continuum, respectively. Species-specific differences in life history, with fast-lived species having a faster larval growth and development, a lower mass at emergence and a shorter life span, suggested that time constraints in the larval stage were predictably driving life-history evolution both in the larval stage and across metamorphosis in the adult stage. Across species, females were consistently more slow-lived than males, reflecting that a large body size and a long life span are generally more important for females. In contrast to the POLS hypothesis, there was only little evidence for the expected positive coupling between life-history pace and proactivity. Pesticide exposure decreased larval growth rate and affected life-history/personality covariation in the most fast-lived species. Our study supports the existence of life-history and behavioural continua with limited support for life-history/personality covariation. Variation in digestive physiology may explain this decoupling of life history and behaviour and provide valuable mechanistic insights to understand and predict the occurrence of life-history/personality covariation patterns. © 2016 The Authors. Journal of Animal Ecology © 2016 British Ecological Society.

Life's Still Lifes

NASA Astrophysics Data System (ADS)

McIntosh, Harold V.

The de Bruijn diagram describing those decompositions of the neighborhoods of a one dimensional cellular automaton which conform to predetermined requirements of periodicity and translational symmetry shows how to construct extended configurations satisfying the same requirements. Similar diagrams, formed by stages, describe higher dimensional automata, although they become more laborious to compute with increasing neighborhood size. The procedure is illustrated by computing some still lifes for Conway's game of Life, a widely known two dimensional cellular automaton. This paper is written in September 10, 1988.

Early-life stress impacts the developing hippocampus and primes seizure occurrence: cellular, molecular, and epigenetic mechanisms

PubMed Central

Huang, Li-Tung

2014-01-01

Early-life stress includes prenatal, postnatal, and adolescence stress. Early-life stress can affect the development of the hypothalamic-pituitary-adrenal (HPA) axis, and cause cellular and molecular changes in the developing hippocampus that can result in neurobehavioral changes later in life. Epidemiological data implicate stress as a cause of seizures in both children and adults. Emerging evidence indicates that both prenatal and postnatal stress can prime the developing brain for seizures and an increase in epileptogenesis. This article reviews the cellular and molecular changes encountered during prenatal and postnatal stress, and assesses the possible link between these changes and increases in seizure occurrence and epileptogenesis in the developing hippocampus. In addititon, the priming effect of prenatal and postnatal stress for seizures and epileptogenesis is discussed. Finally, the roles of epigenetic modifications in hippocampus and HPA axis programming, early-life stress, and epilepsy are discussed. PMID:24574961

Lifespan extension by cranberry supplementation partially requires SOD2 and is life stage independent.

PubMed

Sun, Yaning; Yolitz, Jason; Alberico, Thomas; Sun, Xiaoping; Zou, Sige

2014-02-01

Many nutraceuticals and pharmaceuticals have been shown to promote healthspan and lifespan. However, the mechanisms underlying the beneficial effects of prolongevity interventions and the time points at which interventions should be implemented to achieve beneficial effects are not well characterized. We have previously shown that a cranberry-containing nutraceutical can promote lifespan in worms and flies and delay age-related functional decline of pancreatic cells in rats. Here we investigated the mechanism underlying lifespan extension induced by cranberry and the effects of short-term or life stage-specific interventions with cranberry on lifespan in Drosophila. We found that lifespan extension induced by cranberry was associated with reduced phosphorylation of ERK, a component of oxidative stress response MAPK signaling, and slightly increased phosphorylation of AKT, a component of insulin-like signaling. Lifespan extension was also associated with a reduced level of 4-hydroxynonenal protein adducts, a biomarker of lipid oxidation. Moreover, lifespan extension induced by cranberry was partially suppressed by knockdown of SOD2, a major mitochondrial superoxide scavenger. Furthermore, cranberry supplementation was administered in three life stages of adult flies, health span (3-30 days), transition span (31-60 days) and senescence span (61 days to the end when all flies died). Cranberry supplementation during any of these life stages extended the remaining lifespan relative to the non-supplemented and life stage-matched controls. These findings suggest that cranberry supplementation is sufficient to promote longevity when implemented during any life stage, likely through reducing oxidative damage. Published by Elsevier Inc.

Life-Span Exposure to Low Doses of Aspartame Beginning during Prenatal Life Increases Cancer Effects in Rats

PubMed Central

Soffritti, Morando; Belpoggi, Fiorella; Tibaldi, Eva; Esposti, Davide Degli; Lauriola, Michelina

2007-01-01

Background In a previous study conducted at the Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation (CMCRC/ERF), we demonstrated for the first time that aspartame (APM) is a multipotent carcinogenic agent when various doses are administered with feed to Sprague-Dawley rats from 8 weeks of age throughout the life span. Objective The aim of this second study is to better quantify the carcinogenic risk of APM, beginning treatment during fetal life. Methods We studied groups of 70–95 male and female Sprague-Dawley rats administered APM (2,000, 400, or 0 ppm) with feed from the 12th day of fetal life until natural death. Results Our results show a) a significant dose-related increase of malignant tumor–bearing animals in males (p < 0.01), particularly in the group treated with 2,000 ppm APM (p < 0.01); b) a significant increase in incidence of lymphomas/leukemias in males treated with 2,000 ppm (p < 0.05) and a significant dose-related increase in incidence of lymphomas/leukemias in females (p < 0.01), particularly in the 2,000-ppm group (p < 0.01); and c) a significant dose-related increase in incidence of mammary cancer in females (p < 0.05), particularly in the 2,000-ppm group (p < 0.05). Conclusions The results of this carcinogenicity bioassay confirm and reinforce the first experimental demonstration of APM’s multipotential carcinogenicity at a dose level close to the acceptable daily intake for humans. Furthermore, the study demonstrates that when life-span exposure to APM begins during fetal life, its carcinogenic effects are increased. PMID:17805418

Developmental change in proactive interference across the life span: evidence from two working memory tasks.

PubMed

Loosli, Sandra V; Rahm, Benjamin; Unterrainer, Josef M; Weiller, Cornelius; Kaller, Christoph P

2014-04-01

Working memory (WM) as the ability to temporarily maintain and manipulate various kinds of information is known to be affected by proactive interference (PI) from previously relevant contents, but studies on developmental changes in the susceptibility to PI are scarce. In the present study, we investigated life span development of item-specific PI. To this end, 92 individuals between the ages of 8 and 74 years completed a recent-probes task and an n-back task that both composed experimental manipulations of PI. Regarding global WM development, young adults had higher WM performance than children and older adults in both tasks. Significant PI × Age interactions revealed that susceptibility to PI changed over the life span in both tasks, whereas the developmental course of PI differed between the tasks: Children committed more PI-related errors than young adults in the recent-probes task but showed marginally less PI in the n-back task. Regarding reaction time costs, children did not differ from adults in the recent-probes task and were less affected than adults in the n-back. Older adults showed more PI-related errors than young adults in both tasks. Therefore, as expected, item-specific PI changed over the life span with the young adults being less susceptible to PI than children and older adults. The diverging developmental effects of PI across both tasks, especially in the children, are supposed to reflect different causes for the difficulties regarding resisting PI in children and older adults. These might concern differently developed underlying cognitive processes such as inhibition or recollection, or different responses to task demands across both tasks. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Photosynthetic thermotolerance of woody savanna species in China is correlated with leaf life span

PubMed Central

Zhang, Jiao-Lin; Poorter, L.; Hao, Guang-You; Cao, Kun-Fang

2012-01-01

Background and Aims Photosynthetic thermotolerance (PT) is important for plant survival in tropical and sub-tropical savannas. However, little is known about thermotolerance of tropical and sub-tropical wild plants and its association with leaf phenology and persistence. Longer-lived leaves of savanna plants may experience a higher risk of heat stress. Foliar Ca is related to cell integrity of leaves under stresses. In this study it is hypothesized that (1) species with leaf flushing in the hot-dry season have greater PT than those with leaf flushing in the rainy season; and (2) PT correlates positively with leaf life span, leaf mass per unit area (LMA) and foliar Ca concentration ([Ca]) across woody savanna species. Methods The temperature-dependent increase in minimum fluorescence was measured to assess PT, together with leaf dynamics, LMA and [Ca] for a total of 24 woody species differing in leaf flushing time in a valley-type savanna in south-west China. Key Results The PT of the woody savanna species with leaf flushing in the hot-dry season was greater than that of those with leaf flushing in the rainy season. Thermotolerance was positively associated with leaf life span and [Ca] for all species irrespective of the time of flushing. The associations of PT with leaf life span and [Ca] were evolutionarily correlated. Thermotolerance was, however, independent of LMA. Conclusions Chinese savanna woody species are adapted to hot-dry habitats. However, the current maximum leaf temperature during extreme heat stress (44·3 °C) is close to the critical temperature of photosystem II (45·2 °C); future global warming may increase the risk of heat damage to the photosynthetic apparatus of Chinese savanna species. PMID:22875810

Hour Glass Half-Full or Half-Empty? Future Time Perspective and Preoccupation with Negative Events Across the Life Span

PubMed Central

Strough, JoNell; de Bruin, Wändi Bruine; Parker, Andrew M.; Lemaster, Philip; Pichayayothin, Nipat; Delaney, Rebecca

2016-01-01

According to socioemotional selectivity theory, older adults' emotional well-being stems from having limited future time perspective that motivates them to maximize well-being in the “here and now.” Presumably, then, older adults' time horizons are associated with emotional competencies that boost positive affect and dampen negative affect, but little research has addressed this. Using a US national adult life-span sample (N= 3,933, 18-93 yrs), we found that a two-factor model of future time perspective (focus on future opportunities; focus on limited time) fit the data better than a one-factor model. Through middle age, people perceived the life-span hourglass as half full—they focused more on future opportunities than limited time. Around age 60, the balance changed to increasingly perceiving the life-span hourglass as half empty—they focused less on future opportunities and more on limited time. This pattern held even after accounting for perceived health, self-reported decision-making ability, and retirement status. At all ages, women's time horizons focused more on future opportunities compared to men's, and men's focused more on limited time. Focusing on future opportunities was associated with reporting less preoccupation with negative events, whereas focusing on limited time was associated with reporting more preoccupation. Older adults reported less preoccupation with negative events and this association was stronger after controlling for their perceptions of limited time and fewer future opportunities, suggesting that other pathways may explain older adults' reports of their ability to disengage from negative events. Insights gained and questions raised by measuring future time perspective as two dimensions are discussed. PMID:27267222

Late-onset temperature reduction can retard the aging process in aged fish via a combined action of an anti-oxidant system and the insulin/insulin-like growth factor 1 signaling pathway.

PubMed

Wang, Xia; Chang, Qingyun; Wang, Yu; Su, Feng; Zhang, Shicui

2014-12-01

Two different mechanisms are considered to be related to aging. Cumulative molecular damage caused by reactive oxygen species (ROS), the by-products of oxidative phosphorylation, is one of these mechanisms (ROS concept). Deregulated nutrient sensing by the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway is the second mechanism (IIS concept). Temperature reduction (TR) is known to modulate aging and prolong life span in a variety of organisms, but the mechanisms remain poorly defined. Here we first demonstrate that late-onset TR from 26 °C to 22 °C extends mean life span and maximum life span by approximately 5.2 and 3 weeks, respectively, in the annual fish Nothobranchius guentheri. We then show that TR is able to decrease the accumulation of the histological aging markers senescence-associated β-galactosidase (SA-β-Gal) in the epithelium and lipofuscin (LF) in the liver and to reduce protein oxidation and lipid peroxidation levels in the muscle. We also show that TR can enhance the activities of catalase, glutathione peroxidase, and superoxide dismutase, and stimulate the synthesis of SirT1 and FOXO3A/FOXO1A, both of which are the downstream regulators of the IIS pathway. Taken together, our findings suggest that late-onset TR, a simple non-intrusion intervention, can retard the aging process in aged fish, resulting in their life span extension, via a synergistic action of an anti-oxidant system and the IIS pathway. This also suggests that combined assessment of the ROS and IIS concepts will contribute to providing a more comprehensive view of the anti-aging process.

eRapa Restores A Normal Life Span in a FAP Mouse Model

PubMed Central

Hasty, Paul; Livi, Carolina B.; Dodds, Sherry G.; Jones, Diane; Strong, Randy; Javors, Martin; Fischer, Kathleen E.; Sloane, Lauren; Murthy, Kruthi; Hubbard, Gene; Sun, Lishi; Hurez, Vincent; Curiel, Tyler J.; Sharp, Zelton Dave

2014-01-01

Mutation of a single copy of the adenomatous polyposis coli (APC) gene results in familial adenomatous polyposis (FAP), which confers an extremely high risk for colon cancer. ApcMin/+ mice exhibit multiple intestinal neoplasia (MIN) that causes anemia and death from bleeding by 6 months. Mechanistic target of rapamycin complex 1 (mTORC1) inhibitors were shown to improve ApcMin/+ mouse survival when administered by oral gavage or added directly to the chow, but these mice still died from neoplasia well short of a natural life span. The National Institute of Aging Intervention Testing Program showed that enterically targeted rapamycin (eRapa) extended life span for wild type genetically heterogeneous mice in part by inhibiting age-associated cancer. We hypothesized that eRapa would be effective in preventing neoplasia and extend survival of ApcMin/+ mice. We show that eRapa improved survival for ApcMin/+ mice in a dose-dependent manner. Remarkably, and in contrast to previous reports, most of the ApcMin/+ mice fed 42 ppm eRapa lived beyond the median life span reported for wild type syngeneic mice. Furthermore, chronic eRapa did not cause detrimental immune effects in mouse models of cancer, infection or autoimmunity; thus, assuaging concerns that chronic rapamycin treatment suppresses immunity. Our studies suggest that a novel formulation (enteric targeting) of a well-known and widely used drug (rapamycin) can dramatically improve its efficacy in targeted settings. eRapa or other mTORC1 inhibitors could serve as effective cancer preventatives for people with FAP without suppressing the immune system, thus reducing the dependency on surgery as standard therapy. PMID:24282255

Hour glass half full or half empty? Future time perspective and preoccupation with negative events across the life span.

PubMed

Strough, JoNell; Bruine de Bruin, Wändi; Parker, Andrew M; Lemaster, Philip; Pichayayothin, Nipat; Delaney, Rebecca

2016-09-01

According to socioemotional selectivity theory, older adults' emotional well-being stems from having a limited future time perspective that motivates them to maximize well-being in the "here and now." Presumably, then, older adults' time horizons are associated with emotional competencies that boost positive affect and dampen negative affect, but little research has addressed this. Using a U.S. adult life-span sample (N = 3,933; 18-93 years), we found that a 2-factor model of future time perspective (future opportunities; limited time) fit the data better than a 1-factor model. Through middle age, people perceived the life-span hourglass as half full-they focused more on future opportunities than limited time. Around Age 60, the balance changed to increasingly perceiving the life-span hourglass as half empty-they focused less on future opportunities and more on limited time, even after accounting for perceived health, self-reported decision-making ability, and retirement status. At all ages, women's time horizons focused more on future opportunities compared with men's, and men's focused more on limited time. Focusing on future opportunities was associated with reporting less preoccupation with negative events, whereas focusing on limited time was associated with reporting more preoccupation. Older adults reported less preoccupation with negative events, and this association was stronger after controlling for their perceptions of limited time and fewer future opportunities, suggesting that other pathways may explain older adults' reports of their ability to disengage from negative events. Insights gained and questions raised by measuring future time perspective as 2 dimensions are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Up-stream events in the nuclear factor κB activation cascade in response to sparsely ionizing radiation

NASA Astrophysics Data System (ADS)

Hellweg, Christine E.; Langen, Britta; Klimow, Galina; Ruscher, Roland; Schmitz, Claudia; Baumstark-Khan, Christa; Reitz, Günther

2009-10-01

Radiation is a potentially limiting factor for manned long-term space missions. Prolonged exposure to galactic cosmic rays may shorten the healthy life-span after return to Earth due to cancer induction. During the mission, a solar flare can be life threatening. For better risk estimation and development of appropriate countermeasures, the study of the cellular radiation response is necessary. Since apoptosis may be a mechanism the body uses to eliminate damaged cells, the induction by cosmic radiation of the nuclear anti-apoptotic transcription factor nuclear factor κB (NF-κB) could influence the cancer risk of astronauts exposed to cosmic radiation by improving the survival of radiation-damaged cells. In previous studies using a screening assay for the detection of NF-κB-dependent gene induction (HEK-pNF-κB-d2EGFP/Neo cells), the activation of this transcription factor by heavy ions was shown [Baumstark-Khan, C., Hellweg, C.E., Arenz, A., Meier, M.M. Cellular monitoring of the nuclear factor kappa B pathway for assessment of space environmental radiation. Radiat. Res. 164, 527-530, 2005]. Studies with NF-κB inhibitors can map functional details of the NF-κB pathway and the influence of radiation-induced NF-κB activation on various cellular outcomes such as survival or cell cycle arrest. In this work, the efficacy and cytotoxicity of four different NF-κB inhibitors, caffeic acid phenethyl ester (CAPE), capsaicin, the proteasome inhibitor MG-132, and the cell permeable peptide NF-κB SN50 were analyzed using HEK-pNF-κB-d2EGFP/Neo cells. In the recommended concentration range, only CAPE displayed considerable cytotoxicity. CAPE and capsaicin partially inhibited NF-κB activation by the cytokine tumor necrosis factor α. MG-132 completely abolished the activation and was therefore used for experiments with X-rays. NF-κB SN-50 could not reduce NF-κB dependent expression of the reporter destabilized Enhanced Green Fluorescent Protein (d2EGFP). MG-132 entirely suppressed the X-ray induced NF-κB activation in HEK-pNF-κB-d2EGFP/Neo cells. In conclusion, the degradation of the inhibitor of NF-κB (IκB) in the proteasome is essential for X-ray induced NF-κB activation, and MG-132 will be useful in studies of the NF-κB pathway involvement in the cellular response to heavy ion exposure and other space-relevant radiation qualities.

Singlet oxygen Triplet Energy Transfer based imaging technology for mapping protein-protein proximity in intact cells

PubMed Central

To, Tsz-Leung; Fadul, Michael J.; Shu, Xiaokun

2014-01-01

Many cellular processes are carried out by large protein complexes that can span several tens of nanometers. Whereas Forster resonance energy transfer has a detection range of <10 nm, here we report the theoretical development and experimental demonstration of a new fluorescence imaging technology with a detection range of up to several tens of nanometers: singlet oxygen triplet energy transfer. We demonstrate that our method confirms the topology of a large protein complex in intact cells, which spans from the endoplasmic reticulum to the outer mitochondrial membrane and the matrix. This new method is thus suited for mapping protein proximity in large protein complexes. PMID:24905026

Cardiac risk assessment: when and who? [Retrospectroscope].

PubMed

Valentinuzzi, M E; Arini, P D; Laciar, E; Bonomini, M P; Correa, R O

2013-07-01

Think about the above lines taken from the Old Testament: At 130 years of age, Adam begat a son and at 800 he kept going, quitting this earthly life at 930. These numbers surpass by far the limits our current experience teaches us, however, perhaps a life span into the hundreds of years is ? What if, in the future, science were to do away with disease? What then would cause people to die: accidents, killings, wars? How old would old age be? Aging has always been a hot topic for research (with considerable quackery, too). For example, animals with a slow metabolism tend to live longer than those with a fast metabolism. Compare the average life span of a mouse with that of a turtle. Apparently, meditators are able to slow their metabolism down [1].

Longevity of clonal plants: why it matters and how to measure it

PubMed Central

de Witte, Lucienne C.; Stöcklin, Jürg

2010-01-01

Background Species' life-history and population dynamics are strongly shaped by the longevity of individuals, but life span is one of the least accessible demographic traits, particularly in clonal plants. Continuous vegetative reproduction of genets enables persistence despite low or no sexual reproduction, affecting genet turnover rates and population stability. Therefore, the longevity of clonal plants is of considerable biological interest, but remains relatively poorly known. Scope Here, we critically review the present knowledge on the longevity of clonal plants and discuss its importance for population persistence. Direct life-span measurements such as growth-ring analysis in woody plants are relatively easy to take, although, for many clonal plants, these methods are not adequate due to the variable growth pattern of ramets and difficult genet identification. Recently, indirect methods have been introduced in which genet size and annual shoot increments are used to estimate genet age. These methods, often based on molecular techniques, allow the investigation of genet size and age structure of whole populations, a crucial issue for understanding their viability and persistence. However, indirect estimates of clonal longevity are impeded because the process of ageing in clonal plants is still poorly understood and because their size and age are not always well correlated. Alternative estimators for genet life span such as somatic mutations have recently been suggested. Conclusions Empirical knowledge on the longevity of clonal species has increased considerably in the last few years. Maximum age estimates are an indicator of population persistence, but are not sufficient to evaluate turnover rates and the ability of long-lived clonal plants to enhance community stability and ecosystem resilience. In order to understand the dynamics of populations it will be necessary to measure genet size and age structure, not only life spans of single individuals, and to use such data for modelling of genet dynamics. PMID:20880935

Ageless and Timeless: Perspectives on Giftedness across the Life Span

ERIC Educational Resources Information Center

Fiedler, Ellen D.

2016-01-01

Annemarie Roeper's timeless perspectives were demonstrated throughout her long and productive life. Her prolific writings and speeches continue to influence our understanding of giftedness at all ages and stages of life, and the time I spent with her had a profound and meaningful effect on my work. Annemarie incorporated her inner view of…

"Play" across the Life Cycle: From Initiative to Integrity to Transcendence

ERIC Educational Resources Information Center

Jones, Elizabeth

2011-01-01

In this autobiographical journey through life-span developmental theory, the author reflects on her life as a player, embedding it in the context of Erik Erikson and Joan Erikson's stages of human development. The author builds on these basic ideas--theory, storytelling, play, and development--and defines them as simply as possible.

Preparation for Old Age in Different Life Domains: Dimensions and Age Differences

ERIC Educational Resources Information Center

Kornadt, Anna E.; Rothermund, Klaus

2014-01-01

We investigated preparation for age-related changes from a multidimensional, life span perspective and administered a newly developed questionnaire to a large sample aged 30-80 years. Preparing for age-related changes was organized by life domains, with domain-specific types of preparation addressing obstacles and opportunities in the respective…

Life stage dependent responses to desiccation risk in the annual killifish Nothobranchius wattersi.

PubMed

Grégoir, A F; Philippe, C; Pinceel, T; Reniers, J; Thoré, E S J; Vanschoenwinkel, B; Brendonck, L

2017-09-01

To assess whether the annual killifish Nothobranchius wattersi responds plastically to a desiccation risk and whether this response is life stage dependent, life-history traits such as maturation time, fecundity and life span were experimentally measured in N. wattersi that were subjected to a drop in water level either as juveniles, as adults or both as juveniles and adults. Fish that were exposed to simulated pool drying as juveniles did not show changes in reproductive output or life span. Adults reacted by doubling short term egg deposition at the cost of a shorter lifespan. Overall, these results suggest that annual fish species can use phenotypic plasticity to maximize their reproductive output when faced with early pond drying, but this response appears to be life-stage specific. In addition to frogs and aquatic insects, phenotypic plasticity induced by forthcoming drought is now also confirmed in annual fishes and could well be a common feature of the limited number of fish taxa that manage to survive in this extreme environment. © 2017 The Fisheries Society of the British Isles.

Parthanatos, a messenger of death

PubMed Central

David, Karen Kate; Andrabi, Shaida Ahmad; Dawson, Ted Murray; Dawson, Valina Lynn

2015-01-01

Poly-ADP-ribose polymerase-1 (PARP-1)'s multiple roles in the cell span from maintaining life to inducing death. The processes PARP-1 is involved in include, but are not limited to DNA repair, DNA transcription, mitosis, and cell death. Of PARP-1's different cellular functions, its active role in cell death is of particular interest to designing therapies for diseases. Genetic deletion of PARP-1 revealed that PARP-1 over activation underlies cell death in experimental models of stroke, diabetes, inflammation and neurodegeneration. Since interfering with PARP-1 mediated cell death will be clinically beneficial, great effort has been invested into designing PARP-1 inhibitors and understanding mechanisms downstream of PARP-1 over activation. PARP-1 overactivation may kill by depleting cellular energy through nicotinamide adenine dinucleotide (NAD+) consumption, and by releasing the cell death effector apoptosis-inducing factor (AIF). Unexpectedly, recent evidence shows that poly-ADP ribose (PAR) polymer itself, and not the consumption of NAD+ is the source of cytotoxicity. Thus, PAR polymer acts as a cell death effector downstream of PARP-1-mediated cell death signaling. We coined the term parthanatos after Thanatos, the personification of death in Greek mythology, to refer to PAR-mediated cell death. In this review, we will summarize the proposed mechanisms by which PARP-1 overactivation kills. We will present evidence for parthanatos, and the questions raised by these recent findings. It is evident that further understanding of parthanatos opens up new avenues for therapy in ameliorating diseases related to PARP-1 over activation. PMID:19273119

Generation and Characterization of an Immortalized Human Esophageal Myofibroblast Line.

PubMed

Niu, Chao; Chauhan, Uday; Gargus, Matthew; Shaker, Anisa

2016-01-01

Stromal cells with a myofibroblast phenotype present in the normal human esophagus are increased in individuals with gastro-esophageal reflux disease (GERD). We have previously demonstrated that myofibroblasts stimulated with acid and TLR4 agonists increase IL-6 and IL-8 secretion using primary cultures of myofibroblasts established from normal human esophagus. While primary cultures have the advantage of reflecting the in vivo environment, a short life span and unavoidable heterogeneity limits the usefulness of this model in larger scale in vitro cellular signaling studies. The major aim of this paper therefore was to generate a human esophageal myofibroblast line with an extended lifespan. In the work presented here we have generated and characterized an immortalized human esophageal myofibroblast line by transfection with a commercially available GFP-hTERT lentivirus. Immortalized human esophageal myofibroblasts demonstrate phenotypic, genotypic and functional similarity to primary cultures of esophageal myofibroblasts we have previously described. We found that immortalized esophageal myofibroblasts retain myofibroblast spindle-shaped morphology at low and high confluence beyond passage 80, and express α-SMA, vimentin, and CD90 myofibroblast markers. Immortalized human esophageal myofibroblasts also express the putative acid receptor TRPV1 and TLR4 and retain the functional capacity to respond to stimuli encountered in GERD with secretion of IL-6. Finally, immortalized human esophageal myofibroblasts also support the stratified growth of squamous esophageal epithelial cells in 3D organotypic cultures. This newly characterized immortalized human esophageal myofibroblast cell line can be used in future cellular signaling and co-culture studies.

Adipose, Bone and Myeloma: Contributions from the Microenvironment

PubMed Central

McDonald, Michelle; Fairfield, Heather; Falank, Carolyne; Reagan, Michaela R.

2017-01-01

Researchers globally are working towards finding a cure for multiple myeloma (MM), a destructive blood cancer diagnosed yearly in ~750,000 people worldwide [1]. Although MM targets multiple organ systems, it is the devastating skeletal destruction experienced by over 90% of patients that often most severely impacts patient morbidity, pain, and quality of life. Preventing bone disease is therefore a priority in MM treatment, and understanding how and why myeloma cells target the bone marrow (BM) is fundamental to this process. This review focuses on a key area of MM research: the contributions of the bone microenvironment to disease origins, progression, and drug resistance. We describe some of the key cell types in the BM niche: osteoclasts, osteoblasts, osteocytes, adipocytes and mesenchymal stem cells. We then focus on how these key cellular players are, or could be, regulating a range of disease-related processes spanning MM growth, drug resistance, and bone disease (including osteolysis, fracture, and hypercalcemia). We summarize the literature regarding MM-bone cell and MM-adipocyte relationships and subsequent phenotypic changes or adaptations in MM cells, with the aim of providing a deeper understanding of how myeloma cells grow in the skeleton to cause bone destruction. We identify avenues and therapies that intervene in these networks to stop tumor growth and/or induce bone regeneration. Overall, we aim to illustrate how novel therapeutic target molecules, proteins, and cellular mediators may offer new avenues to attack this disease while reviewing currently utilized therapies. PMID:27343063

Clay energetics in chemical evolution

NASA Technical Reports Server (NTRS)

Coyne, L. M.

1986-01-01

Clays have been implicated in the origin of terrestrial life since the 1950's. Originally they were considered agents which aid in selecting, concentrating and promoting oligomerization of the organic monomeric substituents of cellular life forms. However, more recently, it has been suggested that minerals, with particular emphasis on clays, may have played a yet more fundamental role. It has been suggested that clays are prototypic life forms in themselves and that they served as a template which directed the self-assembly of cellular life. If the clay-life theory is to have other than conceptual credibility, clays must be shown by experiment to execute the operations of cellular life, not only individually, but also in a sufficiently concerted manner as to produce some semblance of the functional attributes of living cells. Current studies are focussed on the ability of clays to absorb, store and transfer energy under plausible prebiotic conditions and to use this energy to drive chemistry of prebiotic relevance. Conclusions of the work are applicable to the role of clays either as substrates for organic chemistry, or in fueling their own life-mimetic processes.

The cellular transducer in bone: What is it?

PubMed

Taylor, David; Hazenberg, Jan; Lee, T Clive

2006-01-01

Bone is able to detect its strain environment and respond accordingly. In particular it is able to adapt to over-use and under-use by bone deposition or resorption. How can bone sense strain? Various physical mechanisms have been proposed for the so-called cellular transducer, but there is no conclusive proof for any one of them. This paper examines the theories and evidence, with particular reference to a new theory proposed by the authors, involving damage to cellular processes by microcracks. Experiments on bone samples ex-vivo showed that cracks cannot fracture osteocytes, but that cellular processes which span the crack can be broken. A theoretical model was developed for predicting the number of broken processes as a function of crack size and applied stress. This showed that signals emitted by fractured processes could be used to detect cracks which needed repairing and to provide information on the overall level of damage which could be used to initiate repair and adaptation responses.

Magnetohydrodynamic thermochemotherapy and MRI of mouse tumors

NASA Astrophysics Data System (ADS)

Brusentsov, Nikolay A.; Brusentsova, Tatiana N.; Filinova, Elena Yu.; Jurchenko, Nikolay Y.; Kupriyanov, Dmitry A.; Pirogov, Yuri A.; Dubina, Andry I.; Shumskikh, Maxim N.; Shumakov, Leonid I.; Anashkina, Ekaterina N.; Shevelev, Alexandr A.; Uchevatkin, Andry A.

2007-04-01

A dextran-ferrite magnetic fluid was successfully tested as magnetic resonance imaging (MRI) contrast agent. The same magnetic fluid was then combined with Melphalan, a chemotherapeutic drug, and used for magnetohydrodynamic thermochemotherapy of different tumors. The placement of the tumors in an AC magnetic field led to hyperthermia at 46 °C for 30 min. In combination with tumor slime aspiration, a 30% regression of ˜130 mm 3 non-metastatic P388 tumors in BDF 1 mice was reached, together with a life span increase of 290%. The same procedure associated with cyclophosphamide treatment of ˜500 mm 3 metastases tumor increased the animal's life span by 180%.

An Integrated Socio-Environmental Model of Health and Well-Being: a Conceptual Framework Exploring the Joint Contribution of Environmental and Social Exposures to Health and Disease Over the Life Span.

PubMed

Olvera Alvarez, Hector A; Appleton, Allison A; Fuller, Christina H; Belcourt, Annie; Kubzansky, Laura D

2018-06-01

Environmental and social determinants of health often co-occur, particularly among socially disadvantaged populations, yet because they are usually studied separately, their joint effects on health are likely underestimated. Building on converging bodies of literature, we delineate a conceptual framework to address these issues. Previous models provided a foundation for study in this area, and generated research pointing to additional important issues. These include a stronger focus on biobehavioral pathways, both positive and adverse health outcomes, and intergenerational effects. To accommodate the expanded set of issues, we put forward the Integrated Socio-Environmental Model of Health and Well-Being (ISEM), which examines how social and environmental factors combine and potentially interact, via multi-factorial pathways, to affect health and well-being over the life span. We then provide applied examples including the study of how food environments affect dietary behavior. The ISEM provides a comprehensive, theoretically informed framework to guide future research on the joint contribution of social and environmental factors to health and well-being across the life span.

Time scale matters: genetic analysis does not support adaptation-by-time as the mechanism for adaptive seasonal declines in kokanee reproductive life span

PubMed Central

Morbey, Yolanda E; Jensen, Evelyn L; Russello, Michael A

2014-01-01

Seasonal declines of fitness-related traits are often attributed to environmental effects or individual-level decisions about reproductive timing and effort, but genetic variation may also play a role. In populations of Pacific salmon (Oncorhynchus spp.), seasonal declines in reproductive life span have been attributed to adaptation-by-time, in which divergent selection for different traits occurs among reproductively isolated temporal components of a population. We evaluated this hypothesis in kokanee (freshwater obligate Oncorhynchus nerka) by testing for temporal genetic structure in neutral and circadian-linked loci. We detected no genetic differences in presumably neutral loci among kokanee with different arrival and maturation dates within a spawning season. Similarly, we detected no temporal genetic structure in OtsClock1b, Omy1009uw, or OmyFbxw11, candidate loci associated with circadian function. The genetic evidence from this study and others indicates a lack of support for adaptation-by-time as an important evolutionary mechanism underlying seasonal declines in reproductive life span and a need for greater consideration of other mechanisms such as time-dependent, adaptive adjustment of reproductive effort. PMID:25478160

Lifespan development of pro- and anti-saccades: multiple regression models for point estimates.

PubMed

Klein, Christoph; Foerster, Friedrich; Hartnegg, Klaus; Fischer, Burkhart

2005-12-07

The comparative study of anti- and pro-saccade task performance contributes to our functional understanding of the frontal lobes, their alterations in psychiatric or neurological populations, and their changes during the life span. In the present study, we apply regression analysis to model life span developmental effects on various pro- and anti-saccade task parameters, using data of a non-representative sample of 327 participants aged 9 to 88 years. Development up to the age of about 27 years was dominated by curvilinear rather than linear effects of age. Furthermore, the largest developmental differences were found for intra-subject variability measures and the anti-saccade task parameters. Ageing, by contrast, had the shape of a global linear decline of the investigated saccade functions, lacking the differential effects of age observed during development. While these results do support the assumption that frontal lobe functions can be distinguished from other functions by their strong and protracted development, they do not confirm the assumption of disproportionate deterioration of frontal lobe functions with ageing. We finally show that the regression models applied here to quantify life span developmental effects can also be used for individual predictions in applied research contexts or clinical practice.

A mitochondrial mutator plasmid that causes senescence under dietary restricted conditions

PubMed Central

Maas, Marc FPM; Hoekstra, Rolf F; Debets, Alfons JM

2007-01-01

Background Calorie or dietary restriction extends life span in a wide range of organisms including the filamentous fungus Podospora anserina. Under dietary restricted conditions, P. anserina isolates are several-fold longer lived. This is however not the case in isolates that carry one of the pAL2-1 homologous mitochondrial plasmids. Results We show that the pAL2-1 homologues act as 'insertional mutators' of the mitochondrial genome, which may explain their negative effect on life span extension. Sequencing revealed at least fourteen unique plasmid integration sites, of which twelve were located within the mitochondrial genome and two within copies of the plasmid itself. The plasmids were able to integrate in their entirety, via a non-homologous mode of recombination. Some of the integrated plasmid copies were truncated, which probably resulted from secondary, post-integrative, recombination processes. Integration sites were predominantly located within and surrounding the region containing the mitochondrial rDNA loci. Conclusion We propose a model for the mechanism of integration, based on innate modes of mtDNA recombination, and discuss its possible link with the plasmid's negative effect on dietary restriction mediated life span extension. PMID:17407571

Stochastic variation in telomere shortening rate causes heterogeneity of human fibroblast replicative life span.

PubMed

Martin-Ruiz, Carmen; Saretzki, Gabriele; Petrie, Joanne; Ladhoff, Juliane; Jeyapalan, Jessie; Wei, Wenyi; Sedivy, John; von Zglinicki, Thomas

2004-04-23

The replicative life span of human fibroblasts is heterogeneous, with a fraction of cells senescing at every population doubling. To find out whether this heterogeneity is due to premature senescence, i.e. driven by a nontelomeric mechanism, fibroblasts with a senescent phenotype were isolated from growing cultures and clones by flow cytometry. These senescent cells had shorter telomeres than their cycling counterparts at all population doubling levels and both in mass cultures and in individual subclones, indicating heterogeneity in the rate of telomere shortening. Ectopic expression of telomerase stabilized telomere length in the majority of cells and rescued them from early senescence, suggesting a causal role of telomere shortening. Under standard cell culture conditions, there was a minor fraction of cells that showed a senescent phenotype and short telomeres despite active telomerase. This fraction increased under chronic mild oxidative stress, which is known to accelerate telomere shortening. It is possible that even high telomerase activity cannot fully compensate for telomere shortening in all cells. The data show that heterogeneity of the human fibroblast replicative life span can be caused by significant stochastic cell-to-cell variation in telomere shortening.

Dissociable Changes of Frontal and Parietal Cortices in Inherent Functional Flexibility across the Human Life Span.

PubMed

Yin, Dazhi; Liu, Wenjing; Zeljic, Kristina; Wang, Zhiwei; Lv, Qian; Fan, Mingxia; Cheng, Wenhong; Wang, Zheng

2016-09-28

Extensive evidence suggests that frontoparietal regions can dynamically update their pattern of functional connectivity, supporting cognitive control and adaptive implementation of task demands. However, it is largely unknown whether this flexibly functional reconfiguration is intrinsic and occurs even in the absence of overt tasks. Based on recent advances in dynamics of resting-state functional resonance imaging (fMRI), we propose a probabilistic framework in which dynamic reconfiguration of intrinsic functional connectivity between each brain region and others can be represented as a probability distribution. A complexity measurement (i.e., entropy) was used to quantify functional flexibility, which characterizes heterogeneous connectivity between a particular region and others over time. Following this framework, we identified both functionally flexible and specialized regions over the human life span (112 healthy subjects from 13 to 76 years old). Across brainwide regions, we found regions showing high flexibility mainly in the higher-order association cortex, such as the lateral prefrontal cortex (LPFC), lateral parietal cortex, and lateral temporal lobules. In contrast, visual, auditory, and sensory areas exhibited low flexibility. Furthermore, we observed that flexibility of the right LPFC improved during maturation and reduced due to normal aging, with the opposite occurring for the left lateral parietal cortex. Our findings reveal dissociable changes of frontal and parietal cortices over the life span in terms of inherent functional flexibility. This study not only provides a new framework to quantify the spatiotemporal behavior of spontaneous brain activity, but also sheds light on the organizational principle behind changes in brain function across the human life span. Recent neuroscientific research has demonstrated that the human capability of adaptive task control is primarily the result of the flexible operation of frontal brain networks. However, it remains unclear whether this flexibly functional reconfiguration is intrinsic and occurs in the absence of an overt task. In this study, we propose a probabilistic framework to quantify the functional flexibility of each brain region using resting-state fMRI. We identify regions showing high flexibility mainly in the higher-order association cortex. In contrast, primary and unimodal visual and sensory areas show low flexibility. On the other hand, our findings reveal dissociable changes of frontal and parietal cortices in terms of inherent functional flexibility over the life span. Copyright © 2016 the authors 0270-6474/16/3610060-15$15.00/0.

"A general benevolence dimension that links neural, psychological, economic, and life-span data on altruistic tendencies": Correction to Hubbard et al. (2016).

PubMed

2016-10-01

Reports an error in "A general benevolence dimension that links neural, psychological, economic, and life-span data on altruistic tendencies" by Jason Hubbard, William T. Harbaugh, Sanjay Srivastava, David Degras and Ulrich Mayr ( Journal of Experimental Psychology: General , Advanced Online Publication, Aug 11, 2016, np). In the article, there was an error in the Task, Stimuli, and Procedures section. In the 1st sentence in the 6th paragraph, “Following the scanning phase, participants completed self-report questionnaires meant to reflected the Prosocial Disposition construct: the agreeableness scale from the Big F, which includes empathic concern and perspective-taking, and a scale of personality descriptive adjectives related to altruistic behavior (Wood, Nye, & Saucier, 2010).” should have read: “Following the scanning phase, participants completed self-report questionnaires that contained scales to reflect the Prosocial Disposition construct: the Big Five Inventory (BFI; John et al., 1991), from which we used the agreeableness scale to measure prosocial disposition; the Interpersonal Reactivity Index (IRI; Davis, 1980), from which we used the empathic concern and perspective-taking scales; and a scale of personality descriptive adjectives related to altruistic behavior (Wood, Nye, & Saucier, 2010).” (The following abstract of the original article appeared in record 2016-39037-001.) Individual and life span differences in charitable giving are an important economic force, yet the underlying motives are not well understood. In an adult, life span sample, we assessed manifestations of prosocial tendencies across 3 different measurement domains: (a) psychological self-report measures, (b) actual giving choices, and (c) fMRI-derived, neural indicators of “pure altruism.” The latter expressed individuals’ activity in neural valuation areas when charities received money compared to when oneself received money and thus reflected an altruistic concern for others. Results based both on structural equation modeling and unit-weighted aggregate scores revealed a strong higher-order General Benevolence dimension that accounted for variability across all measurement domains. The fact that the neural measures likely reflect pure altruistic tendencies indicates that General Benevolence is based on a genuine concern for others. Furthermore, General Benevolence exhibited a robust increase across the adult life span, potentially providing an explanation for why older adults typically contribute more to the public good than young adults. PsycINFO Database Record (c) 2016 APA, all rights reserved

Meaning and Purpose in Life across the Life Span: A Cross-Sectional Multivariate Analysis.

ERIC Educational Resources Information Center

Reker, Gary T.; And Others

This paper explores the developmental changes in meaning and purpose across the life course. Thirty males and females at the developmental stages of young adulthood (16-29 years), early middle-age (30-49 years), late middle-age (50-64 years), young-old (65-74 years) and old-old (75+ years) completed the Reker and Peacock (1981) Life Attitude…

The Study of Life Review. An Approach to the Investigation of Intellectual Development across the Life Span. Studien und Berichte 47.

ERIC Educational Resources Information Center

Staudinger, Ursula M.

A study looked for age differences in the quality of responses to the Life Review Task (LRT), studied the LRT itself as a tool for exploring wisdom and intellectual functioning in adulthood, and considered personality characteristics and life experience as alternative predictors of response quality. Sixty-three West German women of different ages…

Life Satisfaction Shows Terminal Decline in Old Age: Longitudinal Evidence from the German Socio-Economic Panel Study (SOEP)

ERIC Educational Resources Information Center

Gerstorf, Denis; Ram, Nilam; Estabrook, Ryne; Schupp, Jurgen; Wagner, Gert G.; Lindenberger, Ulman

2008-01-01

Longitudinal data spanning 22 years, obtained from deceased participants of the German Socio-Economic Panel Study (SOEP; N = 1,637; 70- to 100-year-olds), were used to examine if and how life satisfaction exhibits terminal decline at the end of life. Changes in life satisfaction were more strongly associated with distance to death than with…

Antioxidant Capacity of “Mexican Arnica” Heterotheca inuloides Cass Natural Products and Some Derivatives: Their Anti-Inflammatory Evaluation and Effect on C. elegans Life Span

PubMed Central

Rodríguez-Chávez, José Luis; Nieto-Camacho, Antonio; Delgado-Lamas, Guillermo

2015-01-01

It has been suggested that the accumulation of biomolecular damage caused by reactive oxygen species (ROS) contributes to aging. The antioxidant activity is related to the ability of certain compounds to protect against the potentially harmful effect of processes or reactions involving ROS. This ability is associated with the termination of free radical propagation in biological systems. From Heterotheca inuloides various compounds which have shown to possess antioxidant capacity and scavenging ROS. The aim of this study was to determine the antioxidant capacity of additional natural components isolated from H. inuloides and some semisynthetic derivatives, their anti-inflammatory activity and the effect on Caenorhabditis elegans nematode life span. Compounds showed ability to inhibit various biological processes such as lipid peroxidation, scavenge nonbiological important oxidants such as 1O2, OH∙, H2O2, and HOCl and scavenge non biological stable free radicals (DPPH). Some cadinane type compounds showed possess antioxidant, ROS scavenging capacity, anti-inflammatory activity, and effect on the C. elegans life span. Flavonoid type compounds increased the life of the nematode and quercetin was identified as the compound with the greatest activity. The modification of chemical structure led to a change in the antioxidant capacity, the anti-inflammatory activity, and the survival of the worm. PMID:25821555

The mouse as a model organism in aging research: usefulness, pitfalls and possibilities.

PubMed

Vanhooren, Valerie; Libert, Claude

2013-01-01

The mouse has become the favorite mammalian model. Among the many reasons for this privileged position of mice is their genetic proximity to humans, the possibilities of genetically manipulating their genomes and the availability of many tools, mutants and inbred strains. Also in the field of aging, mice have become very robust and reliable research tools. Since laboratory mice have a life expectancy of only a few years, genetic approaches and other strategies for intervening in aging can be tested by examining their effects on life span and aging parameters during the relatively short period of, for example, a PhD project. Moreover, experiments on mice with an extended life span as well as on mice demonstrating signs of (segmental) premature aging, together with genetic mapping strategies, have provided novel insights into the fundamental processes that drive aging. Finally, the results of studies on caloric restriction and pharmacological anti-aging treatments in mice have a high degree of relevance to humans. In this paper, we review a number of recent genetic mapping studies that have yielded novel insights into the aging process. We discuss the value of the mouse as a model for testing interventions in aging, such as caloric restriction, and we critically discuss mouse strains with an extended or a shortened life span as models of aging. Copyright © 2012 Elsevier B.V. All rights reserved.

Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function

PubMed Central

Jones, Natalie C; Lynn, Megan L; Gaudenz, Karin; Sakai, Daisuke; Aoto, Kazushi; Rey, Jean-Phillipe; Glynn, Earl F; Ellington, Lacey; Du, Chunying; Dixon, Jill; Dixon, Michael J; Trainor, Paul A

2010-01-01

Treacher Collins syndrome (TCS) is a congenital disorder of craniofacial development arising from mutations in TCOF1, which encodes the nucleolar phosphoprotein Treacle. Haploinsufficiency of Tcof1 perturbs mature ribosome biogenesis, resulting in stabilization of p53 and the cyclin G1–mediated cell-cycle arrest that underpins the specificity of neuroepithelial apoptosis and neural crest cell hypoplasia characteristic of TCS. Here we show that inhibition of p53 prevents cyclin G1–driven apoptotic elimination of neural crest cells while rescuing the craniofacial abnormalities associated with mutations in Tcof1 and extending life span. These improvements, however, occur independently of the effects on ribosome biogenesis; thus suggesting that it is p53-dependent neuroepithelial apoptosis that is the primary mechanism underlying the pathogenesis of TCS. Our work further implies that neuroepithelial and neural crest cells are particularly sensitive to cellular stress during embryogenesis and that suppression of p53 function provides an attractive avenue for possible clinical prevention of TCS craniofacial birth defects and possibly those of other neurocristopathies. PMID:18246078

Recent developments in the effort to cure HIV infection: going beyond N = 1.

PubMed

Siliciano, Janet D; Siliciano, Robert F

2016-02-01

Combination antiretroviral therapy (ART) can suppress plasma HIV to undetectable levels, allowing HIV-infected individuals who are treated early a nearly normal life span. Despite the clear ability of ART to prevent morbidity and mortality, it is not curative. Even in individuals who have full suppression of viral replication on ART, there are resting memory CD4+ T cells that harbor stably integrated HIV genomes, which are capable of producing infectious virus upon T cell activation. This latent viral reservoir is considered the primary obstacle to the development of an HIV cure, and recent efforts in multiple areas of HIV research have been brought to bear on the development of strategies to eradicate or develop a functional cure for HIV. Reviews in this series detail progress in our understanding of the molecular and cellular mechanisms of viral latency, efforts to accurately assess the size and composition of the latent reservoir, the characterization and development of HIV-targeted broadly neutralizing antibodies and cytolytic T lymphocytes, and animal models for the study HIV latency and therapeutic strategies.

Wound healing and longevity: Lessons from long-lived αMUPA mice

PubMed Central

Yanai, Hagai; Toren, Dimitri; Vierlinger, Klemens; Hofner, Manuela; Nöhammer, Christa; Chilosi, Marco; Budovsky, Arie; Fraifeld, Vadim E.

2015-01-01

Does the longevity phenotype offer an advantage in wound healing (WH)? In an attempt to answer this question, we explored skin wound healing in the long-lived transgenic αMUPA mice, a unique model of genetically extended life span. These mice spontaneously eat less, preserve their body mass, are more resistant to spontaneous and induced tumorigenesis and live longer, thus greatly mimicking the effects of caloric restriction (CR). We found that αMUPA mice showed a much slower age-related decline in the rate of WH than their wild-type counterparts (FVB/N). After full closure of the wound, gene expression in the skin of old αMUPA mice returned close to basal levels. In contrast, old FVB/N mice still exhibited significant upregulation of genes associated with growth-promoting pathways, apoptosis and cell-cell/cell-extra cellular matrix interaction, indicating an ongoing tissue remodeling or an inability to properly shut down the repair process. It appears that the CR-like longevity phenotype is associated with more balanced and efficient WH mechanisms in old age, which could ensure a long-term survival advantage. PMID:25960543

Acinus integrates AKT1 and subapoptotic caspase activities to regulate basal autophagy.

PubMed

Nandi, Nilay; Tyra, Lauren K; Stenesen, Drew; Krämer, Helmut

2014-10-27

How cellular stresses up-regulate autophagy is not fully understood. One potential regulator is the Drosophila melanogaster protein Acinus (Acn), which is necessary for autophagy induction and triggers excess autophagy when overexpressed. We show that cell type-specific regulation of Acn depends on proteolysis by the caspase Dcp-1. Basal Dcp-1 activity in developing photoreceptors is sufficient for this cleavage without a need for apoptosis to elevate caspase activity. On the other hand, Acn was stabilized by loss of Dcp-1 function or by the presence of a mutation in Acn that eliminates its conserved caspase cleavage site. Acn stability also was regulated by AKT1-mediated phosphorylation. Flies that expressed stabilized forms of Acn, either the phosphomimetic Acn(S641,731D) or the caspase-resistant Acn(D527A), exhibited enhanced basal autophagy. Physiologically, these flies showed improvements in processes known to be autophagy dependent, including increased starvation resistance, reduced Huntingtin-induced neurodegeneration, and prolonged life span. These data indicate that AKT1 and caspase-dependent regulation of Acn stability adjusts basal autophagy levels. © 2014 Nandi et al.

Precision Electrophile Tagging in Caenorhabditis elegans.

PubMed

Long, Marcus J C; Urul, Daniel A; Chawla, Shivansh; Lin, Hong-Yu; Zhao, Yi; Haegele, Joseph A; Wang, Yiran; Aye, Yimon

2018-01-16

Adduction of an electrophile to privileged sensor proteins and the resulting phenotypically dominant responses are increasingly appreciated as being essential for metazoan health. Functional similarities between the biological electrophiles and electrophilic pharmacophores commonly found in covalent drugs further fortify the translational relevance of these small-molecule signals. Genetically encodable or small-molecule-based fluorescent reporters and redox proteomics have revolutionized the observation and profiling of cellular redox states and electrophile-sensor proteins, respectively. However, precision mapping between specific redox-modified targets and specific responses has only recently begun to be addressed, and systems tractable to both genetic manipulation and on-target redox signaling in vivo remain largely limited. Here we engineer transgenic Caenorhabditis elegans expressing functional HaloTagged fusion proteins and use this system to develop a generalizable light-controlled approach to tagging a prototypical electrophile-sensor protein with native electrophiles in vivo. The method circumvents issues associated with low uptake/distribution and toxicity/promiscuity. Given the validated success of C. elegans in aging studies, this optimized platform offers a new lens with which to scrutinize how on-target electrophile signaling influences redox-dependent life span regulation.

Precision Electrophile Tagging in Caenorhabditis elegans

PubMed Central

2017-01-01

Adduction of an electrophile to privileged sensor proteins and the resulting phenotypically dominant responses are increasingly appreciated as being essential for metazoan health. Functional similarities between the biological electrophiles and electrophilic pharmacophores commonly found in covalent drugs further fortify the translational relevance of these small-molecule signals. Genetically encodable or small-molecule-based fluorescent reporters and redox proteomics have revolutionized the observation and profiling of cellular redox states and electrophile–sensor proteins, respectively. However, precision mapping between specific redox-modified targets and specific responses has only recently begun to be addressed, and systems tractable to both genetic manipulation and on-target redox signaling in vivo remain largely limited. Here we engineer transgenic Caenorhabditis elegans expressing functional HaloTagged fusion proteins and use this system to develop a generalizable light-controlled approach to tagging a prototypical electrophile–sensor protein with native electrophiles in vivo. The method circumvents issues associated with low uptake/distribution and toxicity/promiscuity. Given the validated success of C. elegans in aging studies, this optimized platform offers a new lens with which to scrutinize how on-target electrophile signaling influences redox-dependent life span regulation. PMID:28857552

Parthanatos, a messenger of death.

PubMed

David, Karen Kate; Andrabi, Shaida Ahmad; Dawson, Ted Murray; Dawson, Valina Lynn

2009-01-01

Poly-ADP-ribose polymerase-1 (PARP-1)'s roles in the cell span from maintaining life to inducing death. The processes PARP-1 is involved in include DNA repair, DNA transcription, mitosis, and cell death. Of PARP-1's different cellular functions, its role in cell death is of particular interest to designing therapies for diseases. Genetic deletion of PARP-1 revealed that PARP-1 overactivation underlies cell death in models of stroke, diabetes, inflammation and neurodegeneration. Since interfering with PARP-1 mediated cell death will be clinically beneficial, great effort has been invested into understanding mechanisms downstream of PARP-1 overactivation. Recent evidence shows that poly-ADP ribose (PAR) polymer itself can act as a cell death effector downstream of PARP-1. We coined the term parthanatos after Thanatos, the personification of death in Greek mythology, to refer to PAR-mediated cell death. In this review, we will present evidence and questions raised by these recent findings, and summarize the proposed mechanisms by which PARP-1 overactivation kills. It is evident that further understanding of parthanatos opens up new avenues for therapy in ameliorating diseases related to PARP-1 overactivation.

Of macrophages and red blood cells; a complex love story.

PubMed

de Back, Djuna Z; Kostova, Elena B; van Kraaij, Marian; van den Berg, Timo K; van Bruggen, Robin

2014-01-01

Macrophages tightly control the production and clearance of red blood cells (RBC). During steady state hematopoiesis, approximately 10(10) RBC are produced per hour within erythroblastic islands in humans. In these erythroblastic islands, resident bone marrow macrophages provide erythroblasts with interactions that are essential for erythroid development. New evidence suggests that not only under homeostasis but also under stress conditions, macrophages play an important role in promoting erythropoiesis. Once RBC have matured, these cells remain in circulation for about 120 days. At the end of their life span, RBC are cleared by macrophages residing in the spleen and the liver. Current theories about the removal of senescent RBC and the essential role of macrophages will be discussed as well as the role of macrophages in facilitating the removal of damaged cellular content from the RBC. In this review we will provide an overview on the role of macrophages in the regulation of RBC production, maintenance and clearance. In addition, we will discuss the interactions between these two cell types during transfer of immune complexes and pathogens from RBC to macrophages.

Neuropathic pain in a Fabry disease rat model

PubMed Central

Miller, James J.; Aoki, Kazuhiro; Murphy, Carly A.; O’Hara, Crystal L.; Tiemeyer, Michael; Stucky, Cheryl L.; Dahms, Nancy M.

2018-01-01

Fabry disease, the most common lysosomal storage disease, affects multiple organs and results in a shortened life span. This disease is caused by a deficiency of the lysosomal enzyme α-galactosidase A, which leads to glycosphingolipid accumulation in many cell types. Neuropathic pain is an early and severely debilitating symptom in patients with Fabry disease, but the cellular and molecular mechanisms that cause the pain are unknown. We generated a rat model of Fabry disease, the first nonmouse model to our knowledge. Fabry rats had substantial serum and tissue accumulation of α-galactosyl glycosphingolipids and had pronounced mechanical pain behavior. Additionally, Fabry rat dorsal root ganglia displayed global N-glycan alterations, sensory neurons were laden with inclusions, and sensory neuron somata exhibited prominent sensitization to mechanical force. We found that the cation channel transient receptor potential ankyrin 1 (TRPA1) is sensitized in Fabry rat sensory neurons and that TRPA1 antagonism reversed the behavioral mechanical sensitization. This study points toward TRPA1 as a potentially novel target to treat the pain experienced by patients with Fabry disease. PMID:29563343

YCL047C/POF1 Is a Novel Nicotinamide Mononucleotide Adenylyltransferase (NMNAT) in Saccharomyces cerevisiae*

PubMed Central

Kato, Michiko; Lin, Su-Ju

2014-01-01

NAD+ is an essential metabolic cofactor involved in various cellular biochemical processes. Nicotinamide riboside (NR) is an endogenously produced key pyridine metabolite that plays important roles in the maintenance of NAD+ pool. Using a NR-specific cell-based screen, we identified mutants that exhibit altered NR release phenotype. Yeast cells lacking the ORF YCL047C/POF1 release considerably more NR compared with wild type, suggesting that POF1 plays an important role in NR/NAD+ metabolism. The amino acid sequence of Pof1 indicates that it is a putative nicotinamide mononucleotide adenylyltransferase (NMNAT). Unlike other yeast NMNATs, Pof1 exhibits NMN-specific adenylyltransferase activity. Deletion of POF1 significantly lowers NAD+ levels and decreases the efficiency of NR utilization, resistance to oxidative stress, and NR-induced life span extension. We also show that NR is constantly produced by multiple nucleotidases and that the intracellular NR pools are likely to be compartmentalized, which contributes to the regulation of NAD+ homeostasis. Our findings may contribute to the understanding of the molecular basis and regulation of NAD+ metabolism in higher eukaryotes. PMID:24759102

Sex and Race Disparities in Health: Cohort Variations in Life Course Patterns

ERIC Educational Resources Information Center

Yang, Yang; Lee, Linda C.

2009-01-01

This study assesses changes in sex and race disparities in health over the life course and across cohorts by conducting growth curve analyses of nationally representative longitudinal data that spans 15 years. It finds that changes in disparities in depressive symptoms, disability and self-assessments of health across the life course are…

Life Lived Well: A Description of Wellness across the Lifespan of a Senior Woman

ERIC Educational Resources Information Center

Jarnagin, Whitney L.; Woodside, Marianne

2012-01-01

The concept of wellness provides a positive view of life development that can support psychological support and counseling. There is little in the literature about wellness and seniors, especially women. This study describes one senior woman's wellness across the life span by addressing two research questions: (a) What are the experiences of one…

Advanced glycation in health and disease: role of the modern environment.

PubMed

Vlassara, Helen

2005-06-01

It is believed that intracellular and extracellular advanced glycation (AGEs) or lipoxidation end products (ALEs), together with dysregulated glucose and lipid metabolism, are important contributors to oxidant or carbonyl stress, enhanced cellular redox-sensitive transcription factor activity, and impaired innate immune defense, causing over time inappropriate inflammatory responses. However, neither the magnitude nor the persistent nature of this increased prooxidant state are completely understood. A significant correlation has been found between ingested and circulating AGEs in humans in recent years. Based on animal studies, the injurious impact of diet-derived AGEs to vascular and kidney tissues is estimated to rival or even exceed that caused by hyperglycemia or hyperlipidemia. Consistent with this view, dietary AGE restriction has been associated with suppression of several immune defects, insulin resistance, and diabetic complications, whether genetically or diet induced, despite persistent diabetes. These findings are in support of clinical evidence from subjects with diabetes or vascular or kidney disease. Most recently, evidence from animal studies points to AGE restriction as an effective means for extending median life span, similar to that previously shown by marked caloric restriction. We conclude that excessive AGE consumption, in the current dietary/social structure, represents an independent factor for inappropriate oxidant stress responses, which may promote the premature expression of complex diseases associated with adult life, such as diabetes and cardiovascular disease.

Cognitive changes and dementia risk after traumatic brain injury: implications for aging military personnel.

PubMed

Vincent, Andrea S; Roebuck-Spencer, Tresa M; Cernich, Alison

2014-06-01

Traumatic brain injury (TBI) is recognized as an important risk factor for the long-term cognitive health of military personnel, particularly in light of growing evidence that TBI increases risk for Alzheimer's disease and other dementias. In this article, we review the neurocognitive and neuropathologic changes after TBI with particular focus on the potential risk for cognitive decline across the life span in military service members. Implications for monitoring and surveillance of cognition in the aging military population are discussed. Additional studies are needed to clarify the factors that increase risk for later life cognitive decline, define the mechanistic link between these factors and dementia, and provide empirically supported interventions to mitigate the impact of TBI on cognition across the life span. Copyright © 2014 The Alzheimer's Association. All rights reserved.

Conway's Game of Life is a near-critical metastable state in the multiverse of cellular automata.

PubMed

Reia, Sandro M; Kinouchi, Osame

2014-05-01

Conway's cellular automaton Game of Life has been conjectured to be a critical (or quasicritical) dynamical system. This criticality is generally seen as a continuous order-disorder transition in cellular automata (CA) rule space. Life's mean-field return map predicts an absorbing vacuum phase (ρ = 0) and an active phase density, with ρ = 0.37, which contrasts with Life's absorbing states in a square lattice, which have a stationary density of ρ(2D) ≈ 0.03. Here, we study and classify mean-field maps for 6144 outer-totalistic CA and compare them with the corresponding behavior found in the square lattice. We show that the single-site mean-field approach gives qualitative (and even quantitative) predictions for most of them. The transition region in rule space seems to correspond to a nonequilibrium discontinuous absorbing phase transition instead of a continuous order-disorder one. We claim that Life is a quasicritical nucleation process where vacuum phase domains invade the alive phase. Therefore, Life is not at the "border of chaos," but thrives on the "border of extinction."

Conway's game of life is a near-critical metastable state in the multiverse of cellular automata

NASA Astrophysics Data System (ADS)

Reia, Sandro M.; Kinouchi, Osame

2014-05-01

Conway's cellular automaton Game of Life has been conjectured to be a critical (or quasicritical) dynamical system. This criticality is generally seen as a continuous order-disorder transition in cellular automata (CA) rule space. Life's mean-field return map predicts an absorbing vacuum phase (ρ =0) and an active phase density, with ρ =0.37, which contrasts with Life's absorbing states in a square lattice, which have a stationary density of ρ2D≈0.03. Here, we study and classify mean-field maps for 6144 outer-totalistic CA and compare them with the corresponding behavior found in the square lattice. We show that the single-site mean-field approach gives qualitative (and even quantitative) predictions for most of them. The transition region in rule space seems to correspond to a nonequilibrium discontinuous absorbing phase transition instead of a continuous order-disorder one. We claim that Life is a quasicritical nucleation process where vacuum phase domains invade the alive phase. Therefore, Life is not at the "border of chaos," but thrives on the "border of extinction."

The structure of late-life depressive symptoms across a 20-year span: a taxometric investigation.

PubMed

Holland, Jason M; Schutte, Kathleen K; Brennan, Penny L; Moos, Rudolf H

2010-03-01

Past studies of the underlying structure of depressive symptoms have yielded mixed results, with some studies supporting a continuous conceptualization and others supporting a categorical one. However, no study has examined this research question with an exclusively older adult sample, despite the potential uniqueness of late-life depressive symptoms. In the present study, the underlying structure of late-life depressive symptoms was examined among a sample of 1,289 individuals across 3 waves of data collection spanning 20 years. The authors employed a taxometric methodology using indicators of depression derived from the Research Diagnostic Criteria (R. L. Spitzer, J. Endicott, & E. Robins, 1978). Maximum eigenvalue analyses and inchworm consistency tests generally supported a categorical conceptualization and identified a group that was primarily characterized by thoughts about death and suicide. However, compared to a categorical depression variable, depressive symptoms treated continuously were generally better predictors of relevant criterion variables. These findings suggest that thoughts of death and suicide may characterize a specific type of late-life depression, yet a continuous conceptualization still typically maximizes the predictive utility of late-life depressive symptoms.

Lack of robustness of life extension associated with several single-gene P element mutations in Drosophila melanogaster.

PubMed

Mockett, Robin J; Nobles, Amber C

2013-10-01

The hypothesis tested in this study was that single-gene mutations found previously to extend the life span of Drosophila melanogaster could do so consistently in both long-lived y w and standard w (1118) genetic backgrounds. GAL4 drivers were used to express upstream activation sequence (UAS)-responder transgenes globally or in the nervous system. Transgenes associated with oxidative damage prevention (UAS-hSOD1 and UAS-GCLc) or removal (EP-UAS-Atg8a and UAS-dTOR (FRB) ) failed to increase mean life spans in any expression pattern in either genetic background. Flies containing a UAS-EGFP-bMSRA (C) transgene associated with protein repair were found not to exhibit life extension or detectable enhanced green fluorescent protein (EGFP) activity. The presence of UAS-responder transgenes was confirmed by PCR amplification and sequencing at the 5' and 3' end of each insertion. These results cast doubt on the robustness of life extension in flies carrying single-gene mutations and suggest that the effects of all such mutations should be tested independently in multiple genetic backgrounds and laboratory environments.

Carbon Fiber Reinforced Polymer Grids for Shear and End Zone Reinforcement in Bridge Beams

DOT National Transportation Integrated Search

2018-01-01

Corrosion of reinforcing steel reduces life spans of bridges throughout the United States; therefore, using non-corroding carbon fiber reinforced polymer (CFRP) reinforcement is seen as a way to increase service life. The use of CFRP as the flexural ...

Embracing covariation in brain evolution: Large brains, extended development, and flexible primate social systems

PubMed Central

Charvet, Christine J.; Finlay, Barbara L.

2012-01-01

Brain size, body size, developmental length, life span, costs of raising offspring, behavioral complexity, and social structures are correlated in mammals due to intrinsic life-history requirements. Dissecting variation and direction of causation in this web of relationships often draw attention away from the factors that correlate with basic life parameters. We consider the “social brain hypothesis,” which postulates that overall brain and the isocortex are selectively enlarged to confer social abilities in primates, as an example of this enterprise and pitfalls. We consider patterns of brain scaling, modularity, flexibility of brain organization, the “leverage,” and direction of selection on proposed dimensions. We conclude that the evidence supporting selective changes in isocortex or brain size for the isolated ability to manage social relationships is poor. Strong covariation in size and developmental duration coupled with flexible brains allow organisms to adapt in variable social and ecological environments across the life span and in evolution. PMID:22230623

Cognitive constraints influence an understanding of life-cycle change.

PubMed

French, Jason A; Menendez, David; Herrmann, Patricia A; Evans, E Margaret; Rosengren, Karl S

2018-05-04

We investigated children's (n = 120; 3- to 11-year-olds) and adults' (n = 18) reasoning about life-cycle changes in biological organisms by examining their endorsements of four different patterns of life-span changes. Participants were presented with two separate tasks: (a) judging possible adult versions of a juvenile animal and (b) judging possible juvenile versions of an adult animal. The stimuli enabled us to examine the endorsement of four different patterns of change: identical growth, natural growth, dramatic change, and speciation. The results suggest that endorsement of the different patterns is influenced by age and familiarity. Young children and individuals confronted with unfamiliar organisms often endorsed an identical growth that emphasizes the stability of features over the life span and between parents and offspring. The results are interpreted as supporting the idea that cognitive constraints influence individuals' reasoning about biological change and that the influence of these constraints is most notable when individuals are young or are presented with unfamiliar biological organisms. Copyright © 2018 Elsevier Inc. All rights reserved.

Comparison of biochemical data, blood pressure and physical activity between longevity and non-longevity districts in Japan.

PubMed

Mori, Ichiro; Ishizuka, Tatsuo; Morita, Hiroyuki; Matsumoto, Masami; Uno, Yoshihiro; Kajita, Kazuo; Ikeda, Takahide; Fujioka, Kei; Matsubara, Kenji

2008-10-01

There is controversy about longevity-associated factors, including environmental and genetic factors. Clinical and epidemiological studies suggest that multiple risk factors decrease life-span, but there has not been a definitive report regarding the association of risk factors with longevity. The ultimate aim of the present study was to prevent the overwhelming increase in life-style-related diseases by evaluating this association in 2 districts in Japan. Plasma glucose levels, hemoglobin (Hb) A1c, lipids, dehydroepiandrosterone-sulfate, adiponectin and physical activity were examined in 133 subjects (M/F 47/86, 67+/-1 years) in Kokufu, a longevity district (mean life span: 80.4 years according to 2000 Japanese census) and 69 subjects (M/F 29/40, 62+/-1 years) in Miyama, a non-longevity district (mean life span 77.4 years, 2000 census). There were significant differences in systolic and diastolic blood pressures (BPs, p < 0.001), exercise capacity (p < 0.0001) and plasma adiponectin levels (p < 0.04) between the districts. Plasma adiponectin level was significantly correlated with high-density lipoprotein-cholesterol (HDL-C) (r = 0.333, p < 0.0001), triglyceride (TG) (r = -0.161, p < 0.04), HbA1c (r = -0.163, p < 0.03) and HOMA-R (r = -0.163, p < 0.03). Life-style-related factors such as BP, exercise capacity and plasma adiponectin levels might play an important role in longevity, and those of HDL-C and TG, as well as glucose tolerance, might be associated with adiponectin levels.

Cellular Automata with Anticipation: Examples and Presumable Applications

NASA Astrophysics Data System (ADS)

Krushinsky, Dmitry; Makarenko, Alexander

2010-11-01

One of the most prospective new methodologies for modelling is the so-called cellular automata (CA) approach. According to this paradigm, the models are built from simple elements connected into regular structures with local interaction between neighbours. The patterns of connections usually have a simple geometry (lattices). As one of the classical examples of CA we mention the game `Life' by J. Conway. This paper presents two examples of CA with anticipation property. These examples include a modification of the game `Life' and a cellular model of crowd movement.

Life Events, Public Policy and the Economic Vulnerability of Children and the Elderly.

ERIC Educational Resources Information Center

Burkhauser, Richard V.; Duncan, Greg J.

This report uses longitudinal data to provide a dynamic picture of the family income experiences of children and the elderly. In contrast to the image of fairly stable incomes during most life-cycle stages, findings show substantial income volatility at all points in the life span, placing substantial numbers of the population at risk of suffering…

Life-History Traits of the Model Organism Pristionchus pacificus Recorded Using the Hanging Drop Method: Comparison with Caenorhabditis elegans.

PubMed

Gilarte, Patricia; Kreuzinger-Janik, Bianca; Majdi, Nabil; Traunspurger, Walter

2015-01-01

The nematode Pristionchus pacificus is of growing interest as a model organism in evolutionary biology. However, despite multiple studies of its genetics, developmental cues, and ecology, the basic life-history traits (LHTs) of P. pacificus remain unknown. In this study, we used the hanging drop method to follow P. pacificus at the individual level and thereby quantify its LHTs. This approach allowed direct comparisons with the LHTs of Caenorhabditis elegans recently determined using this method. When provided with 5×10(9) Escherichia coli cells ml(-1) at 20°C, the intrinsic rate of natural increase of P. pacificus was 1.125 (individually, per day); mean net production was 115 juveniles produced during the life-time of each individual, and each nematode laid an average of 270 eggs (both fertile and unfertile). The mean age of P. pacificus individuals at first reproduction was 65 h, and the average life span was 22 days. The life cycle of P. pacificus is therefore slightly longer than that of C. elegans, with a longer average life span and hatching time and the production of fewer progeny.

The human NAD metabolome: Functions, metabolism and compartmentalization

PubMed Central

Nikiforov, Andrey; Kulikova, Veronika; Ziegler, Mathias

2015-01-01

Abstract The metabolism of NAD has emerged as a key regulator of cellular and organismal homeostasis. Being a major component of both bioenergetic and signaling pathways, the molecule is ideally suited to regulate metabolism and major cellular events. In humans, NAD is synthesized from vitamin B3 precursors, most prominently from nicotinamide, which is the degradation product of all NAD-dependent signaling reactions. The scope of NAD-mediated regulatory processes is wide including enzyme regulation, control of gene expression and health span, DNA repair, cell cycle regulation and calcium signaling. In these processes, nicotinamide is cleaved from NAD+ and the remaining ADP-ribosyl moiety used to modify proteins (deacetylation by sirtuins or ADP-ribosylation) or to generate calcium-mobilizing agents such as cyclic ADP-ribose. This review will also emphasize the role of the intermediates in the NAD metabolome, their intra- and extra-cellular conversions and potential contributions to subcellular compartmentalization of NAD pools. PMID:25837229

General Protein Diffusion Barriers create Compartments within Bacterial Cells

PubMed Central

Schlimpert, Susan; Klein, Eric A.; Briegel, Ariane; Hughes, Velocity; Kahnt, Jörg; Bolte, Kathrin; Maier, Uwe G.; Brun, Yves V.; Jensen, Grant J.; Gitai, Zemer; Thanbichler, Martin

2013-01-01

SUMMARY In eukaryotes, the differentiation of cellular extensions such as cilia or neuronal axons depends on the partitioning of proteins to distinct plasma membrane domains by specialized diffusion barriers. However, examples of this compartmentalization strategy are still missing for prokaryotes, although complex cellular architectures are widespread among this group of organisms. This study reveals the existence of a protein-mediated membrane diffusion barrier in the stalked bacterium Caulobacter crescentus. We show that the Caulobacter cell envelope is compartmentalized by macromolecular complexes that prevent the exchange of both membrane and soluble proteins between the polar stalk extension and the cell body. The barrier structures span the cross-sectional area of the stalk and comprise at least four proteins that assemble in a cell cycle-dependent manner. Their presence is critical for cellular fitness, as they minimize the effective cell volume, allowing faster adaptation to environmental changes that require de novo synthesis of envelope proteins. PMID:23201141

Cellular Mechanisms of Somatic Stem Cell Aging

PubMed Central

Jung, Yunjoon

2014-01-01

Tissue homeostasis and regenerative capacity rely on rare populations of somatic stem cells endowed with the potential to self-renew and differentiate. During aging, many tissues show a decline in regenerative potential coupled with a loss of stem cell function. Cells including somatic stem cells have evolved a series of checks and balances to sense and repair cellular damage to maximize tissue function. However, during aging the mechanisms that protect normal cell function begin to fail. In this review, we will discuss how common cellular mechanisms that maintain tissue fidelity and organismal lifespan impact somatic stem cell function. We will highlight context-dependent changes and commonalities that define aging, by focusing on three age-sensitive stem cell compartments: blood, neural, and muscle. Understanding the interaction between extrinsic regulators and intrinsic effectors that operate within different stem cell compartments is likely to have important implications for identifying strategies to improve health span and treat age-related degenerative diseases. PMID:24439814

A High-Performance Cellular Automaton Model of Tumor Growth with Dynamically Growing Domains

PubMed Central

Poleszczuk, Jan; Enderling, Heiko

2014-01-01

Tumor growth from a single transformed cancer cell up to a clinically apparent mass spans many spatial and temporal orders of magnitude. Implementation of cellular automata simulations of such tumor growth can be straightforward but computing performance often counterbalances simplicity. Computationally convenient simulation times can be achieved by choosing appropriate data structures, memory and cell handling as well as domain setup. We propose a cellular automaton model of tumor growth with a domain that expands dynamically as the tumor population increases. We discuss memory access, data structures and implementation techniques that yield high-performance multi-scale Monte Carlo simulations of tumor growth. We discuss tumor properties that favor the proposed high-performance design and present simulation results of the tumor growth model. We estimate to which parameters the model is the most sensitive, and show that tumor volume depends on a number of parameters in a non-monotonic manner. PMID:25346862

Materialism across the life span: An age-period-cohort analysis.

PubMed

Jaspers, Esther D T; Pieters, Rik G M

2016-09-01

This research examined the development of materialism across the life span. Two initial studies revealed that (a) lay beliefs were that materialism declines with age and (b) previous research findings also implied a modest, negative relationship between age and materialism. Yet, previous research has considered age only as a linear control variable, thereby precluding the possibility of more intricate relationships between age and materialism. Moreover, prior studies have relied on cross-sectional data and thus confound age and cohort effects. To improve on this, the main study used longitudinal data from 8 waves spanning 9 years of over 4,200 individuals (16 to 90 years) to examine age effects on materialism while controlling for cohort and period effects. Using a multivariate multilevel latent growth model, it found that materialism followed a curvilinear trajectory across the life span, with the lowest levels at middle age and higher levels before and after that. Thus, in contrast to lay beliefs, materialism increased in older age. Moreover, age effects on materialism differed markedly between 3 core themes of materialism: acquisition centrality, possession-defined success, and acquisition as the pursuit of happiness. In particular, acquisition centrality and possession-defined success were higher at younger and older age. Independent of these age effects, older birth cohorts were oriented more toward possession-defined success, whereas younger birth cohorts were oriented more toward acquisition centrality. The economic downturn since 2008 led to a decrease in acquisition as the pursuit of happiness and in desires for personal growth, but to an increase in desires for achievement. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Insulin-like growth factors and insulin: at the crossroad between tumor development and longevity.

PubMed

Novosyadlyy, Ruslan; Leroith, Derek

2012-06-01

Numerous lines of evidence indicate that insulin-like growth factor signaling plays an important role in the regulation of life span and tumor development. In the present paper, the role of individual components of insulin-like growth factor signaling in aging and tumor development has been extensively analyzed. The molecular mechanisms underlying aging and tumor development are frequently overlapping. Although the link between reduced insulin-like growth factor signaling and suppressed tumor growth and development is well established, it remains unclear whether extended life span results from direct suppression of insulin-like growth factor signaling or this effect is caused by indirect mechanisms such as improved insulin sensitivity.

A 'slow pace of life' in Australian old-endemic passerine birds is not accompanied by low basal metabolic rates.

PubMed

Bech, Claus; Chappell, Mark A; Astheimer, Lee B; Londoño, Gustavo A; Buttemer, William A

2016-05-01

Life history theory suggests that species experiencing high extrinsic mortality rates allocate more resources toward reproduction relative to self-maintenance and reach maturity earlier ('fast pace of life') than those having greater life expectancy and reproducing at a lower rate ('slow pace of life'). Among birds, many studies have shown that tropical species have a slower pace of life than temperate-breeding species. The pace of life has been hypothesized to affect metabolism and, as predicted, tropical birds have lower basal metabolic rates (BMR) than temperate-breeding birds. However, many temperate-breeding Australian passerines belong to lineages that evolved in Australia and share 'slow' life-history traits that are typical of tropical birds. We obtained BMR from 30 of these 'old-endemics' and ten sympatric species of more recently arrived passerine lineages (derived from Afro-Asian origins or introduced by Europeans) with 'faster' life histories. The BMR of 'slow' temperate-breeding old-endemics was indistinguishable from that of new-arrivals and was not lower than the BMR of 'fast' temperate-breeding non-Australian passerines. Old-endemics had substantially smaller clutches and longer maximal life spans in the wild than new arrivals, but neither clutch size nor maximum life span was correlated with BMR. Our results suggest that low BMR in tropical birds is not functionally linked to their 'slow pace of life' and instead may be a consequence of differences in annual thermal conditions experienced by tropical versus temperate species.

Élie Metchnikoff (1845-1916): celebrating 100 years of cellular immunology and beyond.

PubMed

Underhill, David M; Gordon, Siamon; Imhof, Beat A; Núñez, Gabriel; Bousso, Philippe

2016-10-01

The year 2016 marks 100 years since the death of Élie Metchnikoff (1845-1916), the Russian zoologist who pioneered the study of cellular immunology and who is widely credited with the discovery of phagocytosis, for which he was jointly awarded the Nobel Prize in Physiology or Medicine in 1908. However, his long scientific career spanned many disciplines and has had far-reaching effects on modern immunology beyond the study of phagocytosis. In this Viewpoint article, five leading immunologists from the fields of phagocytosis, macrophage biology, leukocyte migration, the microbiota and intravital imaging tell Nature Reviews Immunology how Metchnikoff's work has influenced past, present and future research in their respective fields.

Productive interaction between transmembrane mutants of the bovine papillomavirus E5 protein and the platelet-derived growth factor beta receptor.

PubMed

Lai, Char-Chang; Edwards, Anne P B; DiMaio, Daniel

2005-02-01

The bovine papillomavirus E5 protein is a 44-amino-acid transmembrane protein that transforms cells by binding to the transmembrane region of the cellular platelet-derived growth factor (PDGF) beta receptor, resulting in sustained receptor signaling. However, there are published reports that certain mutants with amino acid substitutions in the membrane-spanning segment of the E5 protein transform cells without activating the PDGF beta receptor. We re-examined several of these transmembrane mutants, and here we present five lines of evidence that these mutants do in fact activate the PDGF beta receptor, resulting in cellular signaling and transformation.

The Household School as Life-Span Learning Center.

ERIC Educational Resources Information Center

Warnat, Winifred I.

A constructive, effective, and realistic national educational policy should be established which takes into account the contributions of the household school to individual learning in areas of life roles, feelings, values formation, and behavior development. The adversary relationship between formal educational institutions and the family will be…

Families as Life Span Experts

ERIC Educational Resources Information Center

Brendtro, Larry K.; Mitchell, Martin L.

2011-01-01

Professionals dealing with challenging behavior frequently operate detached from the other relationships in the child's life. This narrow approach has been called the unilateral strategy based on the belief that the child's outside world can be ignored and behavior can be changed by administering specific corrective interventions. In contrast,…

Prayer Life of a Professor

ERIC Educational Resources Information Center

Baesler, E. James

2009-01-01

This autoethnographic account describes interconnections among the author's personal prayer life, teaching, and research. The contextual frame for the story includes episodes and observations from a twelve-year span, encompassing postacademic tenure and promotion to the present. The author's prayer is that others might resonate with parts of this…

Cellular metabolic rate is influenced by life-history traits in tropical and temperate birds.

PubMed

Jimenez, Ana Gabriela; Van Brocklyn, James; Wortman, Matthew; Williams, Joseph B

2014-01-01

In general, tropical birds have a "slow pace of life," lower rates of whole-animal metabolism and higher survival rates, than temperate species. A fundamental challenge facing physiological ecologists is the understanding of how variation in life-history at the whole-organism level might be linked to cellular function. Because tropical birds have lower rates of whole-animal metabolism, we hypothesized that cells from tropical species would also have lower rates of cellular metabolism than cells from temperate species of similar body size and common phylogenetic history. We cultured primary dermal fibroblasts from 17 tropical and 17 temperate phylogenetically-paired species of birds in a common nutritive and thermal environment and then examined basal, uncoupled, and non-mitochondrial cellular O2 consumption (OCR), proton leak, and anaerobic glycolysis (extracellular acidification rates [ECAR]), using an XF24 Seahorse Analyzer. We found that multiple measures of metabolism in cells from tropical birds were significantly lower than their temperate counterparts. Basal and uncoupled cellular metabolism were 29% and 35% lower in cells from tropical birds, respectively, a decrease closely aligned with differences in whole-animal metabolism between tropical and temperate birds. Proton leak was significantly lower in cells from tropical birds compared with cells from temperate birds. Our results offer compelling evidence that whole-animal metabolism is linked to cellular respiration as a function of an animal's life-history evolution. These findings are consistent with the idea that natural selection has uniquely fashioned cells of long-lived tropical bird species to have lower rates of metabolism than cells from shorter-lived temperate species.

Cellular Metabolic Rate Is Influenced by Life-History Traits in Tropical and Temperate Birds

PubMed Central

Jimenez, Ana Gabriela; Van Brocklyn, James; Wortman, Matthew; Williams, Joseph B.

2014-01-01

In general, tropical birds have a “slow pace of life,” lower rates of whole-animal metabolism and higher survival rates, than temperate species. A fundamental challenge facing physiological ecologists is the understanding of how variation in life-history at the whole-organism level might be linked to cellular function. Because tropical birds have lower rates of whole-animal metabolism, we hypothesized that cells from tropical species would also have lower rates of cellular metabolism than cells from temperate species of similar body size and common phylogenetic history. We cultured primary dermal fibroblasts from 17 tropical and 17 temperate phylogenetically-paired species of birds in a common nutritive and thermal environment and then examined basal, uncoupled, and non-mitochondrial cellular O2 consumption (OCR), proton leak, and anaerobic glycolysis (extracellular acidification rates [ECAR]), using an XF24 Seahorse Analyzer. We found that multiple measures of metabolism in cells from tropical birds were significantly lower than their temperate counterparts. Basal and uncoupled cellular metabolism were 29% and 35% lower in cells from tropical birds, respectively, a decrease closely aligned with differences in whole-animal metabolism between tropical and temperate birds. Proton leak was significantly lower in cells from tropical birds compared with cells from temperate birds. Our results offer compelling evidence that whole-animal metabolism is linked to cellular respiration as a function of an animal’s life-history evolution. These findings are consistent with the idea that natural selection has uniquely fashioned cells of long-lived tropical bird species to have lower rates of metabolism than cells from shorter-lived temperate species. PMID:24498080

Melt-processed polymeric cellular dosage forms for immediate drug release.

PubMed

Blaesi, Aron H; Saka, Nannaji

2015-12-28

The present immediate-release solid dosage forms, such as the oral tablets and capsules, comprise granular matrices. While effective in releasing the drug rapidly, they are fraught with difficulties inherent in processing particulate matter. By contrast, liquid-based processes would be far more predictable; but the standard cast microstructures are unsuited for immediate-release because they resist fluid percolation and penetration. In this article, we introduce cellular dosage forms that can be readily prepared from polymeric melts by incorporating the nucleation, growth, and coalescence of microscopic gas bubbles in a molding process. We show that the cell topology and formulation of such cellular structures can be engineered to reduce the length-scale of the mass-transfer step, which determines the time of drug release, from as large as the dosage form itself to as small as the thickness of the cell wall. This allows the cellular dosage forms to achieve drug release rates over an order of magnitude faster compared with those of cast matrices, spanning the entire spectrum of immediate-release and beyond. The melt-processed polymeric cellular dosage forms enable predictive design of immediate-release solid dosage forms by tailoring microstructures, and could be manufactured efficiently in a single step.

Exposure To Harmful Workplace Practices Could Account For Inequality In Life Spans Across Different Demographic Groups.

PubMed

Goh, Joel; Pfeffer, Jeffrey; Zenios, Stefanos

2015-10-01

The existence of important socioeconomic disparities in health and mortality is a well-established fact. Many pathways have been adduced to explain inequality in life spans. In this article we examine one factor that has been somewhat neglected: People with different levels of education get sorted into jobs with different degrees of exposure to workplace attributes that contribute to poor health. We used General Social Survey data to estimate differential exposures to workplace conditions, results from a meta-analysis that estimated the effect of workplace conditions on mortality, and a model that permitted us to estimate the overall effects of workplace practices on health. We conclude that 10-38 percent of the difference in life expectancy across demographic groups can be explained by the different job conditions their members experience. Project HOPE—The People-to-People Health Foundation, Inc.

The Biology of Aging: Citizen Scientists and Their Pets as a Bridge Between Research on Model Organisms and Human Subjects.

PubMed

Kaeberlein, M

2016-03-01

A fundamental goal of research into the basic mechanisms of aging is to develop translational strategies that improve human health by delaying the onset and progression of age-related pathology. Several interventions have been discovered that increase life span in invertebrate organisms, some of which have similar effects in mice. These include dietary restriction and inhibition of the mechanistic target of rapamycin by treatment with rapamycin. Key challenges moving forward will be to assess the extent to which these and other interventions improve healthy longevity and increase life span in mice and to develop practical strategies for extending this work to the clinic. Companion animals may provide an optimal intermediate between laboratory models and humans. By improving healthy longevity in companion animals, important insights will be gained regarding human aging while improving the quality of life for people and their pets. © The Author(s) 2015.

Minocycline, but not ascorbic acid, increases motor activity and extends the life span of Drosophila melanogaster.

PubMed

Mora, Marylhi; Medina-Leendertz, Shirley J; Bonilla, Ernesto; Terán, Raikelin E; Paz, Milagros C; Arcaya, José Luis

2013-06-01

In the present study we compared the effects of minocycline and ascorbic acid in the life span, motor activity and lipid peroxidation of Drosophila melanogaster, in an effort to find a substance capable of providing protection against oxidative stress in aging. In the flies treated with minocycline a very significant increase in the life span (101 +/- 1.33 days) was observed when compared to those treated with ascorbic acid and controls (42.3% and 38.4%, respectively). The motor activity of minocycline treated flies also increased significantly with respect to control and ascorbic acid fed flies, from the 3rd to the 9th week of treatment. With regard to lipid peroxidation, it was found that the levels of malondialdehyde (MDA) in flies treated with minocycline showed no statistical differences to the control on the first day of treatment, but a significantly lower content on the day of 50% survival. In contrast, in flies treated with ascorbic acid significantly elevated levels of MDA compared to control and minocycline treated flies were detected throughout. These results suggest a protective effect of minocycline against oxidative stress and aging in D. melanogaster. An inhibitory effect on reactive oxygen species production may be an important contributing factor.

Life span and structure of ephemeral root modules of different functional groups from a desert system.

PubMed

Liu, Bo; He, Junxia; Zeng, Fanjiang; Lei, Jiaqiang; Arndt, Stefan K

2016-07-01

The terminal branch orders of plant root systems have been proposed as short-lived 'ephemeral' modules specialized for resource absorption. The occurrence of ephemeral root modules has so far only been reported for a temperate tree species and it is unclear if the concept also applies to other woody (shrub, tree) and herb species. Fine roots of 12 perennial dicotyledonous herb, shrub and tree species were monitored for two growing seasons using a branch-order classification, sequential sampling and rhizotrons in the Taklamakan desert. Two root modules existed in all three plant functional groups. Among the first five branch orders, the first two (perennial herbs, shrubs) or three (trees) root orders were ephemeral and had a primary anatomical structure, high nitrogen (N) concentrations, high respiration rates and very short life spans of 1-4 months, whereas the last two branch orders in all functional groups were perennial, with thicker diameters, no or collapsed cortex, distinct secondary growth, low N concentrations, low respiration rates, but much longer life spans. Ephemeral, short-lived root modules and long-lived, persistent root modules seem to be a general feature across many plant functional groups and could represent a basic root system design. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Mice Deficient in Both Mn Superoxide Dismutase and Glutathione Peroxidase-1 Have Increased Oxidative Damage and a Greater Incidence of Pathology but No Reduction in Longevity

PubMed Central

Zhang, Yiqiang; Ikeno, Yuji; Qi, Wenbo; Chaudhuri, Asish; Li, Yan; Bokov, Alex; Thorpe, Suzanne R.; Baynes, John W.; Epstein, Charles; Richardson, Arlan

2009-01-01

To test the impact of increased mitochondrial oxidative stress as a mechanism underlying aging and age-related pathologies, we generated mice with a combined deficiency in two mitochondrial-localized antioxidant enzymes, Mn superoxide dismutase (MnSOD) and glutathione peroxidase-1 (Gpx-1). We compared life span, pathology, and oxidative damage in Gpx1−/−, Sod2+/−Gpx1+/−, Sod2+/−Gpx1−/−, and wild-type control mice. Oxidative damage was elevated in Sod2+/−Gpx1−/− mice, as shown by increased DNA oxidation in liver and skeletal muscle and increased protein oxidation in brain. Surprisingly, Sod2+/−Gpx1−/− mice showed no reduction in life span, despite increased levels of oxidative damage. Consistent with the important role for oxidative stress in tumorigenesis during aging, the incidence of neoplasms was significantly increased in the older Sod2+/−Gpx1−/− mice (28–30 months). Thus, these data do not support a significant role for increased oxidative stress as a result of compromised mitochondrial antioxidant defenses in modulating life span in mice and do not support the oxidative stress theory of aging. PMID:19776219

Controls on declining carbon balance with leaf age among 10 woody species in Australian woodland: do leaves have zero daily net carbon balances when they die?

PubMed

Reich, Peter B; Falster, Daniel S; Ellsworth, David S; Wright, Ian J; Westoby, Mark; Oleksyn, Jacek; Lee, Tali D

2009-01-01

* Here, we evaluated how increased shading and declining net photosynthetic capacity regulate the decline in net carbon balance with increasing leaf age for 10 Australian woodland species. We also asked whether leaves at the age of their mean life-span have carbon balances that are positive, zero or negative. * The net carbon balances of 2307 leaves on 53 branches of the 10 species were estimated. We assessed three-dimensional architecture, canopy openness, photosynthetic light response functions and dark respiration rate across leaf age sequences on all branches. We used YPLANT to estimate light interception and to model carbon balance along the leaf age sequences. * As leaf age increased to the mean life-span, increasing shading and declining photosynthetic capacity each separately reduced daytime carbon gain by approximately 39% on average across species. Together, they reduced daytime carbon gain by 64% on average across species. * At the age of their mean life-span, almost all leaves had positive daytime carbon balances. These per leaf carbon surpluses were of a similar magnitude to the estimated whole-plant respiratory costs per leaf. Thus, the results suggest that a whole-plant economic framework, including respiratory costs, may be useful in assessing controls on leaf longevity.

Mitochondrial maintenance failure in aging and role of sexual dimorphism

PubMed Central

Tower, John

2014-01-01

Gene expression changes during aging are partly conserved across species, and suggest that oxidative stress, inflammation and proteotoxicity result from mitochondrial malfunction and abnormal mitochondrial-nuclear signaling. Mitochondrial maintenance failure may result from trade-offs between mitochondrial turnover versus growth and reproduction, sexual antagonistic pleiotropy and genetic conflicts resulting from uni-parental mitochondrial transmission, as well as mitochondrial and nuclear mutations and loss of epigenetic regulation. Aging phenotypes and interventions are often sex-specific, indicating that both male and female sexual differentiation promote mitochondrial failure and aging. Studies in mammals and invertebrates implicate autophagy, apoptosis, AKT, PARP, p53 and FOXO in mediating sex-specific differences in stress resistance and aging. The data support a model where the genes Sxl in Drosophila, sdc-2 in C. elegans, and Xist in mammals regulate mitochondrial maintenance across generations and in aging. Several interventions that increase life span cause a mitochondrial unfolded protein response (UPRmt), and UPRmt is also observed during normal aging, indicating hormesis. The UPRmt may increase life span by stimulating mitochondrial turnover through autophagy, and/or by inhibiting the production of hormones and toxic metabolites. The data suggest that metazoan life span interventions may act through a common hormesis mechanism involving liver UPRmt, mitochondrial maintenance and sexual differentiation. PMID:25447815

The influence of the hot water extract from shiitake medicinal mushroom, Lentinus edodes (higher Basidiomycetes) on the food intake, life span, and age-related locomotor activity of Drosophila melanogaster.

PubMed

Matjuskova, Natalya; Azena, Elena; Serstnova, Ksenija; Muiznieks, Indrikis

2014-01-01

Shiitake medicinal mushroom, Lentinus edodes, is among the most widely cultivated edible mushrooms in the world and is a well-studied source of nutrients and biologically active compounds. We have studied the influence of the dietary supplement of the polysaccharides containing a hot water extract of the mushroom L. edodes on the fruit fly Drosophila melanogaster in terms of food intake, body weight, life span, and age-related locomotor activity. L. edodes extract, when added to the D. melanogaster feeding substrate at a 0.003-0.030% concentration (calculated for the dry weight of the polysaccharide fraction) did not influence food intake or body weight of the flies. It increased the life span and locomotor activities of male flies but was associated with early mortality and decreased locomotor activity of female flies. We conclude that the observed anti-aging effects of L. edodes extracts in the male D. melanogaster are not the result of dietary restriction. We propose that D. melanogaster is a suitable model organism for researching the molecular basis of the anti-aging effect of the shiitake mushroom extracts and sex linkage of these effects.

Reduced mitochondrial SOD displays mortality characteristics reminiscent of natural aging

PubMed Central

Paul, Anirban; Belton, Amy; Nag, Sanjay; Martin, Ian; Grotewiel, Michael S.; Duttaroy, Atanu

2009-01-01

Manganese superoxide dismutase (MnSOD or SOD2) is a key mitochondrial enzymatic antioxidant. Arguably the most striking phenotype associated with complete loss of SOD2 in flies and mice is shortened life span. To further explore the role of SOD2 in protecting animals from aging and age-associated pathology, we generated a unique collection of Drosophila mutants that progressively reduce SOD2 expression and function. Mitochondrial aconitase activity was substantially reduced in the Sod2 mutants, suggesting that SOD2 normally ensures the functional capacity of mitochondria. Flies with severe reductions in SOD2 expression exhibited accelerated senescence of olfactory behavior as well as precocious neurodegeneration and DNA strand breakage in neurons. Furthermore, life span was progressively shortened and age-dependent mortality was increased in conjunction with reduced SOD2 expression, while initial mortality and developmental viability were unaffected. Interestingly, life span and age-dependent mortality varied exponentially with SOD2 activity, indicating that there might normally be a surplus of this enzyme for protecting animals from premature death. Our data support a model in which disruption of the protective effects of SOD2 on mitochondria manifests as profound changes in behavioral and demographic aging as well as exacerbated age-related pathology in the nervous system. PMID:18078670

Assimilation of Endogenous Nicotinamide Riboside Is Essential for Calorie Restriction-mediated Life Span Extension in Saccharomyces cerevisiae*

PubMed Central

Lu, Shu-Ping; Kato, Michiko; Lin, Su-Ju

2009-01-01

NAD+ (nicotinamide adenine dinucleotide) is an essential cofactor involved in various biological processes including calorie restriction-mediated life span extension. Administration of nicotinamide riboside (NmR) has been shown to ameliorate deficiencies related to aberrant NAD+ metabolism in both yeast and mammalian cells. However, the biological role of endogenous NmR remains unclear. Here we demonstrate that salvaging endogenous NmR is an integral part of NAD+ metabolism. A balanced NmR salvage cycle is essential for calorie restriction-induced life span extension and stress resistance in yeast. Our results also suggest that partitioning of the pyridine nucleotide flux between the classical salvage cycle and the NmR salvage branch might be modulated by the NAD+-dependent Sir2 deacetylase. Furthermore, two novel deamidation steps leading to nicotinic acid mononucleotide and nicotinic acid riboside production are also uncovered that further underscore the complexity and flexibility of NAD+ metabolism. In addition, utilization of extracellular nicotinamide mononucleotide requires prior conversion to NmR mediated by a periplasmic phosphatase Pho5. Conversion to NmR may thus represent a strategy for the transport and assimilation of large nonpermeable NAD+ precursors. Together, our studies provide a molecular basis for how NAD+ homeostasis factors confer metabolic flexibility. PMID:19416965