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Sample records for age underlying disease

  1. Discover the network mechanisms underlying the connections between aging and age-related diseases.

    PubMed

    Yang, Jialiang; Huang, Tao; Song, Won-Min; Petralia, Francesca; Mobbs, Charles V; Zhang, Bin; Zhao, Yong; Schadt, Eric E; Zhu, Jun; Tu, Zhidong

    2016-01-01

    Although our knowledge of aging has greatly expanded in the past decades, it remains elusive why and how aging contributes to the development of age-related diseases (ARDs). In particular, a global mechanistic understanding of the connections between aging and ARDs is yet to be established. We rely on a network modelling named "GeroNet" to study the connections between aging and more than a hundred diseases. By evaluating topological connections between aging genes and disease genes in over three thousand subnetworks corresponding to various biological processes, we show that aging has stronger connections with ARD genes compared to non-ARD genes in subnetworks corresponding to "response to decreased oxygen levels", "insulin signalling pathway", "cell cycle", etc. Based on subnetwork connectivity, we can correctly "predict" if a disease is age-related and prioritize the biological processes that are involved in connecting to multiple ARDs. Using Alzheimer's disease (AD) as an example, GeroNet identifies meaningful genes that may play key roles in connecting aging and ARDs. The top modules identified by GeroNet in AD significantly overlap with modules identified from a large scale AD brain gene expression experiment, supporting that GeroNet indeed reveals the underlying biological processes involved in the disease. PMID:27582315

  2. Discover the network mechanisms underlying the connections between aging and age-related diseases

    PubMed Central

    Yang, Jialiang; Huang, Tao; Song, Won-min; Petralia, Francesca; Mobbs, Charles V.; Zhang, Bin; Zhao, Yong; Schadt, Eric E.; Zhu, Jun; Tu, Zhidong

    2016-01-01

    Although our knowledge of aging has greatly expanded in the past decades, it remains elusive why and how aging contributes to the development of age-related diseases (ARDs). In particular, a global mechanistic understanding of the connections between aging and ARDs is yet to be established. We rely on a network modelling named “GeroNet” to study the connections between aging and more than a hundred diseases. By evaluating topological connections between aging genes and disease genes in over three thousand subnetworks corresponding to various biological processes, we show that aging has stronger connections with ARD genes compared to non-ARD genes in subnetworks corresponding to “response to decreased oxygen levels”, “insulin signalling pathway”, “cell cycle”, etc. Based on subnetwork connectivity, we can correctly “predict” if a disease is age-related and prioritize the biological processes that are involved in connecting to multiple ARDs. Using Alzheimer’s disease (AD) as an example, GeroNet identifies meaningful genes that may play key roles in connecting aging and ARDs. The top modules identified by GeroNet in AD significantly overlap with modules identified from a large scale AD brain gene expression experiment, supporting that GeroNet indeed reveals the underlying biological processes involved in the disease. PMID:27582315

  3. Mechanisms underlying the production of false memories for famous people's names in aging and Alzheimer's disease.

    PubMed

    Plancher, Gaën; Guyard, Anne; Nicolas, Serge; Piolino, Pascale

    2009-10-01

    It is well known that the occurrence of false memories increases with aging, but the results remain inconsistent concerning Alzheimer's disease (AD). Moreover, the mechanisms underlying the production of false memories are still unclear. Using an experimental episodic memory test with material based on the names of famous people in a procedure derived from the DRM paradigm [Roediger, H. L., III, & McDermott, K. B. (1995). Creating false memories: Remembering words not presented in lists. Journal of Experimental Psychology: Learning, Memory & Cognition, 21, 803-814], we examined correct and false recall and recognition in 30 young adults, 40 healthy older adults, and 30 patients with AD. Moreover, we evaluated the relationships between false memory performance, correct episodic memory performance, and a set of neuropsychological assessments evaluating the semantic memory and executive functions. The results clearly indicated that correct recall and recognition performance decreased with the subjects' age, but it decreased even more with AD. In addition, semantically related false recalls and false recognitions increased with age but not with dementia. On the contrary, non-semantically related false recalls and false recognitions increased with AD. Finally, the regression analyses showed that executive functions mediated related false memories and episodic memory mediated related and unrelated false memories in aging. Moreover, executive functions predicted related and unrelated false memories in AD, and episodic and semantic memory predicted semantically related and unrelated false memories in AD. In conclusion, the results obtained are consistent with the current constructive models of memory suggesting that false memory creation depends on different cognitive functions and, consequently, that the impairments of these functions influence the production of false memories.

  4. Survival characteristics of the mollusc Lymnaea stagnalis under constant culture conditions: effects of aging and disease.

    PubMed

    Janse, C; Slob, W; Popelier, C M; Vogelaar, J W

    1988-03-01

    Survival characteristics of seven different populations of the mollusc Lymnaea stagnalis were studied under constant culture conditions. On the basis of these characteristics four populations were considered as healthy and three as infected. In the healthy populations senescence started at an age of about 200 days, 50% survival age varied from 282 to 372 days, 10% survival age from 417 to 508 days and the maximum age from 528 to 673 days. Infected populations differed from healthy ones: (1) in behaviour of the animals; and (2) in shape of survival curve and age-specific death rate. It is concluded that in aging studies in addition to the absolute age of the animals, the following information should be given: the percentage of survival of the population at the time of sampling and a quantitative estimate of the quality of the cultures from which the animals were sampled. The parameters of the Weibull function seem to be suitable for such estimations.

  5. Alzheimer's Disease as Subcellular `Cancer' --- The Scale-Invariant Principles Underlying the Mechanisms of Aging ---

    NASA Astrophysics Data System (ADS)

    Murase, M.

    1996-01-01

    Alzheimer's disease (AD) is characterized by the slow onset of neurodegeneration leading to dementia in many elderly people. The pathological hallmarks of AD are: the extracellular β-amyloid deposition in the senile plaques; the β-amyloid deposition in cerebral blood vessel walls especially in hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D); the intracellular neurofibrillary tangle formation composed of paired helical filaments (PHF), the principal component of which is a hyperphosphorylated form of the microtubule-binding protein, tau; and neurological dysfuction and neuronal cell death in limited regions and pathways of the central nervous system. Note that β-amyloid is a truncated form of a cell surface integral membrane glycoprotein: amyloid precursor protein (APP). Despite these hallmarks, the pathogenesis of AD has been poorly understood. In the present paper, a theory of aging is proposed to give a coherent account of the origins and causes of neurodegeneration common to the diverse neurodegenerative disorders such as AD and prion (proteinaceous infectious particles) diseases in comparison with the pathogenesis of cancers. Surprisingly, the self-aggregation of denatured proteins -- such as β-amyloid, PHF and prions -- responsible for neuronal cell death resembles, in many respects, the development (or the clonal evolution) of malignant cells at the expense of the entire organism harboring them. Although neurodegenerative disorders and cancers apparently differe in pathology, they nevertheless seem to follow the same priciples regardless of the level and scale of the biological organization. It is the general principles of heritable variations and natural selection as well as the general principles of self-organization that operate, not only on different molecules, but also at different hierarchical levels and scales of the biological organizaiton, independent of the details of diseases. Traditionally, natural selection, along

  6. Mild cognitive impairment due to alzheimer disease is less likely under the age of 65.

    PubMed

    Shin, Soojeong; Kim, Jong Hun; Cho, Jeong Hee; Kim, Gyu Sik; Choi, Sun-Ah; Lee, Jun Hong

    2015-01-01

    Patients with amnestic mild cognitive impairment (aMCI) are considered to have a high risk for Alzheimer dementia (AD). Even high positive predictive values, however, cannot be guaranteed even by tests with high sensitivity and specificity when disease prevalence is low. If we regard the clinical criteria for aMCI as a test for predicting aMCI due to AD, the positive predictive value of the criteria will be low by definition in young patients with aMCI (age below 65 years) because of the low prevalence of AD in this age group. To test this hypothesis, we compared CSF biomarkers for AD between young (age below 65 years) and old (age 65 years or older) age groups of normal cognition, aMCI, and AD of the Alzheimer's Disease Neuroimaging Initiative database. Using these biomarkers, we observed that the prevalence of aMCI due to AD differed significantly between the young and the old. For example, only 28.2% young aMCI, but 63.2% old aMCI, had abnormal CSF amyloid measures consistent with AD pathology. As posited, the presence of aMCI due to AD was lower in young aMCI than in old aMCI. Given that the likelihood of aMCI due to AD is reduced in younger subjects, more attention to and evaluation of alternative diagnoses need to be considered in this group.

  7. Aging and liver disease

    PubMed Central

    Kim, Hee; Kisseleva, Tatiana; Brenner, David A.

    2016-01-01

    Purpose of review Aging is a condition in which a person gradually loses the ability to maintain homeostasis, due to structural alteration or dysfunction. Aging is a major risk factor for most chronic diseases. As the liver has a remarkable ability to regenerate, this review assessed the effect of aging on clinical liver disease with references to preclinical models when relevant to pathogenesis. Recent findings Aging has been shown to not only enhance vulnerability to acute liver injury but also increase susceptibility of the fibrotic response. Aging is associated with the severity and poor prognosis of various liver diseases including nonalcoholic fatty liver disease, alcoholic liver disease, hepatitis C, and liver transplantation. Summary Treatment of older patients with liver disease may require different or longer interventions. Transplantation of an older liver will be less tolerant of subsequent injury. Future studies are needed to understand more about the molecular mechanism of aging and contribute to the development of a noble treatment strategy that can block the progression of aging-induced liver diseases. PMID:25850346

  8. Hospitalizations and Deaths Because of Respiratory and Diarrheal Diseases Among Haitian Children Under Five Years of Age, 2011–2013

    PubMed Central

    Vinekar, Kavita; Schaad, Nicolas; Lucien, Mentor Ali Ber; Leshem, Eyal; Oboho, Ikwo K.; Joseph, Gerard; Juin, Stanley; Dawood, Fatimah S.; Parashar, Umesh; Katz, Mark A.; Tohme, Rania A.

    2015-01-01

    Background Respiratory and diarrheal diseases are leading causes of morbidity and mortality among children younger than 5 years in developing countries. Data on the burden of these diseases in Haiti are scarce. Methods We conducted a retrospective review of hospital admission registries during January 1, 2011–December 31, 2013 for children younger than 5 years in 6 hospitals in Haiti. We recorded the number of all-cause, respiratory and diarrheal disease admissions and deaths by epidemiologic week and age. Results A total of 31,565 hospital admissions and 1763 deaths were recorded among children aged <5 years during the study period. Respiratory diseases accounted for 9183 (29%) hospitalizations and 301 (17%) deaths. Children aged 6–23 months had the highest percentage of hospitalizations attributable to respiratory diseases (38%), whereas children aged 36–47 months had the highest proportion of deaths attributable to respiratory diseases (37%). Respiratory disease hospitalizations followed a bimodal seasonal pattern, with peaks during May–June and October–December. Diarrheal diseases accounted for 8063 (26%) hospitalizations and 224 (13%) deaths. Children aged 6–11 months had the highest percentage of diarrhea-associated hospitalizations (39%) and deaths (29%). Diarrheal disease admissions peaked in January–April before the rainy season. Conclusions Respiratory and diarrheal diseases contributed to more than half of hospitalizations and almost a third of deaths in children younger than 5 years in Haiti. These data are essential to assess the impact of pneumococcal and rotavirus vaccines and other interventions in Haiti. PMID:26244833

  9. Lumbar Interbody Fusion Outcomes in Degenerative Lumbar Disease : Comparison of Results between Patients Over and Under 65 Years of Age

    PubMed Central

    Jo, Dae-Jean; Jun, Jae-Kyun; Kim, Ki-Tack

    2010-01-01

    Objective To evaluate the clinical and radiological outcomes of lumbar interbody fusion and its correlation with various factors (e.g., age, comorbidities, fusion level, bone quality) in patients over and under 65 years of age who underwent lumbar fusion surgery for degenerative lumbar disease. Methods One-hundred-thirty-three patients with lumbar degenerative disease underwent lumbar fusion surgery between June 2006 and June 2007 and were followed for more than one year. Forty-eight (36.1%) were older than 65 years of age (group A) and 85 (63.9%) were under 65 years of age (group B). Diagnosis, comorbidities, length of hospital stay, and perioperative complications were recorded. The analysis of clinical outcomes was based on the visual analogue scale (VAS). Radiological results were evaluated using plain radiographs. Clinical outcomes, radiological outcomes, length of hospital stay, and complication rates were analyzed in relation to lumbar fusion level, the number of comorbidities, bone mineral density (BMD), and age. Results The mean age of the patients was 61.2 years (range, 33-86 years) and the mean BMD was -2.2 (range, -4.8 to -2.8). The mean length of hospital stay was 15.0 days (range, 5-60 days) and the mean follow-up was 23.0 months (range, 18-30 months). Eighty-five (64.0%) patients had more than one preoperative comorbidities. Perioperative complications occurred in 27 of 133 patients (20.3%). The incidence of overall complication was 22.9% in group A, and 18.8% in group B but there was no statistical difference between the two groups. The mean VAS scores for the back and leg were significantly decreased in both groups (p < 0.05), and bony fusion was achieved in 125 of 133 patients (94.0%). There was no significant difference in bony union rates between groups A and B (91.7% in group A vs. 95.3% in group B, p = 0.398). In group A, perioperative complications were more common with the increase in fusion level (p = 0.027). Perioperative complications in

  10. Aging, frailty and age-related diseases.

    PubMed

    Fulop, T; Larbi, A; Witkowski, J M; McElhaney, J; Loeb, M; Mitnitski, A; Pawelec, G

    2010-10-01

    The concept of frailty as a medically distinct syndrome has evolved based on the clinical experience of geriatricians and is clinically well recognizable. Frailty is a nonspecific state of vulnerability, which reflects multisystem physiological change. These changes underlying frailty do not always achieve disease status, so some people, usually very elderly, are frail without a specific life threatening illness. Current thinking is that not only physical but also psychological, cognitive and social factors contribute to this syndrome and need to be taken into account in its definition and treatment. Together, these signs and symptoms seem to reflect a reduced functional reserve and consequent decrease in adaptation (resilience) to any sort of stressor and perhaps even in the absence of extrinsic stressors. The overall consequence is that frail elderly are at higher risk for accelerated physical and cognitive decline, disability and death. All these characteristics associated with frailty can easily be applied to the definition and characterization of the aging process per se and there is little consensus in the literature concerning the physiological/biological pathways associated with or determining frailty. It is probably true to say that a consensus view would implicate heightened chronic systemic inflammation as a major contributor to frailty. This review will focus on the relationship between aging, frailty and age-related diseases, and will highlight possible interventions to reduce the occurrence and effects of frailty in elderly people. PMID:20559726

  11. Stop Aging Disease! ICAD 2014

    PubMed Central

    Ilia, Stambler

    2015-01-01

    On November 1–2, 2014, there took place in Beijing, China, the first International Conference on Aging and Disease (ICAD 2014) of the International Society on Aging and Disease (ISOAD). The conference participants presented a wide and exciting front of work dedicated to amelioration of aging-related conditions, ranging from regenerative medicine through developing geroprotective substances, elucidating a wide range of mechanisms of aging and aging-related diseases, from energy metabolism through genetics and immunomodulation to systems biology. The conference further emphasized the need to intensify and support research on aging and aging-related diseases to provide solutions for the urgent health challenges of the aging society. PMID:25821637

  12. Chronic kidney disease and premature ageing.

    PubMed

    Kooman, Jeroen P; Kotanko, Peter; Schols, Annemie M W J; Shiels, Paul G; Stenvinkel, Peter

    2014-12-01

    Chronic kidney disease (CKD) shares many phenotypic similarities with other chronic diseases, including heart failure, chronic obstructive pulmonary disease, HIV infection and rheumatoid arthritis. The most apparent similarity is premature ageing, involving accelerated vascular disease and muscle wasting. We propose that in addition to a sedentary lifestyle and psychosocial and socioeconomic determinants, four major disease-induced mechanisms underlie premature ageing in CKD: an increase in allostatic load, activation of the 'stress resistance response', activation of age-promoting mechanisms and impairment of anti-ageing pathways. The most effective current interventions to modulate premature ageing-treatment of the underlying disease, optimal nutrition, correction of the internal environment and exercise training-reduce systemic inflammation and oxidative stress and induce muscle anabolism. Deeper mechanistic insight into the phenomena of premature ageing as well as early diagnosis of CKD might improve the application and efficacy of these interventions and provide novel leads to combat muscle wasting and vascular impairment in chronic diseases.

  13. Autoimmune diseases and reproductive aging

    PubMed Central

    Bove, Riley

    2013-01-01

    As the population ages, more individuals with autoimmune diseases are experiencing reproductive senescence. Understanding the impact of menopause and age-related androgen decline on disease onset and course, as well as the potential for hormonal interventions, is critically important. In men, lupus erythematosis (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS) are associated with lower androgen levels. However, the impact of age-related declines in testosterone, as well as of testosterone replacement, on disease course remains underexplored. In women, the course of all three diseases with onset after the age of menopause differs from that with onset before menopause. Early age at menopause is associated with increased disease risk, and after menopause, disease course changes in SLE and RA. Less is known about MS. This article summarizes what is known about the relationship between reproductive aging and autoimmune diseases in men and women, and highlights areas for further investigation. PMID:23522436

  14. Acute diarrhoeal disease in children under 7 years of age in a peri-urban slum of Santiago, Chile.

    PubMed Central

    Araya, M.; Figueroa, G.; Espinoza, J.; Montesinos, N.; Spencer, E.; Brunser, O.

    1985-01-01

    A group of 168 families who lived in a peri-urban slum in Santiago were surveyed for 9 months. All of them had a child under 7 years of age. Medical activities and data collection were carried out at a Field Station and by means of twice-weekly visits to each home, at which time cases of diarrhoea were recorded and investigated. Faecal samples for bacteriological, parasitological and rotavirus studies were obtained during each episode. The characteristics of clinical course, hygienic practices in the family, and monthly anthropometric measurements of infants and toddlers were also recorded. The mean monthly incidence of diarrhoea was 7.1 episodes per 100 children. Of the episodes, 44.2% were associated with pathogenic bacteria, 14.4% with rotavirus, 38.4% with parasites and in 27.9% no enteropathogens were identified. It was found that adequate hygienic habits were not associated with a decreased risk of developing diarrhoea and that about 60% of children did not have diarrhoea throughout the study period. The nutritional status was adequate in most cases: weight-for-age was below the 5th percentile in 11.5% of subjects and the height-for-age was normal in all. No moderate or severe cases of malnutrition were detected. PMID:4067299

  15. A Prospective Hospital-based Surveillance to Estimate Rotavirus Disease Burden in Bhutanese Children under 5 Years of Age

    PubMed Central

    Wangchuk, Sonam; Dorji, Tshering; Tsheten; Tshering, Karchung; Zangmo, Sangay; Pem Tshering, Kunzang; Dorji, Tandin; Nishizono, Akira; Ahmed, Kamruddin

    2015-01-01

    As part of efforts to develop an informed policy for rotavirus vaccination, this prospective study was conducted to estimate the burden of rotavirus diarrhea among children less than 5 years old attended to the Department of Pediatrics, Jigme Dorji Wangchuk National Referral Hospital (JDWNRH), Thimphu, Bhutan. The duration of the study was three years, extending from February 2010 through December 2012. We estimated the frequency of hospitalization in the pediatric ward and dehydration treatment unit (DTU) for diarrhea and the number of events attributable to rotavirus infection among children under 5 years of age. During the study period, a total of 284 children (1 in 45) were hospitalized in the pediatric ward, and 2,220 (1 in 6) in the DTU with diarrhea among children residing in the Thimphu district. Group A rotavirus was detected in 32.5% and 18.8% of the stool samples from children hospitalized in the pediatric ward, respectively. Overall, 22.3% of the stool samples were rotavirus-positive, and the majority (90.8%) of them was detected in children under 2 years of age. From this study, we estimated that the annual incidence of hospitalization in the pediatric ward and DTU due to rotavirus diarrhea was 2.4/1000 (95% CI 1.7–3.4) and 10.8/1000 (95% CI 9.1–12.7) children, respectively. This study revealed that rotavirus is a major cause of diarrhea in Bhutanese children in Thimphu district and since no study has been performed previously, represents an important finding for policy discussions regarding the adoption of a rotavirus vaccine in Bhutan. PMID:25859154

  16. Endocrine Disease in Aged Horses.

    PubMed

    Durham, Andy E

    2016-08-01

    Aging horses may be at particular risk of endocrine disease. Two major equine endocrinopathies, pituitary pars intermedia dysfunction and equine metabolic syndrome, are commonly encountered in an aging population and may present with several recognizable signs, including laminitis. Investigation, treatment, and management of these diseases are discussed. Additionally, aging may be associated with development of rarer endocrinopathic problems, often associated with neoplasia, including diabetes mellitus and other confounders of glucose homeostasis, as well as thyroid, parathyroid, and adrenal diseases. Brief details of the recognition and management of these conditions are presented. PMID:27449391

  17. Vision from next generation sequencing: multi-dimensional genome-wide analysis for producing gene regulatory networks underlying retinal development, aging and disease.

    PubMed

    Yang, Hyun-Jin; Ratnapriya, Rinki; Cogliati, Tiziana; Kim, Jung-Woong; Swaroop, Anand

    2015-05-01

    Genomics and genetics have invaded all aspects of biology and medicine, opening uncharted territory for scientific exploration. The definition of "gene" itself has become ambiguous, and the central dogma is continuously being revised and expanded. Computational biology and computational medicine are no longer intellectual domains of the chosen few. Next generation sequencing (NGS) technology, together with novel methods of pattern recognition and network analyses, has revolutionized the way we think about fundamental biological mechanisms and cellular pathways. In this review, we discuss NGS-based genome-wide approaches that can provide deeper insights into retinal development, aging and disease pathogenesis. We first focus on gene regulatory networks (GRNs) that govern the differentiation of retinal photoreceptors and modulate adaptive response during aging. Then, we discuss NGS technology in the context of retinal disease and develop a vision for therapies based on network biology. We should emphasize that basic strategies for network construction and analyses can be transported to any tissue or cell type. We believe that specific and uniform guidelines are required for generation of genome, transcriptome and epigenome data to facilitate comparative analysis and integration of multi-dimensional data sets, and for constructing networks underlying complex biological processes. As cellular homeostasis and organismal survival are dependent on gene-gene and gene-environment interactions, we believe that network-based biology will provide the foundation for deciphering disease mechanisms and discovering novel drug targets for retinal neurodegenerative diseases. PMID:25668385

  18. Vision from next generation sequencing: Multi-dimensional genome-wide analysis for producing gene regulatory networks underlying retinal development, aging and disease

    PubMed Central

    Yang, Hyun-Jin; Ratnapriya, Rinki; Cogliati, Tiziana; Kim, Jung-Woong; Swaroop, Anand

    2015-01-01

    Genomics and genetics have invaded all aspects of biology and medicine, opening uncharted territory for scientific exploration. The definition of “gene” itself has become ambiguous, and the central dogma is continuously being revised and expanded. Computational biology and computational medicine are no longer intellectual domains of the chosen few. Next generation sequencing (NGS) technology, together with novel methods of pattern recognition and network analyses, has revolutionized the way we think about fundamental biological mechanisms and cellular pathways. In this review, we discuss NGS-based genome-wide approaches that can provide deeper insights into retinal development, aging and disease pathogenesis. We first focus on gene regulatory networks (GRNs) that govern the differentiation of retinal photoreceptors and modulate adaptive response during aging. Then, we discuss NGS technology in the context of retinal disease and develop a vision for therapies based on network biology. We should emphasize that basic strategies for network construction and analyses can be transported to any tissue or cell type. We believe that specific and uniform guidelines are required for generation of genome, transcriptome and epigenome data to facilitate comparative analysis and integration of multi-dimensional data sets, and for constructing networks underlying complex biological processes. As cellular homeostasis and organismal survival are dependent on gene-gene and gene-environment interactions, we believe that network-based biology will provide the foundation for deciphering disease mechanisms and discovering novel drug targets for retinal neurodegenerative diseases. PMID:25668385

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

    PubMed

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

    2009-09-01

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

  20. Effect of Aging in the Perception of Health-Related Quality of Life in End-Stage Renal Disease Patients under Online-Hemodiafiltration.

    PubMed

    Moura, Alexandra; Madureira, José; Alija, Pablo; Fernandes, João Carlos; Oliveira, José Gerardo; Lopez, Martin; Filgueiras, Madalena; Amado, Leonilde; Sameiro-Faria, Maria; Miranda, Vasco; Santos-Silva, Alice; Costa, Elísio

    2015-02-01

    This work aimed to evaluate how aging could influence patients' perception of health quality of life (HRQOL), as well as, the effect of aging on dialysis adequacy and in hematological, iron status, inflammatory and nutritional markers. In this transversal study were enrolled 305 ESRD patients under online-hemodiafiltration (OL-HDF) (59.67% males; 64.9 ± 14.3 years old). Data about comorbidities, hematological data, iron status, dialysis adequacy, nutritional and inflammatory markers were collected from patient's records. Moreover, HRQOL score, by using the Kidney Disease Quality of Life-Short Form (KDQOL-SF), was assessed. Analyzing the results according to quartiles of age, significant differences were found for some parameters evaluated by the KDQOL-SF instrument, namely for work status, physical functioning and role-physical, which decreased with increasing age. We also found a higher proportion of diabetic patients, a decrease in creatinine, iron, albumin serum levels, transferrin saturation and nPCR, with increasing age. Moreover, significant negative correlations were found between age and mean cell hemoglobin concentration, iron, transferrin saturation, albumin, nPCR, work status, physical functioning and role-physical. In conclusion, our results showed that aging is associated with a decreased work status, physical functioning and role-physical, with a decreased dialysis adequacy, iron availability and nutritional status, and with an increased proportion of diabetic patients and of patients using central venous catheter, as the vascular access. The knowledge of these changes associated with aging, which have impact in the quality of life of the patients, could be useful in their management.

  1. Cognitive aging and Alzheimer's disease

    PubMed Central

    Vandenberghe, R; Tournoy, J

    2005-01-01

    Cognitive aging and clinically probable Alzheimer's disease can be discriminated by means of clinical and neuropsychological testing, and structural and functional imaging techniques. Research at the level of cognitive brain systems and at the molecular level provides exciting new insights into the relation between aging and neurodegeneration. The advances at the clinical and at the basic research levels are necessary if we wish to meet the formidable challenge that the increasing prevalence of Alzheimer's disease poses to the medical community. PMID:15937198

  2. Aging and dry eye disease.

    PubMed

    Ding, Juan; Sullivan, David A

    2012-07-01

    Dry eye disease is a prevalent eye disorder that in particular affects the elderly population. One of the major causes of dry eye, meibomian gland dysfunction (MGD), shows increased prevalence with aging. MGD is caused by hyperkeratinization of the ductal epithelium of meibomian gland and reduced quantity and/or quality of meibum, the holocrine product that stabilizes and prevents the evaporation of the tear film. Of note, retinoids which are used in current anti-aging cosmetics may promote the development of MGD and dry eye disease. In this review, we will discuss the possible mechanisms of age-related MGD.

  3. Aging and dry eye disease

    PubMed Central

    Ding, Juan; Sullivan, David A.

    2012-01-01

    Dry eye disease is a prevalent eye disorder that in particular affects the elderly population. One of the major causes of dry eye, meibomian gland dysfunction (MGD), shows increased prevalence with aging. MGD is caused by hyperkeratinization of the ductal epithelium of meibomian gland and reduced quantity and/or quality of meibum, the holocrine product that stabilizes and prevents the evaporation of the tear film. Of note, retinoids which are used in current anti-aging cosmetics may promote the development of MGD and dry eye disease. In this review, we will discuss the possible mechanisms of age-related MGD. PMID:22569356

  4. Cerebrovascular disease in ageing and Alzheimer's disease.

    PubMed

    Love, Seth; Miners, J Scott

    2016-05-01

    Cerebrovascular disease (CVD) and Alzheimer's disease (AD) have more in common than their association with ageing. They share risk factors and overlap neuropathologically. Most patients with AD have Aβ amyloid angiopathy and degenerative changes affecting capillaries, and many have ischaemic parenchymal abnormalities. Structural vascular disease contributes to the ischaemic abnormalities in some patients with AD. However, the stereotyped progression of hypoperfusion in this disease, affecting first the precuneus and cingulate gyrus, then the frontal and temporal cortex and lastly the occipital cortex, suggests that other factors are more important, particularly in early disease. Whilst demand for oxygen and glucose falls in late disease, functional MRI, near infrared spectroscopy to measure the saturation of haemoglobin by oxygen, and biochemical analysis of myelin proteins with differential susceptibility to reduced oxygenation have all shown that the reduction in blood flow in AD is primarily a problem of inadequate blood supply, not reduced metabolic demand. Increasing evidence points to non-structural vascular dysfunction rather than structural abnormalities of vessel walls as the main cause of cerebral hypoperfusion in AD. Several mediators are probably responsible. One that is emerging as a major contributor is the vasoconstrictor endothelin-1 (EDN1). Whilst there is clearly an additive component to the clinical and pathological effects of hypoperfusion and AD, experimental and clinical observations suggest that the disease processes also interact mechanistically at a cellular level in a manner that exacerbates both. The elucidation of some of the mechanisms responsible for hypoperfusion in AD and for the interactions between CVD and AD has led to the identification of several novel therapeutic approaches that have the potential to ameliorate ischaemic damage and slow the progression of neurodegenerative disease. PMID:26711459

  5. The Intricate Interplay between Mechanisms Underlying Aging and Cancer.

    PubMed

    Piano, Amanda; Titorenko, Vladimir I

    2015-02-01

    Age is the major risk factor in the incidence of cancer, a hyperplastic disease associated with aging. Here, we discuss the complex interplay between mechanisms underlying aging and cancer as a reciprocal relationship. This relationship progresses with organismal age, follows the history of cell proliferation and senescence, is driven by common or antagonistic causes underlying aging and cancer in an age-dependent fashion, and is maintained via age-related convergent and divergent mechanisms. We summarize our knowledge of these mechanisms, outline the most important unanswered questions and suggest directions for future research.

  6. Effectiveness of Pneumococcal Conjugate Vaccines (PCV7 and PCV13) against Invasive Pneumococcal Disease among Children under Two Years of Age in Germany

    PubMed Central

    van der Linden, Mark; Falkenhorst, Gerhard; Perniciaro, Stephanie; Fitzner, Christina; Imöhl, Matthias

    2016-01-01

    Background In this study we calculate the effectiveness of pneumococcal conjugate vaccines (PCV) against invasive pneumococcal disease (IPD) among children under the age of two years using the indirect cohort method. We also discuss the timeliness of vaccination and the residual cases of vaccine type IPD. Methods and Findings From July 2006 until June 2015, 921 IPD cases were reported and for 618 children (67.1%), the vaccination status at the time of infection could be accurately determined. Of these, 379 (61.3%) were vaccinated and 239 (38.7%) were not vaccinated. The adjusted vaccine effectiveness (VE) of PCV7 for all included serotypes + 6A was 80% (95% CI: 63–89) for at least one dose, 97% (89–100) after three primary doses (post primary) and 95% (57–100) post booster. The adjusted overall VE of PCV13 was 86% (74–93) for at least one dose, 85% (62–94) post primary and 91% (61–99) post booster. For the additional serotypes included in PCV13, the adjusted VE was 82% (66–91), 80% (46–93) and 90% (54–98) respectively. The serotype specific VE for at least one dose was high for serotypes 1 (83%; 15–97), 3 (74%; 2–93), 7F (84%; 18–98) and 19A (77%; 47–90). Only 39.5% of children with IPD obtained their first dose of PCV7 according to schedule (2nd dose: 32.9%, 3rd dose: 22.0%, booster dose: 63.6%). For children vaccinated with PCV13 values were slightly better: 43.8%, 33.5%, 26.3% and 74.3% respectively. Among 90 residual cases with PCV7 serotypes, 73 (81.1%) were in unvaccinated children, and 15 (16.7%) in children who had not obtained the number of doses recommended for their age, and only two (2.2%) in children vaccinated according to age. Of 82 cases with PCV13 serotypes occurring after the switch from PCV7 to PCV13, 56 (68.3%) were not vaccinated, 22 (26.8%) were incompletely vaccinated, and four (4.9%) were vaccinated according to age. Conclusions Our data show a high effectiveness of pneumococcal conjugate vaccination in Germany

  7. Aging Changes in Retinal Microglia and their Relevance to Age-related Retinal Disease.

    PubMed

    Ma, Wenxin; Wong, Wai T

    2016-01-01

    Age-related retinal diseases, such as age-related macular degeneration (AMD) and glaucoma, contain features of chronic retinal inflammation that may promote disease progression. However, the relationship between aging and neuroinflammation is unclear. Microglia are long-lived, resident immune cells of the retina, and mediate local neuroinflammatory reactions. We hypothesize that aging changes in microglia may be causally linked to neuroinflammatory changes underlying age-dependent retinal diseases. Here, we review the evidence for (1) how the retinal microglial phenotype changes with aging, (2) the factors that drive microglial aging in the retina, and (3) aging-related changes in microglial gene expression. We examine how these aspects of microglial aging changes may relate to pathogenic mechanisms of immune dysregulation driving the progression of age-related retinal disease. These relationships can highlight microglial aging as a novel target for the prevention and treatment of retinal disease.

  8. The aging-disease false dichotomy: understanding senescence as pathology

    PubMed Central

    Gems, David

    2015-01-01

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

  9. Distinct Mechanisms of Impairment in Cognitive Ageing and Alzheimer's Disease

    ERIC Educational Resources Information Center

    Mapstone, Mark; Dickerson, Kathryn; Duffy, Charles J.

    2008-01-01

    Similar manifestations of functional decline in ageing and Alzheimer's disease obscure differences in the underlying cognitive mechanisms of impairment. We sought to examine the contributions of top-down attentional and bottom-up perceptual factors to visual self-movement processing in ageing and Alzheimer's disease. We administered a novel…

  10. Nutrition and age-related eye diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vision loss among the elderly is an important health problem. Approximately one person in three has some form of vision-reducing eye disease by the age of 65 [1]. Age-related cataract, age-related macular degeneration (AMD), diabetic retinopathy and glaucoma are the major diseases resulting in visu...

  11. Telomere length variations in aging and age-related diseases.

    PubMed

    Rizvi, Saliha; Raza, Syed Tasleem; Mahdi, Farzana

    2014-01-01

    Telomeres are gene sequences present at chromosomal ends and are responsible for maintaining genome integrity. Telomere length is maximum at birth and decreases progressively with advancing age and thus is considered as a biomarker of chronological aging. This age associated decrease in the length of telomere is linked to various ageing associated diseases like diabetes, hypertension, Alzheimer's disease, cancer etc. and their associated complications. Telomere length is a result of combined effect of oxidative stress, inflammation and repeated cell replication on it, and thus forming an association between telomere length and chronological aging and related diseases. Thus, decrease in telomere length was found to be important in determining both, the variations in longevity and age-related diseases in an individual. Ongoing and progressive research in the field of telomere length dynamics has proved that aging and age-related diseases apart from having a synergistic effect on telomere length were also found to effect telomere length independently also. Here a short description about telomere length variations and its association with human aging and age-related diseases is reviewed.

  12. Pathophysiology of ageing, longevity and age related diseases

    PubMed Central

    Bürkle, Alexander; Caselli, Graziella; Franceschi, Claudio; Mariani, Erminia; Sansoni, Paolo; Santoni, Angela; Vecchio, Giancarlo; Witkowski, Jacek M; Caruso, Calogero

    2007-01-01

    On April 18, 2007 an international meeting on Pathophysiology of Ageing, Longevity and Age-Related Diseases was held in Palermo, Italy. Several interesting topics on Cancer, Immunosenescence, Age-related inflammatory diseases and longevity were discussed. In this report we summarize the most important issues. However, ageing must be considered an unavoidable end point of the life history of each individual, nevertheless the increasing knowledge on ageing mechanisms, allows envisaging many different strategies to cope with, and delay it. So, a better understanding of pathophysiology of ageing and age-related disease is essential for giving everybody a reasonable chance for living a long and enjoyable final part of the life. PMID:17683521

  13. Modulating Human Aging and Age-Associated Diseases

    PubMed Central

    Fontana, Luigi

    2009-01-01

    Population aging is progressing rapidly in many industrialized countries. The United States population aged 65 and over is expected to double in size within the next 25 years. In sedentary people eating Western diets aging is associated with the development of serious chronic diseases, including type 2 diabetes mellitus, cancer and cardiovascular diseases. About 80 percent of adults over 65 years of age have at least one chronic disease, and 50 percent have at least two chronic diseases. These chronic diseases are the most important cause of illness and mortality burden, and they have become the leading driver of healthcare costs, constituting an important burden for our society. Data from epidemiological studies and clinical trials indicate that many age-associated chronic diseases can be prevented, and even reversed, with the implementation of healthy lifestyle interventions. Several recent studies suggest that more drastic interventions (i.e. calorie restriction without malnutrition and moderate protein restriction with adequate nutrition) may have additional beneficial effects on several metabolic and hormonal factors that are implicated in the biology of aging itself. Additional studies are needed to understand the complex interactions of factors that regulate aging and age-associated chronic disease. PMID:19364477

  14. Translational strategies in aging and age-related disease.

    PubMed

    Armanios, Mary; de Cabo, Rafael; Mannick, Joan; Partridge, Linda; van Deursen, Jan; Villeda, Saul

    2015-12-01

    Aging is a risk factor for several of the world's most prevalent diseases, including neurodegenerative disorders, cancer, cardiovascular disease and metabolic disease. Although our understanding of the molecular pathways that contribute to the aging process and age-related disease is progressing through the use of model organisms, how to apply this knowledge in the clinic is less clear. In September, Nature Medicine, in collaboration with the Volkswagen Foundation, hosted a conference at the beautiful Herrenhausen Palace in Hannover, Germany with the goal of broadening our understanding of the aging process and its meaning as a 'risk factor' in disease. Here, several of the speakers at that conference answer questions posed by Nature Medicine.

  15. Translational strategies in aging and age-related disease.

    PubMed

    Armanios, Mary; de Cabo, Rafael; Mannick, Joan; Partridge, Linda; van Deursen, Jan; Villeda, Saul

    2015-12-01

    Aging is a risk factor for several of the world's most prevalent diseases, including neurodegenerative disorders, cancer, cardiovascular disease and metabolic disease. Although our understanding of the molecular pathways that contribute to the aging process and age-related disease is progressing through the use of model organisms, how to apply this knowledge in the clinic is less clear. In September, Nature Medicine, in collaboration with the Volkswagen Foundation, hosted a conference at the beautiful Herrenhausen Palace in Hannover, Germany with the goal of broadening our understanding of the aging process and its meaning as a 'risk factor' in disease. Here, several of the speakers at that conference answer questions posed by Nature Medicine. PMID:26646495

  16. The Effect of Exclusive Breastfeeding on Hospital Stay and Morbidity due to Various Diseases in Infants under 6 Months of Age: A Prospective Observational Study.

    PubMed

    Kaur, Amarpreet; Singh, Karnail; Pannu, M S; Singh, Palwinder; Sehgal, Neeraj; Kaur, Rupinderjeet

    2016-01-01

    Background. Mother's milk is the best for the babies. Protective and preventive role of breast milk was evaluated in this study by assessing the relation of type of feeding and duration of hospital stay or morbidity. Methods. This prospective study was conducted in a tertiary care hospital and 232 infants in the age group of 14 weeks to 6 months formed the sample. There are two groups of infants, that is, one for breastfed and one for top fed infants. Statistical analysis was done and results were calculated up to 95% to 99% level of significance to find effect of feeding pattern on hospital stay due to various diseases and morbidity. Results. Prolonged hospital stay, that is, >7 days, was lesser in breastfed infants and results were statistically significant in case of gastroenteritis (p value < 0.001), bronchopneumonia (p value = 0.0012), bronchiolitis (p value = 0.005), otitis media (p value = 0.003), and skin diseases (p value = 0.047). Lesser morbidity was seen in breastfed infants with gastroenteritis (p value 0.0414), bronchopneumonia (p value 0.03705), bronchiolitis (p value 0.036706), meningitis (p value 0.043), and septicemia (p value 0.04). Conclusions. Breastfed infants have shorter hospital stay and lesser morbidity in regard to various diseases as compared to top fed infants.

  17. The Effect of Exclusive Breastfeeding on Hospital Stay and Morbidity due to Various Diseases in Infants under 6 Months of Age: A Prospective Observational Study.

    PubMed

    Kaur, Amarpreet; Singh, Karnail; Pannu, M S; Singh, Palwinder; Sehgal, Neeraj; Kaur, Rupinderjeet

    2016-01-01

    Background. Mother's milk is the best for the babies. Protective and preventive role of breast milk was evaluated in this study by assessing the relation of type of feeding and duration of hospital stay or morbidity. Methods. This prospective study was conducted in a tertiary care hospital and 232 infants in the age group of 14 weeks to 6 months formed the sample. There are two groups of infants, that is, one for breastfed and one for top fed infants. Statistical analysis was done and results were calculated up to 95% to 99% level of significance to find effect of feeding pattern on hospital stay due to various diseases and morbidity. Results. Prolonged hospital stay, that is, >7 days, was lesser in breastfed infants and results were statistically significant in case of gastroenteritis (p value < 0.001), bronchopneumonia (p value = 0.0012), bronchiolitis (p value = 0.005), otitis media (p value = 0.003), and skin diseases (p value = 0.047). Lesser morbidity was seen in breastfed infants with gastroenteritis (p value 0.0414), bronchopneumonia (p value 0.03705), bronchiolitis (p value 0.036706), meningitis (p value 0.043), and septicemia (p value 0.04). Conclusions. Breastfed infants have shorter hospital stay and lesser morbidity in regard to various diseases as compared to top fed infants. PMID:27190526

  18. The Effect of Exclusive Breastfeeding on Hospital Stay and Morbidity due to Various Diseases in Infants under 6 Months of Age: A Prospective Observational Study

    PubMed Central

    Kaur, Amarpreet; Singh, Karnail; Pannu, M. S.; Singh, Palwinder; Sehgal, Neeraj; Kaur, Rupinderjeet

    2016-01-01

    Background. Mother's milk is the best for the babies. Protective and preventive role of breast milk was evaluated in this study by assessing the relation of type of feeding and duration of hospital stay or morbidity. Methods. This prospective study was conducted in a tertiary care hospital and 232 infants in the age group of 14 weeks to 6 months formed the sample. There are two groups of infants, that is, one for breastfed and one for top fed infants. Statistical analysis was done and results were calculated up to 95% to 99% level of significance to find effect of feeding pattern on hospital stay due to various diseases and morbidity. Results. Prolonged hospital stay, that is, >7 days, was lesser in breastfed infants and results were statistically significant in case of gastroenteritis (p value < 0.001), bronchopneumonia (p value = 0.0012), bronchiolitis (p value = 0.005), otitis media (p value = 0.003), and skin diseases (p value = 0.047). Lesser morbidity was seen in breastfed infants with gastroenteritis (p value 0.0414), bronchopneumonia (p value 0.03705), bronchiolitis (p value 0.036706), meningitis (p value 0.043), and septicemia (p value 0.04). Conclusions. Breastfed infants have shorter hospital stay and lesser morbidity in regard to various diseases as compared to top fed infants. PMID:27190526

  19. Long noncoding RNAs in aging and age-related diseases.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2016-03-01

    Aging is the universal, intrinsic, genetically-controlled, evolutionarily-conserved and time-dependent intricate biological process characterised by the cumulative decline in the physiological functions and their coordination in an organism after the attainment of adulthood resulting in the imbalance of neurological, immunological and metabolic functions of the body. Various biological processes and mechanisms along with altered levels of mRNAs and proteins have been reported to be involved in the progression of aging. It is one of the major risk factors in the patho-physiology of various diseases and disorders. Recently, the discovery of pervasive transcription of a vast pool of heterogeneous regulatory noncoding RNAs (ncRNAs), including small ncRNAs (sncRNAs) and long ncRNAs (lncRNAs), in the mammalian genome have provided an alternative way to study and explore the missing links in the aging process, its mechanism(s) and related diseases in a whole new dimension. The involvement of small noncoding RNAs in aging and age-related diseases have been extensively studied and recently reviewed. However, lncRNAs, whose function is far less explored in relation to aging, have emerged as a class of major regulators of genomic functions. Here, we have described some examples of known as well as novel lncRNAs that have been implicated in the progression of the aging process and age-related diseases. This may further stimulate research on noncoding RNAs and the aging process.

  20. Long noncoding RNAs in aging and age-related diseases.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2016-03-01

    Aging is the universal, intrinsic, genetically-controlled, evolutionarily-conserved and time-dependent intricate biological process characterised by the cumulative decline in the physiological functions and their coordination in an organism after the attainment of adulthood resulting in the imbalance of neurological, immunological and metabolic functions of the body. Various biological processes and mechanisms along with altered levels of mRNAs and proteins have been reported to be involved in the progression of aging. It is one of the major risk factors in the patho-physiology of various diseases and disorders. Recently, the discovery of pervasive transcription of a vast pool of heterogeneous regulatory noncoding RNAs (ncRNAs), including small ncRNAs (sncRNAs) and long ncRNAs (lncRNAs), in the mammalian genome have provided an alternative way to study and explore the missing links in the aging process, its mechanism(s) and related diseases in a whole new dimension. The involvement of small noncoding RNAs in aging and age-related diseases have been extensively studied and recently reviewed. However, lncRNAs, whose function is far less explored in relation to aging, have emerged as a class of major regulators of genomic functions. Here, we have described some examples of known as well as novel lncRNAs that have been implicated in the progression of the aging process and age-related diseases. This may further stimulate research on noncoding RNAs and the aging process. PMID:26655093

  1. NK Cells in Healthy Aging and Age-Associated Diseases

    PubMed Central

    Camous, Xavier; Pera, Alejandra; Solana, Rafael; Larbi, Anis

    2012-01-01

    NK cells exhibit the highest cytotoxic capacity within the immune system. Alteration of their number or functionality may have a deep impact on overall immunity. This is of particular relevance in aging where the elderly population becomes more susceptible to infection, cancer, autoimmune diseases, and neurodegenerative diseases amongst others. As the fraction of elderly increases worldwide, it becomes urgent to better understand the aging of the immune system to prevent and cure the elderly population. For this, a better understanding of the function and phenotype of the different immune cells and their subsets is necessary. We review here NK cell functions and phenotype in healthy aging as well as in various age-associated diseases. PMID:23251076

  2. NK cells in healthy aging and age-associated diseases.

    PubMed

    Camous, Xavier; Pera, Alejandra; Solana, Rafael; Larbi, Anis

    2012-01-01

    NK cells exhibit the highest cytotoxic capacity within the immune system. Alteration of their number or functionality may have a deep impact on overall immunity. This is of particular relevance in aging where the elderly population becomes more susceptible to infection, cancer, autoimmune diseases, and neurodegenerative diseases amongst others. As the fraction of elderly increases worldwide, it becomes urgent to better understand the aging of the immune system to prevent and cure the elderly population. For this, a better understanding of the function and phenotype of the different immune cells and their subsets is necessary. We review here NK cell functions and phenotype in healthy aging as well as in various age-associated diseases.

  3. Nutritional influences on epigenetics and age-related disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutritional epigenetics has emerged as a novel mechanism underlying gene–diet interactions, further elucidating the modulatory role of nutrition in aging and age-related disease development. Epigenetics is defined as a heritable modification to the DNA that regulates chromosome architecture and modu...

  4. Nut consumption and age-related disease.

    PubMed

    Grosso, G; Estruch, R

    2016-02-01

    Current knowledge on the effects of nut consumption on human health has rapidly increased in recent years and it now appears that nuts may play a role in the prevention of chronic age-related diseases. Frequent nut consumption has been associated with better metabolic status, decreased body weight as well as lower body weight gain over time and thus reduce the risk of obesity. The effect of nuts on glucose metabolism, blood lipids, and blood pressure is still controversial. However, significant decreased cardiovascular risk has been reported in a number of observational and clinical intervention studies. Thus, findings from cohort studies show that increased nut consumption is associated with a reduced risk of cardiovascular disease and mortality (especially that due to cardiovascular-related causes). Similarly, nut consumption has been also associated with reduced risk of certain cancers, such as colorectal, endometrial, and pancreatic neoplasms. Evidence regarding nut consumption and neurological or psychiatric disorders is scarce, but a number of studies suggest significant protective effects against depression, mild cognitive disorders and Alzheimer's disease. The underlying mechanisms appear to include antioxidant and anti-inflammatory actions, particularly related to their mono- and polyunsaturated fatty acids (MUFA and PUFA, as well as vitamin and polyphenol content). MUFA have been demonstrated to improve pancreatic beta-cell function and regulation of postprandial glycemia and insulin sensitivity. PUFA may act on the central nervous system protecting neuronal and cell-signaling function and maintenance. The fiber and mineral content of nuts may also confer health benefits. Nuts therefore show promise as useful adjuvants to prevent, delay or ameliorate a number of chronic conditions in older people. Their association with decreased mortality suggests a potential in reducing disease burden, including cardiovascular disease, cancer, and cognitive impairments

  5. Nut consumption and age-related disease.

    PubMed

    Grosso, G; Estruch, R

    2016-02-01

    Current knowledge on the effects of nut consumption on human health has rapidly increased in recent years and it now appears that nuts may play a role in the prevention of chronic age-related diseases. Frequent nut consumption has been associated with better metabolic status, decreased body weight as well as lower body weight gain over time and thus reduce the risk of obesity. The effect of nuts on glucose metabolism, blood lipids, and blood pressure is still controversial. However, significant decreased cardiovascular risk has been reported in a number of observational and clinical intervention studies. Thus, findings from cohort studies show that increased nut consumption is associated with a reduced risk of cardiovascular disease and mortality (especially that due to cardiovascular-related causes). Similarly, nut consumption has been also associated with reduced risk of certain cancers, such as colorectal, endometrial, and pancreatic neoplasms. Evidence regarding nut consumption and neurological or psychiatric disorders is scarce, but a number of studies suggest significant protective effects against depression, mild cognitive disorders and Alzheimer's disease. The underlying mechanisms appear to include antioxidant and anti-inflammatory actions, particularly related to their mono- and polyunsaturated fatty acids (MUFA and PUFA, as well as vitamin and polyphenol content). MUFA have been demonstrated to improve pancreatic beta-cell function and regulation of postprandial glycemia and insulin sensitivity. PUFA may act on the central nervous system protecting neuronal and cell-signaling function and maintenance. The fiber and mineral content of nuts may also confer health benefits. Nuts therefore show promise as useful adjuvants to prevent, delay or ameliorate a number of chronic conditions in older people. Their association with decreased mortality suggests a potential in reducing disease burden, including cardiovascular disease, cancer, and cognitive impairments.

  6. Parkinson's disease as a result of aging.

    PubMed

    Rodriguez, Manuel; Rodriguez-Sabate, Clara; Morales, Ingrid; Sanchez, Alberto; Sabate, Magdalena

    2015-06-01

    It is generally considered that Parkinson's disease is induced by specific agents that degenerate a clearly defined population of dopaminergic neurons. Data commented in this review suggest that this assumption is not as clear as is often thought and that aging may be critical for Parkinson's disease. Neurons degenerating in Parkinson's disease also degenerate in normal aging, and the different agents involved in the etiology of this illness are also involved in aging. Senescence is a wider phenomenon affecting cells all over the body, whereas Parkinson's disease seems to be restricted to certain brain centers and cell populations. However, reviewed data suggest that Parkinson's disease may be a local expression of aging on cell populations which, by their characteristics (high number of synaptic terminals and mitochondria, unmyelinated axons, etc.), are highly vulnerable to the agents promoting aging. The development of new knowledge about Parkinson's disease could be accelerated if the research on aging and Parkinson's disease were planned together, and the perspective provided by gerontology gains relevance in this field.

  7. Parkinson's disease as a result of aging

    PubMed Central

    Rodriguez, Manuel; Rodriguez-Sabate, Clara; Morales, Ingrid; Sanchez, Alberto; Sabate, Magdalena

    2015-01-01

    It is generally considered that Parkinson's disease is induced by specific agents that degenerate a clearly defined population of dopaminergic neurons. Data commented in this review suggest that this assumption is not as clear as is often thought and that aging may be critical for Parkinson's disease. Neurons degenerating in Parkinson's disease also degenerate in normal aging, and the different agents involved in the etiology of this illness are also involved in aging. Senescence is a wider phenomenon affecting cells all over the body, whereas Parkinson's disease seems to be restricted to certain brain centers and cell populations. However, reviewed data suggest that Parkinson's disease may be a local expression of aging on cell populations which, by their characteristics (high number of synaptic terminals and mitochondria, unmyelinated axons, etc.), are highly vulnerable to the agents promoting aging. The development of new knowledge about Parkinson's disease could be accelerated if the research on aging and Parkinson's disease were planned together, and the perspective provided by gerontology gains relevance in this field. PMID:25677794

  8. Is aging part of Alzheimer's disease, or is Alzheimer's disease part of aging?

    PubMed

    Swerdlow, Russell H

    2007-10-01

    For 70 years after Alois Alzheimer described a disorder of tangle-and-plaque dementia, Alzheimer's disease was a condition of the relatively young. Definitions of Alzheimer's disease (AD) have, however, changed over the past 30 years and under the revised view AD has truly become an age-related disease. Most now diagnosed with AD are elderly and would not have been diagnosed with AD as originally conceived. Accordingly, younger patients that qualify for a diagnosis of AD under both original and current Alzheimer's disease constructs now represent an exceptionally small percentage of the diagnosed population. The question of whether pathogenesis of the "early" and "late" onset cases is similar enough to qualify as a single disease was previously raised although not conclusively settled. Interestingly, debate on this issue has not kept pace with advancing knowledge about the molecular, biochemical and clinical underpinnings of tangle-and-plaque dementias. Since the question of whether both forms of AD share a common pathogenesis could profoundly impact diagnostic and treatment development efforts, it seems worthwhile to revisit this debate.

  9. Curcumin, inflammation, ageing and age-related diseases.

    PubMed

    Sikora, E; Scapagnini, Giovanni; Barbagallo, Mario

    2010-01-17

    A Symposium regarding the Pathophysiology of Successful and Unsuccessful Ageing was held in Palermo, Italy between April 7 and 8th 2009. Here the lecture by Sikora with some input from the chairpersons Scapagnini and Barbagallo is summarized. Ageing is manifested by the decreasing health status and increasing probability to acquire age-related disease such as cancer, Alzheimer's disease, atherosclerosis, metabolic disorders and others. They are likely caused by low grade inflammation driven by oxygen stress and manifested by the increased level of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-alpha, encoded by genes activated by the transcription factor NF-kappaB. It is believed that ageing is plastic and can be slowed down by caloric restriction as well as by some nutraceuticals. Accordingly, slowing down ageing and postponing the onset of age-related diseases might be achieved by blocking the NF-kappaB-dependent inflammation. In this review we consider the possibility of the spice curcumin, a powerful antioxidant and anti-inflammatory agent possibly capable of improving the health status of the elderly.

  10. Age-at-onset in Huntington disease

    PubMed Central

    Orth, Michael; Schwenke, Carsten

    2011-01-01

    Background: In Huntington disease, the accurate determination of age-at-onset is critical to identify modifiers and therapies that aim to delay it. Methods: Retrospective data from the European Huntington’s Disease Network’s REGISTRY and PREDICT-HD, a longitudinal study in prodromal huntingtin gene expansion mutation carriers. Data (age, gender, CAG repeat length, parent affected, and Unified Huntington’s Disease Rating Scale motor score, total functional capacity) from at least three visits in 423 REGISTRY and 124 PREDICT-HD participants were included. Data based extrapolations of individual age-at-onset using generalized linear mixed models based on individual slopes of motor score or total functional capacity, and predictions using the Langbehn, or Ranen formula, were compared with clinicians’ estimates. Results: Concordance was best for the observed age-at-onset in PREDICT-HD and the calculated onset using the PREDICT-HD UHDRS longitudinal motor scores. This was superior to the REGISTRY data. For total functional capacity, the investigator’s estimate was 4 years before the data derived age-at-onset. The concordance of predictions of probability of age-at-onset is better with the observed age-at-onset in the PREDICT-HD data (difference in 25%tile -5 to 10 years) than the REGISTRY data (±20 years). Conclusions: Estimating or predicting age-at-onset in Huntington disease may be inaccurate. It can be useful to 1) add in the manifest population motor score regression derived age-at-onset as additional motor onset and 2) add total functional capacity regression derived age-at-onset for the onset of functional impact of Huntington disease when patients are in mid- to late-stage. PMID:22453877

  11. The aging mouth: differentiating normal aging from disease.

    PubMed

    Lamster, Ira B; Asadourian, Lynda; Del Carmen, Tessa; Friedman, Paula K

    2016-10-01

    Aging is the physiologic change that occurs over time. In humans, this change occurs at different rates and are related to lifestyle, environment and genetics. It can be challenging to differentiate normal aging from disease. In the oral cavity, with increasing age the teeth demonstrate wearing of the enamel, chipping and fracture lines, and a darker color. The pulp chamber and canals are reduced in size as a result of the deposition of secondary dentin. Coronal or root caries, however, represent disease. A limited amount of periodontal attachment loss occurs in association with aging, usually manifesting as recession on the buccal surface of teeth. Severe periodontitis occurs in 10.5-12% of the population, with the peak incidence being observed at 35-40 years of age. Changes to the mucosal tissue that occur with age include reduced wound-healing capacity. However, environmental factors, such as smoking, dramatically increase the risk of mucosal pathology. Reduced salivary gland function is often seen in association with medication usage, as well as with disorders such as diabetes mellitus. Both medication use and chronic disorders are more common in older adults. Masticatory function is of particular importance for older adults. Maintenance of a nutritionally complete diet is important for avoiding sarcopenia and the frailty syndrome. Successful oral aging is associated with adequate function and comfort. A reduced, but functional, dentition of 20 teeth in occlusion has been proposed as a measure of successful oral aging. Healthy oral aging is important to healthy aging from both biological and social perspectives. PMID:27501493

  12. Leprosy among children under 15 years of age: literature review*

    PubMed Central

    de Oliveira, Marcela Bahia Barretto; Diniz, Lucia Martins

    2016-01-01

    Leprosy is a chronic infectious disease caused by Mycobacterium leprae, representing a public health issue in some countries. Though more prevalent in adults, the detection of new cases in children under 15 years of age reveals an active circulation of bacillus, continued transmission and lack of disease control by the health system, as well as aiding in the monitoring of the endemic. Among patients under 15 years of age, the most affected age group is children between 10 and 14 years of age, although cases of patients of younger than 1 year of age have also been reported. Household contacts are the primary source of infection, given that caretakers, such as babysitters and others, must be considered in this scenario. Paucibacillary forms of the disease prevailed, especially borderline-tuberculoid leprosy, with a single lesion in exposed areas of the body representing the main clinical manifestation. Reactional states: Lepra reactions are rare, although some authors have reported high frequencies of this phenomenon, the most frequent of which is Type 1 Lepra Reaction. Peripheral nerve involvement has been described at alarming rates in some studies, which increases the chance of deformities, a serious problem, especially if one considers the age of these patients. The protective effect of BCG vaccination was found in some studies, but no consensus has been reached among different authors. Children must receive the same multidrug therapy regimen and the doses should, ideally, be calculated based on the child´s weight. Adverse reactions to this therapy are rare within this age group. This article aims to review epidemiological, clinical, and therapeutic aspects of leprosy in patients under 15 years of age. PMID:27192519

  13. Leprosy among children under 15 years of age: literature review.

    PubMed

    Oliveira, Marcela Bahia Barretto de; Diniz, Lucia Martins

    2016-04-01

    Leprosy is a chronic infectious disease caused by Mycobacterium leprae, representing a public health issue in some countries. Though more prevalent in adults, the detection of new cases in children under 15 years of age reveals an active circulation of bacillus, continued transmission and lack of disease control by the health system, as well as aiding in the monitoring of the endemic. Among patients under 15 years of age, the most affected age group is children between 10 and 14 years of age, although cases of patients of younger than 1 year of age have also been reported. Household contacts are the primary source of infection, given that caretakers, such as babysitters and others, must be considered in this scenario. Paucibacillary forms of the disease prevailed, especially borderline-tuberculoid leprosy, with a single lesion in exposed areas of the body representing the main clinical manifestation. Reactional states: Lepra reactions are rare, although some authors have reported high frequencies of this phenomenon, the most frequent of which is Type 1 Lepra Reaction. Peripheral nerve involvement has been described at alarming rates in some studies, which increases the chance of deformities, a serious problem, especially if one considers the age of these patients. The protective effect of BCG vaccination was found in some studies, but no consensus has been reached among different authors. Children must receive the same multidrug therapy regimen and the doses should, ideally, be calculated based on the child´s weight. Adverse reactions to this therapy are rare within this age group. This article aims to review epidemiological, clinical, and therapeutic aspects of leprosy in patients under 15 years of age. PMID:27192519

  14. Brain aging, Alzheimer's disease, and mitochondria

    PubMed Central

    Swerdlow, Russell H.

    2011-01-01

    The relationship between brain aging and Alzheimer’s disease (AD) is contentious. One view holds AD results when brain aging surpasses a threshold. The other view postulates AD is not a consequence of brain aging. This review discusses this conundrum from the perspective of different investigative lines that have tried to address it, as well as from the perspective of the mitochondrion, an organelle that appears to play a role in both AD and brain aging. Specific issues addressed include the question of whether AD and brain aging should be conceptually lumped or split, the extent to which AD and brain aging potentially share common molecular mechanisms, whether beta amyloid should be primarily considered a marker of AD or simply brain aging, and the definition of AD itself. PMID:21920438

  15. NAD+ and sirtuins in aging and disease.

    PubMed

    Imai, Shin-ichiro; Guarente, Leonard

    2014-08-01

    Nicotinamide adenine dinucleotide (NAD(+)) is a classical coenzyme mediating many redox reactions. NAD(+) also plays an important role in the regulation of NAD(+)-consuming enzymes, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38/157 ectoenzymes. NAD(+) biosynthesis, particularly mediated by nicotinamide phosphoribosyltransferase (NAMPT), and SIRT1 function together to regulate metabolism and circadian rhythm. NAD(+) levels decline during the aging process and may be an Achilles' heel, causing defects in nuclear and mitochondrial functions and resulting in many age-associated pathologies. Restoring NAD(+) by supplementing NAD(+) intermediates can dramatically ameliorate these age-associated functional defects, counteracting many diseases of aging, including neurodegenerative diseases. Thus, the combination of sirtuin activation and NAD(+) intermediate supplementation may be an effective antiaging intervention, providing hope to aging societies worldwide. PMID:24786309

  16. Aging, inflammation, immunity and periodontal disease.

    PubMed

    Ebersole, Jeffrey L; Graves, Christina L; Gonzalez, Octavio A; Dawson, Dolph; Morford, Lorri A; Huja, Pinar Emecen; Hartsfield, James K; Huja, Sarandeep S; Pandruvada, Subramanya; Wallet, Shannon M

    2016-10-01

    The increased prevalence and severity of periodontal disease have long been associated with aging, such that this oral condition affects the majority of the adult population over 50 years of age. Although the immune system is a critical component for maintaining health, aging can be characterized by quantitative and qualitative modifications of the immune system. This process, termed 'immunosenescence', is a progressive modification of the immune system that leads to greater susceptibility to infections, neoplasia and autoimmunity, presumably reflecting the prolonged antigenic stimulation and/or stress responses that occur across the lifespan. Interestingly, the global reduction in the host capability to respond effectively to these challenges is coupled with a progressive increase in the general proinflammatory status, termed 'inflammaging'. Consistent with the definition of immunosenescence, it has been suggested that the cumulative effect of prolonged exposure of the periodontium to microbial challenge is, at least in part, a contributor to the effects of aging on these tissues. Thus, it has also been hypothesized that alterations in the function of resident immune and nonimmune cells of the periodontium contribute to the expression of inflammaging in periodontal disease. Although the majority of aging research has focused on the adaptive immune response, it is becoming increasingly clear that the innate immune compartment is also highly affected by aging. Thus, the phenomenon of immunosenescence and inflammaging, expressed as age-associated changes within the periodontium, needs to be more fully understood in this era of precision and personalized medicine and dentistry. PMID:27501491

  17. Parkinson's disease and age: The obvious but largely unexplored link.

    PubMed

    Abdullah, Rashed; Basak, Indranil; Patil, Ketan S; Alves, Guido; Larsen, Jan Petter; Møller, Simon Geir

    2015-08-01

    Parkinson's disease is a chronic, progressive neurodegenerative disorder with increased prevalence in the aging population. It is estimated that approximately 1.5 million individuals in the US alone suffer from Parkinson's disease and with the extension of life expectancy this number is expected to rise dramatically within the next twenty-five years. The majority of Parkinson's disease cases are sporadic. But mutations in genes such as α-synuclein, Parkin, PINK1, DJ-1 and LRRK2, have been conclusively associated with both early- and late-onset of the disease. Although the genetics of Parkinson's disease is starting to become unraveled, the interplay between genetic and environmental factors is largely unknown as are the underlying mechanisms that trigger the disease as the brain ages. The risk of Parkinson's disease increases dramatically in individuals over the age of 60 and it is estimated that more than 1% of all seniors have some form of the condition. In this review, we will highlight some of the central proteins associated with Parkinson's disease and how they may be linked to processes and factors associated with age.

  18. The relevance of aging-related changes in brain function to rehabilitation in aging-related disease

    PubMed Central

    Crosson, Bruce; McGregor, Keith M.; Nocera, Joe R.; Drucker, Jonathan H.; Tran, Stella M.; Butler, Andrew J.

    2015-01-01

    The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered. PMID:26074807

  19. Cardiac and Respiratory Disease in Aged Horses.

    PubMed

    Marr, Celia M

    2016-08-01

    Respiratory and cardiac diseases are common in older horses. Advancing age is a specific risk factor for cardiac murmurs and these are more likely in males and small horses. Airway inflammation is the most common respiratory diagnosis. Recurrent airway obstruction can lead to irreversible structural change and bronchiectasis; with chronic hypoxia, right heart dysfunction and failure can develop. Valvular heart disease most often affects the aortic and/or the mitral valve. Management of comorbidity is an essential element of the therapeutic approach to cardiac and respiratory disease in older equids.

  20. So! What's aging? Is cardiovascular aging a disease?

    PubMed

    Lakatta, Edward G

    2015-06-01

    "Inside every old person is a young person wondering what happened." So, what is aging? Aging is a manifestation of progressive, time-dependent failure of molecular mechanisms that create disorder within a system of DNA and its environment (nuclear, cytosolic, tissue, organ, organism, other organisms, society, terra firma, atmosphere, universe). Continuous signaling, transmitted with different kinetics across each of these environments, confers a "mutual enslavement" that creates ordered functions among the components within the system. Accrual of this molecular disorder over time, i.e. during aging, causes progressive changes in the structure and function of the heart and arteries that are quite similar in humans, non-human primates, rabbits and rats that compromise cardiovascular reserve function, and confer a marked risk for incident cardiovascular disease. Nearly all aspects of signaling within the DNA environment system within the heart and arteries become disordered with advancing age: Signals change, as does sensing of the signals, transmission of signals and responses to signals, impaired cell renewal, changes in the proteome due to alterations in genomic transcription, mRNA translation, and proteostasis. The density of some molecules becomes reduced, and post-translational modifications, e.g. oxidation and nitration phosphorylation, lead to altered misfolding and disordered molecular interactions. The stoichiometry and kinetics of enzymatic and those reactions which underlie crucial cardiac and vascular cell functions and robust reserve mechanisms that remove damaged organelles and proteins deteriorate. The CV cells generate an inflammatory defense in an attempt to limit the molecular disorder. The resultant proinflammatory milieu is not executed by "professional" inflammatory cells (i.e. white blood cells), however, but by activation of renin-angiotensin-aldosterone endothelin signaling cascades that leads to endothelial and vascular smooth muscle and

  1. So! What's aging? Is cardiovascular aging a disease?

    PubMed

    Lakatta, Edward G

    2015-06-01

    "Inside every old person is a young person wondering what happened." So, what is aging? Aging is a manifestation of progressive, time-dependent failure of molecular mechanisms that create disorder within a system of DNA and its environment (nuclear, cytosolic, tissue, organ, organism, other organisms, society, terra firma, atmosphere, universe). Continuous signaling, transmitted with different kinetics across each of these environments, confers a "mutual enslavement" that creates ordered functions among the components within the system. Accrual of this molecular disorder over time, i.e. during aging, causes progressive changes in the structure and function of the heart and arteries that are quite similar in humans, non-human primates, rabbits and rats that compromise cardiovascular reserve function, and confer a marked risk for incident cardiovascular disease. Nearly all aspects of signaling within the DNA environment system within the heart and arteries become disordered with advancing age: Signals change, as does sensing of the signals, transmission of signals and responses to signals, impaired cell renewal, changes in the proteome due to alterations in genomic transcription, mRNA translation, and proteostasis. The density of some molecules becomes reduced, and post-translational modifications, e.g. oxidation and nitration phosphorylation, lead to altered misfolding and disordered molecular interactions. The stoichiometry and kinetics of enzymatic and those reactions which underlie crucial cardiac and vascular cell functions and robust reserve mechanisms that remove damaged organelles and proteins deteriorate. The CV cells generate an inflammatory defense in an attempt to limit the molecular disorder. The resultant proinflammatory milieu is not executed by "professional" inflammatory cells (i.e. white blood cells), however, but by activation of renin-angiotensin-aldosterone endothelin signaling cascades that leads to endothelial and vascular smooth muscle and

  2. Seasonal Changes in Circadian Peripheral Plasma Concentrations of Melatonin, Serotonin, Dopamine and Cortisol in Aged Horses with Cushing’s Disease under Natural Photoperiod

    PubMed Central

    Haritou, S J A; Zylstra, R; Ralli, C; Turner, S; Tortonese, D J

    2008-01-01

    Equine pituitary pars intermedia dysfunction (PPID) is a common and serious condition that gives rise to Cushing’s disease. In the older horse, it results in hyperadrenocorticism and disrupted energy metabolism, the severity of which varies with the time of year. To gain insight into the mechanism of its pathogenesis, 24-h profiles for peripheral plasma melatonin, serotonin, dopamine and cortisol concentrations were determined at the winter and summer solstices, and the autumn and spring equinoxes in six horses diagnosed with Cushing’s disease and six matched controls. The nocturnal rises in plasma melatonin concentrations, although different across seasons, were broadly of the same duration and similar amplitude in both groups of animals (P > 0.05). The plasma concentrations of cortisol did not show seasonal variation and were different in diseased horses only in the summer when they were higher across the entire 24-h period (P < 0.05). Serotonin concentrations were not significantly affected by time of year but tended to be lower in Cushingoid horses (P = 0.07). By contrast, dopamine output showed seasonal variation and was significantly lower in the Cushing’s group in the summer and autumn (P < 0.05). The finding that the profiles of circulating melatonin are similar in Cushingoid and control horses reveals that the inability to read time of year by animals suffering from Cushing’s syndrome is an unlikely reason for the disease. In addition, the results provide evidence that alterations in the dopaminergic and serotoninergic systems may participate in the pathogenesis of PPID. PMID:18540997

  3. Fluency in Parkinson's disease: disease duration, cognitive status and age.

    PubMed

    Brabo, Natalia Casagrande; Minett, Thais Soares C; Ortiz, Karin Zazo

    2014-05-01

    The objective of this study was to determine the frequency of occurrence and to characterize the typology of dysfluencies in individuals with Parkinson's disease (PD), including the variables age, gender, schooling, disease duration, score on the Hoehn and Yahr scale and cognitive status (score on Mini-Mental State Examination). A cross-sectional study of a sample comprising 60 adults matched for gender, age and schooling was conducted. Group I comprised 30 adults with idiopathic PD, and Group II comprised 30 healthy adults. For assessment of fluency of speech, subjects were asked to utter a narrative based on a sequence of drawings and a transcription of 200 fluent syllables was performed to identify speech dysfluencies. PD patients exhibited a higher overall number of dysfluencies in speech with a large number of atypical dysfluencies. Additionally, results showed an influence of the variables cognitive status, disease duration and age on occurrence of dysfluencies. PMID:24863510

  4. Telomeres in aging and disease: lessons from zebrafish

    PubMed Central

    Carneiro, Madalena C.; de Castro, Inês Pimenta

    2016-01-01

    ABSTRACT Age is the highest risk factor for some of the most prevalent human diseases, including cancer. Telomere shortening is thought to play a central role in the aging process in humans. The link between telomeres and aging is highlighted by the fact that genetic diseases causing telomerase deficiency are associated with premature aging and increased risk of cancer. For the last two decades, this link has been mostly investigated using mice that have long telomeres. However, zebrafish has recently emerged as a powerful and complementary model system to study telomere biology. Zebrafish possess human-like short telomeres that progressively decline with age, reaching lengths in old age that are observed when telomerase is mutated. The extensive characterization of its well-conserved molecular and cellular physiology makes this vertebrate an excellent model to unravel the underlying relationship between telomere shortening, tissue regeneration, aging and disease. In this Review, we explore the advantages of using zebrafish in telomere research and discuss the primary discoveries made in this model that have contributed to expanding our knowledge of how telomere attrition contributes to cellular senescence, organ dysfunction and disease. PMID:27482813

  5. Growth factors, aging and age-related diseases.

    PubMed

    Balasubramanian, Priya; Longo, Valter D

    2016-06-01

    Simple organisms including yeast and flies with mutations in the IGF-1 and Tor-S6K pathways are dwarfs, are highly protected from toxins, and survive up to 3 times longer. Similarly, dwarf mice with deficiencies in the growth hormone-IGF-I axis are also long lived and protected from diseases. We recently reported that humans with Growth Hormone Receptor Deficiency (GHRD) rarely develop cancer or diabetes. These findings are in agreement with the effect of defects in the Tor-S6K pathways in causing dwarfism and protection of DNA. Because protein restriction reduces both GHR-IGF-1 axis and Tor-S6K activity, we examined links between protein intake, disease, and mortality in over 6000 US subjects in the NHANES CDC database. Respondents aged 50-65 reporting a high protein intake displayed an increase in IGF-I levels, a 75% increased risk of overall mortality and a 3-4 fold increased risk of cancer mortality in agreement with findings in mouse experiments. These studies point to a conserved link between proteins and amino acids, GHR-IGF-1/insulin, Tor-S6k signaling, aging, and diseases. PMID:26883276

  6. Neuropharmacology of depression in aging and age-related diseases.

    PubMed

    Gareri, Pietro; De Fazio, Pasquale; De Sarro, Giovambattista

    2002-02-01

    Depression in the elderly is nowadays a predominant health care problem, mainly due to the progressive aging of the population. It results from psychosocial stress, polypathology, as well as some biochemical changes which occur in the aged brain and can lead to cognitive impairments, increased symptoms from medical illness, higher utilization of health care services and increased rates of suicide and non-suicide mortality. Depression may be also caused by a various number of drugs currently administered; this is remarkable especially in elderly people, where polypathology is often associated with polypharmacotherapy. However, the pathogenesis of geriatric depression is not well understood; major depression may arise from dysfunction of the limbic-hypothalamic-pituitary-adrenal axis. Some clinical observations also suggest that striato-frontal dysfunction is associated with late life depression. A number of hypotheses have been made, focusing that mood disturbances are probably linked to a disturbed central metabolism of monoamines 5-hydroxytryptamine, noradrenaline and dopamine; however most of this knowledge is derived from animal models. Parkinson's and Alzheimer's diseases are age-related diseases associated to decreased activity or brain lesions in the orbital frontal cortex and basal ganglia. These observations lead to the hypothesis that the dysfunction of one or more of the cortical basal ganglia-thalamic neuronal loops are involved in the pathophysiology of primary and secondary depression. This dysfunction may be mediated by decreased serotonin release and probably, also by reduction in serotonin receptors. Development of novel approaches such as dynamic brain imaging methods, together with indirect knowledge coming from the effects of new antidepressants, will increase the understanding of neurochemistry of depression in old age. PMID:12039452

  7. Prolonged Sleep under Stone Age Conditions

    PubMed Central

    Piosczyk, Hannah; Landmann, Nina; Holz, Johannes; Feige, Bernd; Riemann, Dieter; Nissen, Christoph; Voderholzer, Ulrich

    2014-01-01

    Study Objectives: We report on a unique experiment designed to investigate the impact of prehistoric living conditions on sleep-wake behavior. Methods: A group of five healthy adults were assessed during life in a Stone Age-like settlement over two months. Results: The most notable finding was that nocturnal time in bed and estimated sleep time, as measured by actigraphy, markedly increased during the experimental period compared to the periods prior to and following the experiment. These increases were primarily driven by a phase-advance shift of sleep onset. Subjective assessments of health and functioning did not reveal any relevant changes across the study. Conclusions: Our observations provide further evidence for the long-held belief that the absence of modern living conditions is associated with an earlier sleep phase and prolonged sleep duration. Commentary: A commentary on this article appears in this issue on page 723. Citation: Piosczyk H, Landmann N, Holz J, Feige B, Riemann D, Nissen C, Voderholzer U. Prolonged sleep under Stone Age conditions. J Clin Sleep Med 2014;10(7):719-722. PMID:25024647

  8. Cellular Senescence and the Biology of Aging, Disease, and Frailty.

    PubMed

    LeBrasseur, Nathan K; Tchkonia, Tamara; Kirkland, James L

    2015-01-01

    Population aging simultaneously highlights the remarkable advances in science, medicine, and public policy, and the formidable challenges facing society. Indeed, aging is the primary risk factor for many of the most common chronic diseases and frailty, which result in profound social and economic costs. Population aging also reveals an opportunity, i.e. interventions to disrupt the fundamental biology of aging could significantly delay the onset of age-related conditions as a group, and, as a result, extend the healthy life span, or health span. There is now considerable evidence that cellular senescence is an underlying mechanism of aging and age-related conditions. Cellular senescence is a process in which cells lose the ability to divide and damage neighboring cells by the factors they secrete, collectively referred to as the senescence-associated secretory phenotype (SASP). Herein, we discuss the concept of cellular senescence, review the evidence that implicates cellular senescence and SASP in age-related deterioration, hyperproliferation, and inflammation, and propose that this underlying mechanism of aging may play a fundamental role in the biology of frailty. PMID:26485647

  9. 42 CFR 436.224 - Individuals under age 21 who are under State adoption assistance agreements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Individuals under age 21 who are under State....224 Individuals under age 21 who are under State adoption assistance agreements. (a) The agency may provide Medicaid to individuals under the age of 21 (or, at State option, age 20, 19, or 18)— (1) For...

  10. NADPH oxidases: key modulators in aging and age-related cardiovascular diseases?

    PubMed Central

    Sahoo, Sanghamitra; Meijles, Daniel N.; Pagano, Patrick J.

    2016-01-01

    Reactive oxygen species (ROS) and oxidative stress have long been linked to aging and diseases prominent in the elderly such as hypertension, atherosclerosis, diabetes and atrial fibrillation (AF). NADPH oxidases (Nox) are a major source of ROS in the vasculature and are key players in mediating redox signalling under physiological and pathophysiological conditions. In this review, we focus on the Nox-mediated ROS signalling pathways involved in the regulation of ‘longevity genes’ and recapitulate their role in age-associated vascular changes and in the development of age-related cardiovascular diseases (CVDs). This review is predicated on burgeoning knowledge that Nox-derived ROS propagate tightly regulated yet varied signalling pathways, which, at the cellular level, may lead to diminished repair, the aging process and predisposition to CVDs. In addition, we briefly describe emerging Nox therapies and their potential in improving the health of the elderly population. PMID:26814203

  11. Connective tissue diseases, multimorbidity and the ageing lung.

    PubMed

    Spagnolo, Paolo; Cordier, Jean-François; Cottin, Vincent

    2016-05-01

    Connective tissue diseases encompass a wide range of heterogeneous disorders characterised by immune-mediated chronic inflammation often leading to tissue damage, collagen deposition and possible loss of function of the target organ. Lung involvement is a common complication of connective tissue diseases. Depending on the underlying disease, various thoracic compartments can be involved but interstitial lung disease is a major contributor to morbidity and mortality. Interstitial lung disease, pulmonary hypertension or both are found most commonly in systemic sclerosis. In the elderly, the prevalence of connective tissue diseases continues to rise due to both longer life expectancy and more effective and better-tolerated treatments. In the geriatric population, connective tissue diseases are almost invariably accompanied by age-related comorbidities, and disease- and treatment-related complications, which contribute to the significant morbidity and mortality associated with these conditions, and complicate treatment decision-making. Connective tissue diseases in the elderly represent a growing concern for healthcare providers and an increasing burden of global health resources worldwide. A better understanding of the mechanisms involved in the regulation of the immune functions in the elderly and evidence-based guidelines specifically designed for this patient population are instrumental to improving the management of connective tissue diseases in elderly patients.

  12. 42 CFR 435.227 - Individuals under age 21 who are under State adoption assistance agreements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Individuals under age 21 who are under State... age 21 who are under State adoption assistance agreements. (a) The agency may provide Medicaid to individuals under the age of 21 (or, at State option, age 20, 19, or 18)— (1) For whom an adoption...

  13. Chronic depression as a model disease for cerebral aging.

    PubMed

    Bewernick, Bettina H; Schlaepfer, Thomas E

    2013-03-01

    Conceptualizations of the underlying neurobiology of major depression have changed their focus from dysfunctions of neurotransmission to dysfunctions of neurogenesis and neuroprotection. The "neurogenesis hypothesis of depression" posits that changes in the rate of neurogenesis are the underlying mechanism in the pathology and treatment of major depression. Stress, neuroinflammation, dysfunctional insulin regulation, oxidative stress, and alterations in neurotrophic factors possibly contribute to the development of depression. The influence of antidepressant therapies, namely pharmacotherapy and neuroprotectants, on cellular plasticity are summarized. A dysfunction of complex neuronal networks as a consequence of neural degeneration in neuropsychiatric diseases has led to the application of deep brain stimulation. We discuss the way depression seen in the light of the neurogenesis hypothesis can be used as a model disease for cerebral aging. A common pathological mechanism in depression and cerebral aging-a dysfunction of neuroprotection and neurogenesis-is discussed. This has implications for new treatment methods.

  14. Medical bioremediation of age-related diseases

    PubMed Central

    Mathieu, Jacques M; Schloendorn, John; Rittmann, Bruce E; Alvarez, Pedro JJ

    2009-01-01

    Catabolic insufficiency in humans leads to the gradual accumulation of a number of pathogenic compounds associated with age-related diseases, including atherosclerosis, Alzheimer's disease, and macular degeneration. Removal of these compounds is a widely researched therapeutic option, but the use of antibodies and endogenous human enzymes has failed to produce effective treatments, and may pose risks to cellular homeostasis. Another alternative is "medical bioremediation," the use of microbial enzymes to augment missing catabolic functions. The microbial genetic diversity in most natural environments provides a resource that can be mined for enzymes capable of degrading just about any energy-rich organic compound. This review discusses targets for biodegradation, the identification of candidate microbial enzymes, and enzyme-delivery methods. PMID:19358742

  15. Brain atrophy in Alzheimer's Disease and aging.

    PubMed

    Pini, Lorenzo; Pievani, Michela; Bocchetta, Martina; Altomare, Daniele; Bosco, Paolo; Cavedo, Enrica; Galluzzi, Samantha; Marizzoni, Moira; Frisoni, Giovanni B

    2016-09-01

    Thanks to its safety and accessibility, magnetic resonance imaging (MRI) is extensively used in clinical routine and research field, largely contributing to our understanding of the pathophysiology of neurodegenerative disorders such as Alzheimer's disease (AD). This review aims to provide a comprehensive overview of the main findings in AD and normal aging over the past twenty years, focusing on the patterns of gray and white matter changes assessed in vivo using MRI. Major progresses in the field concern the segmentation of the hippocampus with novel manual and automatic segmentation approaches, which might soon enable to assess also hippocampal subfields. Advancements in quantification of hippocampal volumetry might pave the way to its broader use as outcome marker in AD clinical trials. Patterns of cortical atrophy have been shown to accurately track disease progression and seem promising in distinguishing among AD subtypes. Disease progression has also been associated with changes in white matter tracts. Recent studies have investigated two areas often overlooked in AD, such as the striatum and basal forebrain, reporting significant atrophy, although the impact of these changes on cognition is still unclear. Future integration of different MRI modalities may further advance the field by providing more powerful biomarkers of disease onset and progression. PMID:26827786

  16. Brain atrophy in Alzheimer's Disease and aging.

    PubMed

    Pini, Lorenzo; Pievani, Michela; Bocchetta, Martina; Altomare, Daniele; Bosco, Paolo; Cavedo, Enrica; Galluzzi, Samantha; Marizzoni, Moira; Frisoni, Giovanni B

    2016-09-01

    Thanks to its safety and accessibility, magnetic resonance imaging (MRI) is extensively used in clinical routine and research field, largely contributing to our understanding of the pathophysiology of neurodegenerative disorders such as Alzheimer's disease (AD). This review aims to provide a comprehensive overview of the main findings in AD and normal aging over the past twenty years, focusing on the patterns of gray and white matter changes assessed in vivo using MRI. Major progresses in the field concern the segmentation of the hippocampus with novel manual and automatic segmentation approaches, which might soon enable to assess also hippocampal subfields. Advancements in quantification of hippocampal volumetry might pave the way to its broader use as outcome marker in AD clinical trials. Patterns of cortical atrophy have been shown to accurately track disease progression and seem promising in distinguishing among AD subtypes. Disease progression has also been associated with changes in white matter tracts. Recent studies have investigated two areas often overlooked in AD, such as the striatum and basal forebrain, reporting significant atrophy, although the impact of these changes on cognition is still unclear. Future integration of different MRI modalities may further advance the field by providing more powerful biomarkers of disease onset and progression.

  17. Extracellular vesicles and their synthetic analogues in aging and age-associated brain diseases

    PubMed Central

    Smith, J. A.; Leonardi, T.; Huang, B.; Iraci, N.; Vega, B.; Pluchino, S.

    2015-01-01

    Multicellular organisms rely upon diverse and complex intercellular communications networks for a myriad of physiological processes. Disruption of these processes is implicated in the onset and propagation of disease and disorder, including the mechanisms of senescence at both cellular and organismal levels. In recent years, secreted extracellular vesicles (EVs) have been identified as a particularly novel vector by which cell-to-cell communications are enacted. EVs actively and specifically traffic bioactive proteins, nucleic acids, and metabolites between cells at local and systemic levels, modulating cellular responses in a bidirectional manner under both homeostatic and pathological conditions. EVs are being implicated not only in the generic aging process, but also as vehicles of pathology in a number of age-related diseases, including cancer and neurodegenerative and disease. Thus, circulating EVs—or specific EV cargoes—are being utilised as putative biomarkers of disease. On the other hand, EVs, as targeted intercellular shuttles of multipotent bioactive payloads, have demonstrated promising therapeutic properties, which can potentially be modulated and enhanced through cellular engineering. Furthermore, there is considerable interest in employing nanomedicinal approaches to mimic the putative therapeutic properties of EVs by employing synthetic analogues for targeted drug delivery. Herein we describe what is known about the origin and nature of EVs and subsequently review their putative roles in biology and medicine (including the use of synthetic EV analogues), with a particular focus on their role in aging and age-related brain diseases. PMID:24973266

  18. Fracture, aging and disease in bone

    SciTech Connect

    Ager, J.W.; Balooch, G.; Ritchie, R.O.

    2006-02-01

    fracture resistance, whereas regulating the level of the cytokine TGF-beta can offer significant improvements in the stiffness, strength and toughness of bone, and as such may be considered as a therapeutic target to treat increased bone fragility induced by aging, drugs, and disease.

  19. 20 CFR 404.1038 - Domestic employees under age 18.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Domestic employees under age 18. 404.1038 Section 404.1038 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND... from Employment § 404.1038 Domestic employees under age 18. Domestic services you perform in a...

  20. 20 CFR 404.1038 - Domestic employees under age 18.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Domestic employees under age 18. 404.1038 Section 404.1038 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND... from Employment § 404.1038 Domestic employees under age 18. Domestic services you perform in a...

  1. 20 CFR 404.1038 - Domestic employees under age 18.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false Domestic employees under age 18. 404.1038 Section 404.1038 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND... from Employment § 404.1038 Domestic employees under age 18. Domestic services you perform in a...

  2. 20 CFR 404.1038 - Domestic employees under age 18.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Domestic employees under age 18. 404.1038 Section 404.1038 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND... from Employment § 404.1038 Domestic employees under age 18. Domestic services you perform in a...

  3. 20 CFR 404.1038 - Domestic employees under age 18.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false Domestic employees under age 18. 404.1038 Section 404.1038 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND... from Employment § 404.1038 Domestic employees under age 18. Domestic services you perform in a...

  4. Control of mitochondrial integrity in ageing and disease

    PubMed Central

    Szklarczyk, Radek; Nooteboom, Marco; Osiewacz, Heinz D.

    2014-01-01

    Various molecular and cellular pathways are active in eukaryotes to control the quality and integrity of mitochondria. These pathways are involved in keeping a ‘healthy’ population of this essential organelle during the lifetime of the organism. Quality control (QC) systems counteract processes that lead to organellar dysfunction manifesting as degenerative diseases and ageing. We discuss disease- and ageing-related pathways involved in mitochondrial QC: mtDNA repair and reorganization, regeneration of oxidized amino acids, refolding and degradation of severely damaged proteins, degradation of whole mitochondria by mitophagy and finally programmed cell death. The control of the integrity of mtDNA and regulation of its expression is essential to remodel single proteins as well as mitochondrial complexes that determine mitochondrial functions. The redundancy of components, such as proteases, and the hierarchies of the QC raise questions about crosstalk between systems and their precise regulation. The understanding of the underlying mechanisms on the genomic, proteomic, organellar and cellular levels holds the key for the development of interventions for mitochondrial dysfunctions, degenerative processes, ageing and age-related diseases resulting from impairments of mitochondria. PMID:24864310

  5. Lycopene Deficiency in Ageing and Cardiovascular Disease

    PubMed Central

    Petyaev, Ivan M.

    2016-01-01

    Lycopene is a hydrocarbon phytochemical belonging to the tetraterpene carotenoid family and is found in red fruit and vegetables. Eleven conjugated double bonds predetermine the antioxidant properties of lycopene and its ability to scavenge lipid peroxyl radicals, reactive oxygen species, and nitric oxide. Lycopene has a low bioavailability rate and appears in the blood circulation incorporated into chylomicrons and other apo-B containing lipoproteins. The recent body of evidence suggests that plasma concentration of lycopene is not only a function of intestinal absorption rate but also lycopene breakdown via enzymatic and oxidative pathways in blood and tissues. Oxidative stress and the accumulation of reactive oxygen species and nitric oxide may represent a major cause of lycopene depletion in ageing, cardiovascular disease, and type 2 diabetes mellitus. It has been shown recently that low carotenoid levels, and especially decreased serum lycopene levels, are strongly predictive of all-cause mortality and poor outcomes of cardiovascular disease. However, there is a poor statistical association between dietary and serum lycopene levels which occurs due to limited bioavailability of lycopene from dietary sources. Hence, it is very unlikely that nutritional intervention alone could be instrumental in the correction of lycopene and carotenoid deficiency. Therefore, new nutraceutical formulations of carotenoids with enhanced bioavailability are urgently needed. PMID:26881023

  6. Genetic evidence for common pathways in human age-related diseases.

    PubMed

    Johnson, Simon C; Dong, Xiao; Vijg, Jan; Suh, Yousin

    2015-10-01

    Aging is the single largest risk factor for chronic disease. Studies in model organisms have identified conserved pathways that modulate aging rate and the onset and progression of multiple age-related diseases, suggesting that common pathways of aging may influence age-related diseases in humans as well. To determine whether there is genetic evidence supporting the notion of common pathways underlying age-related diseases, we analyzed the genes and pathways found to be associated with five major categories of age-related disease using a total of 410 genomewide association studies (GWAS). While only a small number of genes are shared among all five disease categories, those found in at least three of the five major age-related disease categories are highly enriched for apoliprotein metabolism genes. We found that a more substantial number of gene ontology (GO) terms are shared among the 5 age-related disease categories and shared GO terms include canonical aging pathways identified in model organisms, such as nutrient-sensing signaling, translation, proteostasis, stress responses, and genome maintenance. Taking advantage of the vast amount of genetic data from the GWAS, our findings provide the first direct evidence that conserved pathways of aging simultaneously influence multiple age-related diseases in humans as has been demonstrated in model organisms.

  7. Neurovascular and neurometabolic derailment in aging and Alzheimer's disease

    PubMed Central

    Lourenço, Cátia F.; Ledo, Ana; Dias, Cândida; Barbosa, Rui M.; Laranjinha, João

    2015-01-01

    The functional and structural integrity of the brain requires local adjustment of blood flow and regulated delivery of metabolic substrates to meet the metabolic demands imposed by neuronal activation. This process—neurovascular coupling—and ensued alterations of glucose and oxygen metabolism—neurometabolic coupling—are accomplished by concerted communication between neural and vascular cells. Evidence suggests that neuronal-derived nitric oxide (•NO) is a key player in both phenomena. Alterations in the mechanisms underlying the intimate communication between neural cells and vessels ultimately lead to neuronal dysfunction. Both neurovascular and neurometabolic coupling are perturbed during brain aging and in age-related neuropathologies in close association with cognitive decline. However, despite decades of intense investigation, many aspects remain poorly understood, such as the impact of these alterations. In this review, we address neurovascular and neurometabolic derailment in aging and Alzheimer's disease (AD), discussing its significance in connection with •NO-related pathways. PMID:26074816

  8. Developmental determinants in non-communicable chronic diseases and ageing.

    PubMed

    Bousquet, J; Anto, J M; Berkouk, K; Gergen, P; Antunes, J Pinto; Augé, P; Camuzat, T; Bringer, J; Mercier, J; Best, N; Bourret, R; Akdis, M; Arshad, S H; Bedbrook, A; Berr, C; Bush, A; Cavalli, G; Charles, M A; Clavel-Chapelon, F; Gillman, M; Gold, D R; Goldberg, M; Holloway, J W; Iozzo, P; Jacquemin, S; Jeandel, C; Kauffmann, F; Keil, T; Koppelman, G H; Krauss-Etschmann, S; Kuh, D; Lehmann, S; Carlsen, K C Lodrup; Maier, D; Méchali, M; Melén, E; Moatti, J P; Momas, I; Nérin, P; Postma, D S; Ritchie, K; Robine, J M; Samolinski, B; Siroux, V; Slagboom, P E; Smit, H A; Sunyer, J; Valenta, R; Van de Perre, P; Verdier, J M; Vrijheid, M; Wickman, M; Yiallouros, P; Zins, M

    2015-06-01

    Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases.

  9. Motives and methods of under-age casino gamblers.

    PubMed

    Giacopassi, David; Stitt, B Grant; Nichols, Mark

    2006-12-01

    Numerous studies have documented that under-age gambling is quite common. The present study employs interviews of 48 university students who gambled under-age to determine the motives and methods associated with casino gambling by minors. The information gathered in these interviews indicates that access to casinos is easily attained, that the risk of exposure once gambling is minimal, and the motivations of under-age gamblers differ in important ways from that of adults, as access to alcohol, accompanying parents, and the desire to experience the "forbidden fruit" of casino gambling are commonly mentioned motivations by under-age gamblers.

  10. Understanding Vascular Diseases: Lessons From Premature Aging Syndromes.

    PubMed

    Ikeda, Yuichi; Kumagai, Hidetoshi; Motozawa, Yoshihiro; Suzuki, Jun-Ichi; Akazawa, Hiroshi; Komuro, Issei

    2016-05-01

    Early human mummies examined recently by computed tomography demonstrated a high prevalence of vascular calcification, a pathognomonic sign of atherosclerosis, which was correlated with estimated age at death. Early populations had little exposure to modern-day metabolic risk factors: these observations thus suggest that humans have an inherent age-dependent predisposition to atherosclerosis. Premature aging syndromes are extremely rare genetic disorders that exhibit clinical phenotypes resembling accelerated aging, including severe atherosclerosis, but those phenotypes are usually segmental. Controversy persists, therefore, regarding the extent to which the molecular mechanisms underlying premature aging syndromes overlap with those of physiological aging. Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome are well-characterized premature aging syndromes. HGPS is caused by gain-of-function mutations in the LMNA gene, which result in the accumulation of a mutant nuclear protein, called "progerin," at the nuclear rim. In contrast, loss-of-function mutations in Werner syndrome ATP-dependent helicase (WRN) lead to Werner syndrome. Mesenchymal stem cells (MSCs), which can differentiate into vascular cells to maintain vascular homeostasis in response to injury, are severely affected in these syndromes. Mechanistically, either aberrant expression of progerin or loss of WRN protein in MSCs alters heterochromatin structure, resulting in premature senescence and exhaustion of functional MSCs in premature aging syndromes. Surprisingly, vascular cells and MSCs in elderly healthy individuals have shown progerin expression and decreased expression levels of WRN, respectively. Studying these rare genetic disorders could thus provide valuable insights into age-related vascular diseases that occur in the general population. PMID:26948039

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

    PubMed

    Harel, Itamar; Brunet, Anne

    2015-01-01

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

  12. [Car driving, cognitive aging and Alzheimer disease].

    PubMed

    Fabrigoule, Colette; Lafont, Sylviane

    2015-10-01

    Older drivers are more numerous on the roads. They are expert drivers, but with increasing age certain physiological changes can interfere with driving, which is a complex activity of daily living. Older drivers are involved in fewer accidents than younger drivers, but they have a higher accident rate per kilometer driven. The elderly are heavily represented in the balance sheet of road deaths, being motorists or pedestrians. This high mortality is largely explained by their physical frailty. In the presence of deficits, self-regulation of driving habits, changes/reductions or stopping in driving activity occur in the elderly. But cognitive deficits are associated with an increased risk of accidents. Among drivers with Alzheimer's disease, there is a heterogeneity of driving ability, making difficult the advisory role of a physician for driving. A protocol for physicians was developed to assess cognitive impairments that may affect driving in an elderly patient. The car plays an important role in the autonomy of the elderly and patient advice on stopping driving should take into account the risk/benefit ratio. PMID:26009241

  13. Differential Effects of Aging on Processes Underlying Task Switching

    ERIC Educational Resources Information Center

    West, Robert; Travers, Stephanie

    2008-01-01

    In this study, we used event-related brain potentials (ERPs) to examine the effects of aging on processes underlying task switching. The response time data revealed an age-related increase in mixing costs before controlling for general slowing and no effect of aging on switching costs. In the cue-locked epoch, the ERP data revealed little effect…

  14. Aging Is Not a Disease: Distinguishing Age-Related Macular Degeneration from Aging

    PubMed Central

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-01-01

    Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD. PMID:23933169

  15. Aging is not a disease: distinguishing age-related macular degeneration from aging.

    PubMed

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-11-01

    Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD.

  16. Chronic Respiratory Diseases of School-Age Children

    ERIC Educational Resources Information Center

    McGovern, John P.

    1976-01-01

    The author examines the problems of chronic respiratory disease in school-age children from a medical viewpoint, including recognition and diagnosis, commonly encountered diseases, their effect on participation in physical exercise, emotional factors, medication, and emergency care. (MB)

  17. Mitochondrial and Ubiquitin Proteasome System Dysfunction in Ageing and Disease: Two Sides of the Same Coin?

    PubMed Central

    Ross, Jaime M.; Olson, Lars; Coppotelli, Giuseppe

    2015-01-01

    Mitochondrial dysfunction and impairment of the ubiquitin proteasome system have been described as two hallmarks of the ageing process. Additionally, both systems have been implicated in the etiopathogenesis of many age-related diseases, particularly neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease. Interestingly, these two systems are closely interconnected, with the ubiquitin proteasome system maintaining mitochondrial homeostasis by regulating organelle dynamics, the proteome, and mitophagy, and mitochondrial dysfunction impairing cellular protein homeostasis by oxidative damage. Here, we review the current literature and argue that the interplay of the two systems should be considered in order to better understand the cellular dysfunction observed in ageing and age-related diseases. Such an approach may provide valuable insights into molecular mechanisms underlying the ageing process, and further discovery of treatments to counteract ageing and its associated diseases. Furthermore, we provide a hypothetical model for the heterogeneity described among individuals during ageing. PMID:26287188

  18. Stem cell transplantation improves aging-related diseases

    PubMed Central

    Ikehara, Susumu; Li, Ming

    2014-01-01

    Aging is a complex process of damage accumulation, and has been viewed as experimentally and medically intractable. The number of patients with age-associated diseases such as type 2 diabetes mellitus (T2DM), osteoporosis, Alzheimer's disease (AD), Parkinson's disease, atherosclerosis, and cancer has increased recently. Aging-related diseases are related to a deficiency of the immune system, which results from an aged thymus and bone marrow cells. Intra bone marrow-bone marrow transplantation (IBM-BMT) is a useful method to treat intractable diseases. This review summarizes findings that IBM-BMT can improve and treat aging-related diseases, including T2DM, osteoporosis and AD, in animal models. PMID:25364723

  19. Antioxidant Supplementation in the Treatment of Aging-Associated Diseases

    PubMed Central

    Conti, Valeria; Izzo, Viviana; Corbi, Graziamaria; Russomanno, Giusy; Manzo, Valentina; De Lise, Federica; Di Donato, Alberto; Filippelli, Amelia

    2016-01-01

    Oxidative stress is generally considered as the consequence of an imbalance between pro- and antioxidants species, which often results into indiscriminate and global damage at the organismal level. Elderly people are more susceptible to oxidative stress and this depends, almost in part, from a decreased performance of their endogenous antioxidant system. As many studies reported an inverse correlation between systemic levels of antioxidants and several diseases, primarily cardiovascular diseases, but also diabetes and neurological disorders, antioxidant supplementation has been foreseen as an effective preventive and therapeutic intervention for aging-associated pathologies. However, the expectations of this therapeutic approach have often been partially disappointed by clinical trials. The interplay of both endogenous and exogenous antioxidants with the systemic redox system is very complex and represents an issue that is still under debate. In this review a selection of recent clinical studies concerning antioxidants supplementation and the evaluation of their influence in aging-related diseases is analyzed. The controversial outcomes of antioxidants supplementation therapies, which might partially depend from an underestimation of the patient specific metabolic demand and genetic background, are presented. PMID:26903869

  20. Brain Molecular Aging, Promotion of Neurological Disease and Modulation by Sirtuin5 Longevity Gene Polymorphism

    PubMed Central

    Glorioso, Christin; Oh, Sunghee; Douillard, Gaelle Guilloux; Sibille, Etienne

    2010-01-01

    Mechanisms determining characteristic age of onset for neurological diseases are largely unknown. Normal brain aging associates with robust and progressive transcriptome changes (“molecular aging”), but the intersection with disease pathways is mostly uncharacterized. Here, using cross-cohort microarray analysis of four human brain areas, we show that neurological disease pathways largely overlap with molecular aging and that subjects carrying a newly-characterized low-expressing polymorphism in a putative longevity gene (Sirtuin5; SIRT5prom2) have older brain molecular ages. Specifically, molecular aging was remarkably conserved across cohorts and brain areas, and included numerous developmental and transcription-regulator genes. Neurological disease-associated genes were highly overrepresented within age-related genes and changed almost unanimously in pro-disease directions, together suggesting an underlying genetic “program” of aging that progressively promotes disease. To begin testing this putative pathway, we developed and used an age-biosignature to assess five candidate longevity gene polymorphisms association with molecular aging rates. Most robustly, aging was accelerated in cingulate, but not amygdala, of subjects carrying a SIRT5 promoter polymorphism (+9yrs, p=0.004), in concordance with cingulate-specific decreased SIRT5 expression. This effect was driven by a set of core transcripts (+24 yrs, p=0.0004), many of which were mitochondrial, including Parkinson’s disease genes, PINK1 and DJ1/PARK7, hence suggesting that SIRT5prom2 may represent a risk factor for mitochondrial dysfunction-related diseases, including Parkinson s, through accelerated molecular aging of disease-related genes. Based on these results we speculate that a “common mechanism” may underlie age of onset across several neurological diseases. Confirming this pathway and its regulation by common genetic variants would provide new strategies for predicting, delaying, and

  1. Similarly Strong Purifying Selection Acts on Human Disease Genes of All Evolutionary Ages

    PubMed Central

    Cai, James J.; Borenstein, Elhanan; Chen, Rong

    2009-01-01

    A number of studies have showed that recently created genes differ from the genes created in deep evolutionary past in many aspects. Here, we determined the age of emergence and propensity for gene loss (PGL) of all human protein–coding genes and compared disease genes with non-disease genes in terms of their evolutionary rate, strength of purifying selection, mRNA expression, and genetic redundancy. The older and the less prone to loss, non-disease genes have been evolving 1.5- to 3-fold slower between humans and chimps than young non-disease genes, whereas Mendelian disease genes have been evolving very slowly regardless of their ages and PGL. Complex disease genes showed an intermediate pattern. Disease genes also have higher mRNA expression heterogeneity across multiple tissues than non-disease genes regardless of age and PGL. Young and middle-aged disease genes have fewer similar paralogs as non-disease genes of the same age. We reasoned that genes were more likely to be involved in human disease if they were under a strong functional constraint, expressed heterogeneously across tissues, and lacked genetic redundancy. Young human genes that have been evolving under strong constraint between humans and chimps might also be enriched for genes that encode important primate or even human-specific functions. PMID:20333184

  2. Polymerase Gamma Disease through the Ages

    ERIC Educational Resources Information Center

    Saneto, Russell P.; Naviaux, Robert K.

    2010-01-01

    The most common group of mitochondrial disease is due to mutations within the mitochondrial DNA polymerase, polymerase gamma 1 ("POLG"). This gene product is responsible for replication and repair of the small mitochondrial DNA genome. The structure-function relationship of this gene product produces a wide variety of diseases that at times, seems…

  3. SIRT3 regulates progression and development of diseases of aging

    PubMed Central

    Bomze, Howard M.; Hirschey, Matthew D.

    2015-01-01

    The mitochondrial sirtuin SIRT3 is a protein deacylase that regulates almost every major aspect of mitochondrial biology, including nutrient oxidation, ATP generation, reactive oxygen species detoxification, mitochondrial dynamics, and the mitochondrial unfolded protein response. Interestingly, mice lacking SIRT3 (SIRT3KO), either spontaneously or when crossed with mouse models of disease, develop several diseases of aging at an accelerated pace, such as cancer, metabolic syndrome, cardiovascular disease, and neurodegenerative diseases, and thus might be a valuable model of accelerated aging. In this review we discuss SIRT3 functions in pathways involved in diseases of aging, how lack of SIRT3 might accelerate the aging process, and suggest that further studies on SIRT3 might help uncover important new pathways driving the aging process. PMID:26138757

  4. Aging of beryllium bronze under programmed loading conditions

    SciTech Connect

    Duraev, P.P.; Kaplun, Yu.A.

    1987-07-01

    Results are provided from a study of different aging methods for beryllium bronze BrBNT1.9Mg under tensile stress conditions created by an applied load. Aging, both in the original hardened condition and after low-temperature treatment, is found to lead to an increase in yield strength and elastic limit. Ultimate breaking strength, hardness, and ductility do not change. An increase in deformation resistance after aging is connected with oriented precipitation of gamma-phase particles.

  5. Adult Stem Cells and Diseases of Aging

    PubMed Central

    Boyette, Lisa B.; Tuan, Rocky S.

    2014-01-01

    Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan. PMID:24757526

  6. Alloimmunization in multitransfused liver disease patients: Impact of underlying disease

    PubMed Central

    Bajpai, Meenu; Gupta, Shruti; Jain, Priyanka

    2016-01-01

    Introduction: Transfusion support is vital to the management of patients with liver diseases. Repeated transfusions are associated with many risks such as transfusion-transmitted infection, transfusion immunomodulation, and alloimmunization. Materials and Methods: A retrospective data analysis of antibody screening and identification was done from February 2012 to February 2014 to determine the frequency and specificity of irregular red-cell antibodies in multitransfused liver disease patients. The clinical and transfusion records were reviewed. The data was compiled, statistically analyzed, and reviewed. Results: A total of 842 patients were included in our study. Alloantibodies were detected in 5.22% of the patients. Higher rates of alloimmunization were seen in patients with autoimmune hepatitis, cryptogenic liver disease, liver damage due to drugs/toxins, and liver cancer patients. Patients with alcoholic liver disease had a lower rate of alloimmunization. The alloimmunization was 12.7% (23/181) in females and 3.17% (21/661) in males. Antibodies against the Rh system were the most frequent with 27 of 44 alloantibodies (61.36%). The most common alloantibody identified was anti-E (11/44 cases, 25%), followed by anti-C (6/44 cases, 13.63%). Conclusion: Our findings suggest that alloimmunization rate is affected by underlying disease. Provision of Rh and Kell phenotype-matched blood can significantly reduce alloimmunization. PMID:27605851

  7. Alloimmunization in multitransfused liver disease patients: Impact of underlying disease

    PubMed Central

    Bajpai, Meenu; Gupta, Shruti; Jain, Priyanka

    2016-01-01

    Introduction: Transfusion support is vital to the management of patients with liver diseases. Repeated transfusions are associated with many risks such as transfusion-transmitted infection, transfusion immunomodulation, and alloimmunization. Materials and Methods: A retrospective data analysis of antibody screening and identification was done from February 2012 to February 2014 to determine the frequency and specificity of irregular red-cell antibodies in multitransfused liver disease patients. The clinical and transfusion records were reviewed. The data was compiled, statistically analyzed, and reviewed. Results: A total of 842 patients were included in our study. Alloantibodies were detected in 5.22% of the patients. Higher rates of alloimmunization were seen in patients with autoimmune hepatitis, cryptogenic liver disease, liver damage due to drugs/toxins, and liver cancer patients. Patients with alcoholic liver disease had a lower rate of alloimmunization. The alloimmunization was 12.7% (23/181) in females and 3.17% (21/661) in males. Antibodies against the Rh system were the most frequent with 27 of 44 alloantibodies (61.36%). The most common alloantibody identified was anti-E (11/44 cases, 25%), followed by anti-C (6/44 cases, 13.63%). Conclusion: Our findings suggest that alloimmunization rate is affected by underlying disease. Provision of Rh and Kell phenotype-matched blood can significantly reduce alloimmunization.

  8. Chaperonomics, a new tool to study ageing and associated diseases.

    PubMed

    Brocchieri, Luciano; Conway de Macario, Everly; Macario, Alberto J L

    2007-01-01

    The participation of molecular chaperones in the process of senescence and in the mechanisms of age-related diseases is currently under investigation in many laboratories. However, accurate, complete information about the number and diversity of chaperone genes in any given genome is scarce. Consequently, the results of efforts aimed at elucidating the role of chaperones in ageing and disease are often confusing and contradictory. To remedy this situation, we have developed chaperonomics, including means to identify and characterize chaperone genes and their families applicable to humans and model organisms. The problem is difficult because in eukaryotic organisms chaperones have evolved into complex multi-gene families. For instance, the occurrence of multiple paralogs in a single genome makes it difficult to interpret results if consideration is not given to the fact that similar but distinct chaperone genes can be differentially expressed in separate cellular compartments, tissues, and developmental stages. The availability of complete genome sequences allows implementation of chaperonomics with the purpose of understanding the composition of chaperone families in all cell compartments, their evolutionary and functional relations and, ultimately, their role in pathogenesis. Here, we present a series of concatenated, complementary procedures for identifying, characterizing, and classifying chaperone genes in genomes and for elucidating evolutionary relations and structural features useful in predicting functional properties. We illustrate the procedures with applications to the complex family of hsp70 genes and show that the kind of data obtained can provide a solid basis for future research.

  9. Heart Disease Affects Women of All Ages

    MedlinePlus

    ... 64 have a heart attack. About half of women who have a heart attack before age 65 die within 8 years. Heart ... have another within 6 years. About half of women who have a heart attack will be disabled with heart failure within 6 ...

  10. Cell-Nonautonomous Mechanisms Underlying Cellular and Organismal Aging.

    PubMed

    Medkour, Younes; Svistkova, Veronika; Titorenko, Vladimir I

    2016-01-01

    Cell-autonomous mechanisms underlying cellular and organismal aging in evolutionarily distant eukaryotes have been established; these mechanisms regulate longevity-defining processes within a single eukaryotic cell. Recent findings have provided valuable insight into cell-nonautonomous mechanisms modulating cellular and organismal aging in eukaryotes across phyla; these mechanisms involve a transmission of various longevity factors between different cells, tissues, and organisms. Herein, we review such cell-nonautonomous mechanisms of aging in eukaryotes. We discuss the following: (1) how low molecular weight transmissible longevity factors modulate aging and define longevity of cells in yeast populations cultured in liquid media or on solid surfaces, (2) how communications between proteostasis stress networks operating in neurons and nonneuronal somatic tissues define longevity of the nematode Caenorhabditis elegans by modulating the rates of aging in different tissues, and (3) how different bacterial species colonizing the gut lumen of C. elegans define nematode longevity by modulating the rate of organismal aging.

  11. Impairment of age estimation from faces in Alzheimer's disease.

    PubMed

    Moyse, Evelyne; Bastin, Christine; Salmon, Eric; Brédart, Serge

    2015-01-01

    A prerequisite for any function in social cognition is the perception and processing of social cues. Age estimation is a skill that is used in everyday life and is fundamental in social interactions. This study evaluated whether facial age estimation is impaired in patients with mild to moderate Alzheimer's disease (AD). The current age of faces is known to have an impact on age estimation, and therefore stimuli belonging to different age groups (young, middle-aged, and older adults' faces) were used. As expected, an impairment of age estimation from faces was observed in mild to moderate AD patients. However, the profile of impairment depended on the age of faces and stage of the disease. Mild AD patients presented difficulties mainly in assessing the age of middle-aged adults. In moderate disease stage, these difficulties also affected the age estimation of young adult faces. Interestingly, AD patients remained relatively good at estimating the age of older adults' faces, compared to healthy controls. PMID:25589725

  12. Low grade inflammation as a common pathogenetic denominator in age-related diseases: novel drug targets for anti-ageing strategies and successful ageing achievement.

    PubMed

    Candore, G; Caruso, C; Jirillo, E; Magrone, T; Vasto, S

    2010-01-01

    Nowadays, people are living much longer than they used to do, however they are not free from ageing. Ageing, an inexorable intrinsic process that affects all cells, tissues, organs and individuals, is a post-maturational process that, due to a diminished homeostasis and increased organism frailty, causes a reduction of the response to environmental stimuli and, in general, is associated to an increased predisposition to illness and death. However, the high incidence of death due to infectious, cardiovascular and cancer diseases underlies a common feature in these pathologies that is represented by dysregulation of both instructive and innate immunity. Several studies show that a low-grade systemic inflammation characterizes ageing and that inflammatory markers are significant predictors of mortality in old humans. This pro-inflammatory status of the elderly underlies biological mechanisms responsible for physical function decline and age-related diseases such as Alzheimer's disease and atherosclerosis are initiated or worsened by systemic inflammation. Understanding of the ageing process should have a prominent role in new strategies for extending the health old population. Accordingly, as extensively discussed in the review and in the accompanying related papers, investigating ageing pathophysiology, particularly disentangling age-related low grade inflammation, is likely to provide important clues about how to develop drugs that can slow or delay ageing.

  13. Mitochondria as a Therapeutic Target for Aging and Neurodegenerative Diseases

    PubMed Central

    Reddy, P. Hemachandra; Reddy, Tejaswini P.

    2012-01-01

    Mitochondria are cytoplasmic organelles responsible for life and death. Extensive evidence from animal models, postmortem brain studies of and clinical studies of aging and neurodegenerative diseases suggests that mitochondrial function is defective in aging and neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Several lines of research suggest that mitochondrial abnormalities, including defects in oxidative phosphorylation, increased accumulation of mitochondrial DNA defects, impaired calcium influx, accumulation of mutant proteins in mitochondria, and mitochondrial membrane potential dissipation are important cellular changes in both early and late-onset neurodegenerative diseases. Further, emerging evidence suggests that structural changes in mitochondria, including increased mitochondrial fragmentation and decreased mitochondrial fusion, are critical factors associated with mitochondrial dysfunction and cell death in aging and neurodegenerative diseases. This paper discusses research that elucidates features of mitochondria that are associated with cellular dysfunction in aging and neurodegenerative diseases and discusses mitochondrial structural and functional changes, and abnormal mitochondrial dynamics in neurodegenerative diseases. It also outlines mitochondria-targeted therapeutics in neurodegenerative diseases. PMID:21470101

  14. [Mechanisms of the immune system ageing and some age-associated diseases].

    PubMed

    Witkowski, Jacek M

    2014-01-01

    In this paper the concept of homeostenosis (progressive reduction of ability to adapt producing loss of effectiveness) of the immune system is presented as a cause of the system ageing. In particular, the progression of immune system homeostenosis was shown to be associated with previous or ongoing chronic inflammatory diseases, including rheumatoid arthritis, type 2 diabetes, chronic kidney disease and Alzheimer's disease.

  15. Mechanisms of yogic practices in health, aging, and disease.

    PubMed

    Kuntsevich, Viktoriya; Bushell, William C; Theise, Neil D

    2010-01-01

    Mechanisms underlying the modulating effects of yogic cognitive-behavioral practices (eg, meditation, yoga asanas, pranayama breathing, caloric restriction) on human physiology can be classified into 4 transduction pathways: humoral factors, nervous system activity, cell trafficking, and bioelectromagnetism. Here we give examples of these transduction pathways and how, through them, yogic practices might optimize health, delay aging, and ameliorate chronic illness and stress from disability. We also recognize that most studies of these mechanisms remain embedded in a reductionist paradigm, investigating small numbers of elements of only 1 or 2 pathways. Moreover, often, subjects are not long-term practitioners, but recently trained. The models generated from such data are, in turn, often limited, top-down, without the explanatory power to describe beneficial effects of long-term practice or to provide foundations for comparing one practice to another. More flexible and useful models require a systems-biology approach to gathering and analysis of data. Such a paradigm is needed to fully appreciate the deeper mechanisms underlying the ability of yogic practice to optimize health, delay aging, and speed efficient recovery from injury or disease. In this regard, 3 different, not necessarily competing, hypotheses are presented to guide design of future investigations, namely, that yogic practices may: (1) promote restoration of physiologic setpoints to normal after derangements secondary to disease or injury, (2) promote homeostatic negative feedback loops over nonhomeostatic positive feedback loops in molecular and cellular interactions, and (3) quench abnormal "noise" in cellular and molecular signaling networks arising from environmental or internal stresses.

  16. Neuroinflamm-aging and neurodegenerative diseases: an overview.

    PubMed

    Pizza, Vincenzo; Agresta, Anella; D'Acunto, Cosimo W; Festa, Michela; Capasso, Anna

    2011-08-01

    Neuroinflammation is considered a chronic activation of the immune response in the central nervous system (CNS) in response to different injuries. This brain immune activation results in various events: circulating immune cells infiltrate the CNS; resident cells are activated; and pro-inflammatory mediators produced and released induce neuroinflammatory brain disease. The effect of immune diffusible mediators on synaptic plasticity might result in CNS dysfunction during neuroinflammatory brain diseases. The CNS dysfunction may induce several human pathological conditions associated with both cognitive impairment and a variable degree of neuroinflammation. Furthermore, age has a powerful effect on enhanced susceptibility to neurodegenerative diseases and age-dependent enhanced neuroinflammatory processes may play an important role in toxin generation that causes death or dysfunction of neurons in neurodegenerative diseases This review will address current understanding of the relationship between ageing, neuroinflammation and neurodegenerative disease by focusing on the principal mechanisms by which the immune system influences the brain plastic phenomena. Also, the present review considers the principal human neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis and psychiatric disorders caused by aging and neuroinflammation.

  17. Stone age diseases and modern AIDS

    PubMed Central

    Koch, Arthur L

    2008-01-01

    The great advantage of being a sexually transmitted disease is the ability to survive and specialize solely on a host species that is present in low numbers and widely distributed so that contact between infected and uninfected organisms by chance is rare. Pathogens of a sparse, but widely distributed host species, must either: i) have an alternative host; ii) be able to survive in a dormant state; or iii) be non-destructive to their host. For the pathogens of a diploid there is a particularly effective strategy, that of being sexually transmitted. Then the hosts' themselves transfer the pathogen. PMID:18687115

  18. Glycation: the angiogenic paradox in aging and age-related disorders and diseases.

    PubMed

    Roca, F; Grossin, N; Chassagne, P; Puisieux, F; Boulanger, E

    2014-05-01

    Angiogenesis is generally a quiescent process which, however, may be modified by different physiological and pathological conditions. The "angiogenic paradox" has been described in diabetes because this disease impairs the angiogenic response in a manner that differs depending on the organs involved and disease evolution. Aging is also associated with pro- and antiangiogenic processes. Glycation, the post-translational modification of proteins, increases with aging and the progression of diabetes. The effect of glycation on angiogenesis depends on the type of glycated proteins and cells involved. This complex link could be responsible for the "angiogenic paradox" in aging and age-related disorders and diseases. Using diabetes as a model, the present work has attempted to review the age-related angiogenic paradox, in particular the effects of glycation on angiogenesis during aging.

  19. Use of Metformin in Diseases of Aging

    PubMed Central

    Miles, John M.; Rule, Andrew D.; Borlaug, Barry A.

    2014-01-01

    Metformin is the most commonly prescribed medication for type 2 diabetes (T2DM) in the world. It has primacy in the treatment of this disease because of its safety record and also because of evidence for reduction in the risk of cardiovascular events. Evidence has accumulated indicating that metformin is safe in people with stage 3 chronic kidney disease (CKD-3). It is estimated that roughly one-quarter of people with CKD-3 and T2DM in the United States (well over 1 million) are ineligible for metformin treatment because of elevated serum creatinine levels. This could be overcome if a scheme, perhaps based on pharmacokinetic studies, could be developed to prescribe reduced doses of metformin in these individuals. There is also substantial evidence from epidemiological studies to indicate that metformin may not only be safe, but may actually benefit people with heart failure (HF). Prospective, randomized trials of the use of metformin in HF are needed to investigate this possibility. PMID:24752835

  20. Aging is not a disease: implications for intervention.

    PubMed

    Rattan, Suresh I S

    2014-06-01

    Aging of biological systems occurs in spite of numerous complex pathways of maintenance, repair and defense. There are no gerontogenes which have the specific evolutionary function to cause aging. Although aging is the common cause of all age-related diseases, aging in itself cannot be considered a disease. This understanding of aging as a process should transform our approach towards interventions from developing illusory anti-aging treatments to developing realistic and practical methods for maintaining health throughout the lifespan. The concept of homeodynamic space can be a useful one in order to identify a set of measurable, evidence-based and demonstratable parameters of health, robustness and resilience. Age-induced health problems, for which there are no other clear-cut causative agents, may be better tackled by focusing on health mechanisms and their maintenance, rather than only disease management and treatment. Continuing the disease-oriented research and treatment approaches, as opposed to health-oriented and preventive strategies, are economically, socially and psychologically unsustainable.

  1. ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases

    PubMed Central

    Davalli, Pierpaola; Mitic, Tijana; Caporali, Andrea; Lauriola, Angela; D'Arca, Domenico

    2016-01-01

    The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression and metabolic control, the aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS) and/or Reactive Nitrosative Species (RNS). Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. Causal connection between ROS, aging, age-related pathologies, and cell senescence is studied intensely. Senescent cells have been proposed as a target for interventions to delay the aging and its related diseases or to improve the diseases treatment. Therapeutic interventions towards senescent cells might allow restoring the health and curing the diseases that share basal processes, rather than curing each disease in separate and symptomatic way. Here, we review observations on ROS ability of inducing cell senescence through novel mechanisms that underpin aging processes. Particular emphasis is addressed to the novel mechanisms of ROS involvement in epigenetic regulation of cell senescence and aging, with the aim to individuate specific pathways, which might promote healthy lifespan and improve aging. PMID:27247702

  2. Hearing-Impaired Children under Age 6: 1977 and 1984.

    ERIC Educational Resources Information Center

    Schildroth, Arthur

    1986-01-01

    A review of annual survey data revealed that hearing impaired children under age 6 reported in 1984, when compared to those reported in 1977, tended to be younger; had higher percentages of heredity, meningitis, and prematurity as causes of hearing loss; and were more likely to have additional handicaps. (CL)

  3. Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

    PubMed

    Rastogi, Neelesh; Smith, R Theodore

    2016-01-01

    Age-related macular degeneration is the leading cause of adult blindness in the developed world. Thus, major endeavors to understand the risk factors and pathogenesis of this disease have been undertaken. Reticular macular disease is a proposed subtype of age-related macular degeneration correlating histologically with subretinal drusenoid deposits located between the retinal pigment epithelium and the inner segment ellipsoid zone. Reticular lesions are more prevalent in females and in older age groups and are associated with a higher mortality rate. Risk factors for developing age-related macular degeneration include hypertension, smoking, and angina. Several genes related to increased risk for age-related macular degeneration and reticular macular disease are also associated with cardiovascular disease. Better understanding of the clinical and genetic risk factors for age-related macular degeneration and reticular macular disease has led to the hypothesis that these eye diseases are systemic. A systemic origin may help to explain why reticular disease is diagnosed more frequently in females as males suffer cardiovascular mortality at an earlier age, before the age of diagnosis of reticular macular disease and age-related macular degeneration.

  4. Cellular senescence in aging and age-related disease: from mechanisms to therapy

    PubMed Central

    Childs, Bennett G; Durik, Matej; Baker, Darren J; van Deursen, Jan M

    2016-01-01

    Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease, and it is an attractive target for therapeutic exploitation. A wealth of information about senescence in cultured cells has been acquired over the past half century; however, senescence in living organisms is poorly understood, largely because of technical limitations relating to the identification and characterization of senescent cells in tissues and organs. Furthermore, newly recognized beneficial signaling functions of senescence suggest that indiscriminately targeting senescent cells or modulating their secretome for anti-aging therapy may have negative consequences. Here we discuss current progress and challenges in understanding the stressors that induce senescence in vivo, the cell types that are prone to senesce, and the autocrine and paracrine properties of senescent cells in the contexts of aging and age-related diseases as well as disease therapy. PMID:26646499

  5. Cellular senescence in aging and age-related disease: from mechanisms to therapy.

    PubMed

    Childs, Bennett G; Durik, Matej; Baker, Darren J; van Deursen, Jan M

    2015-12-01

    Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease, and it is an attractive target for therapeutic exploitation. A wealth of information about senescence in cultured cells has been acquired over the past half century; however, senescence in living organisms is poorly understood, largely because of technical limitations relating to the identification and characterization of senescent cells in tissues and organs. Furthermore, newly recognized beneficial signaling functions of senescence suggest that indiscriminately targeting senescent cells or modulating their secretome for anti-aging therapy may have negative consequences. Here we discuss current progress and challenges in understanding the stressors that induce senescence in vivo, the cell types that are prone to senesce, and the autocrine and paracrine properties of senescent cells in the contexts of aging and age-related diseases as well as disease therapy.

  6. Chronic kidney disease: a clinical model of premature aging.

    PubMed

    Stenvinkel, Peter; Larsson, Tobias E

    2013-08-01

    Premature aging is a process associated with a progressive accumulation of deleterious changes over time, an impairment of physiologic functions, and an increase in the risk of disease and death. Regardless of genetic background, aging can be accelerated by the lifestyle choices and environmental conditions to which our genes are exposed. Chronic kidney disease is a common condition that promotes cellular senescence and premature aging through toxic alterations in the internal milieu. This occurs through several mechanisms, including DNA and mitochondria damage, increased reactive oxygen species generation, persistent inflammation, stem cell exhaustion, phosphate toxicity, decreased klotho expression, and telomere attrition. Because recent evidence suggests that both increased local signaling of growth factors (through the nutrient-sensing mammalian target of rapamycin) and decreased klotho expression are important modulators of aging, interventions that target these should be tested in this prematurely aged population.

  7. Immune aging, dysmetabolism, and inflammation in neurological diseases

    PubMed Central

    Deleidi, Michela; Jäggle, Madeline; Rubino, Graziella

    2015-01-01

    As we age, the immune system undergoes a process of senescence accompanied by the increased production of proinflammatory cytokines, a chronic subclinical condition named as “inflammaging”. Emerging evidence from human and experimental models suggest that immune senescence also affects the central nervous system and promotes neuronal dysfunction, especially within susceptible neuronal populations. In this review we discuss the potential role of immune aging, inflammation and metabolic derangement in neurological diseases. The discovery of novel therapeutic strategies targeting age-linked inflammation may promote healthy brain aging and the treatment of neurodegenerative as well as neuropsychiatric disorders. PMID:26089771

  8. Normal aging modulates prefrontoparietal networks underlying multiple memory processes

    PubMed Central

    Sambataro, Fabio; Safrin, Martin; Lemaitre, Herve S.; Steele, Sonya U.; Das, Saumitra B.; Callicott, Joseph H; Weinberger, Daniel R.; Mattay, Venkata S.

    2012-01-01

    Functional decline of brain regions underlying memory processing represents a hallmark of cognitive aging. Although a rich literature documents age-related differences in several memory domains, the effect of aging on networks that underlie multiple memory processes has been relatively unexplored. Here we used functional magnetic resonance imaging during working memory and incidental episodic encoding memory to investigate patterns of age-related differences in activity and functional covariance patterns common across multiple memory domains. Relative to younger subjects, older subjects showed increased activation in left dorso-lateral prefrontal cortex along with decreased deactivation in the posterior cingulate. Older subjects showed greater functional covariance during both memory tasks in a set of regions that included a positive prefronto-parietal-occipital networkas well as a negative network that spanned the default mode regions. These findings suggest that the memory process-invariant recruitment of brain regions within prefronto-parietal-occipital network increases with aging.Our results are in line with the dedifferentiation hypothesis of neurocognitive aging, thereby suggesting a decreased specialization of the brain networks supporting different memory networks. PMID:22909094

  9. Path dependence of lithium ion cells aging under storage conditions

    NASA Astrophysics Data System (ADS)

    Su, Laisuo; Zhang, Jianbo; Huang, Jun; Ge, Hao; Li, Zhe; Xie, Fengchao; Liaw, Bor Yann

    2016-05-01

    This work investigates path dependence of lithium ion cells that are stored under static and non-static conditions. In the static storage tests, the levels of temperature and state of charge (SOC) are kept constant. The results of 12 tests from a combination of three temperatures and four SOCs show that, as expected, the cell ages faster at higher temperature and higher SOC. However, the cell aging mode, while consistent for all the evaluated temperatures, is different at 95% SOC from that at lower SOCs. In the non-static storage tests, the levels of temperature and SOC vary with time during the test process. The effect of the sequence of stress levels on cell aging is studied statistically using the statistical method of analysis of variation (ANOVA). It is found that cell capacity fade is path independent of both SOC and temperature, while cell resistance increase is path dependent on SOC and path independent of temperature. Finally, rate-based empirical aging models are adopted to fit the cell aging in the static storage tests. The aging model for capacity fade is demonstrated to be applicable to the non-static tests with errors between -3% and +3% for all the tested conditions over 180 days.

  10. NADPH oxidase deficiency underlies dysfunction of aged CD8+ Tregs

    PubMed Central

    Wen, Zhenke; Shimojima, Yasuhiro; Shirai, Tsuyoshi; Li, Yinyin; Ju, Jihang; Yang, Zhen; Tian, Lu; Goronzy, Jörg J.

    2016-01-01

    Immune aging results in progressive loss of both protective immunity and T cell–mediated suppression, thereby conferring susceptibility to a combination of immunodeficiency and chronic inflammatory disease. Here, we determined that older individuals fail to generate immunosuppressive CD8+CCR7+ Tregs, a defect that is even more pronounced in the age-related vasculitic syndrome giant cell arteritis. In young, healthy individuals, CD8+CCR7+ Tregs are localized in T cell zones of secondary lymphoid organs, suppress activation and expansion of CD4 T cells by inhibiting the phosphorylation of membrane-proximal signaling molecules, and effectively inhibit proliferative expansion of CD4 T cells in vitro and in vivo. We identified deficiency of NADPH oxidase 2 (NOX2) as the molecular underpinning of CD8 Treg failure in the older individuals and in patients with giant cell arteritis. CD8 Tregs suppress by releasing exosomes that carry preassembled NOX2 membrane clusters and are taken up by CD4 T cells. Overexpression of NOX2 in aged CD8 Tregs promptly restored suppressive function. Together, our data support NOX2 as a critical component of the suppressive machinery of CD8 Tregs and suggest that repairing NOX2 deficiency in these cells may protect older individuals from tissue-destructive inflammatory disease, such as large-vessel vasculitis. PMID:27088800

  11. MicroRNAs in age-related diseases.

    PubMed

    Dimmeler, Stefanie; Nicotera, Pierluigi

    2013-02-01

    Aging is a complex process that is linked to an increased incidence of major diseases such as cardiovascular and neurodegenerative disease, but also cancer and immune disorders. MicroRNAs (miRNAs) are small non-coding RNAs, which post-transcriptionally control gene expression by inhibiting translation or inducing degradation of targeted mRNAs. MiRNAs target up to hundreds of mRNAs, thereby modulating gene expression patterns. Many miRNAs appear to be dysregulated during cellular senescence, aging and disease. However, only few miRNAs have been so far linked to age-related changes in cellular and organ functions. The present article will discuss these findings, specifically focusing on the cardiovascular and neurological systems.

  12. [Credibility of allegations of under age minors regarding sexual abuse].

    PubMed

    Hayez, J Y; Vervier, J F; Charlier, D

    1994-01-01

    When a child under age states he/she has been sexually abused, there seldom exists an objective certainty to support the allegation. Whereas clinicians know that a child who speaks spontaneously probably speaks the truth, it is nonetheless difficult to exclude the possibility of fabulating, lying or mistaking. The error probability is sharply increased when abuse is referred by a parent, specially in a context of parental separation. This article thus presents a review of criteria which help to better assess the truth or error of allegations. Criteria include analysis of the child's talk, application of projective techniques, observation of his/her behavior, etc. The author also describes some differential diagnoses based on the behaviors and sexual allegations of children under age. PMID:7878137

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

    PubMed Central

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

    2013-01-01

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

  14. Age impact on autoimmune thyroid disease in females

    NASA Astrophysics Data System (ADS)

    Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius

    2013-10-01

    Thyroid autoimmune disease, a widespread phenomenon in female population, impairs thyroid function during pregnancy. Identifying cases, which will develop hypothyroidism during pregnancy, is crucial in the follow-up process. The study group comprised 108 females, with ages between 20-40 years; with known inactive autoimmune thyroid disease, before pregnancy that became pregnant in the study follow-up period. They were monitored by means of clinical, hormonal and immunological assays. Supplemental therapy with thyroid hormones was used, where needed. Maternal age and level of anti-thyroid antibodies were used to predict thyroid functional impairment.

  15. Performance of bolted closure joint elastomers under cask aging conditions

    SciTech Connect

    Verst, C.; Sindelar, R.; Skidmore, E.; Daugherty, W.

    2015-07-23

    The bolted closure joint of a bare spent fuel cask is susceptible to age-related degradation and potential loss of confinement function under long-term storage conditions. Elastomeric seals, a component of the joint typically used to facilitate leak testing of the primary seal that includes the metallic seal and bolting, is susceptible to degradation over time by several mechanisms, principally via thermo-oxidation, stress-relaxation, and radiolytic degradation under time and temperature condition. Irradiation and thermal exposure testing and evaluation of an ethylene-propylene diene monomer (EPDM) elastomeric seal material similar to that used in the CASTOR® V/21 cask for a matrix of temperature and radiation exposure conditions relevant to the cask extended storage conditions, and development of semiempirical predictive models for loss of sealing force is in progress. A special insert was developed to allow Compressive Stress Relaxation (CSR) measurements before and after the irradiation and/or thermal exposure without unloading the elastomer. A condition of the loss of sealing force for the onset of leakage was suggested. The experimentation and modeling being performed could enable acquisition of extensive coupled aging data as well as an estimation of the timeframe when loss of sealing function under aging (temperature/radiation) conditions may occur.

  16. REST and stress resistance in ageing and Alzheimer's disease.

    PubMed

    Lu, Tao; Aron, Liviu; Zullo, Joseph; Pan, Ying; Kim, Haeyoung; Chen, Yiwen; Yang, Tun-Hsiang; Kim, Hyun-Min; Drake, Derek; Liu, X Shirley; Bennett, David A; Colaiácovo, Monica P; Yankner, Bruce A

    2014-03-27

    Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer's disease. Chromatin immunoprecipitation with deep sequencing and expression analysis show that REST represses genes that promote cell death and Alzheimer's disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid β-protein toxicity, and conditional deletion of REST in the mouse brain leads to age-related neurodegeneration. A functional orthologue of REST, Caenorhabditis elegans SPR-4, also protects against oxidative stress and amyloid β-protein toxicity. During normal ageing, REST is induced in part by cell non-autonomous Wnt signalling. However, in Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies, REST is lost from the nucleus and appears in autophagosomes together with pathological misfolded proteins. Finally, REST levels during ageing are closely correlated with cognitive preservation and longevity. Thus, the activation state of REST may distinguish neuroprotection from neurodegeneration in the ageing brain. PMID:24670762

  17. REST and stress resistance in ageing and Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Lu, Tao; Aron, Liviu; Zullo, Joseph; Pan, Ying; Kim, Haeyoung; Chen, Yiwen; Yang, Tun-Hsiang; Kim, Hyun-Min; Drake, Derek; Liu, X. Shirley; Bennett, David A.; Colaiácovo, Monica P.; Yankner, Bruce A.

    2014-03-01

    Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer's disease. Chromatin immunoprecipitation with deep sequencing and expression analysis show that REST represses genes that promote cell death and Alzheimer's disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid β-protein toxicity, and conditional deletion of REST in the mouse brain leads to age-related neurodegeneration. A functional orthologue of REST, Caenorhabditis elegans SPR-4, also protects against oxidative stress and amyloid β-protein toxicity. During normal ageing, REST is induced in part by cell non-autonomous Wnt signalling. However, in Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies, REST is lost from the nucleus and appears in autophagosomes together with pathological misfolded proteins. Finally, REST levels during ageing are closely correlated with cognitive preservation and longevity. Thus, the activation state of REST may distinguish neuroprotection from neurodegeneration in the ageing brain.

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

    PubMed

    Harel, Itamar; Brunet, Anne

    2015-01-01

    Why and how organisms age remains a mystery, and it defines one of the biggest challenges in biology. Aging is also the primary risk factor for many human pathologies, such as cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases. Thus, manipulating the aging rate and potentially postponing the onset of these devastating diseases could have a tremendous impact on human health. Recent studies, relying primarily on nonvertebrate short-lived model systems, have shown the importance of both genetic and environmental factors in modulating the aging rate. However, relatively little is known about aging in vertebrates or what processes may be unique and specific to these complex organisms. Here we discuss how advances in genomics and genome editing have significantly expanded our ability to probe the aging process in a vertebrate system. We highlight recent findings from a naturally short-lived vertebrate, the African turquoise killifish, which provides an attractive platform for exploring mechanisms underlying vertebrate aging and age-related diseases. PMID:26642856

  19. Perspective: Does brown fat protect against diseases of aging?

    PubMed

    Mattson, Mark P

    2010-01-01

    The most commonly studied laboratory rodents possess a specialized form of fat called brown adipose tissue (BAT) that generates heat to help maintain body temperature in cold environments. In humans, BAT is abundant during embryonic and early postnatal development, but is absent or present in relatively small amounts in adults where it is located in paracervical and supraclavicular regions. BAT cells can 'burn' fatty acid energy substrates to generate heat because they possess large numbers of mitochondria in which oxidative phosphorylation is uncoupled from ATP production as a result of a transmembrane proton leak mediated by uncoupling protein 1 (UCP1). Studies of rodents in which BAT levels are either increased or decreased have revealed a role for BAT in protection against diet-induced obesity. Data suggest that individuals with low levels of BAT are prone to obesity, insulin resistance and cardiovascular disease, whereas those with higher levels of BAT maintain lower body weights and exhibit superior health as they age. BAT levels decrease during aging, and dietary energy restriction increases BAT activity and protects multiple organ systems including the nervous system against age-related dysfunction and degeneration. Future studies in which the effects of specific manipulations of BAT levels and thermogenic activity on disease processes in animal models (diabetes, cardiovascular disease, cancers, neurodegenerative diseases) are determined will establish if and how BAT affects the development and progression of age-related diseases. Data from animal studies suggest that BAT and mitochondrial uncoupling can be targeted for interventions to prevent and treat obesity and age-related diseases. Examples include: diet and lifestyle changes; specific regimens of mild intermittent stress; drugs that stimulate BAT formation and activity; induction of brown adipose cell progenitors in muscle and other tissues; and transplantation of brown adipose cells.

  20. Diseases of Old Age in Two Paintings by Rembrandt

    PubMed Central

    Weisz, George M.; Albury, William R.

    2015-01-01

    Two paintings of older men by Rembrandt (1609–1669) are examined to demonstrate that historical attitudes toward diseases of old age and the ageing person’s response to illness can be investigated in paintings. The works selected are of different genres and date from different stages of Rembrandt’s own life, one from his youth and one from his old age. Both paintings show figures who have joint pathologies typically associated with the ageing process, the first involving the subject’s foot and the second involving the subject’s hand. Despite the sometimes painful nature of these conditions, the subjects are shown accommodating their illnesses while maintaining both their intellectual and social engagement and their emotional composure. Although the seventeenth century offered older people very little effective medical treatment in comparison with what is presently available, these paintings nevertheless present a view of illness as a subsidiary rather than a dominant feature of old age. PMID:26886771

  1. Diseases of Old Age in Two Paintings by Rembrandt.

    PubMed

    Weisz, George M; Albury, William R

    2015-10-26

    Two paintings of older men by Rembrandt (1609-1669) are examined to demonstrate that historical attitudes toward diseases of old age and the ageing person's response to illness can be investigated in paintings. The works selected are of different genres and date from different stages of Rembrandt's own life, one from his youth and one from his old age. Both paintings show figures who have joint pathologies typically associated with the ageing process, the first involving the subject's foot and the second involving the subject's hand. Despite the sometimes painful nature of these conditions, the subjects are shown accommodating their illnesses while maintaining both their intellectual and social engagement and their emotional composure. Although the seventeenth century offered older people very little effective medical treatment in comparison with what is presently available, these paintings nevertheless present a view of illness as a subsidiary rather than a dominant feature of old age.

  2. Emerging role of autophagy in kidney function, diseases and aging.

    PubMed

    Huber, Tobias B; Edelstein, Charles L; Hartleben, Björn; Inoki, Ken; Jiang, Man; Koya, Daisuke; Kume, Shinji; Lieberthal, Wilfred; Pallet, Nicolas; Quiroga, Alejandro; Ravichandran, Kameswaran; Susztak, Katalin; Yoshida, Sei; Dong, Zheng

    2012-07-01

    Autophagy is a highly conserved process that degrades cellular long-lived proteins and organelles. Accumulating evidence indicates that autophagy plays a critical role in kidney maintenance, diseases and aging. Ischemic, toxic, immunological, and oxidative insults can cause an induction of autophagy in renal epithelial cells modifying the course of various kidney diseases. This review summarizes recent insights on the role of autophagy in kidney physiology and diseases alluding to possible novel intervention strategies for treating specific kidney disorders by modifying autophagy. PMID:22692002

  3. Temporal evolution of age data under transient pumping conditions

    NASA Astrophysics Data System (ADS)

    Leray, S.; de Dreuzy, J.-R.; Aquilina, L.; Vergnaud-Ayraud, V.; Labasque, T.; Bour, O.; Le Borgne, T.

    2014-04-01

    While most age data derived from tracers have been analyzed in steady-state flow conditions, we determine their temporal evolution when starting a pumping. Our study is based on a model made up of a shallowly dipping aquifer overlain by a less permeable aquitard characteristic of the crystalline aquifer of Plœmeur (Brittany, France). Under a pseudo transient flow assumption (instantaneous shift between two steady-state flow fields), we solve the transport equation with a backward particle-tracking method and determine the temporal evolution of the concentrations at the pumping well of CFC-11, CFC-12, CFC-113 and SF6. Apparent ages evolve because of the modifications of the flow pattern and because of the non-linear evolution of the tracer atmospheric concentrations. To identify the respective role of these two causes, we propose two successive analyses. We first convolute residence time distributions initially arising at different times at the same sampling time. We secondly convolute one residence time distribution at various sampling times. We show that flow pattern modifications control the apparent ages evolution in the first pumping year when the residence time distribution is modified from a piston-like distribution to a much broader distribution. In the first pumping year, the apparent age evolution contains transient information that can be used to better constrain hydrogeological systems and slightly compensate for the small number of tracers. Later, the residence time distribution hardly evolves and apparent ages only evolve because of the tracer atmospheric concentrations. In this phase, apparent age time-series do not reflect any evolution in the flow pattern.

  4. Temporal evolution of age data under transient pumping conditions

    NASA Astrophysics Data System (ADS)

    Leray, S.; De Dreuzy, J.; Aquilina, L.; Vergnaud, V.; Labasque, T.; Bour, O.; Le Borgne, T.

    2013-12-01

    While most age data derived from tracers have been analyzed in steady-state flow conditions, we determine their temporal evolution under transient pumping conditions. Starting pumping in a well modifies the natural flow patterns induced by the topographical gradient to a mainly convergent flow to the well. Our study is based on a set of models made up of a shallowly dipping aquifer overlain by a less permeable aquitard. These settings are characteristic of the crystalline aquifer of Plœmeur (Brittany, France) located in a highly fractured zone at the contact between a granite and micaschists. Under a pseudo steady-state flow assumption (instantaneous shift between two steady-state flow fields), we solve the transport equation with a backward particle-tracking method and determine the temporal evolution of the concentrations at the pumping well of the four atmospheric tracers CFC 11, CFC 12, CFC 113 and SF6. We show that apparent ages deduced from these concentrations evolve both because of the flow patterns modifications and because of the non-linear evolution of the atmospheric tracer concentrations. Flow patterns modifications only intervene just after the start of pumping, when the initially piston-like residence time distribution is transformed to a broader distribution mixing residence times from a wide variety of flow lines. Later, while flow patterns and the supplying volume of the pumping well still evolve, the residence time distributions are hardly modified and apparent ages are solely altered by the non-linear atmospheric tracer concentrations that progressively modifies the weighting of the residence time distribution. These results are confirmed by the observations at the site of Plœmeur in the pumping area. First, long term chloride observations confirm the quick evolution of the flow patterns after the start of pumping. Second, posterior and more recent evolutions of apparent ages derived from CFCs are consistent with the modeling results revealing

  5. Childhood Misfortune as a Threat to Successful Aging: Avoiding Disease

    ERIC Educational Resources Information Center

    Schafer, Markus H.; Ferraro, Kenneth F.

    2012-01-01

    Purpose: The purpose of this study was to examine whether childhood misfortune reduces the likelihood of being disease free in adulthood. Design and Methods: This article used a sample of 3,000+ American adults, aged 25-74, who were first interviewed in 1995 and reinterviewed in 2005. Logistic regression was used to estimate the odds of avoiding…

  6. Aged and Diseased Neurons Get Lost in Transport.

    PubMed

    Tamburrino, Anna; Decressac, Mickael

    2016-04-01

    The maintenance of nucleocytoplasmic compartmentalization is essential for proper cellular function. Recent studies from the Gage and the Hipp labs report impairments in transport across the nuclear envelope in models of normal and pathological neuronal senescence, providing a mechanistic link between cerebral aging and neurodegenerative diseases. PMID:26970902

  7. Innate immunity and inflammation in ageing: a key for understanding age-related diseases

    PubMed Central

    Licastro, Federico; Candore, Giuseppina; Lio, Domenico; Porcellini, Elisa; Colonna-Romano, Giuseppina; Franceschi, Claudio; Caruso, Calogero

    2005-01-01

    The process of maintaining life for the individual is a constant struggle to preserve his/her integrity. This can come at a price when immunity is involved, namely systemic inflammation. Inflammation is not per se a negative phenomenon: it is the response of the immune system to the invasion of viruses or bacteria and other pathogens. During evolution the human organism was set to live 40 or 50 years; today, however, the immune system must remain active for much a longer time. This very long activity leads to a chronic inflammation that slowly but inexorably damages one or several organs: this is a typical phenomenon linked to ageing and it is considered the major risk factor for age-related chronic diseases. Alzheimer's disease, atherosclerosis, diabetes and even sarcopenia and cancer, just to mention a few – have an important inflammatory component, though disease progression seems also dependent on the genetic background of individuals. Emerging evidence suggests that pro-inflammatory genotypes are related to unsuccessful ageing, and, reciprocally, controlling inflammatory status may allow a better chance of successful ageing. In other words, age-related diseases are "the price we pay" for a life-long active immune system: this system has also the potential to harm us later, as its fine tuning becomes compromised. Our immune system has evolved to control pathogens, so pro-inflammatory responses are likely to be evolutionarily programmed to resist fatal infections with pathogens aggressively. Thus, inflammatory genotypes are an important and necessary part of the normal host responses to pathogens in early life, but the overproduction of inflammatory molecules might also cause immune-related inflammatory diseases and eventually death later. Therefore, low responder genotypes involved in regulation of innate defence mechanisms, might better control inflammatory responses and age-related disease development, resulting in an increased chance of long life survival

  8. Optic Nerve Head Biomechanics in Aging and Disease

    PubMed Central

    Downs, J. Crawford

    2015-01-01

    This nontechnical review is focused upon educating the reader on optic nerve head biomechanics in both aging and disease along two main themes: what is known about how mechanical forces and the resulting deformations are distributed in the posterior pole and ONH (biomechanics) and what is known about how the living system responds to those deformations (mechanobiology). We focus on how ONH responds to IOP elevations as a structural system, insofar as the acute mechanical response of the lamina cribrosa is confounded with the responses of the peripapillary sclera, prelaminar neural tissues, and retrolaminar optic nerve. We discuss the biomechanical basis for IOP-driven changes in connective tissues, blood flow, and cellular responses. We use glaucoma as the primary framework to present the important aspects of ONH biomechanics in aging and disease, as ONH biomechanics, aging, and the posterior pole extracellular matrix (ECM) are thought to be centrally involved in glaucoma susceptibility, onset and progression. PMID:25819451

  9. The endoplasmic reticulum stress response in aging and age-related diseases

    PubMed Central

    Brown, Marishka K.; Naidoo, Nirinjini

    2012-01-01

    The endoplasmic reticulum(ER) is a multifunctional organelle within which protein folding, lipid biosynthesis, and calcium storage occurs. Perturbations such as energy or nutrient depletion, disturbances in calcium or redox status that disrupt ER homeostasis lead to the misfolding of proteins, ER stress and up-regulation of several signaling pathways coordinately called the unfolded protein response (UPR). The UPR is characterized by the induction of chaperones, degradation of misfolded proteins and attenuation of protein translation. The UPR plays a fundamental role in the maintenance of cellular homeostasis and thus is central to normal physiology. However, sustained unresolved ER stress leads to apoptosis. Aging linked declines in expression and activity of key ER molecular chaperones and folding enzymes compromise proper protein folding and the adaptive response of the UPR. One mechanism to explain age associated declines in cellular functions and age-related diseases is a progressive failure of chaperoning systems. In many of these diseases, proteins or fragments of proteins convert from their normally soluble forms to insoluble fibrils or plaques that accumulate in a variety of organs including the liver, brain or spleen. This group of diseases, which typically occur late in life includes Alzheimer's, Parkinson's, type II diabetes and a host of less well known but often equally serious conditions such as fatal familial insomnia. The UPR is implicated in many of these neurodegenerative and familial protein folding diseases as well as several cancers and a host of inflammatory diseases including diabetes, atherosclerosis, inflammatory bowel disease and arthritis. This review will discuss age-related changes in the ER stress response and the role of the UPR in age-related diseases. PMID:22934019

  10. Translocator protein (TSPO) role in aging and Alzheimer's disease.

    PubMed

    Repalli, Jayanthi

    2014-01-01

    Cellular damage and deregulated apoptotic cell death lead to functional impairment, and a main consequence of these events is aging. Cellular damage is initiated by different stress/risk factors such as oxidative stress, inflammation, and heavy metals. These stress/risk factors affect the cellular homeostasis by altering methylation status of several aging and Alzheimer's disease associated genes; these effects can be manifested immediately after exposure to stress and at later stages of life. However, when cellular damage exceeds certain threshold levels apoptosis is initiated. This review discusses the stress factors involved in cellular damage and the role and potential of TSPO-mediated cell death in aging as well as in Alzheimer's disease, which is also characterized by extensive cell death. Mitochondrial-mediated apoptotic death through the release of cytochrome c is regulated by TSPO, and increased expression of this protein is observed in both elderly people and in patients with Alzheimer's disease. TSPO forms and mediates opening of the mitochondrial membrane pore, mPTP and oxidizes cardiolipin, and these events lead to the leakage of apoptotic death mediators, such as cytochrome c, resulting in cell death. However, TSPO has many proposed functions and can also increase steroid synthesis, which leads to inhibition of inflammation and inhibition of the release of apoptotic factors, thereby decreasing cell damage and promoting cell survival. Thus, TSPO mediates apoptosis and decreases the cell damage, which in turn dictates the process of aging as well as the functionality of organs such as the brain. TSPO modulation with ligands in the Alzheimer's disease mouse model showed improvement in behavioral symptoms, and studies in Drosophila species showed increased cell survival and prolonged lifespan in flies after TSPO inhibition. These data suggest that since effects/signs of stress can manifest at any time, prevention through change in lifestyle and TSPO

  11. Electroencephalographic Fractal Dimension in Healthy Ageing and Alzheimer's Disease.

    PubMed

    Smits, Fenne Margreeth; Porcaro, Camillo; Cottone, Carlo; Cancelli, Andrea; Rossini, Paolo Maria; Tecchio, Franca

    2016-01-01

    Brain activity is complex; a reflection of its structural and functional organization. Among other measures of complexity, the fractal dimension is emerging as being sensitive to neuronal damage secondary to neurological and psychiatric diseases. Here, we calculated Higuchi's fractal dimension (HFD) in resting-state eyes-closed electroencephalography (EEG) recordings from 41 healthy controls (age: 20-89 years) and 67 Alzheimer's Disease (AD) patients (age: 50-88 years), to investigate whether HFD is sensitive to brain activity changes typical in healthy aging and in AD. Additionally, we considered whether AD-accelerating effects of the copper fraction not bound to ceruloplasmin (also called "free" copper) are reflected in HFD fluctuations. The HFD measure showed an inverted U-shaped relationship with age in healthy people (R2 = .575, p < .001). Onset of HFD decline appeared around the age of 60, and was most evident in central-parietal regions. In this region, HFD decreased with aging stronger in the right than in the left hemisphere (p = .006). AD patients demonstrated reduced HFD compared to age- and education-matched healthy controls, especially in temporal-occipital regions. This was associated with decreasing cognitive status as assessed by mini-mental state examination, and with higher levels of non-ceruloplasmin copper. Taken together, our findings show that resting-state EEG complexity increases from youth to maturity and declines in healthy, aging individuals. In AD, brain activity complexity is further reduced in correlation with cognitive impairment. In addition, elevated levels of non-ceruloplasmin copper appear to accelerate the reduction of neural activity complexity. Overall, HDF appears to be a proper indicator for monitoring EEG-derived brain activity complexity in healthy and pathological aging. PMID:26872349

  12. Electroencephalographic Fractal Dimension in Healthy Ageing and Alzheimer's Disease.

    PubMed

    Smits, Fenne Margreeth; Porcaro, Camillo; Cottone, Carlo; Cancelli, Andrea; Rossini, Paolo Maria; Tecchio, Franca

    2016-01-01

    Brain activity is complex; a reflection of its structural and functional organization. Among other measures of complexity, the fractal dimension is emerging as being sensitive to neuronal damage secondary to neurological and psychiatric diseases. Here, we calculated Higuchi's fractal dimension (HFD) in resting-state eyes-closed electroencephalography (EEG) recordings from 41 healthy controls (age: 20-89 years) and 67 Alzheimer's Disease (AD) patients (age: 50-88 years), to investigate whether HFD is sensitive to brain activity changes typical in healthy aging and in AD. Additionally, we considered whether AD-accelerating effects of the copper fraction not bound to ceruloplasmin (also called "free" copper) are reflected in HFD fluctuations. The HFD measure showed an inverted U-shaped relationship with age in healthy people (R2 = .575, p < .001). Onset of HFD decline appeared around the age of 60, and was most evident in central-parietal regions. In this region, HFD decreased with aging stronger in the right than in the left hemisphere (p = .006). AD patients demonstrated reduced HFD compared to age- and education-matched healthy controls, especially in temporal-occipital regions. This was associated with decreasing cognitive status as assessed by mini-mental state examination, and with higher levels of non-ceruloplasmin copper. Taken together, our findings show that resting-state EEG complexity increases from youth to maturity and declines in healthy, aging individuals. In AD, brain activity complexity is further reduced in correlation with cognitive impairment. In addition, elevated levels of non-ceruloplasmin copper appear to accelerate the reduction of neural activity complexity. Overall, HDF appears to be a proper indicator for monitoring EEG-derived brain activity complexity in healthy and pathological aging.

  13. Molecular mechanisms underlying the onset of degenerative aortic valve disease.

    PubMed

    Hakuno, Daihiko; Kimura, Naritaka; Yoshioka, Masatoyo; Fukuda, Keiichi

    2009-01-01

    Morbidity from degenerative aortic valve disease is increasing worldwide, concomitant with the ageing of the general population and the habitual consumption of diets high in calories and cholesterol. Immunohistologic studies have suggested that the molecular mechanism occurring in the degenerate aortic valve resembles that of atherosclerosis, prompting the testing of HMG CoA reductase inhibitors (statins) for the prevention of progression of native and bioprosthetic aortic valve degeneration. However, the effects of these therapies remain controversial. Although the molecular mechanisms underlying the onset of aortic valve degeneration are largely unknown, research in this area is advancing rapidly. The signaling components involved in embryonic valvulogenesis, such as Wnt, TGF-beta(1), BMP, and Notch, are also involved in the onset of aortic valve degeneration. Furthermore, investigations into extracellular matrix remodeling, angiogenesis, and osteogenesis in the aortic valve have been reported. Having noted avascularity of normal cardiac valves, we recently identified chondromodulin-I (chm-I) as a crucial anti-angiogenic factor. The expression of chm-I is restricted to cardiac valves from late embryogenesis to adulthood in the mouse, rat, and human. In human degenerate atherosclerotic valves, the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases and angiogenesis is observed in the area of chm-I downregulation. Gene targeting of chm-I resulted in VEGF expression, angiogenesis, and calcification in the aortic valves of aged mice, and aortic stenosis is detected by echocardiography, indicating that chm-I is a crucial factor for maintaining normal cardiac valvular function by preventing angiogenesis. The present review focuses on the animal models of aortic valve degeneration and recent studies on the molecular mechanisms underlying the onset of degenerative aortic valve disease. PMID:18766323

  14. Fatigue in inflammatory bowel diseases: relationship with age and disease activity.

    PubMed

    Pellino, Gianluca; Sciaudone, Guido; Caserta, Violetta; Candilio, Giuseppe; De Fatico, G Serena; Gagliardi, Silvana; Landino, Isabella; Patturelli, Marta; Riegler, Gabriele; Di Caprio, Ester Livia; Canonico, Silvestro; Gritti, Paolo; Selvaggi, Francesco

    2014-01-01

    A higher rate of patients suffering from inflammatory bowel diseases (IBD) are reported to experience the symptom of fatigue compared with general population. Fatigue can impair quality of life of IBD patients by limiting their daily functioning. However, this problem is poorly understood and addressed. Our aim was to investigate the impact of fatigue in IBD patients compared with controls, and to seek for relation between age and disease activity. IBD patients aged between 16 and 75 years observed at our Unit from June 2011 through June 2012 were evaluated for fatigue. Patients were asked to fill the fatigue impact scale (FIS) questionnaire. A cohort of age- and sex-matched patients observed for other-than-IBD diseases were prospectively enrolled to act as controls. Patients diagnosed with malignancies were excluded from evaluation. Each group included 16 patients, of whom half aged over 65 years. Fatigue was more severe in IBD patients than in controls (p = 0.02), irrespective of age and disease activity. IBD patients with moderate to severe disease activity showed worse fatigue compared with controls at any age (p < 0.0001). Young IBD patients with low disease activity showed a trend toward worse FIS score when compared with old IBD counterparts (p = 0.06). IBD significantly impacted on fatigue in our series. Considering IBD patients in remission, younger patients may experience worse fatigue. Further studies are needed to explore the effects of fatigue on quality of life and the potential of appropriate intervention strategies.

  15. 42 CFR 435.308 - Medically needy coverage of individuals under age 21.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Medically needy coverage of individuals under age....308 Medically needy coverage of individuals under age 21. (a) If the agency provides Medicaid to the medically needy, it may provide Medicaid to individuals under age 21 (or, at State option, under age 20,...

  16. 42 CFR 436.308 - Medically needy coverage of individuals under age 21.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Medically needy coverage of individuals under age... individuals under age 21. (a) If the agency provides Medicaid to the medically needy, it may provide Medicaid to individuals under age 21 (or at State option, under age 20, 19, or 18) as specified in...

  17. The Biology of Proteostasis in Aging and Disease

    PubMed Central

    Labbadia, Johnathan; Morimoto, Richard I.

    2015-01-01

    Loss of protein homeostasis (proteostasis) is a common feature of aging and disease that is characterized by the appearance of nonnative protein aggregates in various tissues. Protein aggregation is routinely suppressed by the proteostasis network (PN), a collection of macromolecular machines that operate in diverse ways to maintain proteome integrity across subcellular compartments and between tissues to ensure a healthy life span. Here, we review the composition, function, and organizational properties of the PN in the context of individual cells and entire organisms and discuss the mechanisms by which disruption of the PN, and related stress response pathways, contributes to the initiation and progression of disease. We explore emerging evidence that disease susceptibility arises from early changes in the composition and activity of the PN and propose that a more complete understanding of the temporal and spatial properties of the PN will enhance our ability to develop effective treatments for protein conformational diseases. PMID:25784053

  18. The Immunoproteasome in oxidative stress, aging, and disease.

    PubMed

    Johnston-Carey, Helen K; Pomatto, Laura C D; Davies, Kelvin J A

    2015-01-01

    The Immunoproteasome has traditionally been viewed primarily for its role in peptide production for antigen presentation by the major histocompatibility complex, which is critical for immunity. However, recent research has shown that the Immunoproteasome is also very important for the clearance of oxidatively damaged proteins in homeostasis, and especially during stress and disease. The importance of the Immunoproteasome in protein degradation has become more evident as diseases characterized by protein aggregates have also been linked to deficiencies of the Immunoproteasome. Additionally, there are now diseases defined by mutations or polymorphisms within Immunoproteasome-specific subunit genes, further suggesting its crucial role in cytokine signaling and protein homeostasis (or "proteostasis"). The purpose of this review is to highlight our growing understanding of the importance of the Immunoproteasome in the management of protein quality control, and the detrimental impact of its dysregulation during disease and aging. PMID:27098648

  19. Managing nut genetic resources under disease threat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The USDA ARS, National Clonal Germplasm Repository (NCGR) Corvallis, Oregon, is assigned to preserve genetic resources of hazelnuts (Corylus L.) and butternuts (Juglans cinerea L.). Both crops are threatened by fungal diseases. Hazelnuts are challenged by Eastern filbert blight (EFB) [caused by Anis...

  20. [The relationship between the polymorphism of immunity genes and both aging and age-related diseases].

    PubMed

    Ruan, Qing-Wei; Yu, Zhuo-Wei; Bao, Zhi-Jun; Ma, Yong-Xing

    2013-07-01

    Aging is acommon, progressive and irreversible state of multi-cell dysfunction. Immune aging mainly includes the declines of regenerative capacity and lymphoid lineage differentiation potential, the hyporesponsive to infection and vaccination, the hyperresponsive in the context of inflammatory pathology, and the increased risk of autoimmunity. The dysfunction of aged immune system accelerates the occurrence of aging and age-related diseases. The mutation of immunity genes that affect immune responses accelerates or slows aging process and age-related diseases. The frequencies of acquired immunity genes, such as immune protective HLA II DRB1*11 and DRB*16-associated haplotype, are increased in the longevity populations. The increased susceptibility of immune inflammatory response, morbidity and mortality in the elderly is often associated with decreased frequencies of anti-inflammatory factor IL-10 -1082G allele, TNF-β1 haplotype cnd10T/C, cnd25G/G, -988C/C, -800G/A, low proinflammatory fator TNFa level related extended TNF-A genotype -1031C/C, -863C/A, -857C/C, IL-6-174 CC and IFN-γ+874 T allele as well. The innate immunity genes, such as highly expressed anti-inflammatory +896 G KIR4 allele, CCR5Δ32 variant, -765 C Cox-2 allele, -1708 G and 21 C 5-Lox alleles are detected in centenarians. In age-related diseases, a higher CMV-specific IgG antibody level in elderly individuals is associated with a decreased frequency of KIR haplotypes KIR2DS5 and A1B10 and an increased frequency of MBL2 haplotypes LYPB, LYQC and HYPD that result in the absence of MBL2 protein. The increased frequencies of CRP ATG haplotypes and CFH 402 His allele indicate high mortality in the elderly. In the present study, we review the advances in the polymorphism and haplotype of innate and adoptive immunity genes, and their association with both aging and age-related diseases. To strengthen the analysis of extended haplotypes, epigenetic studies of immunity genes and genetic study of

  1. [Suicide attempts in children under 12 years of age].

    PubMed

    Stordeur, C; Acquaviva, E; Galdon, L; Mercier, J-C; Titomanlio, L; Delorme, R

    2015-03-01

    Suicide attempts (SA) in children are often considered rare and poorly studied. The aim of this study was to explore the clinical characteristics of SA in children under 12 years of age. A retrospective assessment was conducted in 30 consecutive SAs reported in children under 12 years of age admitted to the emergency department at the Robert-Debré University Hospital (Paris, France) from 2007 to 2010 and the Regional University Hospital (Besançon, France) from 2000 to 2008. All suicide attempters were directly assessed at the somatic and psychiatric level. Patients were 8-11 years old (mean, 10.2±0.8). The sex ratio was 0.9 boys for 1 girl. The leading SA methods were poisoning by medication (53.3%), hanging or strangulation (23.3%), jumping from a height (16.7%), poisoning by chemicals (3.3%), and lesions inflicted by sharp objects (3.3%). In addition, SAs were characterized by high lethality (43.7%) contrasting with their low to moderate suicidal intentionality (43.8% and 56.2%, respectively). In conclusion, we reported that SA in children differs from those of adolescents by their greater lethality related to the methods used, but contrasting with the low intentionality mentioned by these patients.

  2. Striatal function in normal aging: Implications for Parkinson's disease

    SciTech Connect

    Sawle, G.V.; Colebatch, J.G.; Shah, A.; Brooks, D.J.; Marsden, C.D.; Frackowiak, R.S. )

    1990-12-01

    Central to several current theories of the etiology of Parkinson's disease is the premise that the nigrostriatal dopaminergic system degenerates with normal aging. Much of the evidence for this assertion has come from postmortem neurochemical studies. We have used L-6-({sup 18}F) fluoro-Dopa and positron emission tomography in 26 healthy volunteers (age range, 27-76 years) to examine striatal and frontal cortical tracer uptake. Data have been analyzed by using a graphical approach to calculate an influx constant (Ki) for L-6-({sup 18}F)fluoro-Dopa uptake into the caudate, putamen, and medial frontal cortex of each subject. In the population studied, there was no decline in Ki with age for any of these structures. A series of physiological measurements made on the older subjects also showed few significant changes with age. The positron emission tomographic findings demonstrate preservation of nigrostriatal dopaminergic function in normal aging. The pathological process causing Parkinson's disease may operate closer to the time of presentation than has been suggested.

  3. Parabiosis for the study of age-related chronic disease

    PubMed Central

    Eggel, Alexander; Wyss-Coray, Tony

    2014-01-01

    Summary Modern medicine wields the power to treat large numbers of diseases and injuries most of us would have died from just a hundred years ago. In view of this tremendous achievement, it can seem as if progress has slowed, and we have been unable to impact the most devastating diseases of our time. Chronic diseases of age such as cardiovascular disease, diabetes, osteoarthritis, or Alzheimer’s disease turn out to be of a complexity that may require transformative ideas and paradigms to understand and treat them. Parabiosis, which mimics aspects of the naturally occurring shared blood supply in conjoined twins in humans and certain animals, may just have the power to be such a transformative experimental paradigm. Forgotten and now shunned in many countries, it has contributed to major breakthroughs in tumor biology, endocrinology, and transplantation research in the past century, and a set of new studies in the US and Britain report stunning advances in stem cell biology and tissue regeneration using parabiosis between young and old mice. We review here briefly the history of parabiosis and discuss its utility to study physiological and pathophysiological processes. We argue that parabiosis is a technique that should enjoy wider acceptance and application, and that policies should be revisited especially if one is to study complex age-related, chronic disorders. PMID:24496774

  4. The microbiota and microbiome in aging: potential implications in health and age-related diseases.

    PubMed

    Zapata, Heidi J; Quagliarello, Vincent J

    2015-04-01

    Advances in bacterial deoxyribonucleic acid sequencing allow for characterization of the human commensal bacterial community (microbiota) and its corresponding genome (microbiome). Surveys of healthy adults reveal that a signature composite of bacteria characterizes each unique body habitat (e.g., gut, skin, oral cavity, vagina). A myriad of clinical changes, including a basal proinflammatory state (inflamm-aging), that directly interface with the microbiota of older adults and enhance susceptibility to disease accompany aging. Studies in older adults demonstrate that the gut microbiota correlates with diet, location of residence (e.g., community dwelling, long-term care settings), and basal level of inflammation. Links exist between the microbiota and a variety of clinical problems plaguing older adults, including physical frailty, Clostridium difficile colitis, vulvovaginal atrophy, colorectal carcinoma, and atherosclerotic disease. Manipulation of the microbiota and microbiome of older adults holds promise as an innovative strategy to influence the development of comorbidities associated with aging.

  5. The Marmoset as a Model of Aging and Age-Related Diseases

    PubMed Central

    Tardif, Suzette D.; Mansfield, Keith G.; Ratnam, Rama; Ross, Corinna N.; Ziegler, Toni E.

    2013-01-01

    The common marmoset (Callithrix jacchus) is poised to become a standard nonhuman primate aging model. With an average lifespan of 5 to 7 years and a maximum lifespan of 16.5 years, marmosets are the shortest-lived anthropoid primates. They display age-related changes in pathologies that mirror those seen in humans, such as cancer, amyloidosis, diabetes, and chronic renal disease. They also display predictable age-related differences in lean mass, calf circumference, circulating albumin, hemoglobin, and hematocrit. Features of spontaneous sensory and neurodegenerative change—for example, reduced neurogenesis, β-amyloid deposition in the cerebral cortex, loss of calbindin D28k binding, and evidence of presbycusis—appear between the ages of 7 and 10 years. Variation among colonies in the age at which neurodegenerative change occurs suggests the interesting possibility that marmosets could be specifically managed to produce earlier versus later occurrence of degenerative conditions associated with differing rates of damage accumulation. In addition to the established value of the marmoset as a model of age-related neurodegenerative change, this primate can serve as a model of the integrated effects of aging and obesity on metabolic dysfunction, as it displays evidence of such dysfunction associated with high body weight as early as 6 to 8 years of age. PMID:21411858

  6. Mitochondrial DNA mutations in ageing and disease: implications for HIV?

    PubMed

    Payne, Brendan A I; Gardner, Kristian; Chinnery, Patrick F

    2015-01-01

    Mitochondrial DNA (mtDNA) mutations cause neurological and multisystem disease. Somatic (acquired) mtDNA mutations are also associated with degenerative diseases and with normal human ageing. It is well established that certain nucleoside reverse transcriptase inhibitor (NRTI) antiretroviral drugs cause inhibition of the mtDNA polymerase, pol γ, leading to a reduction in mtDNA content (depletion). Given this effect of NRTI therapy on mtDNA replication, it is plausible that NRTI treatment may also lead to increased mtDNA mutations. Here we review recent evidence for an effect of HIV infection or NRTI therapy on mtDNA mutations, as well as discussing the methodological challenges in addressing this question. Finally, we discuss the possible implications for HIV-infected persons, with particular reference to ageing.

  7. Benefits from dietary polyphenols for brain aging and Alzheimer's disease.

    PubMed

    Rossi, L; Mazzitelli, S; Arciello, M; Capo, C R; Rotilio, G

    2008-12-01

    Brain aging and the most diffused neurodegenerative diseases of the elderly are characterized by oxidative damage, redox metals homeostasis impairment and inflammation. Food polyphenols can counteract these alterations in vitro and are therefore suggested to have potential anti-aging and brain-protective activities, as also indicated by the results of some epidemiological studies. Despite the huge and increasing amount of the in vitro studies trying to unravel the mechanisms of action of dietary polyphenols, the research in this field is still incomplete, and questions about bioavailability, biotransformation, synergism with other dietary factors, mechanisms of the antioxidant activity, risks inherent to their possible pro-oxidant activities are still unanswered. Most of all, the capacity of the majority of these compounds to cross the blood-brain barrier and reach brain is still unknown. This commentary discusses recent data on these aspects, particularly focusing on effects of curcumin, resveratrol and catechins on Alzheimer's disease.

  8. Independent Role of Underlying Kidney Disease on Renal Prognosis of Patients with Chronic Kidney Disease under Nephrology Care

    PubMed Central

    De Nicola, Luca; Provenzano, Michele; Chiodini, Paolo; Borrelli, Silvio; Garofalo, Carlo; Pacilio, Mario; Liberti, Maria Elena; Sagliocca, Adelia; Conte, Giuseppe; Minutolo, Roberto

    2015-01-01

    Primary kidney disease is suggested to affect renal prognosis of CKD patients; however, whether nephrology care modifies this association is unknown. We studied patients with CKD stage I-IV treated in a renal clinic and with established diagnosis of CKD cause to evaluate whether the risk of renal event (composite of end-stage renal disease and eGFR decline ≥40%) linked to the specific diagnosis is modified by the achievement or maintenance in the first year of nephrology care of therapeutic goals for hypertension (BP ≤130/80 mmHg in patients with proteinuria ≥150 mg/24h and/or diabetes and ≤140/90 in those with proteinuria <150 mg/24h and without diabetes) anemia (hemoglobin, Hb ≥11 g/dL), and proteinuria (≤0.5 g/24h). Survival analysis started after first year of nephrology care. We studied 729 patients (age 64±15 y; males 59.1%; diabetes 34.7%; cardiovascular disease (CVD) 44.9%; hypertensive nephropathy, HTN 53.8%; glomerulonephritis, GN 17.3%; diabetic nephropathy, DN 15.9%; tubule-interstitial nephropathy, TIN 9.5%; polycystic kidney disease, PKD 3.6%). During first year of Nephrology care, therapy was overall intensified in most patients and prevalence of main therapeutic goals generally improved. During subsequent follow up (median 3.3 years, IQR 1.9-5.1), 163 renal events occurred. Cox analysis disclosed a higher risk for PKD (Hazard Ratio 5.46, 95% Confidence Intervals 2.28–10.6) and DN (1.28,2.99–3.05), versus HTN (reference), independently of age, gender, CVD, BMI, eGFR or CKD stage, use of RAS inhibitors and achievement or maintenance in the first year of nephrology care of each of the three main therapeutic goals. No interaction was found on the risk of CKD progression between diagnostic categories and month-12 eGFR (P=0.737), as with control of BP (P=0.374), Hb (P=0.248) or proteinuria (P=0.590). Therefore, in CKD patients under nephrology care, diagnosis of kidney disease should be considered in conjunction with the main risk factors

  9. The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases.

    PubMed

    Maessen, Dionne E M; Stehouwer, Coen D A; Schalkwijk, Casper G

    2015-06-01

    The formation and accumulation of advanced glycation endproducts (AGEs) are related to diabetes and other age-related diseases. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is the major precursor in the formation of AGEs. MGO is mainly formed as a byproduct of glycolysis. Under physiological circumstances, MGO is detoxified by the glyoxalase system into D-lactate, with glyoxalase I (GLO1) as the key enzyme in the anti-glycation defence. New insights indicate that increased levels of MGO and the major MGO-derived AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1), and dysfunctioning of the glyoxalase system are linked to several age-related health problems, such as diabetes, cardiovascular disease, cancer and disorders of the central nervous system. The present review summarizes the mechanisms through which MGO is formed, its detoxification by the glyoxalase system and its effect on biochemical pathways in relation to the development of age-related diseases. Although several scavengers of MGO have been developed over the years, therapies to treat MGO-associated complications are not yet available for application in clinical practice. Small bioactive inducers of GLO1 can potentially form the basis for new treatment strategies for age-related disorders in which MGO plays a pivotal role.

  10. Principles and practice of hormetic treatment of aging and age-related diseases.

    PubMed

    Rattan, Suresh Is

    2008-02-01

    Aging is characterized by stochastic accumulation of molecular damage, progressive failure of maintenance and repair, and consequent onset of age-related diseases. Applying hormesis in aging research and therapy is based on the principle of stimulation of maintenance and repair pathways by repeated exposure to mild stress. Studies on the beneficial biological effects of repeated mild heat shock on human cells in culture, and other studies on the anti-aging and life-prolonging effects of proxidants, hypergravity, irradiation and ethanol on cells and organisms suggest that hormesis as an antiaging and gerontomodulatory approach has a promising future. Its clinical applications include prevention and treatment of diabetes, cataract, osteoporosis, dementia and some cancers.

  11. Metabolomics of human brain aging and age-related neurodegenerative diseases.

    PubMed

    Jové, Mariona; Portero-Otín, Manuel; Naudí, Alba; Ferrer, Isidre; Pamplona, Reinald

    2014-07-01

    Neurons in the mature human central nervous system (CNS) perform a wide range of motor, sensory, regulatory, behavioral, and cognitive functions. Such diverse functional output requires a great diversity of CNS neuronal and non-neuronal populations. Metabolomics encompasses the study of the complete set of metabolites/low-molecular-weight intermediates (metabolome), which are context-dependent and vary according to the physiology, developmental state, or pathologic state of the cell, tissue, organ, or organism. Therefore, the use of metabolomics can help to unravel the diversity-and to disclose the specificity-of metabolic traits and their alterations in the brain and in fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of aging and neurodegenerative diseases. Here, we review the current applications of metabolomics in studies of CNS aging and certain age-related neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Neurometabolomics will increase knowledge of the physiologic and pathologic functions of neural cells and will place the concept of selective neuronal vulnerability in a metabolic context.

  12. Eyeblink classical conditioning differentiates normal aging from Alzheimer's disease.

    PubMed

    Woodruff-Pak, D S

    2001-01-01

    Eyeblink classical conditioning is a useful paradigm for the study of the neurobiology of learning, memory, and aging, which also has application in the differential diagnosis of neurodegenerative diseases expressed in advancing age. Converging evidence from studies of eyeblink conditioning in neurological patients and brain imaging in normal adults document parallels in the neural substrates of this form of associative learning in humans and non-human mammals. Age differences in the short-delay procedure (400 ms CS-US interval) appear in middle age in humans and may be caused at least in part by cerebellar cortical changes such as loss of Purkinje cells. Whereas the hippocampus is not essential for conditioning in the delay procedure, disruption of hippocampal cholinergic neurotransmission impairs acquisition and slows the rate of learning. Alzheimer's disease (AD) profoundly disrupts the hippocampaL cholinergic system, and patients with AD consistently perform poorly in eyeblink conditioning. We hypothesize that disruption of hippocampal cholinergic pathways in AD in addition to age-associated Purkinje cell loss results in severely impaired eyeblink conditioning. The earliest pathology in AD occurs in entorhinal cortical input to hippocampus, and eyeblink conditioning may detect this early disruption before declarative learning and memory circuits become impaired. A case study is presented in which eyeblink conditioning detected impending dementia six years before changes on other screening tests indicated impairment. Because eyeblink conditioning is simple, non-threatening, and non-invasive, it may become a useful addition to test batteries designed to differentiate normal aging from mild cognitive impairment that progresses to AD and AD from other types of dementia.

  13. Scurvy in pediatric age group – A disease often forgotten?

    PubMed Central

    Agarwal, Anil; Shaharyar, Abbas; Kumar, Anubrat; Bhat, Mohd Shafi; Mishra, Madhusudan

    2015-01-01

    Scurvy is caused by prolonged severe dietary deficiency of vitamin C. Being rare as compared to other nutritional deficiencies, it is seldom suspected and this frequently leads to delayed recognition of this disorder. Children with abnormal dietary habits, mental illness or physical disabilities are prone to develop this disease. The disease spectrum of scurvy is quite varied and includes dermatological, dental, bone and systemic manifestations. Subperiosteal hematoma, ring epiphysis, metaphyseal white line and rarefaction zone along with epiphyseal slips are common radiological findings. High index of suspicion, detailed history and bilateral limb radiographs aids physician in diagnosing this eternal masquerader. We searched Pubmed for recent literature (2009–2014) with search terms “scurvy” “vitamin C deficiency” “ascorbic acid deficiency” “scurvy and children” “scurvy and pediatric age group”. There were a total of 36 articles relevant to pediatric scurvy in children (7 reviews and 29 case reports) which were retrieved. The review briefly recapitulates the role of vitamin C, the various disease manifestations and the treatment of scurvy to create awareness of the disease which still is reported from our country, although sporadically. The recent advances related to scurvy and its management in pediatric age group are also incorporated. PMID:25983516

  14. Scurvy in pediatric age group - A disease often forgotten?

    PubMed

    Agarwal, Anil; Shaharyar, Abbas; Kumar, Anubrat; Bhat, Mohd Shafi; Mishra, Madhusudan

    2015-06-01

    Scurvy is caused by prolonged severe dietary deficiency of vitamin C. Being rare as compared to other nutritional deficiencies, it is seldom suspected and this frequently leads to delayed recognition of this disorder. Children with abnormal dietary habits, mental illness or physical disabilities are prone to develop this disease. The disease spectrum of scurvy is quite varied and includes dermatological, dental, bone and systemic manifestations. Subperiosteal hematoma, ring epiphysis, metaphyseal white line and rarefaction zone along with epiphyseal slips are common radiological findings. High index of suspicion, detailed history and bilateral limb radiographs aids physician in diagnosing this eternal masquerader. We searched Pubmed for recent literature (2009-2014) with search terms "scurvy" "vitamin C deficiency" "ascorbic acid deficiency" "scurvy and children" "scurvy and pediatric age group". There were a total of 36 articles relevant to pediatric scurvy in children (7 reviews and 29 case reports) which were retrieved. The review briefly recapitulates the role of vitamin C, the various disease manifestations and the treatment of scurvy to create awareness of the disease which still is reported from our country, although sporadically. The recent advances related to scurvy and its management in pediatric age group are also incorporated. PMID:25983516

  15. Scurvy in pediatric age group - A disease often forgotten?

    PubMed

    Agarwal, Anil; Shaharyar, Abbas; Kumar, Anubrat; Bhat, Mohd Shafi; Mishra, Madhusudan

    2015-06-01

    Scurvy is caused by prolonged severe dietary deficiency of vitamin C. Being rare as compared to other nutritional deficiencies, it is seldom suspected and this frequently leads to delayed recognition of this disorder. Children with abnormal dietary habits, mental illness or physical disabilities are prone to develop this disease. The disease spectrum of scurvy is quite varied and includes dermatological, dental, bone and systemic manifestations. Subperiosteal hematoma, ring epiphysis, metaphyseal white line and rarefaction zone along with epiphyseal slips are common radiological findings. High index of suspicion, detailed history and bilateral limb radiographs aids physician in diagnosing this eternal masquerader. We searched Pubmed for recent literature (2009-2014) with search terms "scurvy" "vitamin C deficiency" "ascorbic acid deficiency" "scurvy and children" "scurvy and pediatric age group". There were a total of 36 articles relevant to pediatric scurvy in children (7 reviews and 29 case reports) which were retrieved. The review briefly recapitulates the role of vitamin C, the various disease manifestations and the treatment of scurvy to create awareness of the disease which still is reported from our country, although sporadically. The recent advances related to scurvy and its management in pediatric age group are also incorporated.

  16. 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.

  17. Pancreatic injuries in under-age Australian rules footballers.

    PubMed

    Burton, Paul; Fenton, Edmond

    2007-04-01

    Blunt injury to the pancreas is rare in children. It has significant physiological effects and can result in death. The most common injury mechanism is a high-velocity motor vehicle accident. Bicycle accidents, non-accidental injuries and falls can also cause pancreatic injury.(1) Given the protected retroperitoneal location of the pancreas, it is not surprising that low-velocity injuries are an uncommon cause of pancreatic injury. Over a 12-month period we have observed three cases of blunt pancreatic injury, occurring during under-age Australian rules football (AFL) matches. These represented a spectrum of injuries from 'traumatic pancreatitis' to a devascularized distal pancreas requiring initial percutaneous drainage complicated by pseudocyst development requiring cyst gastrostomy. AFL is a free flowing game that combines certain attributes of soccer and rugby. There is an emphasis on physical contact and high-velocity interpersonal collisions are frequent.

  18. Graves' Disease Pharmacotherapy in Women of Reproductive Age.

    PubMed

    Prunty, Jeremy J; Heise, Crystal D; Chaffin, David G

    2016-01-01

    Graves' disease is an autoimmune disorder in which inappropriate stimulation of the thyroid gland results in unregulated secretion of thyroid hormones resulting in hyperthyroidism. Graves' disease is the most common cause of autoimmune hyperthyroidism during pregnancy. Treatment options for Graves' disease include thioamide therapy, partial or total thyroidectomy, and radioactive iodine. In this article, we review guideline recommendations for Graves' disease treatment in women of reproductive age including the recent guideline from the American College of Obstetricians and Gynecologists. Controversy regarding appropriate thioamide therapy before, during, and after pregnancy is reviewed. Surgical and radioactive iodine therapy considerations in this patient population are also reviewed. In patients who may find themselves pregnant during therapy or develop Graves' disease during their pregnancy, consideration should be given to the most appropriate treatment course for the mother and fetus. Thioamide therapy should be used with either propylthiouracil or methimazole at appropriate doses that target the upper range of normal to slightly hyperthyroid to avoid creating hypothyroidism in the fetus. Consideration should also be given to the adverse effects of thioamide, such as agranulocytosis and hepatotoxicity, with appropriate patient consultation regarding signs and symptoms. Individuals who wish to breastfeed their infants while taking thioamide should receive the lowest effective dose. Surgery should be reserved for extreme cases and limited to the second trimester, if possible. Radioactive iodine therapy may be used in nonpregnant individuals, with limited harm to future fertility. Radioactive iodine therapy should be withheld in pregnant women and those who are actively breastfeeding. Clinicians should keep abreast of developments in clinical trials and evidence-based recommendations regarding Graves' disease in reproductive-age women for any changes in evidence

  19. Aging effects on the structure underlying balance abilities tests.

    PubMed

    Urushihata, Toshiya; Kinugasa, Takashi; Soma, Yuki; Miyoshi, Hirokazu

    2010-01-01

    Balance impairment is one of the biggest risk factors for falls reducing inactivity, resulting in nursing care. Therefore, balance ability is crucial to maintain the activities of independent daily living of older adults. Many tests to assess balance ability have been developed. However, few reports reveal the structure underlying results of balance performance tests comparing young and older adults. Covariance structure analysis is a tool that is used to test statistically whether factorial structure fits data. This study examined aging effects on the factorial structure underlying balance performance tests. Participants comprised 60 healthy young women aged 22 ± 3 years (young group) and 60 community-dwelling older women aged 69 ± 5 years (older group). Six balance tests: postural sway, one-leg standing, functional reach, timed up and go (TUG), gait, and the EquiTest were employed. Exploratory factor analysis revealed that three clearly interpretable factors were extracted in the young group. The first factor had high loadings on the EquiTest, and was interpreted as 'Reactive'. The second factor had high loadings on the postural sway test, and was interpreted as 'Static'. The third factor had high loadings on TUG and gait test, and was interpreted as 'Dynamic'. Similarly, three interpretable factors were extracted in the older group. The first factor had high loadings on the postural sway test and the EquiTest and therefore was interpreted as 'Static and Reactive'. The second factor, which had high loadings on the EquiTest, was interpreted as 'Reactive'. The third factor, which had high loadings on TUG and the gait test, was interpreted as 'Dynamic'. A covariance structure model was applied to the test data: the second-order factor was balance ability, and the first-order factors were static, dynamic and reactive factors which were assumed to be measured based on the six balance tests. Goodness-of-fit index (GFI) of the models were acceptable (young group, GFI

  20. Aging Effects on the Structure Underlying Balance Abilities Tests

    PubMed Central

    Kinugasa, Takashi; Soma, Yuki; Miyoshi, Hirokazu

    2010-01-01

    Balance impairment is one of the biggest risk factors for falls reducing inactivity, resulting in nursing care. Therefore, balance ability is crucial to maintain the activities of independent daily living of older adults. Many tests to assess balance ability have been developed. However, few reports reveal the structure underlying results of balance performance tests comparing young and older adults. Covariance structure analysis is a tool that is used to test statistically whether factorial structure fits data. This study examined aging effects on the factorial structure underlying balance performance tests. Participants comprised 60 healthy young women aged 22 ± 3 years (young group) and 60 community-dwelling older women aged 69 ± 5 years (older group). Six balance tests: postural sway, one-leg standing, functional reach, timed up and go (TUG), gait, and the EquiTest were employed. Exploratory factor analysis revealed that three clearly interpretable factors were extracted in the young group. The first factor had high loadings on the EquiTest, and was interpreted as ‘Reactive’. The second factor had high loadings on the postural sway test, and was interpreted as ‘Static’. The third factor had high loadings on TUG and gait test, and was interpreted as ‘Dynamic’. Similarly, three interpretable factors were extracted in the older group. The first factor had high loadings on the postural sway test and the EquiTest and therefore was interpreted as ‘Static and Reactive’. The second factor, which had high loadings on the EquiTest, was interpreted as ‘Reactive’. The third factor, which had high loadings on TUG and the gait test, was interpreted as ‘Dynamic’. A covariance structure model was applied to the test data: the second-order factor was balance ability, and the first-order factors were static, dynamic and reactive factors which were assumed to be measured based on the six balance tests. Goodness-of-fit index (GFI) of the models were

  1. Cardiac Aging: From Molecular Mechanisms to Significance in Human Health and Disease

    PubMed Central

    Dai, Dao-Fu; Chen, Tony; Johnson, Simon C.; Szeto, Hazel

    2012-01-01

    Abstract Cardiovascular diseases (CVDs) are the major causes of death in the western world. The incidence of cardiovascular disease as well as the rate of cardiovascular mortality and morbidity increase exponentially in the elderly population, suggesting that age per se is a major risk factor of CVDs. The physiologic changes of human cardiac aging mainly include left ventricular hypertrophy, diastolic dysfunction, valvular degeneration, increased cardiac fibrosis, increased prevalence of atrial fibrillation, and decreased maximal exercise capacity. Many of these changes are closely recapitulated in animal models commonly used in an aging study, including rodents, flies, and monkeys. The application of genetically modified aged mice has provided direct evidence of several critical molecular mechanisms involved in cardiac aging, such as mitochondrial oxidative stress, insulin/insulin-like growth factor/PI3K pathway, adrenergic and renin angiotensin II signaling, and nutrient signaling pathways. This article also reviews the central role of mitochondrial oxidative stress in CVDs and the plausible mechanisms underlying the progression toward heart failure in the susceptible aging hearts. Finally, the understanding of the molecular mechanisms of cardiac aging may support the potential clinical application of several “anti-aging” strategies that treat CVDs and improve healthy cardiac aging. PMID:22229339

  2. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease.

    PubMed

    Sepe, Sara; Milanese, Chiara; Gabriels, Sylvia; Derks, Kasper W J; Payan-Gomez, Cesar; van IJcken, Wilfred F J; Rijksen, Yvonne M A; Nigg, Alex L; Moreno, Sandra; Cerri, Silvia; Blandini, Fabio; Hoeijmakers, Jan H J; Mastroberardino, Pier G

    2016-05-31

    The underlying relation between Parkinson's disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mutant mice with mildly compromised NER exhibit typical PD-like pathological alterations, including decreased striatal dopaminergic innervation, increased phospho-synuclein levels, and defects in mitochondrial respiration. Ercc1 mouse mutants are also more sensitive to the prototypical PD toxin MPTP, and their transcriptomic landscape shares important similarities with that of PD patients. Our results demonstrate that specific defects in DNA repair impact the dopaminergic system and are associated with human PD pathology and might therefore constitute an age-related risk factor for PD. PMID:27210754

  3. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease.

    PubMed

    Sepe, Sara; Milanese, Chiara; Gabriels, Sylvia; Derks, Kasper W J; Payan-Gomez, Cesar; van IJcken, Wilfred F J; Rijksen, Yvonne M A; Nigg, Alex L; Moreno, Sandra; Cerri, Silvia; Blandini, Fabio; Hoeijmakers, Jan H J; Mastroberardino, Pier G

    2016-05-31

    The underlying relation between Parkinson's disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mutant mice with mildly compromised NER exhibit typical PD-like pathological alterations, including decreased striatal dopaminergic innervation, increased phospho-synuclein levels, and defects in mitochondrial respiration. Ercc1 mouse mutants are also more sensitive to the prototypical PD toxin MPTP, and their transcriptomic landscape shares important similarities with that of PD patients. Our results demonstrate that specific defects in DNA repair impact the dopaminergic system and are associated with human PD pathology and might therefore constitute an age-related risk factor for PD.

  4. 42 CFR 435.118 - Infants and children under age 19.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Infants and children under age 19. 435.118 Section... Coverage of Pregnant Women, Children Under 8, and Newborn Children § 435.118 Infants and children under age... to children under age 19 whose household income is at or below the income standard established by...

  5. 42 CFR 435.118 - Infants and children under age 19.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Infants and children under age 19. 435.118 Section..., Children Under 19, and Newborn Children § 435.118 Infants and children under age 19. (a) Basis. This...); and 1931(b) and (d) of the Act. (b) Scope. The agency must provide Medicaid to children under age...

  6. 42 CFR 435.118 - Infants and children under age 19.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Infants and children under age 19. 435.118 Section..., Children Under 19, and Newborn Children § 435.118 Infants and children under age 19. (a) Basis. This...); and 1931(b) and (d) of the Act. (b) Scope. The agency must provide Medicaid to children under age...

  7. 42 CFR 440.160 - Inpatient psychiatric services for individuals under age 21.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Definitions § 440.160 Inpatient psychiatric services for individuals under age 21. “Inpatient psychiatric services for individuals under age 21” means services that— (a) Are provided under the direction of a... under age 21. 440.160 Section 440.160 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES,...

  8. 42 CFR 440.160 - Inpatient psychiatric services for individuals under age 21.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Definitions § 440.160 Inpatient psychiatric services for individuals under age 21. “Inpatient psychiatric services for individuals under age 21” means services that— (a) Are provided under the direction of a... under age 21. 440.160 Section 440.160 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES,...

  9. 42 CFR 440.160 - Inpatient psychiatric services for individuals under age 21.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Definitions § 440.160 Inpatient psychiatric services for individuals under age 21. “Inpatient psychiatric services for individuals under age 21” means services that— (a) Are provided under the direction of a... under age 21. 440.160 Section 440.160 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES,...

  10. 42 CFR 440.160 - Inpatient psychiatric services for individuals under age 21.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Definitions § 440.160 Inpatient psychiatric services for individuals under age 21. “Inpatient psychiatric services for individuals under age 21” means services that— (a) Are provided under the direction of a... under age 21. 440.160 Section 440.160 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES,...

  11. Ages of celiac disease: From changing environment to improved diagnostics

    PubMed Central

    Tommasini, Alberto; Not, Tarcisio; Ventura, Alessandro

    2011-01-01

    From the time of Gee’s landmark writings, the recent history of celiac disease (CD) can be divided into many ages, each driven by a diagnostic advance and a deeper knowledge of disease pathogenesis. At the same time, these advances were paralleled by the identification of new clinical patterns associated with CD and by a continuous redefinition of the prevalence of the disease in population. In the beginning, CD was considered a chronic indigestion, even if the causative food was not known; later, the disease was proven to depend on an intolerance to wheat gliadin, leading to typical mucosal changes in the gut and to a malabsorption syndrome. This knowledge led to curing the disease with a gluten-free diet. After the identification of antibodies to gluten (AGA) in the serum of patients and the identification of gluten-specific lymphocytes in the mucosa, CD was described as an immune disorder, resembling a chronic “gluten infection”. The use of serological testing for AGA allowed identification of the higher prevalence of this disorder, revealing atypical patterns of presentation. More recently, the characterization of autoantibodies to endomysium and to transglutaminase shifted the attention to a complex autoimmune pathogenesis and to the increased risk of developing autoimmune disorders in untreated CD. New diagnostic assays, based on molecular technologies, will introduce new changes, with the promise of better defining the spectrum of gluten reactivity and the real burden of gluten related-disorders in the population. Herein, we describe the different periods of CD experience, and further developments for the next celiac age will be proposed. PMID:21990947

  12. Human stem cells as targets for the aging and diseases of aging processes.

    PubMed

    Trosko, James E

    2003-03-01

    While many theories have been proposed for the aging process, and many debates on the matter of aging and the diseases of aging being either the result of the same or independent processes, most have not considered humans as a hierarchical system made up of cybernetically interacting levels of organization. To understand the aging process and the diseases of aging, one must view the human as the result of the total genomic DNA in the single fertilized egg that proliferates, differentiates and develops into an individual of about 100 trillion cells, organized by different cell types (pluri-potent stem cells, progenitor stem cells, terminally differentiated cells) into multiple tissue, organ and organ systems which interact with each other via endogenous factors and with exogenous factors. Our hypothesis is that both aging and diseases of aging are dependent of the normal functioning of the pluri-potent stem cell pool. Specifically, the concept involves the cybernetic feedback between the 'quantity' of the stem cell pool in each tissue niche with the 'quality' of the stem cells in the pool. The process of gap junctional inter-cellular communication (GJIC), which has been implicated in the evolution from the single cell organism to the multi-cellular organisms, requiring growth control, differentiation, apoptosis, adaptive response capability of differentiated cells and senescence, is speculated to be a shared mechanism in stem cell biology and in many chronic disease processes (teratogenesis; carcinogenesis, atherogenesis, diabetigenesis, etc.). Specifically, stem cells are assumed to be 'immortal' until induced to express their connexin genes and have functional GJIC, at which time they can differentiate and become 'mortal'. As long as the stem cells are communicating with their differentiated daughters via some extra-cellular soluble negative growth factor, the homeostatic control of their growth and differentiation is maintained for the organism. However, if the

  13. White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease.

    PubMed

    Klosinski, Lauren P; Yao, Jia; Yin, Fei; Fonteh, Alfred N; Harrington, Michael G; Christensen, Trace A; Trushina, Eugenia; Brinton, Roberta Diaz

    2015-12-01

    White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical. PMID:26844268

  14. White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease.

    PubMed

    Klosinski, Lauren P; Yao, Jia; Yin, Fei; Fonteh, Alfred N; Harrington, Michael G; Christensen, Trace A; Trushina, Eugenia; Brinton, Roberta Diaz

    2015-12-01

    White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical.

  15. White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease

    PubMed Central

    Klosinski, Lauren P.; Yao, Jia; Yin, Fei; Fonteh, Alfred N.; Harrington, Michael G.; Christensen, Trace A.; Trushina, Eugenia; Brinton, Roberta Diaz

    2015-01-01

    White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical. PMID:26844268

  16. The role of DNA methylation in aging, rejuvenation, and age-related disease.

    PubMed

    Johnson, Adiv A; Akman, Kemal; Calimport, Stuart R G; Wuttke, Daniel; Stolzing, Alexandra; de Magalhães, João Pedro

    2012-10-01

    DNA methylation is a major control program that modulates gene expression in a plethora of organisms. Gene silencing through methylation occurs through the activity of DNA methyltransferases, enzymes that transfer a methyl group from S-adenosyl-L-methionine to the carbon 5 position of cytosine. DNA methylation patterns are established by the de novo DNA methyltransferases (DNMTs) DNMT3A and DNMT3B and are subsequently maintained by DNMT1. Aging and age-related diseases include defined changes in 5-methylcytosine content and are generally characterized by genome-wide hypomethylation and promoter-specific hypermethylation. These changes in the epigenetic landscape represent potential disease biomarkers and are thought to contribute to age-related pathologies, such as cancer, osteoarthritis, and neurodegeneration. Some diseases, such as a hereditary form of sensory neuropathy accompanied by dementia, are directly caused by methylomic changes. Epigenetic modifications, however, are reversible and are therefore a prime target for therapeutic intervention. Numerous drugs that specifically target DNMTs are being tested in ongoing clinical trials for a variety of cancers, and data from finished trials demonstrate that some, such as 5-azacytidine, may even be superior to standard care. DNMTs, demethylases, and associated partners are dynamically shaping the methylome and demonstrate great promise with regard to rejuvenation.

  17. The Role of DNA Methylation in Aging, Rejuvenation, and Age-Related Disease

    PubMed Central

    Johnson, Adiv A.; Akman, Kemal; Calimport, Stuart R.G.; Wuttke, Daniel; de Magalhães, João Pedro

    2012-01-01

    Abstract DNA methylation is a major control program that modulates gene expression in a plethora of organisms. Gene silencing through methylation occurs through the activity of DNA methyltransferases, enzymes that transfer a methyl group from S-adenosyl-l-methionine to the carbon 5 position of cytosine. DNA methylation patterns are established by the de novo DNA methyltransferases (DNMTs) DNMT3A and DNMT3B and are subsequently maintained by DNMT1. Aging and age-related diseases include defined changes in 5-methylcytosine content and are generally characterized by genome-wide hypomethylation and promoter-specific hypermethylation. These changes in the epigenetic landscape represent potential disease biomarkers and are thought to contribute to age-related pathologies, such as cancer, osteoarthritis, and neurodegeneration. Some diseases, such as a hereditary form of sensory neuropathy accompanied by dementia, are directly caused by methylomic changes. Epigenetic modifications, however, are reversible and are therefore a prime target for therapeutic intervention. Numerous drugs that specifically target DNMTs are being tested in ongoing clinical trials for a variety of cancers, and data from finished trials demonstrate that some, such as 5-azacytidine, may even be superior to standard care. DNMTs, demethylases, and associated partners are dynamically shaping the methylome and demonstrate great promise with regard to rejuvenation. PMID:23098078

  18. Management of the aging risk factor for Parkinson's disease.

    PubMed

    Phillipson, Oliver T

    2014-04-01

    The aging risk factor for Parkinson's disease is described in terms of specific disease markers including mitochondrial and gene dysfunctions relevant to energy metabolism. This review details evidence for the ability of nutritional agents to manage these aging risk factors. The combination of alpha lipoic acid, acetyl-l-carnitine, coenzyme Q10, and melatonin supports energy metabolism via carbohydrate and fatty acid utilization, assists electron transport and adenosine triphosphate synthesis, counters oxidative and nitrosative stress, and raises defenses against protein misfolding, inflammatory stimuli, iron, and other endogenous or xenobiotic toxins. These effects are supported by gene expression via the antioxidant response element (ARE; Keap/Nrf2 pathway), and by peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1 alpha), a transcription coactivator, which regulates gene expression for energy metabolism and mitochondrial biogenesis, and maintains the structural integrity of mitochondria. The effectiveness and synergies of the combination against disease risks are discussed in relation to gene action, dopamine cell loss, and the accumulation and spread of pathology via misfolded alpha-synuclein. In addition there are potential synergies to support a neurorestorative role via glial derived neurotrophic factor expression.

  19. A mitochondrial superoxide theory for oxidative stress diseases and aging.

    PubMed

    Indo, Hiroko P; Yen, Hsiu-Chuan; Nakanishi, Ikuo; Matsumoto, Ken-Ichiro; Tamura, Masato; Nagano, Yumiko; Matsui, Hirofumi; Gusev, Oleg; Cornette, Richard; Okuda, Takashi; Minamiyama, Yukiko; Ichikawa, Hiroshi; Suenaga, Shigeaki; Oki, Misato; Sato, Tsuyoshi; Ozawa, Toshihiko; Clair, Daret K St; Majima, Hideyuki J

    2015-01-01

    Fridovich identified CuZnSOD in 1969 and manganese superoxide dismutase (MnSOD) in 1973, and proposed "the Superoxide Theory," which postulates that superoxide (O2 (•-)) is the origin of most reactive oxygen species (ROS) and that it undergoes a chain reaction in a cell, playing a central role in the ROS producing system. Increased oxidative stress on an organism causes damage to cells, the smallest constituent unit of an organism, which can lead to the onset of a variety of chronic diseases, such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis and other neurological diseases caused by abnormalities in biological defenses or increased intracellular reactive oxygen levels. Oxidative stress also plays a role in aging. Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q10) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich's seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging.

  20. Positive oxidative stress in aging and aging-related disease tolerance.

    PubMed

    Yan, Liang-Jun

    2014-01-01

    It is now well established that reactive oxygen species (ROS), reactive nitrogen species (RNS), and a basal level of oxidative stress are essential for cell survival. It is also well known that while severe oxidative stress often leads to widespread oxidative damage and cell death, a moderate level of oxidative stress, induced by a variety of stressors, can yield great beneficial effects on adaptive cellular responses to pathological challenges in aging and aging-associated disease tolerance such as ischemia tolerance. Here in this review, I term this moderate level of oxidative stress as positive oxidative stress, which usually involves imprinting molecular signatures on lipids and proteins via formation of lipid peroxidation by-products and protein oxidation adducts. As ROS/RNS are short-lived molecules, these molecular signatures can thus execute the ultimate function of ROS/RNS. Representative examples of lipid peroxidation products and protein oxidation adducts are presented to illustrate the role of positive oxidative stress in a variety of pathological settings, demonstrating that positive oxidative stress could be a valuable prophylactic and/or therapeutic approach targeting aging and aging-associated diseases.

  1. Picture priming in normal aging and Alzheimer's disease.

    PubMed

    Ballesteros, Soledad; Reales, José M; Mayas, Julia

    2007-05-01

    The present study investigated age invariance for naming pictures and whether implicit memory is spared in Alzheimer's disease (AD). During the study phase, young adults, AD patients, and older controls were shown outlines of familiar pictures. After a distracter task, implicit memory was assessed incidentally. The results showed similar visual priming for the three groups, although young adults responded faster than the two older groups. Moreover, the number of errors was smaller for studied than for non-studied pictures. This pattern of results was repeated across the three groups, although AD patients produced more errors than young adults and older controls, and there were no differences between these latter groups. These results confirmed previous visual and haptic findings showing unimpaired perceptual priming in normal aging and AD patients when implicit memory is assessed using identification tasks. These results are interpreted from a cognitive neuroscience perspective. PMID:17425893

  2. Picture priming in normal aging and Alzheimer's disease.

    PubMed

    Ballesteros, Soledad; Reales, José M; Mayas, Julia

    2007-05-01

    The present study investigated age invariance for naming pictures and whether implicit memory is spared in Alzheimer's disease (AD). During the study phase, young adults, AD patients, and older controls were shown outlines of familiar pictures. After a distracter task, implicit memory was assessed incidentally. The results showed similar visual priming for the three groups, although young adults responded faster than the two older groups. Moreover, the number of errors was smaller for studied than for non-studied pictures. This pattern of results was repeated across the three groups, although AD patients produced more errors than young adults and older controls, and there were no differences between these latter groups. These results confirmed previous visual and haptic findings showing unimpaired perceptual priming in normal aging and AD patients when implicit memory is assessed using identification tasks. These results are interpreted from a cognitive neuroscience perspective.

  3. Proteostasis and the Aging Proteome in Health and Disease

    PubMed Central

    2014-01-01

    The maintenance of the proteome is essential to preserve cell functionality and the ability to respond and adapt to the changing environment. This is regulated by the proteostasis network, a dedicated set of molecular components comprised of molecular chaperones and protein clearance mechanisms, regulated by cell stress signaling pathways, that prevents the toxicity associated with protein misfolding and accumulation of toxic aggregates in different subcellular compartments and tissues. The efficiency of the proteostasis network declines with age and this failure in protein homeostasis has been proposed to underlie the basis of common age-related human disorders. The current advances in the understanding of the mechanisms and regulation of proteostasis and of the different types of digressions in this process in aging have turned the attention toward the therapeutic opportunities offered by the restoration of proteostasis in age-associated degenerative diseases. Here, we discuss some of the unresolved questions on proteostasis that need to be addressed to enhance healthspan and to diminish the pathology associated with persistent protein damage. PMID:24833584

  4. Genome maintenance and transcription integrity in aging and disease

    PubMed Central

    Wolters, Stefanie; Schumacher, Björn

    2013-01-01

    DNA damage contributes to cancer development and aging. Congenital syndromes that affect DNA repair processes are characterized by cancer susceptibility, developmental defects, and accelerated aging (Schumacher et al., 2008). DNA damage interferes with DNA metabolism by blocking replication and transcription. DNA polymerase blockage leads to replication arrest and can gives rise to genome instability. Transcription, on the other hand, is an essential process for utilizing the information encoded in the genome. DNA damage that interferes with transcription can lead to apoptosis and cellular senescence. Both processes are powerful tumor suppressors (Bartek and Lukas, 2007). Cellular response mechanisms to stalled RNA polymerase II complexes have only recently started to be uncovered. Transcription-coupled DNA damage responses might thus play important roles for the adjustments to DNA damage accumulation in the aging organism (Garinis et al., 2009). Here we review human disorders that are caused by defects in genome stability to explore the role of DNA damage in aging and disease. We discuss how the nucleotide excision repair system functions at the interface of transcription and repair and conclude with concepts how therapeutic targeting of transcription might be utilized in the treatment of cancer. PMID:23443494

  5. Musculoskeletal Disease in Aged Horses and Its Management.

    PubMed

    van Weeren, Paul René; Back, Willem

    2016-08-01

    Musculoskeletal disorders are the most prevalent health problem in aging horses. They are not life threatening, but are painful and an important welfare issue. Chronic joint disease (osteoarthritis) and chronic laminitis are the most prevalent. Treating osteoarthritis in the elderly horse is similar to treating performance horses, but aims at providing a stable situation with optimal comfort. Immediate medical treatment of flare-ups, long-term pain management, and adaptation of exercise and living conditions are the mainstays of treatment. Laminitis in the geriatric horse is related often to pituitary pars intermedia dysfunction, which may be treated with additional pergolide. PMID:27449390

  6. Evidence for age susceptibility of cattle to Johne's disease.

    PubMed

    Windsor, Peter A; Whittington, Richard J

    2010-04-01

    Calf rearing programs for the control of bovine Johne's disease (BJD) in dairy farms have been widely adopted globally and are based on evidence that the most significant risk factor for developing the disease is exposure of young calves to infectious doses of the causative organism Mycobacterium avium subsp. paratuberculosis (Mptb). Hygienic calf rearing practices aim to break the transmission cycle of Mptb by removing neonatal calves from their dams within 12h of birth and segregating replacement heifers from the herd until they are 12 months of age. But compliance with these interventions is difficult for many producers and delaying the removal of calves from their dams and earlier return of heifers to the herd are common practices. However, would changing these practices increase the risk of animals contracting BJD? Evidence for age susceptibility of calves and young adults to Mptb is reviewed. The experimental studies selected for inclusion in an analysis of the evidence were those designed specifically to address the issue and were confined to examination of 140 cattle in experiments conducted by eight groups of workers between the years 1938 and 2006. Approximately 75% of calves <6 months of age, 50% of those aged between 6 and 12 months, and just less than 20% of cattle >12 months old developed lesions indicative of BJD infection when exposed to any of the tested routes of Mptb infection. No direct evidence was found to support the commonly held view that calf removal from the dam for a maximum period of 12h is preferable to 24h. However the studies did show that if exposure to infection occurs at birth, then the risk of infection progressing to BJD is high, particularly in a highly contaminated environment or if the dam is infected.

  7. Chronic hepatitis C: an age wave of disease burden.

    PubMed

    McHutchison, John G; Bacon, Bruce R

    2005-10-01

    There are at least 2.7 million individuals in the United States, most of them in their 40s and 50s, who are chronically infected with hepatitis C virus (HCV). As these infected individuals get older, about 20% will develop cirrhosis, and a significant fraction of those with cirrhosis (about 1 in 10) will then develop serious decompensated liver disease or hepatocellular carcinoma. Currently, HCV is the primary cause of death in 8000 to 12 000 people every year; the virus is also the primary reason for liver transplantation in the United States. Although the number of new cases of HCV infection has been dropping steadily since the introduction of improved blood-supply screening, the "age wave" of existing chronic HCV in baby boomers is expected to contribute to a substantial rise in morbidity, mortality, and costs over the next 2 decades. Although it is difficult to predict which HCV-infected patients will progress to serious liver disease, the availability of a combination drug regimen (peginterferon alfa plus ribavirin) that essentially "cures" the disease in more than half of treated patients now provides clinicians and pharmacists in managed care settings with the tools needed to diminish the impact of the anticipated wave of liver disease. This article reviews the epidemiology, natural history, clinical and economic burden, and screening and treatment options for HCV. PMID:16232012

  8. 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. PMID:26538520

  9. The Age-by-Disease Interaction Hypothesis of Late-Life Depression

    PubMed Central

    McKinney, Brandon Chad; Sibille, Etienne

    2012-01-01

    The phenomenological diagnosis of depression is successful in increasing diagnostic reliability, but it is a classification scheme without biological bases. One subtype of depression for which evidence suggests a unique biological basis is late-life depression (LLD), with first onset of symptoms after the age of 65. LLD is common and poses a significant burden on affected individuals, caretakers, and society. The pathophysiology of LLD includes disruptions of the neural network underlying mood, which can be conceptualized as the result of dysfunction in multiple underlying biological processes. Here, we briefly review current LLD hypotheses and then describe the characteristics of molecular brain aging and their overlap with disease processes. Further, we propose a new hypothesis for LLD, the Age-by-Disease Interaction hypothesis, which posits that the clinical presentation of LLD is the integrated output of specific biological processes that are pushed in LLD-promoting directions by changes in gene expression naturally occurring during brain aging, hence leading the brain to a physiological state that is more susceptible to LLD, since additional pushes by genetic, environmental and biochemical factors may now be sufficient to generate dysfunctional states that produce depressive symptoms. We put our propositions together into a decanalization model to aid in illustrating how age-related biological changes of the brain can shift the repertoire of available functional states in a pro-depression direction, and how additional factors can readily lead the system into distinct and stable maladaptive phenotypes, including LLD. This model brings together basic research on neuropsychiatric and neurodegenerative diseases more closely with the investigation of normal aging. Specifically, identifying biological processes affected during normal aging may inform the development of new interventions for the prevention and treatment of LLD. PMID:23570886

  10. Aging and emotional memory: cognitive mechanisms underlying the positivity effect.

    PubMed

    Spaniol, Julia; Voss, Andreas; Grady, Cheryl L

    2008-12-01

    Younger adults tend to remember negative information better than positive or neutral information (negativity bias). The negativity bias is reduced in aging, with older adults occasionally exhibiting superior memory for positive, as opposed to negative or neutral, information (positivity bias). Two experiments with younger (N=24 in Experiment 1, N=25 in Experiment 2; age range: 18-35 years) and older adults (N=24 in both experiments; age range: 60-85 years) investigated the cognitive mechanisms responsible for age-related differences in recognition memory for emotional information. Results from diffusion model analyses (R. Ratcliff, 1978) indicated that the effects of valence on response bias were similar in both age groups but that Age x Valence interactions emerged in memory retrieval. Specifically, older adults experienced greater overall familiarity for positive items than younger adults. We interpret this finding in terms of an age-related increase in the accessibility of positive information in long-term memory. PMID:19140656

  11. Impairments of Synaptic Plasticity in Aged Animals and in Animal Models of Alzheimer's Disease

    PubMed Central

    Balietti, Marta; Tamagnini, Francesco; Fattoretti, Patrizia; Burattini, Costanza; Casoli, Tiziana; Platano, Daniela; Lattanzio, Fabrizia

    2012-01-01

    Abstract Aging is associated with a gradual decline in cognitive functions, and more dramatic cognitive impairments occur in patients affected by Alzheimer's disease (AD). Electrophysiological and molecular studies performed in aged animals and in animal models of AD have shown that cognitive decline is associated with significant modifications in synaptic plasticity (i.e., activity-dependent changes in synaptic strength) and have elucidated some of the cellular mechanisms underlying this process. Morphological studies have revealed a correlation between the quality of memory performance and the extent of structural changes of synaptic contacts occurring during memory consolidation. We briefly review recent experimental evidence here. PMID:22533439

  12. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease

    PubMed Central

    Potter, Paul K.; Bowl, Michael R.; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E.; Simon, Michelle M.; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V.; Law, Gemma; MacLaren, Robert E.; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H.; Foster, Russell G.; Jackson, Ian J.; Peirson, Stuart N.; Thakker, Rajesh V.; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M.; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D. M.

    2016-01-01

    Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss. PMID:27534441

  13. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease.

    PubMed

    Potter, Paul K; Bowl, Michael R; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E; Simon, Michelle M; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V; Law, Gemma; MacLaren, Robert E; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H; Foster, Russell G; Jackson, Ian J; Peirson, Stuart N; Thakker, Rajesh V; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D M

    2016-08-18

    Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss.

  14. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease.

    PubMed

    Potter, Paul K; Bowl, Michael R; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E; Simon, Michelle M; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V; Law, Gemma; MacLaren, Robert E; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H; Foster, Russell G; Jackson, Ian J; Peirson, Stuart N; Thakker, Rajesh V; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D M

    2016-01-01

    Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss. PMID:27534441

  15. Disease onset and aging in the world of circular RNAs

    PubMed Central

    Maiese, Kenneth

    2016-01-01

    Circular ribonucleic acids (circRNAs) are non-coding RNAs of approximately 100 nucleotides in length with thousands of members in mammalian cells. The presence of circRNAs is believed to be even greater than that of messenger RNAs. Identification of circRNAs occurred approximately 37 years ago with the subsequent demonstration that covalent bonds are necessary for the unique circular structure of these ribonucleic acids. However, present understanding of the complex biological role of circRNAs remains limited and requires further elucidation. CircRNAs may impact aging, multiple disorders, function as biomarkers, and are able to regulate gene expression by acting as effective microRNA (miRNA) sponges. New work suggests that circRNAs are vital for the modulation of cellular senescence and programmed cell death pathways such as apoptosis. These non-coding RNAs can control cell cycle progression, cellular proliferation, and cellular survival impacting disorders linked to aging, cardiovascular disease, and atherosclerosis through pathways that involve cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase inhibitor 1 (p21), and mammalian forkhead transcription factors. In addition, circRNAs can oversee cellular metabolism and disorders such as diabetes mellitus through the regulation of insulin signaling as well as limit tumor progression through Wnt signaling and β-catenin pathways. Further understanding of the biology of circRNAs offers great promise for the targeting of novel strategies against a wide spectrum of disease entities. PMID:27642518

  16. Taste bud homeostasis in health, disease, and aging.

    PubMed

    Feng, Pu; Huang, Liquan; Wang, Hong

    2014-01-01

    The mammalian taste bud is an onion-shaped epithelial structure with 50-100 tightly packed cells, including taste receptor cells, supporting cells, and basal cells. Taste receptor cells detect nutrients and toxins in the oral cavity and transmit the sensory information to gustatory nerve endings in the buds. Supporting cells may play a role in the clearance of excess neurotransmitters after their release from taste receptor cells. Basal cells are precursor cells that differentiate into mature taste cells. Similar to other epithelial cells, taste cells turn over continuously, with an average life span of about 8-12 days. To maintain structural homeostasis in taste buds, new cells are generated to replace dying cells. Several recent studies using genetic lineage tracing methods have identified populations of progenitor/stem cells for taste buds, although contributions of these progenitor/stem cell populations to taste bud homeostasis have yet to be fully determined. Some regulatory factors of taste cell differentiation and degeneration have been identified, but our understanding of these aspects of taste bud homoeostasis remains limited. Many patients with various diseases develop taste disorders, including taste loss and taste distortion. Decline in taste function also occurs during aging. Recent studies suggest that disruption or alteration of taste bud homeostasis may contribute to taste dysfunction associated with disease and aging.

  17. Lipidomics of human brain aging and Alzheimer's disease pathology.

    PubMed

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context.

  18. The hippocampus in aging and disease: From plasticity to vulnerability.

    PubMed

    Bartsch, T; Wulff, P

    2015-11-19

    The hippocampus has a pivotal role in learning and in the formation and consolidation of memory and is critically involved in the regulation of emotion, fear, anxiety, and stress. Studies of the hippocampus have been central to the study of memory in humans and in recent years, the regional specialization and organization of hippocampal functions have been elucidated in experimental models and in human neurological and psychiatric diseases. The hippocampus has long been considered a classic model for the study of neuroplasticity as many examples of synaptic plasticity such as long-term potentiation and -depression have been identified and demonstrated in hippocampal circuits. Neuroplasticity is the ability to adapt and reorganize the structure or function to internal or external stimuli and occurs at the cellular, population, network or behavioral level and is reflected in the cytological and network architecture as well as in intrinsic properties of hippocampal neurons and circuits. The high degree of hippocampal neuroplasticity might, however, be also negatively reflected in the pronounced vulnerability of the hippocampus to deleterious conditions such as ischemia, epilepsy, chronic stress, neurodegeneration and aging targeting hippocampal structure and function and leading to cognitive deficits. Considering this framework of plasticity and vulnerability, we here review basic principles of hippocampal anatomy and neuroplasticity on various levels as well as recent findings regarding the functional organization of the hippocampus in light of the regional vulnerability in Alzheimer's disease, ischemia, epilepsy, neuroinflammation and aging. PMID:26241337

  19. Taste bud homeostasis in health, disease, and aging.

    PubMed

    Feng, Pu; Huang, Liquan; Wang, Hong

    2014-01-01

    The mammalian taste bud is an onion-shaped epithelial structure with 50-100 tightly packed cells, including taste receptor cells, supporting cells, and basal cells. Taste receptor cells detect nutrients and toxins in the oral cavity and transmit the sensory information to gustatory nerve endings in the buds. Supporting cells may play a role in the clearance of excess neurotransmitters after their release from taste receptor cells. Basal cells are precursor cells that differentiate into mature taste cells. Similar to other epithelial cells, taste cells turn over continuously, with an average life span of about 8-12 days. To maintain structural homeostasis in taste buds, new cells are generated to replace dying cells. Several recent studies using genetic lineage tracing methods have identified populations of progenitor/stem cells for taste buds, although contributions of these progenitor/stem cell populations to taste bud homeostasis have yet to be fully determined. Some regulatory factors of taste cell differentiation and degeneration have been identified, but our understanding of these aspects of taste bud homoeostasis remains limited. Many patients with various diseases develop taste disorders, including taste loss and taste distortion. Decline in taste function also occurs during aging. Recent studies suggest that disruption or alteration of taste bud homeostasis may contribute to taste dysfunction associated with disease and aging. PMID:24287552

  20. The hippocampus in aging and disease: From plasticity to vulnerability.

    PubMed

    Bartsch, T; Wulff, P

    2015-11-19

    The hippocampus has a pivotal role in learning and in the formation and consolidation of memory and is critically involved in the regulation of emotion, fear, anxiety, and stress. Studies of the hippocampus have been central to the study of memory in humans and in recent years, the regional specialization and organization of hippocampal functions have been elucidated in experimental models and in human neurological and psychiatric diseases. The hippocampus has long been considered a classic model for the study of neuroplasticity as many examples of synaptic plasticity such as long-term potentiation and -depression have been identified and demonstrated in hippocampal circuits. Neuroplasticity is the ability to adapt and reorganize the structure or function to internal or external stimuli and occurs at the cellular, population, network or behavioral level and is reflected in the cytological and network architecture as well as in intrinsic properties of hippocampal neurons and circuits. The high degree of hippocampal neuroplasticity might, however, be also negatively reflected in the pronounced vulnerability of the hippocampus to deleterious conditions such as ischemia, epilepsy, chronic stress, neurodegeneration and aging targeting hippocampal structure and function and leading to cognitive deficits. Considering this framework of plasticity and vulnerability, we here review basic principles of hippocampal anatomy and neuroplasticity on various levels as well as recent findings regarding the functional organization of the hippocampus in light of the regional vulnerability in Alzheimer's disease, ischemia, epilepsy, neuroinflammation and aging.

  1. Preface: The aging eye: normal changes, age-related diseases, and sight-saving approaches.

    PubMed

    Chader, Gerald J; Taylor, Allen

    2013-12-13

    This volume presents articles based on a workshop held June 14 to 16, 2013 in Rancho Palos Verde, CA sponsored by the Ocular Research Symposia Foundation (ORSF). The mission of the ORSF is to focus attention on unmet needs and current research opportunities in eye research with the objective of accelerating translation of research findings to effective clinical care. In this workshop, the subject of the "The Aging Eye" was addressed, including the prevalence of eye diseases in aging and the economic burden imposed by these diseases. New research work was highlighted on the genetics, biology, biochemistry, neurochemistry, and the impact of nutrition and the environment on function in the older eye. By identifying "low-hanging fruit" (i.e., the best opportunities for successful transition of laboratory research for the prevention of and new treatments and cures for ocular diseases), we seek to spur funding at both the basic research and clinical levels, resulting in sight-saving and sight-restoration measures in the near future.

  2. 36 CFR 1280.6 - Can children under the age of 14 use NARA facilities?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Conduct on NARA Property? General Information on Using Nara Facilities § 1280.6 Can children under the age of 14 use NARA facilities? Children under the age of 14 will be admitted to NARA facilities only if... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Can children under the age...

  3. 78 FR 9765 - Assigning New Social Security Numbers (SSN) for Children Age 13 and Under

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-11

    ... ADMINISTRATION Assigning New Social Security Numbers (SSN) for Children Age 13 and Under AGENCY: Social Security... assigning new SSNs to children age 13 and under. We are requesting information from the public to ensure... an SSN for a child age 13 and under. DATES: To ensure that your comments are considered, we...

  4. Dermatological disease in the older age group: a cross-sectional study in aged care facilities

    PubMed Central

    Deo, Maneka S; Vandal, Alain C; Jarrett, Paul

    2015-01-01

    Objectives To estimate the prevalence of dermatological disease in aged care facilities, and the relationship between cognitive or physical disability and significant disease. Setting 2 large aged care facilities in Auckland, New Zealand, each providing low and high level care. Participants All 161 residents of the facilities were invited to participate. The only exclusion criterion was inability to obtain consent from the individual or designated guardian. 88 participants were recruited—66 females (75%), 22 males (25%) with average age 87.1 years (SD 5.5 years). Primary and secondary outcome measures Primary—presence of significant skin disease (defined as that which in the opinion of the investigators needed treatment or was identified as a patient concern) diagnosed clinically on full dermatological examination by a dermatologist or dermatology trainee. Secondary—functional and cognitive status (Rehabilitation Complexity Scale and Abbreviated Mental Test Score). Results 81.8% were found to have at least one significant condition. The most common disorders were onychomycosis 42 (47.7%), basal cell carcinoma 13 (14.8%), asteototic eczema 11 (12.5%) and squamous cell carcinoma in situ 9 (10.2%). Other findings were invasive squamous cell carcinoma 7 (8%), bullous pemphigoid 2 (2.3%), melanoma 2 (2.3%), lichen sclerosus 2 (2.3%) and carcinoma of the breast 1 (1.1%). Inflammatory disease was more common in those with little physical disability compared with those with serious physical disability (OR 3.69; 95% CI 1.1 to 12.6, p=0.04). No significant association was found between skin disease and cognitive impairment. Conclusions A high rate of dermatological disease was found. Findings ranged from frequent but not life-threatening conditions (eg, onychomycosis), to those associated with a significant morbidity (eg, eczema, lichen sclerosus and bullous pemphigoid), to potentially life-threatening (eg, squamous cell carcinoma, melanoma and breast cancer

  5. Aging syndrome genes and premature coronary artery disease

    PubMed Central

    Low, Adrian F; O'Donnell, Christopher J; Kathiresan, Sekar; Everett, Brendan; Chae, Claudia U; Shaw, Stanley Y; Ellinor, Patrick T; MacRae, Calum A

    2005-01-01

    Background Vascular disease is a feature of aging, and coronary vascular events are a major source of morbidity and mortality in rare premature aging syndromes. One such syndrome is caused by mutations in the lamin A/C (LMNA) gene, which also has been implicated in familial insulin resistance. A second gene related to premature aging in man and in murine models is the KLOTHO gene, a hypomorphic variant of which (KL-VS) is significantly more common in the first-degree relatives of patients with premature coronary artery disease (CAD). We evaluated whether common variants at the LMNA or KLOTHO genes are associated with rigorously defined premature CAD. Methods We identified 295 patients presenting with premature acute coronary syndromes confirmed by angiography. A control group of 145 patients with no evidence of CAD was recruited from outpatient referral clinics. Comprehensive haplotyping of the entire LMNA gene, including the promoter and untranslated regions, was performed using a combination of TaqMan® probes and direct sequencing of 14 haplotype-tagging single nucleotide polymorphisms (SNPs). The KL-VS variant of the KLOTHO gene was typed using restriction digest of a PCR amplicon. Results Two SNPs that were not in Hardy Weinberg equilibrium were excluded from analysis. We observed no significant differences in allele, genotype or haplotype frequencies at the LMNA or KLOTHO loci between the two groups. In addition, there was no evidence of excess homozygosity at the LMNA locus. Conclusion Our data do not support the hypothesis that premature CAD is associated with common variants in the progeroid syndrome genes LMNA and KLOTHO. PMID:16262891

  6. Aging, Transition, and Estimating the Global Burden of Disease

    PubMed Central

    Seligman, Benjamin J.; Cullen, Mark R.; Horwitz, Ralph I.

    2011-01-01

    Background The World Health Organization's Global Burden of Disease (GBD) reports are an important tool for global health policy makers, however the accuracy of estimates for countries undergoing an epidemiologic transition is unclear. We attempted to validate the life table model used to generate estimates for all-cause mortality in developing countries. Methods and Results Data were obtained for males and females from the Human Mortality Database for all countries with available data every ten years from 1900 to 2000. These provided inputs for the GBD life table model and served as comparison observed data. Above age sixty model estimates of survival for both sexes differed substantially from those observed. Prior to the year 1960 for males and 1930 for females, estimated survival tended to be greater than observed; following 1960 for both males and females estimated survival tended to be less than observed. Viewing observed and estimated survival separately, observed survival past sixty increased over the years considered. For males, the increase was from a mean (sd) probability of 0.22 (0.06) to 0.46 (0.1). For females, the increase was from 0.26 (0.06) to 0.65 (0.08). By contrast, estimated survival past sixty decreased over the same period. Among males, estimated survival probability declined from 0.54 (0.2) to 0.09 (0.06). Among females, the decline was from 0.36 (0.12) to 0.15 (0.08). Conclusions These results show that the GBD mortality model did not accurately estimate survival at older ages as developed countries transitioned in the twentieth century and may be similarly flawed in developing countries now undergoing transition. Estimates of the size of older-age populations and their attributable disease burden should be reconsidered. PMID:21629652

  7. The school age child with congenital heart disease.

    PubMed

    Boyle, Lynn; Kelly, Michelle M; Reynolds, Kathryn; Conlan, Misty; Taylor, Felisha

    2015-01-01

    Currently, in the United States, there are approximately 1 in 150 adults living with congenital heart disease (CHD) (). Infant and childhood mortality related to CHD decreased by 31% between 1987 and 2005 (). This survival trend is predicted to increase each year due to advancements in treatment and management of CHD. This significant shift in the epidemiology of CHD requires nurses to take action in preparing children with CHD and their families for their teenage years and young adulthood. The school-age child is the ideal age to begin teaching the child about their healthcare needs and how to care for themselves in preparation for the future. The school-age child with CHD has specific physical, intellectual, emotional, and developmental needs that must be considered and managed using a multidisciplinary approach. Pediatric nurses must be aware of these needs as they help the child and their family seamlessly and successfully transition into young adulthood as a happy and healthy CHD survivor. PMID:25330332

  8. Age structure of owned dogs under compulsory culling in a visceral leishmaniasis endemic area.

    PubMed

    Bortoletto, Danielly Vieira; Utsunomiya, Yuri Tani; Perri, Silvia Helena Venturoli; Ferreira, Fernando; Nunes, Cáris Maroni

    2016-01-01

    The age structure of the dog population is essential for planning and evaluating control programs for zoonotic diseases. We analyzed data of an owned-dog census in order to characterize, for the first time, the structure of a dog population under compulsory culling in a visceral leishmaniasis endemic area (Panorama, São Paulo State, Brazil) that recorded a dog-culling rate of 28% in the year of the study. Data on 1,329 households and 1,671 owned dogs revealed an owned dog:human ratio of 1:7. The mean age of dogs was estimated at 1.73 years; the age pyramid indicated high birth and mortality rates at the first year of age with an estimated cumulative mortality of 78% at the third year of age and expected life span of 2.75 years. In spite of the high mortality, a growth projection simulation suggested that the population has potential to grow in a logarithmic scale over the years. The estimated parameters can be further applied in models to maximize the impact and minimize financial inputs of visceral leishmaniasis control measures. PMID:27598014

  9. Cardiovascular disease and type 1 diabetes: prevalence, prediction and management in an ageing population

    PubMed Central

    Lee, Siang Ing; Patel, Mitesh; Jones, Christopher M.; Narendran, Parth

    2015-01-01

    Cardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes mellitus (T1D). However, evidence of its risks and management is often extrapolated from studies in type 2 diabetic (T2D) patients or the general population. This approach is unsatisfactory given that the underlying pathology, demographics and natural history of the disease differ between T1D and T2D. Furthermore, with a rising life expectancy, a greater number of T1D patients are exposed to the cardiovascular (CV) risk factors associated with an ageing population. The aim of this review is to examine the existing literature around CVD in T1D. We pay particular attention to CVD prevalence, how well we manage risk, potential biomarkers, and whether the studies included the older aged patients (defined as aged over 65). We also discuss approaches to the management of CV risk in the older aged. The available data suggest a significant CVD burden in patients with T1D and poor management of CV risk factors. This is underpinned by a poor evidence base for therapeutic management of CV risk specifically for patients with T1D, and in the most relevant population – the older aged patients. We would suggest that important areas remain to be addressed, particularly exploring the risks and benefits of therapeutic approaches to CVD management in the older aged. PMID:26568811

  10. Hypoxia-Inducible Histone Lysine Demethylases: Impact on the Aging Process and Age-Related Diseases

    PubMed Central

    Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu

    2016-01-01

    Hypoxia is an environmental stress at high altitude and underground conditions but it is also present in many chronic age-related diseases, where blood flow into tissues is impaired. The oxygen-sensing system stimulates gene expression protecting tissues against hypoxic insults. Hypoxia stabilizes the expression of hypoxia-inducible transcription factor-1α (HIF-1α), which controls the expression of hundreds of survival genes related to e.g. enhanced energy metabolism and autophagy. Moreover, many stress-related signaling mechanisms, such as oxidative stress and energy metabolic disturbances, as well as the signaling cascades via ceramide, mTOR, NF-κB, and TGF-β pathways, can also induce the expression of HIF-1α protein to facilitate cell survival in normoxia. Hypoxia is linked to prominent epigenetic changes in chromatin landscape. Screening studies have indicated that the stabilization of HIF-1α increases the expression of distinct histone lysine demethylases (KDM). HIF-1α stimulates the expression of KDM3A, KDM4B, KDM4C, and KDM6B, which enhance gene transcription by demethylating H3K9 and H3K27 sites (repressive epigenetic marks). In addition, HIF-1α induces the expression of KDM2B and KDM5B, which repress transcription by demethylating H3K4me2,3 sites (activating marks). Hypoxia-inducible KDMs support locally the gene transcription induced by HIF-1α, although they can also control genome-wide chromatin landscape, especially KDMs which demethylate H3K9 and H3K27 sites. These epigenetic marks have important role in the control of heterochromatin segments and 3D folding of chromosomes, as well as the genetic loci regulating cell type commitment, proliferation, and cellular senescence, e.g. the INK4 box. A chronic stimulation of HIF-1α can provoke tissue fibrosis and cellular senescence, which both are increasingly present with aging and age-related diseases. We will review the regulation of HIF-1α-dependent induction of KDMs and clarify their role in

  11. In vivo imaging of axonal transport of mitochondria in the diseased and aged mammalian CNS

    PubMed Central

    Takihara, Yuji; Inatani, Masaru; Eto, Kei; Inoue, Toshihiro; Kreymerman, Alexander; Miyake, Seiji; Ueno, Shinji; Nagaya, Masatoshi; Nakanishi, Ayami; Iwao, Keiichiro; Takamura, Yoshihiro; Sakamoto, Hirotaka; Satoh, Keita; Kondo, Mineo; Sakamoto, Tatsuya; Goldberg, Jeffrey L.; Nabekura, Junichi; Tanihara, Hidenobu

    2015-01-01

    The lack of intravital imaging of axonal transport of mitochondria in the mammalian CNS precludes characterization of the dynamics of axonal transport of mitochondria in the diseased and aged mammalian CNS. Glaucoma, the most common neurodegenerative eye disease, is characterized by axon degeneration and the death of retinal ganglion cells (RGCs) and by an age-related increase in incidence. RGC death is hypothesized to result from disturbances in axonal transport and in mitochondrial function. Here we report minimally invasive intravital multiphoton imaging of anesthetized mouse RGCs through the sclera that provides sequential time-lapse images of mitochondria transported in a single axon with submicrometer resolution. Unlike findings from explants, we show that the axonal transport of mitochondria is highly dynamic in the mammalian CNS in vivo under physiological conditions. Furthermore, in the early stage of glaucoma modeled in adult (4-mo-old) mice, the number of transported mitochondria decreases before RGC death, although transport does not shorten. However, with increasing age up to 23–25 mo, mitochondrial transport (duration, distance, and duty cycle) shortens. In axons, mitochondria-free regions increase and lengths of transported mitochondria decrease with aging, although totally organized transport patterns are preserved in old (23- to 25-mo-old) mice. Moreover, axonal transport of mitochondria is more vulnerable to glaucomatous insults in old mice than in adult mice. These mitochondrial changes with aging may underlie the age-related increase in glaucoma incidence. Our method is useful for characterizing the dynamics of axonal transport of mitochondria and may be applied to other submicrometer structures in the diseased and aged mammalian CNS in vivo. PMID:26240337

  12. Spatial statistical analysis of basal stem root disease under natural field epidemic of oil palm

    NASA Astrophysics Data System (ADS)

    Kamu, Assis; Phin, Chong Khim; Seman, Idris Abu; Wan, Hoong Hak; Mun, Ho Chong

    2015-02-01

    Oil palm or scientifically known as Elaeis guineensis Jacq. is the most important commodity crop in Malaysia and has greatly contributed to the economy growth of the country. As far as disease is concerned in the industry, Basal Stem Rot (BSR) caused by Ganoderma boninence remains the most important disease. BSR disease is the most widely studied with information available for oil palm disease in Malaysia. However, there is still limited study on the spatial as well as temporal pattern or distribution of the disease especially under natural field epidemic condition in oil palm plantation. The objective of this study is to spatially identify the pattern of BSR disease under natural field epidemic using two geospatial analytical techniques, which are quadrat analysis for the first order properties of partial pattern analysis and nearest-neighbor analysis (NNA) for the second order properties of partial pattern analysis. Two study sites were selected with different age of tree. Both sites are located in Tawau, Sabah and managed by the same company. The results showed that at least one of the point pattern analysis used which is NNA (i.e. the second order properties of partial pattern analysis) has confirmed the disease is complete spatial randomness. This suggests the spread of the disease is not from tree to tree and the age of palm does not play a significance role in determining the spatial pattern of the disease. From the spatial pattern of the disease, it would help in the disease management program and for the industry in the future. The statistical modelling is expected to help in identifying the right model to estimate the yield loss of oil palm due to BSR disease in the future.

  13. Aberrant subcellular neuronal calcium regulation in aging and Alzheimer's disease.

    PubMed

    Camandola, Simonetta; Mattson, Mark P

    2011-05-01

    In this mini-review/opinion article we describe evidence that multiple cellular and molecular alterations in Alzheimer's disease (AD) pathogenesis involve perturbed cellular calcium regulation, and that alterations in synaptic calcium handling may be early and pivotal events in the disease process. With advancing age neurons encounter increased oxidative stress and impaired energy metabolism, which compromise the function of proteins that control membrane excitability and subcellular calcium dynamics. Altered proteolytic cleavage of the β-amyloid precursor protein (APP) in response to the aging process in combination with genetic and environmental factors results in the production and accumulation of neurotoxic forms of amyloid β-peptide (Aβ). Aβ undergoes a self-aggregation process and concomitantly generates reactive oxygen species that can trigger membrane-associated oxidative stress which, in turn, impairs the functions of ion-motive ATPases and glutamate and glucose transporters thereby rendering neurons vulnerable to excitotoxicity and apoptosis. Mutations in presenilin-1 that cause early-onset AD increase Aβ production, but also result in an abnormal increase in the size of endoplasmic reticulum calcium stores. Some of the events in the neurodegenerative cascade can be counteracted in animal models by manipulations that stabilize neuronal calcium homeostasis including dietary energy restriction, agonists of glucagon-like peptide 1 receptors and drugs that activate mitochondrial potassium channels. Emerging knowledge of the actions of calcium upstream and downstream of Aβ provides opportunities to develop novel preventative and therapeutic interventions for AD. This article is part of a Special Issue entitled: 11th European Symposium on Calcium. PMID:20950656

  14. Parkinson's disease accelerates age-related decline in haptic perception by altering somatosensory integration.

    PubMed

    Konczak, Jürgen; Sciutti, Alessandra; Avanzino, Laura; Squeri, Valentina; Gori, Monica; Masia, Lorenzo; Abbruzzese, Giovanni; Sandini, Giulio

    2012-11-01

    This study investigated how Parkinson's disease alters haptic perception and the underlying mechanisms of somatosensory and sensorimotor integration. Changes in haptic sensitivity and acuity (the abilities to detect and to discriminate between haptic stimuli) due to Parkinson's disease were systematically quantified and contrasted to the performance of healthy older and young adults. Using a robotic force environment, virtual contours of various curvatures were presented. Participants explored these contours with their hands and indicated verbally whether they could detect or discriminate between two contours. To understand what aspects of sensory or sensorimotor integration are altered by ageing and disease, we manipulated the sensorimotor aspect of the task: the robot either guided the hand along the contour or the participant actively moved the hand. Active exploration relies on multimodal sensory and sensorimotor integration, while passive guidance only requires sensory integration of proprioceptive and tactile information. The main findings of the study are as follows: first, a decline in haptic precision can already be observed in adults before the age of 70 years. Parkinson's disease may lead to an additional decrease in haptic sensitivity well beyond the levels typically seen in middle-aged and older adults. Second, the haptic deficit in Parkinson's disease is general in nature. It becomes manifest as a decrease in sensitivity and acuity (i.e. a smaller perceivable range and a diminished ability to discriminate between two perceivable haptic stimuli). Third, thresholds during both active and passive exploration are elevated, but not significantly different from each other. That is, active exploration did not enhance the haptic deficit when compared to passive hand motion. This implies that Parkinson's disease affects early stages of somatosensory integration that ultimately have an impact on processes of sensorimotor integration. Our results suggest that

  15. Empyema and bacteremic pneumococcal pneumonia in children under five years of age*, **

    PubMed Central

    Cardoso, Maria Regina Alves; Nascimento-Carvalho, Cristiana Maria Costa; Ferrero, Fernando; Berezin, Eitan Naaman; Ruvinsky, Raul; Sant'Anna, Clemax Couto; Brandileone, Maria Cristina de Cunto; March, Maria de Fátima Bazhuni Pombo; Maggi, Ruben; Feris-Iglesias, Jesus; Benguigui, Yehuda; Camargos, Paulo Augusto Moreira

    2014-01-01

    We compared bacteremic pneumococcal pneumonia (BPP) and pneumococcal empyema (PE), in terms of clinical, radiological, and laboratory findings, in under-fives. A cross-sectional nested cohort study, involving under-fives (102 with PE and 128 with BPP), was conducted at 12 centers in Argentina, Brazil, and the Dominican Republic. Among those with PE, mean age was higher; disease duration was longer; and tachypnea, dyspnea, and high leukocyte counts were more common. Among those with BPP, fever and lethargy were more common. It seems that children with PE can be distinguished from those with BPP on the basis of clinical and laboratory findings. Because both conditions are associated with high rates of morbidity and mortality, prompt diagnosis is crucial. PMID:24626272

  16. Nonalcoholic fatty liver disease and aging: epidemiology to management.

    PubMed

    Bertolotti, Marco; Lonardo, Amedeo; Mussi, Chiara; Baldelli, Enrica; Pellegrini, Elisa; Ballestri, Stefano; Romagnoli, Dante; Loria, Paola

    2014-10-21

    Nonalcoholic fatty liver disease (NAFLD) is common in the elderly, in whom it carries a more substantial burden of hepatic (nonalcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma) and extra-hepatic manifestations and complications (cardiovascular disease, extrahepatic neoplasms) than in younger age groups. Therefore, proper identification and management of this condition is a major task for clinical geriatricians and geriatric hepatologists. In this paper, the epidemiology and pathophysiology of this condition are reviewed, and a full discussion of the link between NAFLD and the aspects that are peculiar to elderly individuals is provided; these aspects include frailty, multimorbidity, polypharmacy and dementia. The proper treatment strategy will have to consider the peculiarities of geriatric patients, so a multidisciplinary approach is mandatory. Non-pharmacological treatment (diet and physical exercise) has to be tailored individually considering the physical limitations of most elderly people and the need for an adequate caloric supply. Similarly, the choice of drug treatment must carefully balance the benefits and risks in terms of adverse events and pharmacological interactions in the common context of both multiple health conditions and polypharmacy. In conclusion, further epidemiological and pathophysiological insight is warranted. More accurate understanding of the molecular mechanisms of geriatric NAFLD will help in identifying the most appropriate diagnostic and therapeutic approach for individual elderly patients. PMID:25339806

  17. Nonalcoholic fatty liver disease and aging: Epidemiology to management

    PubMed Central

    Bertolotti, Marco; Lonardo, Amedeo; Mussi, Chiara; Baldelli, Enrica; Pellegrini, Elisa; Ballestri, Stefano; Romagnoli, Dante; Loria, Paola

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is common in the elderly, in whom it carries a more substantial burden of hepatic (nonalcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma) and extra-hepatic manifestations and complications (cardiovascular disease, extrahepatic neoplasms) than in younger age groups. Therefore, proper identification and management of this condition is a major task for clinical geriatricians and geriatric hepatologists. In this paper, the epidemiology and pathophysiology of this condition are reviewed, and a full discussion of the link between NAFLD and the aspects that are peculiar to elderly individuals is provided; these aspects include frailty, multimorbidity, polypharmacy and dementia. The proper treatment strategy will have to consider the peculiarities of geriatric patients, so a multidisciplinary approach is mandatory. Non-pharmacological treatment (diet and physical exercise) has to be tailored individually considering the physical limitations of most elderly people and the need for an adequate caloric supply. Similarly, the choice of drug treatment must carefully balance the benefits and risks in terms of adverse events and pharmacological interactions in the common context of both multiple health conditions and polypharmacy. In conclusion, further epidemiological and pathophysiological insight is warranted. More accurate understanding of the molecular mechanisms of geriatric NAFLD will help in identifying the most appropriate diagnostic and therapeutic approach for individual elderly patients. PMID:25339806

  18. Age- and bite-structured models for vector-borne diseases.

    PubMed

    Rock, K S; Wood, D A; Keeling, M J

    2015-09-01

    The biology and behaviour of biting insects is a vitally important aspect in the spread of vector-borne diseases. This paper aims to determine, through the use of mathematical models, what effect incorporating vector senescence and realistic feeding patterns has on disease. A novel model is developed to enable the effects of age- and bite-structure to be examined in detail. This original PDE framework extends previous age-structured models into a further dimension to give a new insight into the role of vector biting and its interaction with vector mortality and spread of disease. Through the PDE model, the roles of the vector death and bite rates are examined in a way which is impossible under the traditional ODE formulation. It is demonstrated that incorporating more realistic functions for vector biting and mortality in a model may give rise to different dynamics than those seen under a more simple ODE formulation. The numerical results indicate that the efficacy of control methods that increase vector mortality may not be as great as predicted under a standard host-vector model, whereas other controls including treatment of humans may be more effective than previously thought. PMID:26342239

  19. Ageing, lifestyle modifications, and cardiovascular disease in developing countries.

    PubMed

    Dominguez, L J; Galioto, A; Ferlisi, A; Pineo, A; Putignano, E; Belvedere, M; Costanza, G; Barbagallo, M

    2006-01-01

    Developing countries face the double menace of still prevalent infectious diseases and increasing cardiovascular disease (CVD) with epidemic proportions in the near future, linked to demographic changes (expansion and ageing), and to urbanisation and lifestyle modifications. It is estimated that the elderly population will increase globally (over 80% during the next 25 years), with a large share of this rise in the developing world because of expanding populations. Increasing longevity prolongs the time exposure to risk factors, resulting in a greater probability of CVD. As a paradox, increased longevity due to improved social and economical conditions associated with lifestyle changes in the direction of a rich diet and sedentary habits in the last century, is one of the main contributors to the incremental trend in CVD. The variable increase rate of CVD in different nations may reflect different stages of "epidemiological transition" and it is probable that the relatively slow changes seen in developing populations through the epidemiological transition may occur at an accelerated pace in individuals migrating from nations in need to affluent societies (i.e. Hispanics to the USA, Africans to Europe). Because of restrained economic conditions in the developing world, the greatest gains in controlling the CVD epidemic lies in its prevention. Healthy foods should be widely available and affordable, and healthy dietary practices such as increased consumption of fresh fruits and vegetables, reduced consumption of saturated fat, salt, and simple sugars, may be promoted in all populations. Specific strategies for smoking and overweight control may be regulation of marketed tobacco and unhealthy fast food and promotion of an active lifestyle. Greater longevity and economic progress are accompanied by an increasing burden of CVD and other chronic diseases with an important decrease in quality of life, which should question the benefit of these additional years without

  20. Polygenic risk of Parkinson disease is correlated with disease age at onset

    PubMed Central

    Escott‐Price, Valentina; Nalls, Mike A.; Morris, Huw R.; Lubbe, Steven; Brice, Alexis; Gasser, Thomas; Heutink, Peter; Wood, Nicholas W.; Hardy, John; Singleton, Andrew B.

    2015-01-01

    Objective We have investigated the polygenic architecture of Parkinson disease (PD) and have also explored the potential relationship between an individual's polygenic risk score and their disease age at onset. Methods This study used genotypic data from 4,294 cases and 10,340 controls obtained from the meta‐analysis of PD genome‐wide association studies. Polygenic score analysis was performed as previously described by the International Schizophrenia Consortium, testing whether the polygenic score alleles identified in 1 association study were significantly enriched in the cases relative to the controls of 3 independent studies. Linear regression was used to investigate the relationship between an individual's polygenic score for PD risk alleles and disease age at onset. Results Our polygenic score analysis has identified significant evidence for a polygenic component enriched in the cases of each of 3 independent PD genome‐wide association cohorts (minimum p = 3.76 × 10−6). Further analysis identified compelling evidence that the average polygenic score in patients with an early disease age at onset was significantly higher than in those with a late age at onset (p = 0.00014). Interpretation This provides strong support for a large polygenic contribution to the overall heritable risk of PD and also suggests that early onset forms of the illness are not exclusively caused by highly penetrant Mendelian mutations, but can also be contributed to by an accumulation of common polygenic alleles with relatively low effect sizes. Ann Neurol 2015;77:582–591 PMID:25773351

  1. 76 FR 73986 - Redelegation of Authority Under the Age Discrimination Act of 1975

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-29

    ... URBAN DEVELOPMENT Redelegation of Authority Under the Age Discrimination Act of 1975 AGENCY: Office of... Age Discrimination Act of 1975, and retains and redelegates this authority, with noted exceptions, to... statutes. Included in that consolidated delegation is the authority to act under the Age Discrimination...

  2. Leukocyte telomere length and prevalence of age-related diseases in semisupercentenarians, centenarians and centenarians' offspring.

    PubMed

    Tedone, Enzo; Arosio, Beatrice; Gussago, Cristina; Casati, Martina; Ferri, Evelyn; Ogliari, Giulia; Ronchetti, Francesco; Porta, Alessandra; Massariello, Francesca; Nicolini, Paola; Mari, Daniela

    2014-10-01

    Centenarians and their offspring are increasingly considered a useful model to study and characterize the mechanisms underlying healthy aging and longevity. The aim of this project is to compare the prevalence of age-related diseases and telomere length (TL), a marker of biological age and mortality, across five groups of subjects: semisupercentenarians (SSCENT) (105-109years old), centenarians (CENT) (100-104years old), centenarians' offspring (CO), age- and gender-matched offspring of parents who both died at an age in line with life expectancy (CT) and age- and gender-matched offspring of both non-long-lived parents (NLO). Information was collected on lifestyle, past and current diseases, medical history and medication use. SSCENT displayed a lower prevalence of acute myocardial infarction (p=0.027), angina (p=0.016) and depression (p=0.021) relative to CENT. CO appeared to be healthier compared to CT who, in turn, displayed a lower prevalence of both arrhythmia (p=0.034) and hypertension (p=0.046) than NLO, characterized by the lowest parental longevity. Interestingly, CO and SSCENT exhibited the longest (p<0.001) and the shortest (p<0.001) telomeres respectively while CENT showed no difference in TL compared to the younger CT and NLO. Our results strengthen the hypothesis that the longevity of parents may influence the health status of their offspring. Moreover, our data also suggest that both CENT and their offspring may be characterized by a better TL maintenance which, in turn, may contribute to their longevity and healthy aging. The observation that SSCENT showed considerable shorter telomeres compared to CENT may suggest a progressive impairment of TL maintenance mechanisms over the transition from centenarian to semisupercentenarian age.

  3. Glutathione as a Biomarker in Parkinson's Disease: Associations with Aging and Disease Severity

    PubMed Central

    Mischley, Laurie K.; Standish, Leanna J.; Weiss, Noel S.; Padowski, Jeannie M.; Kavanagh, Terrance J.; White, Collin C.; Rosenfeld, Michael E.

    2016-01-01

    Objectives. Oxidative stress contributes to Parkinson's disease (PD) pathophysiology and progression. The objective was to describe central and peripheral metabolites of redox metabolism and to describe correlations between glutathione (Glu) status, age, and disease severity. Methods. 58 otherwise healthy individuals with PD were examined during a single study visit. Descriptive statistics and scatterplots were used to evaluate normality and distribution of this cross-sectional sample. Blood tests and magnetic resonance spectroscopy (MRS) were used to collect biologic data. Spearman's rank-order correlation coefficients were used to evaluate the strength and direction of the association. The Unified PD Rating Scale (UPDRS) and the Patient-Reported Outcomes in PD (PRO-PD) were used to rate disease severity using regression analysis. Results. Blood measures of Glu decreased with age, although there was no age-related decline in MRS Glu. The lower the blood Glu concentration, the more severe the UPDRS (P = 0.02, 95% CI: −13.96, −1.14) and the PRO-PD (P = 0.01, 95% CI: −0.83, −0.11) scores. Discussion. These data suggest whole blood Glu may have utility as a biomarker in PD. Future studies should evaluate whether it is a modifiable risk factor for PD progression and whether Glu fortification improves PD outcomes.

  4. Effects of Vitamin E on Cognitive Performance during Ageing and in Alzheimer’s Disease

    PubMed Central

    La Fata, Giorgio; Weber, Peter; Mohajeri, M. Hasan

    2014-01-01

    Vitamin E is an important antioxidant that primarily protects cells from damage associated with oxidative stress caused by free radicals. The brain is highly susceptible to oxidative stress, which increases during ageing and is considered a major contributor to neurodegeneration. High plasma vitamin E levels were repeatedly associated with better cognitive performance. Due to its antioxidant properties, the ability of vitamin E to prevent or delay cognitive decline has been tested in clinical trials in both ageing population and Alzheimer’s disease (AD) patients. The difficulty in performing precise and uniform human studies is mostly responsible for the inconsistent outcomes reported in the literature. Therefore, the benefit of vitamin E as a treatment for neurodegenerative disorders is still under debate. In this review, we focus on those studies that mostly have contributed to clarifying the exclusive function of vitamin E in relation to brain ageing and AD. PMID:25460513

  5. Effect of age on left ventricular function during exercise in patients with coronary artery disease

    SciTech Connect

    Hakki, A.H.; DePace, N.L.; Iskandrian, A.S.

    1983-10-01

    The purpose of this study was to assess the effect of age on left ventricular performance during exercise in 79 patients with coronary artery disease (greater than or equal to 50% narrowing of one or more major coronary arteries). Fifty patients under the age of 60 years (group I) and 29 patients 60 years or older (group II) were studied. Radionuclide angiograms were obtained at rest and during symptom-limited upright bicycle exercise. The history of hypertension, angina or Q wave myocardial infarction was similar in both groups. Multivessel coronary artery disease was present in 30 patients (60%) in group I and in 19 patients (66%) in group II (p . not significant). There were no significant differences between the two groups in the hemodynamic variables (at rest or during exercise) of left ventricular ejection fraction, end-diastolic volume, end-systolic volume and cardiac index. Exercise tolerance was higher in group I than in group II (7.8 +/- 0.4 versus 5.7 +/- 0.4 minutes, p . 0.009), although the exercise heart rate and rate-pressure product were not significantly different between the groups. There was poor correlation between age and ejection fraction, end-diastolic volume and end-systolic volume at rest and during exercise. Abnormal left ventricular function at rest or an abnormal response to exercise was noted in 42 patients (84%) in group I and in 25 patients (86%) in group II (p . not significant). Thus, in patients with coronary artery disease, age does not influence left ventricular function at rest or response to exercise. Older patients with coronary artery disease show changes in left ventricular function similar to those in younger patients with corresponding severity of coronary artery disease.

  6. Feedback-based versus observational classification learning in healthy aging and Parkinson's disease.

    PubMed

    Schmitt-Eliassen, Julia; Ferstl, Roman; Wiesner, Christian; Deuschl, Günther; Witt, Karsten

    2007-04-20

    Previous studies underline the role of dopamine in cognitive reinforcement learning. This has been demonstrated by a striatal involvement in feedback-based probabilistic classification learning. In order to determine to which extent the dopaminergic loss of Parkinson's disease and aging affects the feedback aspect in classification learning, we applied two versions of the same visual classification task. One version had to be learnt by trial-by-trial feedback, the other by observing the correct assignment of stimulus and category. Performance was evaluated in test blocks that were identical under the feedback and the observational conditions. There were 31 patients with Parkinson's disease (PD), 30 older controls and 20 younger controls tested. The results show that younger healthy participants perform better than older participants in the classification task and this difference significantly interacts with the learning condition: both groups show nearly the same level of performance under the observational condition but younger participants show a better performance than older ones under the feedback condition. In contrast, PD patients and older controls did not differ in their performance in the classification task; both groups performed better under the observational than under the feedback condition. These results demonstrate that healthy aging affects feedback-based learning but does not affect learning by observation. The fact that PD patients showed no additional deficit in feedback-based learning is an indication that the loss of dopamine does not play the key role under the feedback condition of our classification task. This finding questions the general role of the striatum in feedback-based learning and demonstrates that healthy aging particularly affects feedback-based learning.

  7. Lung cancer in patients under the age of 40 years

    PubMed Central

    Kaczmarczyk, Grzegorz; Porębska, Irena; Szmygin-Milanowska, Katarzyna; Gołecki, Marcin

    2012-01-01

    Aim of the study In the paper clinical cases of individuals diagnosed with lung cancer below the age of 40 years have been analyzed. Material and methods The analysis included: sex, age, clinical symptoms found before and at the moment of diagnosis, character of changes visible in radiological imaging, time that passed from the first symptoms to reporting to a doctor and to establishing a diagnosis, type of diagnostic method used in establishing the final diagnosis, histopathologic type of cancer, degree of cancer progression. Results The results have been compared with a peer group who had been diagnosed 20 years earlier. Currently 7% of patients were diagnosed at the age of 25 or younger, whereas in the previous cohort patients in this age constituted 2%. The predominant pathological type was adenocarcinoma (currently 33%, previously 4%) in contrast to the earlier group in which 57% of patients had small cell lung cancer (57%). The incidence is equally distributed between both sexes, although there is an evident increase in female lung cancer cases. In the majority of patients the clinical presentation is a peripheral mass on chest X-ray. 20% of patients present pleural effusion on diagnosis. Patients reported the following complaints: breathlessness, chest pain, weight loss and fatigue. The majority of cases were diagnosed in advanced stages on the basis of a bronchoscopy acquired specimen. Time course from symptoms to diagnosis tends to be shorter than 20 years ago. PMID:23788919

  8. 26 CFR 1.7702-2 - Attained age of the insured under a life insurance contract.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... age of the insured under a life insurance contract. (a) In general. This section provides guidance on determining the attained age of an insured under a contract that is a life insurance contract under the... second of the two insureds dies. (ii) Section 1.7702-2(c)(1) provides that if a life insurance...

  9. Epigenetic mechanisms underlying the pathogenesis of neurogenetic diseases.

    PubMed

    Qureshi, Irfan A; Mehler, Mark F

    2014-10-01

    There have been considerable advances in uncovering the complex genetic mechanisms that underlie nervous system disease pathogenesis, particularly with the advent of exome and whole genome sequencing techniques. The emerging field of epigenetics is also providing further insights into these mechanisms. Here, we discuss our understanding of the interplay that exists between genetic and epigenetic mechanisms in these disorders, highlighting the nascent field of epigenetic epidemiology-which focuses on analyzing relationships between the epigenome and environmental exposures, development and aging, other health-related phenotypes, and disease states-and next-generation research tools (i.e., those leveraging synthetic and chemical biology and optogenetics) for examining precisely how epigenetic modifications at specific genomic sites affect disease processes.

  10. 34 CFR 403.92 - Under what circumstances may the age limit under the Sex Equity Program be waived?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Sex Equity Program be waived? 403.92 Section 403.92 Education Regulations of the Offices of the... the Basic Programs? Sex Equity Program § 403.92 Under what circumstances may the age limit under the Sex Equity Program be waived? The individual appointed under § 403.13(a) may waive the requirement...

  11. 34 CFR 403.92 - Under what circumstances may the age limit under the Sex Equity Program be waived?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Sex Equity Program be waived? 403.92 Section 403.92 Education Regulations of the Offices of the... the Basic Programs? Sex Equity Program § 403.92 Under what circumstances may the age limit under the Sex Equity Program be waived? The individual appointed under § 403.13(a) may waive the requirement...

  12. 34 CFR 403.92 - Under what circumstances may the age limit under the Sex Equity Program be waived?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Sex Equity Program be waived? 403.92 Section 403.92 Education Regulations of the Offices of the... the Basic Programs? Sex Equity Program § 403.92 Under what circumstances may the age limit under the Sex Equity Program be waived? The individual appointed under § 403.13(a) may waive the requirement...

  13. 34 CFR 403.92 - Under what circumstances may the age limit under the Sex Equity Program be waived?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Sex Equity Program be waived? 403.92 Section 403.92 Education Regulations of the Offices of the... the Basic Programs? Sex Equity Program § 403.92 Under what circumstances may the age limit under the Sex Equity Program be waived? The individual appointed under § 403.13(a) may waive the requirement...

  14. 34 CFR 403.92 - Under what circumstances may the age limit under the Sex Equity Program be waived?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Sex Equity Program be waived? 403.92 Section 403.92 Education Regulations of the Offices of the... the Basic Programs? Sex Equity Program § 403.92 Under what circumstances may the age limit under the Sex Equity Program be waived? The individual appointed under § 403.13(a) may waive the requirement...

  15. Glomerular diseases and cancer: evaluation of underlying malignancy.

    PubMed

    Pani, Antonello; Porta, Camillo; Cosmai, Laura; Melis, Patrizia; Floris, Matteo; Piras, Doloretta; Gallieni, Maurizio; Rosner, Mitchell; Ponticelli, Claudio

    2016-04-01

    Onconephrology is an emerging medical subspecialty focused on the numerous interconnections between cancer and kidney diseases. Patient with malignancies commonly experience kidney problems including acute kidney injury, tumor lysis syndrome, fluid and electrolyte disorders and chronic kidney disease, often as a consequence of the anti-cancer treatment. Conversely, a number of glomerulopathies, tubulopathies and vascular renal diseases can early signal the presence of an underlying cancer. Furthermore, the administration of immunosuppressive drugs, especially cytotoxic drugs and calcineurin inhibitors, may strongly impair the immune response increasing the risk of cancer. The objective of this review article is to: (i) discuss paraneoplastic glomerular disease, (ii) review cancer as an adverse effect of immunosuppressive agents used to treat glomerulopathies, and (iii) in the absence of international approved guidelines, propose a screening program based on expert opinion aimed at guiding nephrologists to early detect malignancies during their clinical practice. PMID:26498294

  16. College Students' Ageist Behavior: The Role of Aging Knowledge and Perceived Vulnerability to Disease

    ERIC Educational Resources Information Center

    Stahl, Sarah T.; Metzger, Aaron

    2013-01-01

    This cross-sectional study examined the associations among perceived vulnerability to disease, aging knowledge, and ageism (positive and negative) in a sample of undergraduate students enrolled in a human development course (N = 649; M age = 19.94 years, SD = 2.84 years). Perceived vulnerability to disease and aging knowledge were associated with…

  17. Knowledge about Aging and Alzheimer Disease: A Comparison of Professional Caregivers and Noncaregivers

    ERIC Educational Resources Information Center

    Rust, Tiana B.; See, Sheree Kwong

    2007-01-01

    This study assessed professional caregivers of persons with Alzheimer disease (AD) and non-caregivers' knowledge about aging and AD. Participants completed modified versions of the Alzheimer Disease Knowledge Test and the multiple-choice version of the Facts on Aging Quiz #1. Overall, knowledge levels about AD and aging were low. Caregivers were…

  18. Multiple skin neoplasms in subjects under 40 years of age in Goiania, Brazil

    PubMed Central

    Pereira, Samir; Curado, Maria Paula; Ribeiro, Ana Maria Quinteiro

    2015-01-01

    OBJECTIVE To describe the trend for malignant skin neoplasms in subjects under 40 years of age in a region with high ultraviolet radiation indices. METHODS A descriptive epidemiological study on melanoma and nonmelanoma skin cancers that was conducted in Goiania, Midwest Brazil, with 1,688 people under 40 years of age, between 1988 and 2009. Cases were obtained from Registro de Câncer de Base Populacional de Goiânia (Goiania’s Population-Based Cancer File). Frequency, trends, and incidence of cases with single and multiple lesions were analyzed; transplants and genetic skin diseases were found in cases with multiple lesions. RESULTS Over the period, 1,995 skin cancer cases were observed to found, of which 1,524 (90.3%) cases had single lesions and 164 (9.7%) had multiple lesions. Regarding single lesions, incidence on men was observed to have risen from 2.4 to 3.1/100,000 inhabitants; it differed significantly for women, shifting from 2.3 to 5.3/100,000 (Annual percentage change – [APC] 3.0%, p = 0.006). Regarding multiple lesions, incidence on men was observed to have risen from 0.30 to 0.98/100,000 inhabitants; for women, it rose from 0.43 to 1.16/100,000 (APC 8.6%, p = 0.003). Genetic skin diseases or transplants were found to have been correlated with 10.0% of cases with multiple lesions – an average of 5.1 lesions per patient. The average was 2.5 in cases without that correlation. CONCLUSIONS Skin cancer on women under 40 years of age has been observed to be increasing for both cases with single and multiple lesions. It is not unusual to find multiple tumors in young people – in most cases, they are not associated with genetic skin diseases or transplants. It is necessary to avoid excessive exposure to ultraviolet radiation from childhood. PMID:26465667

  19. Mitochondria in health, aging and diseases: the epigenetic perspective.

    PubMed

    D'Aquila, Patrizia; Bellizzi, Dina; Passarino, Giuseppe

    2015-10-01

    The rate/quality of human aging and the development/progression of diseases depend on a complex interplay among genetics, epigenetics and environment. In this scenario, mitochondrial function (or dysfunction) and mitochondrial DNA have emerged as major players. This is mainly due to their crucial role in energetic balance, in modulating epigenetic programs and in influencing cell stress response. Moreover, it is also emerging the existence of epigenetic changes in mitochondrial DNA and of non coding mitochondrial RNAs which, together with the nuclear ones, play regulatory roles in numerous human phenotypes. In this review we will provide an overview on "mitochondrial epigenetics" state of the art, by summarizing the involvement of mitochondrial function and of mitochondria-nucleus communication in regulating nuclear epigenome, as well as the key aspects of the epigenetic marks related to mitochondrial DNA. Despite the limited data available in the literature to date, mainly due to the novelty of the topic, the intriguing interplay of the mitochondrial epigenetic changes in both physiological and pathological conditions will also be presented.

  20. Neurological findings in Alzheimer's disease and normal aging.

    PubMed

    Galasko, D; Kwo-on-Yuen, P F; Klauber, M R; Thal, L J

    1990-06-01

    To determine the potential value of abnormal neurological findings as markers of Alzheimer's disease (AD) and their relationship to the stage of AD, we compared standardized neurological examinations in 135 community-dwelling patients with AD and 91 nondemented elderly individuals. After correcting for differences in age and education between the two groups, we found that rigidity, stooped posture, graphesthesia, neglect of simultaneous tactile stimuli (face-hand test), and snout, grasp, and glabella reflexes were present significantly more often in patients with AD than in control subjects. These findings increased in prevalence in patients with AD according to the severity of dementia. However, in a multivariate logistic regression model only the grasp reflex, graphesthesia, and the face-hand test were statistically significantly associated with the degree of cognitive impairment. Although abnormal neurological findings occur regularly in AD, they are too infrequent early in the course of AD to serve as diagnostic markers. Prospective studies are needed to determine whether patients with the early onset of extrapyramidal or other findings form a distinct subgroup of AD.

  1. Estimation of Heterogeneity in Diagnostic Parameters of Age-related Diseases.

    PubMed

    Blokh, David; Stambler, Ilia

    2014-08-01

    The heterogeneity of parameters is a ubiquitous biological phenomenon, with critical implications for biological systems functioning in normal and diseased states. We developed a method to estimate the level of objects set heterogeneity with reference to particular parameters and applied it to type II diabetes and heart disease, as examples of age-related systemic dysfunctions. The Friedman test was used to establish the existence of heterogeneity. The Newman-Keuls multiple comparison method was used to determine clusters. The normalized Shannon entropy was used to provide the quantitative evaluation of heterogeneity. There was obtained an estimate for the heterogeneity of the diagnostic parameters in healthy subjects, as well as in heart disease and type II diabetes patients, which was strongly related to their age. With aging, as with the diseases, the level of heterogeneity (entropy) was reduced, indicating a formal analogy between these phenomena. The similarity of the patterns in aging and disease suggested a kind of "early aging" of the diseased subjects, or alternatively a "disease-like" aging process, with reference to these particular parameters. The proposed method and its validation on the chronic age-related disease samples may support a way toward a formal mathematical relation between aging and chronic diseases and a formal definition of aging and disease, as determined by particular heterogeneity (entropy) changes. PMID:25110613

  2. Aging study of silica optical fibers under acid environment

    NASA Astrophysics Data System (ADS)

    Severin, I.; El Abdi, R.; Poulain, M.

    2005-05-01

    Optical fibers are key components in telecommunication technologies. Apart from optical specifications, optical fibers are expected to keep most of their physical properties for 10 to 20 years in current operating conditions. The reliability and the expected lifetime of optical links are closely related to the action of the chemical environment on the silica network. However, the coating also contributes largely to the mechanical properties of the fibers. The aim of this work was to study the strength and the mechanical behaviour of the silica optical fibers in an acid environment. A container with ammonium bifluoride acid salt was plunged into hot water at different temperatures (55° and 75°C). This emitted acid vapors which attacked the optical fibers for a period of 1 to 18 days. An aging study was performed on silica optical fibers with standard polyacrylate coating and with hermetic carbon coating. A dynamic two-point bending bench at different faceplate velocities (100, 200, 400 and 800 μm/s) was used. For comparison, the same dynamic measurements were also carried out on non-aged fibers. After acid vapor condensation, salt crystal deposits on the fibers were displayed using an electron scanning microscope. These crystals became visible to the naked eye from the 7th day post exposure.

  3. The Effect of the APOE Genotype on Individual BrainAGE in Normal Aging, Mild Cognitive Impairment, and Alzheimer's Disease.

    PubMed

    Löwe, Luise Christine; Gaser, Christian; Franke, Katja

    2016-01-01

    In our aging society, diseases in the elderly come more and more into focus. An important issue in research is Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) with their causes, diagnosis, treatment, and disease prediction. We applied the Brain Age Gap Estimation (BrainAGE) method to examine the impact of the Apolipoprotein E (APOE) genotype on structural brain aging, utilizing longitudinal magnetic resonance image (MRI) data of 405 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We tested for differences in neuroanatomical aging between carrier and non-carrier of APOE ε4 within the diagnostic groups and for longitudinal changes in individual brain aging during about three years follow-up. We further examined whether a combination of BrainAGE and APOE status could improve prediction accuracy of conversion to AD in MCI patients. The influence of the APOE status on conversion from MCI to AD was analyzed within all allelic subgroups as well as for ε4 carriers and non-carriers. The BrainAGE scores differed significantly between normal controls, stable MCI (sMCI) and progressive MCI (pMCI) as well as AD patients. Differences in BrainAGE changing rates over time were observed for APOE ε4 carrier status as well as in the pMCI and AD groups. At baseline and during follow-up, BrainAGE scores correlated significantly with neuropsychological test scores in APOE ε4 carriers and non-carriers, especially in pMCI and AD patients. Prediction of conversion was most accurate using the BrainAGE score as compared to neuropsychological test scores, even when the patient's APOE status was unknown. For assessing the individual risk of coming down with AD as well as predicting conversion from MCI to AD, the BrainAGE method proves to be a useful and accurate tool even if the information of the patient's APOE status is missing. PMID:27410431

  4. Generative FDG-PET and MRI model of aging and disease progression in Alzheimer's disease.

    PubMed

    Dukart, Juergen; Kherif, Ferath; Mueller, Karsten; Adaszewski, Stanislaw; Schroeter, Matthias L; Frackowiak, Richard S J; Draganski, Bogdan

    2013-04-01

    The failure of current strategies to provide an explanation for controversial findings on the pattern of pathophysiological changes in Alzheimer's Disease (AD) motivates the necessity to develop new integrative approaches based on multi-modal neuroimaging data that captures various aspects of disease pathology. Previous studies using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (sMRI) report controversial results about time-line, spatial extent and magnitude of glucose hypometabolism and atrophy in AD that depend on clinical and demographic characteristics of the studied populations. Here, we provide and validate at a group level a generative anatomical model of glucose hypo-metabolism and atrophy progression in AD based on FDG-PET and sMRI data of 80 patients and 79 healthy controls to describe expected age and symptom severity related changes in AD relative to a baseline provided by healthy aging. We demonstrate a high level of anatomical accuracy for both modalities yielding strongly age- and symptom-severity- dependant glucose hypometabolism in temporal, parietal and precuneal regions and a more extensive network of atrophy in hippocampal, temporal, parietal, occipital and posterior caudate regions. The model suggests greater and more consistent changes in FDG-PET compared to sMRI at earlier and the inversion of this pattern at more advanced AD stages. Our model describes, integrates and predicts characteristic patterns of AD related pathology, uncontaminated by normal age effects, derived from multi-modal data. It further provides an integrative explanation for findings suggesting a dissociation between early- and late-onset AD. The generative model offers a basis for further development of individualized biomarkers allowing accurate early diagnosis and treatment evaluation.

  5. The microbiome and disease: reviewing the links between the oral microbiome, aging, and Alzheimer's disease.

    PubMed

    Shoemark, Deborah K; Allen, Shelley J

    2015-01-01

    This review, gathered from diverse sources, shows how our microbiome influences health and ultimately how well we age. Evidence linking oral bacteria to Alzheimer's disease (AD) is discussed in the context of aging, drawing together data from epidemiological, experimental, genetic, and environmental studies. Immunosenescence results in increased bacterial load as cell-mediated and humoral immune responses wane. The innate immune system gradually takes over; contributing to the rise in circulating proinflammatory cytokines such as TNFα. Maintaining the integrity of the blood-brain barrier (BBB) against a backdrop of increasing bacterial load is important. Aging may favor the proliferation of anaerobes in the mouth eliciting a robust TNFα response from the oral epithelium. Prolonged exposure to high levels of circulating TNFα compromises the integrity of the BBB. Sensitive techniques now detect the "asymptomatic" presence of bacteria in areas previously thought to be sterile, providing new insights into the wider distribution of components of the microbiome. These "immune-tolerated" bacteria may slowly multiply elsewhere until they elicit a chronic inflammatory response; some are now considered causal in instances of atherosclerosis and back pain. Inflammatory processes have long been associated with AD. We propose for a subset of AD patients, aging favors the overgrowth of oral anaerobes established earlier in life provoking a pro-inflammatory innate response that weakens the BBB allowing bacteria to spread and quietly influence the pathogenesis of AD. Finally, we suggest that human polymorphisms considered alongside components of the microbiome may provide new avenues of research for the prevention and treatment of disease.

  6. NOX4 NADPH Oxidase-Dependent Mitochondrial Oxidative Stress in Aging-Associated Cardiovascular Disease

    PubMed Central

    Vendrov, Aleksandr E.; Vendrov, Kimberly C.; Smith, Alberto; Yuan, Jinling; Sumida, Arihiro; Robidoux, Jacques; Madamanchi, Nageswara R.

    2015-01-01

    Abstract Aims: Increased oxidative stress and vascular inflammation are implicated in increased cardiovascular disease (CVD) incidence with age. We and others demonstrated that NOX1/2 NADPH oxidase inhibition, by genetic deletion of p47phox, in Apoe−/− mice decreases vascular reactive oxygen species (ROS) generation and atherosclerosis in young age. The present study examined whether NOX1/2 NADPH oxidases are also pivotal to aging-associated CVD. Results: Both aged (16 months) Apoe−/− and Apoe−/−/p47phox−/− mice had increased atherosclerotic lesion area, aortic stiffness, and systolic dysfunction compared with young (4 months) cohorts. Cellular and mitochondrial ROS (mtROS) levels were significantly higher in aortic wall and vascular smooth muscle cells (VSMCs) from aged wild-type and p47phox−/− mice. VSMCs from aged mice had increased mitochondrial protein oxidation and dysfunction and increased vascular cell adhesion molecule 1 expression, which was abrogated with (2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride (MitoTEMPO) treatment. NOX4 expression was increased in the vasculature and mitochondria of aged mice and its suppression with shRNA in VSMCs from aged mice decreased mtROS levels and improved function. Increased mtROS levels were associated with enhanced mitochondrial NOX4 expression in aortic VSMCs from aged subjects, and NOX4 expression levels in arterial wall correlated with age and atherosclerotic severity. Aged Apoe−/− mice treated with MitoTEMPO and 2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione had decreased vascular ROS levels and atherosclerosis and preserved vascular and cardiac function. Innovation and Conclusion: These data suggest that NOX4, but not NOX1/2, and mitochondrial oxidative stress are mediators of CVD in aging under hyperlipidemic conditions. Regulating NOX4 activity/expression and using mitochondrial antioxidants are

  7. B vitamins and homocysteine in cardiovascular disease and aging.

    PubMed

    Wilcken, D E; Wilcken, B

    1998-11-20

    The sulfur-containing amino acid, homocysteine, is formed from the essential amino acid methionine, and a number of B vitamins are involved in methionine metabolism. Pyridoxine, vitamin B6, is a cofactor for cystathionine beta synthase, which mediates the transformation of homocysteine to cystathionine, the initial step in the transsulfuration pathway and the urinary excretion of sulfur. In a normal diet there is conservation of the carbon skeleton, and about 50% of the homocysteine formed is remethylated to methionine via steps that require folic acid and vitamin B12. A deficiency of any of these three vitamins leads to modest homocyst(e)ine elevation, as does diminished renal function, both of which are common in the elderly. It is also established that homocyst(e)ine elevation of this order is associated with increased cardiovascular risk but is also associated with most established risk factors, although it is thought to be an independent contributor. In the inborn error of metabolism homocystinuria due to cystathionine beta synthase deficiency there is greatly increased circulating homocyst(e)ine and a clear association with precocious vascular disease. In about 50% of these patients there is a vascular event before the age of 30 years. The homocysteine-induced adverse vascular changes appear to result from endothelial and smooth muscle cell effects and increased thrombogenesis. We have documented a highly significant reduction in the occurrence of vascular events during 539 patient years of treatment in 32 patients with cystathionine beta synthase deficiency (mean age 30 years, range 9-66 years) by aggressive homocyst(e)ine lowering with pyridoxine, folic acid, and B12 (p = 0.0001). The 15 pyridoxine nonresponsive patients also received oral betaine. Although a cause and effect relationship is postulated for the increased cardiovascular risk associated with mild homocysteine elevation, a common cause of this elevation is the methylenetetrahydrofolate

  8. Brain Na+, K+-ATPase Activity In Aging and Disease

    PubMed Central

    de Lores Arnaiz, Georgina Rodríguez; Ordieres, María Graciela López

    2014-01-01

    , enzyme changes in diverse neurological diseases as well as during aging, have been summarized. Issues refer mainly to Na+, K+-ATPase studies in ischemia, brain injury, depression and mood disorders, mania, stress, Alzheimer´s disease, learning and memory, and neuronal hyperexcitability and epilepsy. PMID:25018677

  9. Humoral immunity in brain aging and Alzheimer's disease.

    PubMed

    Bouras, Constantin; Riederer, Beat M; Kövari, Enikö; Hof, Patrick R; Giannakopoulos, Panteleimon

    2005-06-01

    Although the contribution of inflammatory processes in the etiology of late-onset Alzheimer's disease (AD) has been suspected for years, most studies were confined to the analysis of cell-mediated immunological reactions thought to represent an epiphenomenon of AD lesion development. Based on the traditional view of the "immunological privilege" of the brain, which excludes a direct access of human immunoglobulins (Ig) to the central nervous system under normal conditions, little attention has been paid to a possible role of humoral immunity in AD pathogenesis. In the first part of this review, we summarize evidences for a blood-brain barrier (BBB) dysfunction in this disorder and critically comment on earlier observations supporting the presence of anti-brain autoantibodies and immunoglobulins (Ig) in AD brains. Current concepts regarding the Ig turnover in the central nervous system and the mechanisms of glial and neuronal Fc receptors activation are also discussed. In the second part, we present new ex vivo and in vitro data suggesting that human immunoglobulins can interact with tau protein and alter both the dynamics and structural organization of microtubules. Subsequent experiments needed to test this new working hypothesis are addressed at the end of the review.

  10. [Functional, involutional and pathological oral changes with age. 6. Systemic disease].

    PubMed

    Castellanos, J L; Díaz Guzman, L

    1990-01-01

    The present study was realized to determine the frequency variety and concentration of old and new health disease in patients attending a school of Dentistry, classification to an age variable. This paper ends a series of articles about estomatological changes associated to an aging process. The main findings indicate that when patients grow older an increment in variety and number of pathological personal background. The results suggest a very well defined difference in the prevalence and concentration among subjects over and under 50 years. The risk factor was 1:1 in patients older than that. The importance of considering the Clinical history in patients as a determining factor in the global dental evaluation, for the decision. making in treatment planning. PMID:2144118

  11. [Functional, involutional and pathological oral changes with age. 6. Systemic disease].

    PubMed

    Castellanos, J L; Díaz Guzman, L

    1990-01-01

    The present study was realized to determine the frequency variety and concentration of old and new health disease in patients attending a school of Dentistry, classification to an age variable. This paper ends a series of articles about estomatological changes associated to an aging process. The main findings indicate that when patients grow older an increment in variety and number of pathological personal background. The results suggest a very well defined difference in the prevalence and concentration among subjects over and under 50 years. The risk factor was 1:1 in patients older than that. The importance of considering the Clinical history in patients as a determining factor in the global dental evaluation, for the decision. making in treatment planning.

  12. Age-specific Parkinson disease risk in GBA mutation carriers: information for genetic counseling

    PubMed Central

    Rana, Huma Q.; Balwani, Manisha; Bier, Louise; Alcalay, Roy N.

    2012-01-01

    Purpose We sought to estimate age-specific risk of Parkinson disease in relatives of patients with Gaucher disease, who are obligate carriers of GBA mutations and who were not ascertained by family history of Parkinson disease. Methods A validated family history of Parkinson disease questionnaire was administered to 119 patients with Gaucher disease who were evaluated at the Mount Sinai School of Medicine from 2009 to 2012; the ages of their parents, siblings, and children, history of Parkinson disease, age at onset of Parkinson disease, and ethnic background were obtained. Kaplan–Meier survival curves were used to estimate age-specific Parkinson disease penetrance among parents of patients with Gaucher disease, who are obligatory GBA mutation carriers. Results Two participants with Gaucher disease were affected by Parkinson disease (5.4% of those who were 60 years or older). Of the 224 informative parents of patients with Gaucher disease, 11 had Parkinson disease (4.9%). Among the parents (obligatory carriers), cumulative risk of Parkinson disease by ages 65 and 85 was estimated to be 2.2% ±2.1% and 10.9% ±7.2%, respectively. Conclusion We provide useful age-specific estimates of Parkinson disease penetrance in patients with Gaucher disease and GBA heterozygous carriers for genetic counseling. Although GBA mutations may increase the risk for PD, the vast majority of patients with Gaucher disease and heterozygotes may not develop the disease. Further studies are needed to identify what modifies the risk of Parkinson disease in GBA mutation carriers. PMID:22935721

  13. Beyond membrane channelopathies: alternative mechanisms underlying complex human disease

    PubMed Central

    Boudoulas, Konstantinos Dean; Mohler, Peter J

    2011-01-01

    Over the past fifteen years, our understanding of the molecular mechanisms underlying human disease has flourished in large part due to the discovery of gene mutations linked with membrane ion channels and transporters. In fact, ion channel defects (“channelopathies” — the focus of this review series) have been associated with a spectrum of serious human disease phenotypes including cystic fibrosis, cardiac arrhythmia, diabetes, skeletal muscle defects, and neurological disorders. However, we now know that human disease, particularly excitable cell disease, may be caused by defects in non-ion channel polypeptides including in cellular components residing well beneath the plasma membrane. For example, over the past few years, a new class of potentially fatal cardiac arrhythmias has been linked with cytoplasmic proteins that include sub-membrane adapters such as ankyrin-B (ANK2), ankyrin-G (ANK3), and alpha-1 syntrophin, membrane coat proteins including caveolin-3 (CAV3), signaling platforms including yotiao (AKAP9), and cardiac enzymes (GPD1L). The focus of this review is to detail the exciting role of lamins, yet another class of gene products that have provided elegant new insight into human disease. PMID:21642948

  14. [Endothelial dysfunction as a marker of vascular aging syndrome on the background of hypertension, coronary heart disease, gout and obesity].

    PubMed

    Vatseba, M O

    2013-09-01

    Under observation were 40 hypertensive patients with coronary heart disease, gout and obesity I and II degree. Patients with hypertension in combination with coronary heart disease, gout and obesity, syndrome of early vascular aging is shown by increased stiffness of arteries, increased peak systolic flow velocity, pulse blood presure, the thickness of the intima-media complex, higher level endotelinemia and reduced endothelial vasodilation. Obtained evidence that losartan in complex combination with basic therapy and metamaks in complex combination with basic therapy positively affect the elastic properties of blood vessels and slow the progression of early vascular aging syndrome.

  15. Scientific truth or false hope? Understanding Alzheimer's disease from an aging perspective.

    PubMed

    Chen, Ming; Maleski, Jerome J; Sawmiller, Darrell R

    2011-01-01

    In this paper, we argue that the current official definition for Alzheimer's disease is misleading, since it defines senile dementia (SD), a long-known incurable senile/geriatric condition, as a discrete/curable disease. This overly optimistic definition was incepted in the 1970s amid the public's fear of the upcoming SD crisis and desperate hope for a cure. Scientifically, however, it has overturned Alois Alzheimer's age-based concept for disease classification-the essence of modern Geriatric Medicine and the National Institute of Aging. Thus, the current definition for SD, though socially and politically appealing, would be scientifically flawed. As an authoritative study guideline, it has caused profound and far-reaching confusions in research by misleading attention to the presumptive pathogenic/erroneous factors as drug targets for "silver bullets". Such well-intentioned studies would generate numerous data, but render SD a scientific and logical enigma. In this context we discuss: 1) why and how senile conditions including SD differ from discrete diseases by origin, thus also by study paradigm and intervention strategy; 2) why senile conditions may not be explained by abnormal/pathogenic factors, but logically should be explained by "normal" elements in life, perhaps advanced aging plus risk factors; and 3) why the "amyloid-β toxicity" controversy, a simple scientific issue, has lasted for so long. Finally, we ask: can scientific inquiry preserve its integrity and objectivity under social pressure? It appears that these fundamental questions warrant serious attention if the scientific nature of SD is to be eventually understood.

  16. 'I hope that I get old before I die': ageing and the concept of disease.

    PubMed

    Schramme, Thomas

    2013-06-01

    Ageing is often deemed bad for people and something that ought to be eliminated. An important aspect of this normative aspect of ageing is whether ageing, i.e., senescence, is a disease. In this essay, I defend a theory of disease that concludes that ageing is not a disease, based on an account of natural function. I also criticize other arguments that lead to the same conclusion. It is important to be clear about valid reasons in this debate, since the failure of bad analyses is exploited by proponents of the view that ageing is indeed a disease. Finally, I argue that there could be other reasons for attempting to eradicate senescence, which have to do with an evaluative assessment of ageing in relation to the good life. I touch on some reasons why ageing might be good for people and conclude that we cannot justify generalized statements in this regard.

  17. Implementation of an active aging model in Mexico for prevention and control of chronic diseases in the elderly

    PubMed Central

    Mendoza-Núñez, Víctor Manuel; Martínez-Maldonado, María de la Luz; Correa-Muñoz, Elsa

    2009-01-01

    Background World Health Organization cites among the main challenges of populational aging the dual disease burden: the greater risk of disability, and the need for care. In this sense, the most frequent chronic diseases during old age worldwide are high blood pressure, type 2 diabetes mellitus, cancer, arthritis, osteoporosis, depression, and dementia. Chronic disease-associated dependency represents an onerous sanitary and financial burden for the older adult, the family, and the health care system. Thus, it is necessary to propose community-level models for chronic disease prevention and control in old age. The aim of the present work is to show our experience in the development and implementation of a model for chronic disease prevention and control in old age at the community level under the active aging paradigm. Methods/Design A longitudinal study will be carried out in a sample of 400 elderly urban and rural-dwelling individuals residing in Hidalgo State, Mexico during five years. All participants will be enrolled in the model active aging. This establishes the formation of 40 gerontological promoters (GPs) from among the older adults themselves. The GPs function as mutual-help group coordinators (gerontological nuclei) and establish self-care and self-promotion actions for elderly well-being and social development. It will be conformed a big-net of social network of 40 mutual-help groups of ten elderly adults each one, in which self-care is a daily practice for chronic disease prevention and control, as well as for achieving maximal well-being and life quality in old age. Indicators of the model's impact will be (i) therapeutic adherence; (ii) the incidence of the main chronic diseases in old age; (iii) life expectancy without chronic diseases at 60 years of age; (iv) disability adjusted life years lost; (v) years of life lost due to premature mortality, and (vi) years lived with disability. Discussion We propose that the implementation of the model active

  18. Roles of O-GlcNAc in chronic diseases of aging.

    PubMed

    Banerjee, Partha S; Lagerlöf, Olof; Hart, Gerald W

    2016-10-01

    O-GlcNAcylation, a dynamic nutrient and stress sensitive post-translational modification, occurs on myriad proteins in the cell nucleus, cytoplasm and mitochondria. O-GlcNAcylation serves as a nutrient sensor to regulate signaling, transcription, translation, cell division, metabolism, and stress sensitivity in all cells. Aberrant protein O-GlcNAcylation plays a critical role both in the development, as well as in the progression of a variety of age related diseases. O-GlcNAcylation underlies the etiology of diabetes, and changes in specific protein O-GlcNAc levels and sites are responsible for insulin expression and sensitivity and glucose toxicity. Abnormal O-GlcNAcylation contributes directly to diabetes related dysfunction of the heart, kidney and eyes and affects progression of cardiomyopathy, nephropathy and retinopathy. O-GlcNAcylation is a critical modification in the brain and plays a role in both plaque and tangle formation, thus making its study important in neurodegenerative disorders. O-GlcNAcylation also affects cellular growth and metabolism during the development and metastasis of cancer. Finally, alterations in O-GlcNAcylation of transcription factors in macrophages and lymphocytes affect inflammation and cytokine production. Thus, O-GlcNAcylation plays key roles in many of the major diseases associated with aging. Elucidation of its specific functions in both normal and diseased tissues is likely to uncover totally novel avenues for therapeutic intervention.

  19. Looking for disease being a model of human aging

    PubMed Central

    Hausmanowa-Petrusewicz, I; Madej-Pilarczyk, A

    2007-01-01

    Summary This paper is a part of an introduction to authors’ study on systemic laminopathies and their role in human aging. Of special interest is progeria – a type of systemic laminopathy associated usually with mutation 1824 C > T and presenting phenotype of preliminary aging. The authors analyse the differences between the progeria and other syndrome of preliminary aging – Werner’s syndrome. PMID:18421896

  20. Changes in sensory reweighting of proprioceptive information during standing balance with age and disease.

    PubMed

    Pasma, J H; Engelhart, D; Maier, A B; Schouten, A C; van der Kooij, H; Meskers, C G M

    2015-12-01

    With sensory reweighting, reliable sensory information is selected over unreliable information during balance by dynamically combining this information. We used system identification techniques to show the weight and the adaptive process of weight change of proprioceptive information during standing balance with age and specific diseases. Ten healthy young subjects (aged between 20 and 30 yr) and 44 elderly subjects (aged above 65 yr) encompassing 10 healthy elderly, 10 with cataract, 10 with polyneuropathy, and 14 with impaired balance, participated in the study. During stance, proprioceptive information of the ankles was disturbed by rotation of the support surface with specific frequency content where disturbance amplitude increased over trials. Body sway and reactive ankle torque were measured to determine sensitivity functions of these responses to the disturbance amplitude. Model fits resulted in a proprioceptive weight (changing over trials), time delay, force feedback, reflexive stiffness, and damping. The proprioceptive weight was higher in healthy elderly compared with young subjects and higher in elderly subjects with cataract and with impaired balance compared with healthy elderly subjects. Proprioceptive weight decreased with increasing disturbance amplitude; decrease was similar in all groups. In all groups, the time delay was higher and the reflexive stiffness was lower compared with young or healthy elderly subjects. In conclusion, proprioceptive information is weighted more with age and in patients with cataract and impaired balance. With age and specific diseases the time delay was higher and reflexive stiffness was lower. These results illustrate the opportunity to detect the underlying cause of impaired balance in the elderly with system identification.

  1. Linear and Curvilinear Trajectories of Cortical Loss with Advancing Age and Disease Duration in Parkinson’s Disease

    PubMed Central

    Claassen, Daniel O.; Dobolyi, David G.; Isaacs, David A.; Roman, Olivia C.; Herb, Joshua; Wylie, Scott A.; Neimat, Joseph S.; Donahue, Manus J.; Hedera, Peter; Zald, David H.; Landman, Bennett A.; Bowman, Aaron B.; Dawant, Benoit M.; Rane, Swati

    2016-01-01

    Advancing age and disease duration both contribute to cortical thinning in Parkinson’s disease (PD), but the pathological interactions between them are poorly described. This study aims to distinguish patterns of cortical decline determined by advancing age and disease duration in PD. A convenience cohort of 177 consecutive PD patients, identified at the Vanderbilt University Movement Disorders Clinic as part of a clinical evaluation for Deep Brain Stimulation (age: M= 62.0, SD 9.3), completed a standardized clinical assessment, along with structural brain Magnetic Resonance Imaging scan. Age and gender matched controls (n=53) were obtained from the Alzheimer Disease Neuroimaging Initiative and Progressive Parkinson’s Marker Initiative (age: M= 63.4, SD 12.2). Estimated changes in cortical thickness were modeled with advancing age, disease duration, and their interaction. The best-fitting model, linear or curvilinear (2nd, or 3rd order natural spline), was defined using the minimum Akaike Information Criterion, and illustrated on a 3-dimensional brain. Three curvilinear patterns of cortical thinning were identified: early decline, late decline, and early-stable-late. In contrast to healthy controls, the best-fit model for age related changes in PD is curvilinear (early decline), particularly in frontal and precuneus regions. With advancing disease duration, a curvilinear model depicts accelerating decline in the occipital cortex. A significant interaction between advancing age and disease duration is evident in frontal, motor, and posterior parietal areas. Study results support the hypothesis that advancing age and disease duration differentially affect regional cortical thickness and display regional dependent linear and curvilinear patterns of thinning. PMID:27330836

  2. Mechanistically linking age-related diseases and dietary carbohydrate via autophagy and the ubiquitin proteolytic systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiological data indicate that consuming diets that deliver sugar to the blood rapidly (called high glycemic index, GI) is associated with enhanced risk for age-related diseases such as cardiovascular disease, type 2 diabetes, cataract and age-related macular degeneration (AMD). These debilities...

  3. Characterization of Finnish Building materials under salt frost artificial ageing

    NASA Astrophysics Data System (ADS)

    Luodes, Nike M.; Torppa, Akseli; Pirinen, Heikki; Bellopede, Rossana; Marini, Paola

    2016-04-01

    Under a national project co financed by the Confederation of Finnish Construction Industries RT (CFCI), the Finnish Natural Stone Association and the Geological Survey of Finland (GTK), and thanks to the cooperation with the Polytechnic of Turin a comprehensive number of Finnish natural stones has been tested according to SFS EN standards for national CE marking and according to non standardized methods for research purposes. The aim was to evaluate the effects of combined salt and frost weathering caused by de-icing salts and to research a possible correlation between laboratory's accelerated decay and site weathering. The materials tested (60 stones in total) are mainly silicate rocks showing good resistance to the weathering. Results have been affected in some cases by uncertainties connected to the variation of material quality. Some materials have been from new quarries and variation of their properties has been higher than the effects of artificial weathering. Material sampled from crop presented higher weathering level and the additional artificial weathering has induced small variations. Results have shown that material weathering has been better represented by variation of flexural strength compared to uniaxial compressive strength. The most probable reason has been that small changes of planarity and perpendicularity had greater effects on the compressive strength than variations by weathering. Fifteen representative typologies of natural stones have been tested with non standardized methodologies to study the changes of the material and finding a possible correlation with methods used on site. Schmidt rebound test and Ultra Pulse Velocity (UPV) have been used on site to assess the durability of stone on construction. Materials tested in laboratory have shown less variation between rebounds compared to site tests, this can be because of a more controlled environment and saw cut surface instead of rocky or chiselled ones. Laboratory tests showed an average

  4. Maqua (therapeutic burn) as an indicator of underlying disease.

    PubMed

    Rosenberg, L; Sagi, A; Stahl, N; Greber, B; Ben-Meir, P

    1988-08-01

    The origin and nature of the maqua (the Arabic therapeutic burn) is presented together with our clinical experience of patients previously treated by this traditional method. Maquas are small deep burns inflicted in areas either in proximity to a diseased organ or in points related traditionally to the original basic problem. These relationships may be rooted in historical ties between old Arab medicine and traditional Oriental, antique Egyptian, and Greco-Roman medicines. Maquas alone only rarely present a threat to the patient, but in many cases they may serve as an indicator of the original underlying disease. This and other folklore treatment modalities, together with the healers themselves, should be acknowledged by us, as markers for health problems or maybe for potential healing methods and doctor-patient relationships. PMID:3041427

  5. Why AMD is a disease of ageing and not of development: mechanisms and insights

    PubMed Central

    Sharma, Kaushal; Sharma, Neel Kamal; Anand, Akshay

    2014-01-01

    Ageing disorders can be defined as the progressive and cumulative outcome of several defective cellular mechanisms as well as metabolic pathways, consequently resulting in degeneration. Environment plays an important role in its pathogenesis. In contrast, developmental disorders arise from inherited mutations and usually the role of environmental factors in development of disease is minimal. Age related macular degeneration (AMD) is one such retinal degenerative disorder which starts with the progression of age. Metabolism plays an important role in initiation of such diseases of ageing. Cholesterol metabolism and their oxidized products like 7-ketocholesterol have been shown to adversely impact retinal pigment epithelium (RPE) cells. These molecules can initiate mitochondrial apoptotic processes and also influence the complements factors and expression of angiogenic proteins like VEGF etc. In this review we highlight why and how AMD is an ageing disorder and not a developmental disease substantiated by disrupted cholesterol metabolism common to several age related diseases. PMID:25071560

  6. The interrelationship between disease and ageing and the implications for longevity.

    PubMed

    Potter, Paul K

    2015-01-01

    Ageing is generally viewed as a detrimental phenotype; with age comes increasing susceptibility to disease and frailty. Recent data also suggests that disease can result in an increase in ageing phenotypes suggesting a positive feedback loop. It is clear that lifespan can be modified genetically and by interventions in certain organisms but the mechanisms by which this is achieved have not yet been fully elucidated, as indeed is the case for the ageing process itself. Because of the intimate relationship between disease, ageing and ultimately lifespan it is difficult to dissect the effects of individual changes. As we learn more about individual pathways and allelic variants influencing ageing and disease we can begin to unravel the influence of natural selection on these processes.

  7. Telomeres and telomerase as therapeutic targets to prevent and treat age-related diseases

    PubMed Central

    Bär, Christian; Blasco, Maria A.

    2016-01-01

    Telomeres, the protective ends of linear chromosomes, shorten throughout an individual’s lifetime. Telomere shortening is a hallmark of molecular aging and is associated with premature appearance of diseases associated with aging. Here, we discuss the role of telomere shortening as a direct cause for aging and age-related diseases. In particular, we draw attention to the fact that telomere length influences longevity. Furthermore, we discuss intrinsic and environmental factors that can impact on human telomere erosion. Finally, we highlight recent advances in telomerase-based therapeutic strategies for the treatment of diseases associated with extremely short telomeres owing to mutations in telomerase, as well as age-related diseases, and ultimately aging itself. PMID:27081482

  8. Consumption of polyphenol plants may slow aging and associated diseases.

    PubMed

    Uysal, Utku; Seremet, Sila; Lamping, Jeffrey W; Adams, Jerome M; Liu, Deede Y; Swerdlow, Russell H; Aires, Daniel J

    2013-01-01

    Slowing aging is a widely shared goal. Plant-derived polyphenols, which are found in commonly consumed food plants such as tea, cocoa, blueberry and grape, have been proposed to have many health benefits, including slowing aging. In-vivo studies have demonstrated the lifespan-extending ability of six polyphenol-containing plants. These include five widely consumed foods (tea, blueberry, cocoa, apple, pomegranate) and a flower commonly used as a folk medicine (betony). These and multiple other plant polyphenols have been shown to have beneficial effects on aging-associated changes across a variety of organisms from worm and fly to rodent and human. PMID:23448445

  9. DNA damage response at telomeres contributes to lung aging and chronic obstructive pulmonary disease.

    PubMed

    Birch, Jodie; Anderson, Rhys K; Correia-Melo, Clara; Jurk, Diana; Hewitt, Graeme; Marques, Francisco Madeira; Green, Nicola J; Moisey, Elizabeth; Birrell, Mark A; Belvisi, Maria G; Black, Fiona; Taylor, John J; Fisher, Andrew J; De Soyza, Anthony; Passos, João F

    2015-11-15

    Cellular senescence has been associated with the structural and functional decline observed during physiological lung aging and in chronic obstructive pulmonary disease (COPD). Airway epithelial cells are the first line of defense in the lungs and are important to COPD pathogenesis. However, the mechanisms underlying airway epithelial cell senescence, and particularly the role of telomere dysfunction in this process, are poorly understood. We aimed to investigate telomere dysfunction in airway epithelial cells from patients with COPD, in the aging murine lung and following cigarette smoke exposure. We evaluated colocalization of γ-histone protein 2A.X and telomeres and telomere length in small airway epithelial cells from patients with COPD, during murine lung aging, and following cigarette smoke exposure in vivo and in vitro. We found that telomere-associated DNA damage foci increase in small airway epithelial cells from patients with COPD, without significant telomere shortening detected. With age, telomere-associated foci increase in small airway epithelial cells of the murine lung, which is accelerated by cigarette smoke exposure. Moreover, telomere-associated foci predict age-dependent emphysema, and late-generation Terc null mice, which harbor dysfunctional telomeres, show early-onset emphysema. We found that cigarette smoke accelerates telomere dysfunction via reactive oxygen species in vitro and may be associated with ataxia telangiectasia mutated-dependent secretion of inflammatory cytokines interleukin-6 and -8. We propose that telomeres are highly sensitive to cigarette smoke-induced damage, and telomere dysfunction may underlie decline of lung function observed during aging and in COPD.

  10. Hippocampal sclerosis and TDP-43 pathology in aging and Alzheimer’s Disease

    PubMed Central

    Nag, Sukriti; Yu, Lei; Capuano, Ana W.; Wilson, Robert S.; Leurgans, Sue E.; Bennett, David A.; Schneider, Julie A.

    2015-01-01

    Objective To investigate the association of hippocampal sclerosis (HS) with TAR-DNA binding protein of 43 kDa (TDP-43) and other common age-related pathologies, dementia, probable Alzheimer’s disease (AD), mild cognitive impairment (MCI) and cognitive domains in community-dwelling older subjects. Methods Diagnoses of dementia, probable AD and MCI in 636 autopsied subjects from the Religious Order Study and the Rush Memory and Aging Project were based on clinical evaluation and cognitive performance tests. HS was defined as severe neuronal loss and gliosis in the hippocampal CA1and/or subiculum. The severity and distribution of TDP-43 was assessed and other age-related pathologies were also documented. Results HS was more common in those aged > 90 years (18.0%) compared to younger subjects (9.2%). HS cases commonly coexisted with TDP-43 pathology (86%), which was more severe (p < 0.001) in HS cases. Although, HS also commonly coexisted with AD and Lewy body (LB) pathology; only TDP-43 pathology increased the odds of HS (OR=2.63; 95% CI 2.07-3.34). In logistic regression models accounting for age, TDP-43 and other common age-related pathologies; HS cases had higher odds of dementia (OR=3.71; 95% CI=1.93-7.16), MCI and probable AD (OR=3.75; 95% CI=2.01-7.02). In linear regression models, including an interaction term for HS and TDP-43 pathology; HS with coexisting TDP-43 was associated with lower function in multiple cognitive domains while HS without TDP-43 did not have statistically significant associations. TDP-43 without HS was separately related to lower episodic memory. Interpretation The combined role of hippocampal sclerosis and TDP-43 pathology are significant factors underlying global cognitive impairment and probable AD in older subjects. PMID:25707479

  11. Epidemiology of Chronic Obstructive Pulmonary Disease (COPD) in Aging Populations.

    PubMed

    Fragoso, Carlos A Vaz

    2016-01-01

    Current epidemiologic practice evaluates COPD based on self-reported symptoms of chronic bronchitis, self-reported physician-diagnosed COPD, spirometry confirmed airflow obstruction, or emphysema diagnosed by volumetric computed chest tomography (CT). Because the highest risk population for having COPD includes a predominance of middle-aged or older persons, aging related changes must also be considered, including: 1) increased multimorbidity, polypharmacy, and severe deconditioning, as these identify mechanisms that underlie respiratory symptoms and can impart a complex differential diagnosis; 2) increased airflow limitation, as this impacts the interpretation of spirometry confirmed airflow obstruction; and 3) "senile" emphysema, as this impacts the specificity of CT-diagnosed emphysema. Accordingly, in an era of rapidly aging populations worldwide, the use of epidemiologic criteria that do not rigorously consider aging related changes will result in increased misidentification of COPD and may, in turn, misinform public health policy and patient care. PMID:26629987

  12. Impact of Typical Aging and Parkinson's Disease on the Relationship among Breath Pausing, Syntax, and Punctuation

    ERIC Educational Resources Information Center

    Huber, Jessica E.; Darling, Meghan; Francis, Elaine J.; Zhang, Dabao

    2012-01-01

    Purpose: The present study examines the impact of typical aging and Parkinson's disease (PD) on the relationship among breath pausing, syntax, and punctuation. Method: Thirty young adults, 25 typically aging older adults, and 15 individuals with PD participated. Fifteen participants were age- and sex-matched to the individuals with PD.…

  13. Age, Predisposing Diseases, and Ultrasonographic Findings in Determining Clinical Outcome of Acute Acalculous Inflammatory Gallbladder Diseases in Children

    PubMed Central

    2016-01-01

    We evaluated clinical factors such as age, gender, predisposing diseases and ultrasonographic findings that determine clinical outcome of acute acalculous inflammatory gallbladder diseases in children. The patients were divided into the four age groups. From March 2004 through February 2014, clinical data from 131 children diagnosed as acute acalculous inflammatory gallbladder disease by ultrasonography were retrospectively reviewed. Systemic infectious diseases were the most common etiology of acute inflammatory gallbladder disease in children and were identified in 50 patients (38.2%). Kawasaki disease was the most common predisposing disease (28 patients, 21.4%). The incidence was highest in infancy and lowest in adolescence. The age groups were associated with different predisposing diseases; noninfectious systemic disease was the most common etiology in infancy and early childhood, whereas systemic infectious disease was the most common in middle childhood and adolescence (P = 0.001). Gallbladder wall thickening was more commonly found in malignancy (100%) and systemic infection (94.0%) (P = 0.002), whereas gallbladder distension was more frequent in noninfectious systemic diseases (60%) (P = 0.000). Ascites seen on ultrasonography was associated with a worse clinical course compared with no ascites (77.9% vs. 37.7%, P = 0.030), and the duration of hospitalization was longer in patients with ascites (11.6 ± 10.7 vs. 8.0 ± 6.6 days, P = 0.020). In conclusion, consideration of age and predisposing disease in addition to ultrasonographic gallbladder findings in children suspected of acute acalculous inflammatory gallbladder disease might result in better outcomes. PMID:27550491

  14. Age, Predisposing Diseases, and Ultrasonographic Findings in Determining Clinical Outcome of Acute Acalculous Inflammatory Gallbladder Diseases in Children.

    PubMed

    Yi, Dae Yong; Chang, Eun Jae; Kim, Ji Young; Lee, Eun Hye; Yang, Hye Ran

    2016-10-01

    We evaluated clinical factors such as age, gender, predisposing diseases and ultrasonographic findings that determine clinical outcome of acute acalculous inflammatory gallbladder diseases in children. The patients were divided into the four age groups. From March 2004 through February 2014, clinical data from 131 children diagnosed as acute acalculous inflammatory gallbladder disease by ultrasonography were retrospectively reviewed. Systemic infectious diseases were the most common etiology of acute inflammatory gallbladder disease in children and were identified in 50 patients (38.2%). Kawasaki disease was the most common predisposing disease (28 patients, 21.4%). The incidence was highest in infancy and lowest in adolescence. The age groups were associated with different predisposing diseases; noninfectious systemic disease was the most common etiology in infancy and early childhood, whereas systemic infectious disease was the most common in middle childhood and adolescence (P = 0.001). Gallbladder wall thickening was more commonly found in malignancy (100%) and systemic infection (94.0%) (P = 0.002), whereas gallbladder distension was more frequent in noninfectious systemic diseases (60%) (P = 0.000). Ascites seen on ultrasonography was associated with a worse clinical course compared with no ascites (77.9% vs. 37.7%, P = 0.030), and the duration of hospitalization was longer in patients with ascites (11.6 ± 10.7 vs. 8.0 ± 6.6 days, P = 0.020). In conclusion, consideration of age and predisposing disease in addition to ultrasonographic gallbladder findings in children suspected of acute acalculous inflammatory gallbladder disease might result in better outcomes. PMID:27550491

  15. [Underlying Mechanisms and Management of Refractory Gastroesophageal Reflux Disease].

    PubMed

    Lee, Kwang Jae

    2015-08-01

    The prevalence of gastroesophageal reflux disease (GERD) in South Korea has increased over the past 10 years. Patients with erosive reflux disease (ERD) shows better response to proton pump inhibitors (PPIs) than those with non-erosive reflux disease (NERD). NERD is a heterogeneous condition, showing pathological gastroesophageal reflux or esophageal hypersensitivity to reflux contents. NERD patients with pathological gastroesophageal reflux or hypersensitivity to acid may respond to PPIs. However, many patients with esophageal hypersensitivity to nonacid or functional heartburn do not respond to PPIs. Therefore, careful history and investigations are required when managing patients with refractory GERD who show poor response to conventional dose PPIs. Combined pH-impedance studies and a PPI diagnostic trial are recommended to reveal underlying mechanisms of refractory symptoms. For those with ongoing reflux-related symptoms, split dose administration, change to long-acting PPIs or PPIs less influenced by CYP2C19 genotypes, increasing dose of PPIs, and the addition of alginate preparations, prokinetics, selective serotonin reuptake inhibitors, or tricyclic antidepressants can be considered. Pain modulators, selective serotonin reuptake inhibitors, or tricyclic antidepressants are more likely to be effective for those with reflux-unrelated symptoms. Surgery or endoscopic per oral fundoplication may be effective in selected patients.

  16. 42 CFR 440.160 - Inpatient psychiatric services for individuals under age 21.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Definitions § 440.160 Inpatient psychiatric services for individuals under age 21. “Inpatient psychiatric... Rehabilitation Facilities, or by any other accrediting organization, with comparable standards, that...

  17. Malnutrition, age and the risk of parasitic disease: visceral leishmaniasis revisited.

    PubMed

    Dye, C; Williams, B G

    1993-10-22

    Children are said to be at greater risk of developing visceral leishmaniasis (VL) when they are younger and more malnourished. If malnutrition really is associated with VL, this potentially fatal and visible disease may be a general indicator of community health among the rural and suburban poor. Previous conclusions reached about the roles of malnutrition and age in VL epidemiology are questionable because they may have been confounded by transmission rate, because they have not been able to distinguish between different mechanisms of acquiring immunity, and because empirical observations have not been compared with theoretical expectations. Here we offer a framework with which to investigate these questions quantitatively, and do so with published data from endemic areas of Brazil. We conclude that children are indeed more susceptible to VL when they are younger and more malnourished, but it remains unclear whether the immunity to VL acquired with age is always acquired as a result of infection. The significance for leishmaniasis control, and for the control of other diseases associated with malnutrition, will depend on underlying mechanisms, which are not yet understood.

  18. Social contact networks and disease eradicability under voluntary vaccination.

    PubMed

    Perisic, Ana; Bauch, Chris T

    2009-02-01

    Certain theories suggest that it should be difficult or impossible to eradicate a vaccine-preventable disease under voluntary vaccination: Herd immunity implies that the individual incentive to vaccinate disappears at high coverage levels. Historically, there have been examples of declining coverage for vaccines, such as MMR vaccine and whole-cell pertussis vaccine, that are consistent with this theory. On the other hand, smallpox was globally eradicated by 1980 despite voluntary vaccination policies in many jurisdictions. Previous modeling studies of the interplay between disease dynamics and individual vaccinating behavior have assumed that infection is transmitted in a homogeneously mixing population. By comparison, here we simulate transmission of a vaccine-preventable SEIR infection through a random, static contact network. Individuals choose whether to vaccinate based on infection risks from neighbors, and based on vaccine risks. When neighborhood size is small, rational vaccinating behavior results in rapid containment of the infection through voluntary ring vaccination. As neighborhood size increases (while the average force of infection is held constant), a threshold is reached beyond which the infection can break through partially vaccinated rings, percolating through the whole population and resulting in considerable epidemic final sizes and a large number vaccinated. The former outcome represents convergence between individually and socially optimal outcomes, whereas the latter represents their divergence, as observed in most models of individual vaccinating behavior that assume homogeneous mixing. Similar effects are observed in an extended model using smallpox-specific natural history and transmissibility assumptions. This work illustrates the significant qualitative differences between behavior-infection dynamics in discrete contact-structured populations versus continuous unstructured populations. This work also shows how disease eradicability in

  19. Oxidative Stress, Aging and CNS disease in the Canine Model of Human Brain Aging

    PubMed Central

    Head, Elizabeth; Rofina, Jaime; Zicker, Steven

    2008-01-01

    SYNOPSIS Decline in cognitive functions that accompany aging in dogs may have a biological basis, and many of the disorders associated with aging in canines may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of both laboratory and clinical studies – antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs. However, determining all effective compounds and combinations, dosage ranges, as well as when to initiate intervention and long term effects constitute gaps in our current knowledge. PMID:18249248

  20. Oxidative stress, aging, and central nervous system disease in the canine model of human brain aging.

    PubMed

    Head, Elizabeth; Rofina, Jaime; Zicker, Steven

    2008-01-01

    Decline in cognitive functions that accompany aging in dogs may have a biologic basis, and many of the disorders associated with aging in dogs may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of laboratory and clinical studies, antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs.

  1. What's on TV? Detecting age-related neurodegenerative eye disease using eye movement scanpaths

    PubMed Central

    Crabb, David P.; Smith, Nicholas D.; Zhu, Haogang

    2014-01-01

    Purpose: We test the hypothesis that age-related neurodegenerative eye disease can be detected by examining patterns of eye movement recorded whilst a person naturally watches a movie. Methods: Thirty-two elderly people with healthy vision (median age: 70, interquartile range [IQR] 64–75 years) and 44 patients with a clinical diagnosis of glaucoma (median age: 69, IQR 63–77 years) had standard vision examinations including automated perimetry. Disease severity was measured using a standard clinical measure (visual field mean deviation; MD). All study participants viewed three unmodified TV and film clips on a computer set up incorporating the Eyelink 1000 eyetracker (SR Research, Ontario, Canada). Eye movement scanpaths were plotted using novel methods that first filtered the data and then generated saccade density maps. Maps were then subjected to a feature extraction analysis using kernel principal component analysis (KPCA). Features from the KPCA were then classified using a standard machine based classifier trained and tested by a 10-fold cross validation which was repeated 100 times to estimate the confidence interval (CI) of classification sensitivity and specificity. Results: Patients had a range of disease severity from early to advanced (median [IQR] right eye and left eye MD was −7 [−13 to −5] dB and −9 [−15 to −4] dB, respectively). Average sensitivity for correctly identifying a glaucoma patient at a fixed specificity of 90% was 79% (95% CI: 58–86%). The area under the Receiver Operating Characteristic curve was 0.84 (95% CI: 0.82–0.87). Conclusions: Huge data from scanpaths of eye movements recorded whilst people freely watch TV type films can be processed into maps that contain a signature of vision loss. In this proof of principle study we have demonstrated that a group of patients with age-related neurodegenerative eye disease can be reasonably well separated from a group of healthy peers by considering these eye movement

  2. 29 CFR 780.321 - Minors 16 years of age or under.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Employment in Agriculture That Is Exempted From the Minimum Wage and Overtime Pay Requirements Under Section... years of age and the employer must pay to such an employee the applicable statutory minimum wage unless..., although section 13(a)(6)(D) provides a minimum wage and overtime exemption for minors 16 years of age...

  3. 29 CFR 780.321 - Minors 16 years of age or under.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Employment in Agriculture That Is Exempted From the Minimum Wage and Overtime Pay Requirements Under Section... years of age and the employer must pay to such an employee the applicable statutory minimum wage unless..., although section 13(a)(6)(D) provides a minimum wage and overtime exemption for minors 16 years of age...

  4. 29 CFR 780.321 - Minors 16 years of age or under.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Employment in Agriculture That Is Exempted From the Minimum Wage and Overtime Pay Requirements Under Section... years of age and the employer must pay to such an employee the applicable statutory minimum wage unless..., although section 13(a)(6)(D) provides a minimum wage and overtime exemption for minors 16 years of age...

  5. 29 CFR 780.321 - Minors 16 years of age or under.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Employment in Agriculture That Is Exempted From the Minimum Wage and Overtime Pay Requirements Under Section... years of age and the employer must pay to such an employee the applicable statutory minimum wage unless..., although section 13(a)(6)(D) provides a minimum wage and overtime exemption for minors 16 years of age...

  6. 29 CFR 780.321 - Minors 16 years of age or under.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Employment in Agriculture That Is Exempted From the Minimum Wage and Overtime Pay Requirements Under Section... years of age and the employer must pay to such an employee the applicable statutory minimum wage unless..., although section 13(a)(6)(D) provides a minimum wage and overtime exemption for minors 16 years of age...

  7. 29 CFR 570.36 - Effect of a certificate of age under this subpart.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION Employment of Minors Between 14 and 16 Years of Age (Child Labor Reg. 3) § 570.36 Effect of a certificate of age under this subpart... be deemed to constitute oppressive child labor within the meaning of the act if the employer...

  8. 29 CFR 570.38 - Effect of a certificate of age under this subpart.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION Employment of Minors Between 14 and 16 Years of Age (Child Labor Reg. 3) § 570.38 Effect of a certificate of age under this subpart... to the periods specified in § 570.35, shall not be deemed to constitute oppressive child labor...

  9. 29 CFR 570.38 - Effect of a certificate of age under this subpart.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION Employment of Minors Between 14 and 16 Years of Age (Child Labor Reg. 3) § 570.38 Effect of a certificate of age under this subpart... to the periods specified in § 570.35, shall not be deemed to constitute oppressive child labor...

  10. 29 CFR 570.38 - Effect of a certificate of age under this subpart.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION Employment of Minors Between 14 and 16 Years of Age (Child Labor Reg. 3) § 570.38 Effect of a certificate of age under this subpart... to the periods specified in § 570.35, shall not be deemed to constitute oppressive child labor...

  11. 29 CFR 570.38 - Effect of a certificate of age under this subpart.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION Employment of Minors Between 14 and 16 Years of Age (Child Labor Reg. 3) § 570.38 Effect of a certificate of age under this subpart... to the periods specified in § 570.35, shall not be deemed to constitute oppressive child labor...

  12. Dental Disease in Aged Horses and Its Management.

    PubMed

    Nicholls, Victoria M; Townsend, Neil

    2016-08-01

    Improved recognition of equine geriatric conditions has resulted in a surge in our aged population with a concurrent escalation of many age-related dental pathologies. Prevention of these disorder is the ultimate aim but early identification and appropriate management can increase an animal's oral comfort and maximise its masticatory ability. There is only a finite amount of tooth available for eruption in the horse and therefore as the teeth become worn and less efficient as a grinding unit, dietary modification becomes a paramount consideration to accommodate this. Geriatric animals have differing requirements for restraint and sedation with treatment of coexisting disorders also an important requirement.

  13. Dental Disease in Aged Horses and Its Management.

    PubMed

    Nicholls, Victoria M; Townsend, Neil

    2016-08-01

    Improved recognition of equine geriatric conditions has resulted in a surge in our aged population with a concurrent escalation of many age-related dental pathologies. Prevention of these disorder is the ultimate aim but early identification and appropriate management can increase an animal's oral comfort and maximise its masticatory ability. There is only a finite amount of tooth available for eruption in the horse and therefore as the teeth become worn and less efficient as a grinding unit, dietary modification becomes a paramount consideration to accommodate this. Geriatric animals have differing requirements for restraint and sedation with treatment of coexisting disorders also an important requirement. PMID:27449389

  14. Aging and Lung Disease. Clinical Impact and Cellular and Molecular Pathways.

    PubMed

    Rojas, Mauricio; Mora, Ana L; Kapetanaki, Maria; Weathington, Nathaniel; Gladwin, Mark; Eickelberg, Oliver

    2015-12-01

    With the expected rapid growth of the aging population worldwide, there is a clear need to understand the complex process of aging to develop interventions that might extend the health span in this group of patients. Aging is associated with increased susceptibility to a variety of chronic diseases, and lung pathologies are no exception. The prevalence of lung diseases such as idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease has been found to increase considerably with age. In October 2014, the Division of Pulmonary, Allergy, and Critical Care of the University of Pittsburgh cohosted the Pittsburgh-Munich Lung Conference focused in aging and lung disease with the Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Ludwig-Maximilians University and Helmholtz Zentrum Munich Germany. The purpose of the conference was to disseminate novel concepts in aging mechanisms that have an impact in lung physiology and pathogenesis of pulmonary diseases that commonly occur in older populations. The conference included 28 presentations on diverse topics, which are summarized in this report. The participants identified priorities for future basic and translational investigations that will assist in the identification of molecular insights involved in the pathogenesis of age-related pulmonary diseases and the design of therapeutic interventions for these lung conditions. PMID:26653202

  15. Classifying aging as a disease in the context of ICD-11.

    PubMed

    Zhavoronkov, Alex; Bhullar, Bhupinder

    2015-01-01

    Aging is a complex continuous multifactorial process leading to loss of function and crystalizing into the many age-related diseases. Here, we explore the arguments for classifying aging as a disease in the context of the upcoming World Health Organization's 11th International Statistical Classification of Diseases and Related Health Problems (ICD-11), expected to be finalized in 2018. We hypothesize that classifying aging as a disease with a "non-garbage" set of codes will result in new approaches and business models for addressing aging as a treatable condition, which will lead to both economic and healthcare benefits for all stakeholders. Actionable classification of aging as a disease may lead to more efficient allocation of resources by enabling funding bodies and other stakeholders to use quality-adjusted life years (QALYs) and healthy-years equivalent (HYE) as metrics when evaluating both research and clinical programs. We propose forming a Task Force to interface the WHO in order to develop a multidisciplinary framework for classifying aging as a disease with multiple disease codes facilitating for therapeutic interventions and preventative strategies. PMID:26583032

  16. Classifying aging as a disease in the context of ICD-11

    PubMed Central

    Zhavoronkov, Alex; Bhullar, Bhupinder

    2015-01-01

    Aging is a complex continuous multifactorial process leading to loss of function and crystalizing into the many age-related diseases. Here, we explore the arguments for classifying aging as a disease in the context of the upcoming World Health Organization’s 11th International Statistical Classification of Diseases and Related Health Problems (ICD-11), expected to be finalized in 2018. We hypothesize that classifying aging as a disease with a “non-garbage” set of codes will result in new approaches and business models for addressing aging as a treatable condition, which will lead to both economic and healthcare benefits for all stakeholders. Actionable classification of aging as a disease may lead to more efficient allocation of resources by enabling funding bodies and other stakeholders to use quality-adjusted life years (QALYs) and healthy-years equivalent (HYE) as metrics when evaluating both research and clinical programs. We propose forming a Task Force to interface the WHO in order to develop a multidisciplinary framework for classifying aging as a disease with multiple disease codes facilitating for therapeutic interventions and preventative strategies. PMID:26583032

  17. Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases

    PubMed Central

    He, Liang; Kernogitski, Yelena; Kulminskaya, Irina; Loika, Yury; Arbeev, Konstantin G.; Loiko, Elena; Bagley, Olivia; Duan, Matt; Yashkin, Arseniy; Ukraintseva, Svetlana V.; Kovtun, Mikhail; Yashin, Anatoliy I.; Kulminski, Alexander M.

    2016-01-01

    the expression of nearby genes. Our mediation analyses suggest that the effects of some SNPs are mediated by specific endophenotypes. In conclusion, these findings indicate that loci with pleiotropic effects on age-related disorders tend to be enriched in genes involved in underlying mechanisms potentially related to nervous, cardiovascular and immune system functions, stress resistance, inflammation, ion channels and hematopoiesis, supporting the hypothesis of shared pathological role of infection, and inflammation in chronic age-related diseases. PMID:27790247

  18. The voices of Iris: Cinematic representations of the aged woman and Alzheimer's disease in Iris (2001).

    PubMed

    Graham, Megan E

    2016-09-01

    Audiences must be critical of film representations of the aged woman living with Alzheimer's disease and of dangerous reinscriptions of stereotypical equations about ageing as deterioration. This paper analyses the representation and decline of the aged woman through the different voices of Iris Murdoch in Richard Eyre's film Iris (2001). Key vocal scenes are considered: On-screen encounters between young and aged Iris, vocal representations of dementia symptoms and silencing Iris as her disease progresses. Further, Iris' recurrent unaccompanied song, "The Lark in the Clear Air," compels audiences to "see" Iris with their ears more than with their eyes, exemplifying the representational power of sound in film. This paper is an appeal for increased debate about sonic representations of aged women, ageing and Alzheimer's disease and dementia in film. The significance of audiences' critical awareness and understanding about the social implications of these representations is discussed.

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

    PubMed

    Meng, Guofeng; Zhong, Xiaoyan; Mei, Hongkang

    2016-01-01

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

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

    PubMed

    Meng, Guofeng; Zhong, Xiaoyan; Mei, Hongkang

    2016-01-01

    Aging, as a complex biological process, is accompanied by the accumulation of functional loses at different levels, which makes age to be the biggest risk factor to many neurological diseases. Even following decades of investigation, the process of aging is still far from being fully understood, especially at a systematic level. In this study, we identified aging related genes in brain by collecting the ones with sustained and consistent gene expression or DNA methylation changes in the aging process. Functional analysis with Gene Ontology to these genes suggested transcriptional regulators to be the most affected genes in the aging process. Transcription regulation analysis found some transcription factors, especially Specificity Protein 1 (SP1), to play important roles in regulating aging related gene expression. Module-based functional analysis indicated these genes to be associated with many well-known aging related pathways, supporting the validity of our approach to select aging related genes. Finally, we investigated the roles of aging related genes on Alzheimer's Disease (AD). We found that aging and AD related genes both involved some common pathways, which provided a possible explanation why aging made the brain more vulnerable to Alzheimer's Disease. PMID:26937969

  1. Surgical experience with persistent truncus arteriosus in symptomatic infants under 1 year of age. Report of 13 consecutive cases.

    PubMed Central

    Musumeci, F; Piccoli, G P; Dickinson, D F; Hamilton, D I

    1981-01-01

    Between January 1974 and November 1980, 13 symptomatic infants under 1 year of age with persistent truncus arteriosus type I or II underwent surgery. Pulmonary artery banding was performed in 10 cases, with five deaths. Among the survivors, one developed severe pulmonary vascular disease and only two underwent late intracardiac repair. Primary total correction was performed in three infants and all are well, though one required conduit replacement five and a half years after the initial procedure. Recently, antibiotic sterilised homograft conduits, rather than heterografts, have been preferred as extracardiac conduits in infancy. Early intracardiac repair followed, if necessary, by later conduit replacement appears to have significant advantages over "conventional" pulmonary artery banding and late total correction. Concern remains on the treatment of choice in infants under 3 months of age. Images PMID:7272128

  2. Lyme disease: an increasing health risk for school-age children.

    PubMed

    Hahn, D B; Pinger, R R; Hahn, E J

    1987-08-01

    Lyme disease, a bacterial infection with noticeable short-term and serious long-term consequences, is the most common tick-borne disease. First described in 1977, Lyme disease poses a significant health threat to school-age children exposed to the tick vector primarily in three specific regions of the United States. This article describes Lyme disease and its clinical signs and symptoms, and discusses the school nurse's role in identification, management, and prevention of this new health risk.

  3. Chronic Diseases in the Pediatric Age Group. Matrix No. 7.

    ERIC Educational Resources Information Center

    Katz, Michael

    This paper briefly outlines current problems associated with chronic diseases in children and youth and provides indications for the types of future research and analysis needed to facilitate the development of solutions. In general, these problems are associated with the following: malignancies, hereditary anemias, cystic fibrosis, other chronic…

  4. The Effect of Alzheimer's Disease and Aging on Conceptual Combination

    ERIC Educational Resources Information Center

    Taler, Vanessa; Chertkow, Howard; Saumier, Daniel

    2005-01-01

    Alzheimer's disease (AD) subjects, healthy elderly, and young adults interpreted a series of novel noun-noun expressions composed of familiar object words. Subjects interpreted each item by selecting one of three possible definitions: a definition in which the referents of each noun were associated together in a particular context (e.g., rabbit…

  5. Epidemiology and unique aspects of aging and infectious diseases.

    PubMed

    Yoshikawa, T T

    2000-06-01

    The elderly population will grow rapidly over the next 25 years. The majority of patients with serious or life-threatening infections will be old. It is imperative that primary care physicians and infectious diseases specialists become aware of and knowledgeable about the special and unique aspects of infections in the geriatric population.

  6. Urban groundwater age modeling under unconfined condition - Impact of underground structures on groundwater age: Evidence of a piston effect

    NASA Astrophysics Data System (ADS)

    Attard, Guillaume; Rossier, Yvan; Eisenlohr, Laurent

    2016-04-01

    In this paper, underground structures are shown to have a major influence on the groundwater mean age distribution described as a dispersive piston effect. Urban underground development does not occur without impacts on subsoil resources. In particular, groundwater resources can be vulnerable and generate disturbances when this space is exploited. Groundwater age spatial distribution data are fundamental for resource management as it can provide operational sustainability indicators. However, the application of groundwater age modeling is neglected regarding the potential effect of underground structures in urban areas. A three dimensional modeling approach was conducted to quantify the impact of two underground structures: (1) an impervious structure and (2) a draining structure. Both structures are shown to cause significant mixing processes occurring between shallow and deeper aquifers. The design technique used for draining structures is shown to have the greatest impact, generating a decrease in mean age of more than 80% under the structure. Groundwater age modeling is shown to be relevant for highlighting the role played by underground structures in advective-dispersive flows in urban areas.

  7. Measuring underreporting and under-ascertainment in infectious disease datasets: a comparison of methods

    PubMed Central

    2014-01-01

    Background Efficient and reliable surveillance and notification systems are vital for monitoring public health and disease outbreaks. However, most surveillance and notification systems are affected by a degree of underestimation (UE) and therefore uncertainty surrounds the 'true’ incidence of disease affecting morbidity and mortality rates. Surveillance systems fail to capture cases at two distinct levels of the surveillance pyramid: from the community since not all cases seek healthcare (under-ascertainment), and at the healthcare-level, representing a failure to adequately report symptomatic cases that have sought medical advice (underreporting). There are several methods to estimate the extent of under-ascertainment and underreporting. Methods Within the context of the ECDC-funded Burden of Communicable Diseases in Europe (BCoDE)-project, an extensive literature review was conducted to identify studies that estimate ascertainment or reporting rates for salmonellosis and campylobacteriosis in European Union Member States (MS) plus European Free Trade Area (EFTA) countries Iceland, Norway and Switzerland and four other OECD countries (USA, Canada, Australia and Japan). Multiplication factors (MFs), a measure of the magnitude of underestimation, were taken directly from the literature or derived (where the proportion of underestimated, under-ascertained, or underreported cases was known) and compared for the two pathogens. Results MFs varied between and within diseases and countries, representing a need to carefully select the most appropriate MFs and methods for calculating them. The most appropriate MFs are often disease-, country-, age-, and sex-specific. Conclusions When routine data are used to make decisions on resource allocation or to estimate epidemiological parameters in populations, it becomes important to understand when, where and to what extent these data represent the true picture of disease, and in some instances (such as priority setting) it is

  8. Aging Stereotypes Must be Taken Into Account for the Diagnosis of Prodromal and Early Alzheimer Disease.

    PubMed

    Régner, Isabelle; Mazerolle, Marie; Alescio-Lautier, Béatrice; Clarys, David; Michel, Bernard; Paccalin, Marc; Piolino, Pascale; Rigalleau, François; Sambuchi, Nathalie; Huguet, Pascal

    2016-01-01

    Because of a dramatic increase of older people worldwide, screening for prodromal state of Alzheimer disease (AD) is a major societal challenge. Many individuals diagnosed with prodromal AD, do not convert to AD, some remaining stable and others reversing back to normal. We argue that an important source of this overdiagnosis comes from negative aging stereotypes (eg, the culturally shared beliefs that aging inescapably causes severe cognitive decline and diseases). Many laboratory studies show that such stereotypes impair memory performance in healthy older adults, producing inflated age differences. Research is needed to examine how aging stereotypes implicitly permeate neuropsychological testing and contribute to false positives.

  9. Alcohol and cardiovascular disease: still unresolved underlying mechanisms.

    PubMed

    Carnevale, Roberto; Nocella, Cristina

    2012-01-01

    Alcoholic (ethanol-containing) beverages are consumed by most societies in the world. Low-to-moderate levels of ethanol consumption have been shown to reduce the risk of cardiovascular diseases and atherosclerosis. The decreased risk is likely due to alcohol's favorable pleiotropic effects on lipids, adhesion molecules, platelet activation and oxidative stress. However, there is also an abundance of clinical, experimental and epidemiological evidence showing that chronic high-dose ethanol consumption increases mortality, cardiovascular complications and also the progression of atherosclerosis. This last phenomenon appears to be due to the metabolism of ethanol, that leads to the formation of acetaldehyde, which is oxidized to acetate, leading to the generation of reactive oxygen species (ROS) and a toxic effect of ethanol on the formation of the atherosclerosis plaque. We will here briefly review the mechanisms through which high intakes of ethanol induce the formation of atherosclerotic plaque, focusing on increased oxidative stress as the main underlying mechanism.

  10. Interventions for increasing fruit and vegetable consumption in children aged 5 years and under

    PubMed Central

    Wolfenden, Luke; Wyse, Rebecca J; Britton, Ben I; Campbell, Karen J; Hodder, Rebecca K; Stacey, Fiona G; McElduff, Patrick; James, Erica L

    2014-01-01

    Background Insufficient consumption of fruits and vegetables in childhood increases the risk of future chronic diseases including cardiovascular disease. Objectives To assess the effectiveness, cost-effectiveness and associated adverse events of interventions designed to increase the consumption of fruit and/or vegetables amongst children aged five years and under. Search methods The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 2, 2010, MEDLINE (1950 to 2010 April week 4), EMBASE (1947 to 2010 week 18), CINAHL (up to 12 May 2010), PsycINFO (up to 12 May 2010) and Proquest Dissertations and Theses (up to February 2011) were searched to identify eligible trials, as well as electronic trial registers (also up to February 2011). The reference lists of included trials were reviewed and handsearches of three international nutrition journals were also performed. Authors of all included trials were contacted in order to identify further potentially relevant trials. Selection criteria We included randomised controlled trials (RCTs), including cluster-randomised controlled trials, of any intervention primarily targeting fruit and/or vegetable consumption among children aged five years and under and incorporating a biochemical or dietary assessment of fruit and/or vegetable consumption. Two review authors independently screened the titles and abstracts of identified papers. A third review author with expertise in review methodology resolved any disagreements regarding study eligibility. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias of the included studies. A third reviewer resolved disagreements between review authors. Fixed-effect models were used to perform meta-analysis for the primary review outcomes where a sufficient number of trials with suitable data and homogeneity were identified. Main results Five trials, with 13 trial arms and 3967 participants were included in

  11. International practice patterns by age and severity of lung disease in cystic fibrosis: data from the Epidemiologic Registry of Cystic Fibrosis (ERCF).

    PubMed

    Koch, C; McKenzie, S G; Kaplowitz, H; Hodson, M E; Harms, H K; Navarro, J; Mastella, G

    1997-08-01

    The Epidemiologic Registry of Cystic Fibrosis provides clinical profiles for more than 6,800 patients and descriptions of practice patterns across eight European countries. Preliminary cross-sectional analysis has been performed by age and pulmonary function as an assessment of disease severity. In general, pulmonary treatments including inhaled bronchodilators and rhDNase increased as lung disease became more severe. Use of a number of treatments, including mucolytic agents and inhaled corticosteroids, varied markedly from country to country. Several widely used therapies are not yet supported by controlled clinical trials, particularly in patients under 6 years of age. Nutritional intervention was more common in patients with advanced lung disease regardless of age. Patients with nasal polyps had less severe lung disease at each age than patients without polyps. It is clear that studies of early interventions are needed to determine the optimal types of treatments and the ages at which to begin treatment.

  12. Age-associated cardiovascular changes in health: impact on cardiovascular disease in older persons.

    PubMed

    Lakatta, Edward G

    2002-01-01

    In the United States, cardiovascular disease, e.g., atherosclerosis and hypertension, that lead to heart failure and stroke, is the leading cause of mortality, accounting for over 40 percent of deaths in those aged 65 years and above. Over 80 percent of all cardio-vascular deaths occur in the same age group. Thus, age, per se, is the major risk factor for cardiovascular disease. Clinical manifestations and prognosis of these cardiovascular diseases likely become altered in older persons with advanced age because interactions occur between age-associated cardiovascular changes in health and specific pathophysiologic mechanisms that underlie a disease. A fundamental understanding of age-associated changes in cardiovascular structure and function ranging in scope from humans to molecules is required for effective and efficient prevention and treatment of cardiovascular disease in older persons. A sustained effort over the past two decades has been applied to characterize the multiple effects of aging in health on cardiovascular structure and function in a single study population, the Baltimore Longitudinal Study on Aging. In these studies, community dwelling, volunteer participants are rigorously screened to detect both clinical and occult cardiovascular disease and characterized with respect to lifestyle, e.g. exercise habits, in an attempt to deconvolute interactions among lifestyle, cardiovascular disease and the aging process in health. This review highlights some specific changes in resting cardiovascular structure and function and cardiovascular reserve capacity that occur with advancing age in healthy humans. Observations from relevant experiments in animal models have been integrated with those in humans to provide possible mechanistic insight.

  13. What determines age-related disease: do we know all the right questions?

    PubMed Central

    2009-01-01

    The average human lifespan has increased throughout the last century due to the mitigation of many infectious diseases. More people now die of age-related diseases than ever before, but these diseases have been resistant to elimination. Progress has been made in treatments and preventative measures to delay the onsets of these diseases, but most cancers and vascular diseases are still with us and they kill about the same fraction of the population year after year. For example, US Caucasian female deaths from breast plus genital cancers have remained a fairly constant ~7% of the age-related disease deaths from 1938 to 1998 and have been consistently ~2-fold greater than female colon plus rectal cancer deaths over that span. This type of stability pattern pervades the age-related diseases and suggests that intrinsic properties within populations determine these fractions. Recognizing this pattern and deciphering its origin will be necessary for the complete understanding of these major causes of death. It would appear that more than the random processes of aging drive this effect. The question is how to meaningfully approach this problem. This commentary discusses the epidemiological and aging perspectives and their current limitations in providing an explanation. The age of bioinformatics offers hope, but only if creative systems approaches are forthcoming. PMID:19904627

  14. Visible aging signs as risk markers for ischemic heart disease: Epidemiology, pathogenesis and clinical implications.

    PubMed

    Christoffersen, Mette; Tybjærg-Hansen, Anne

    2016-01-01

    Association of common aging signs (i.e., male pattern baldness, hair graying, and facial wrinkles) as well as other age-related appearance factors (i.e., arcus corneae, xanthelasmata, and earlobe crease) with increased risk of ischemic heart disease was initially described in anecdotal reports from clinicians observing trends in the physical appearance of patients with ischemic heart disease. Following these early observations numerous epidemiological studies have reported these associations. Since the prevalences of both visible aging signs and ischemic heart disease have a strong correlation with increasing age, it has been extensively debated whether the observed associations could be entirely explained by a common association with age. Furthermore, the etiologies of the visible aging signs are rarely fully understood, and pathophysiological explanations for these associations remain controversial, and are mostly speculative. As a consequence of inconsistent findings and lack of mechanistic explanations for the observed associations with ischemic heart disease, consensus on the clinical importance of these visible aging signs has been lacking. The aim of this review is for each of the visible aging signs to (i) review the etiology, (ii) to discuss the current epidemiological evidence for an association with risk of ischemic heart disease, and (iii) to present possible pathophysiological explanations for these associations. Finally this review discusses the potential clinical implications of these findings.

  15. 26 CFR 1.7702-2 - Attained age of the insured under a life insurance contract.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... age of the insured is determined by applying paragraph (b) of this section as if the youngest... insureds, the youngest surviving insured shall thereafter be treated as the only insured under the contract... determined by applying § 1.7702-2(b) as if the youngest individual were the only insured under the...

  16. 26 CFR 1.7702-2 - Attained age of the insured under a life insurance contract.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... age of the insured is determined by applying paragraph (b) of this section as if the youngest... insureds, the youngest surviving insured shall thereafter be treated as the only insured under the contract... determined by applying § 1.7702-2(b) as if the youngest individual were the only insured under the...

  17. Influence of age on androgen deprivation therapy-associated Alzheimer’s disease

    PubMed Central

    Nead, Kevin T.; Gaskin, Greg; Chester, Cariad; Swisher-McClure, Samuel; Dudley, Joel T.; Leeper, Nicholas J.; Shah, Nigam H.

    2016-01-01

    We recently found an association between androgen deprivation therapy (ADT) and Alzheimer’s disease. As Alzheimer’s disease is a disease of advanced age, we hypothesize that older individuals on ADT may be at greatest risk. We conducted a retrospective multi-institutional analysis among 16,888 individuals with prostate cancer using an informatics approach. We tested the effect of ADT on Alzheimer’s disease using Kaplan–Meier age stratified analyses in a propensity score matched cohort. We found a lower cumulative probability of remaining Alzheimer’s disease-free between non-ADT users age ≥70 versus those age <70 years (p < 0.001) and between ADT versus non-ADT users ≥70 years (p = 0.034). The 5-year probability of developing Alzheimer’s disease was 2.9%, 1.9% and 0.5% among ADT users ≥70, non-ADT users ≥70 and individuals <70 years, respectively. Compared to younger individuals older men on ADT may have the greatest absolute Alzheimer’s disease risk. Future work should investigate the ADT Alzheimer’s disease association in advanced age populations given the greater potential clinical impact. PMID:27752112

  18. Visuomotor learning in immersive 3D virtual reality in Parkinson's disease and in aging.

    PubMed

    Messier, Julie; Adamovich, Sergei; Jack, David; Hening, Wayne; Sage, Jacob; Poizner, Howard

    2007-05-01

    Successful adaptation to novel sensorimotor contexts critically depends on efficient sensory processing and integration mechanisms, particularly those required to combine visual and proprioceptive inputs. If the basal ganglia are a critical part of specialized circuits that adapt motor behavior to new sensorimotor contexts, then patients who are suffering from basal ganglia dysfunction, as in Parkinson's disease should show sensorimotor learning impairments. However, this issue has been under-explored. We tested the ability of 8 patients with Parkinson's disease (PD), off medication, ten healthy elderly subjects and ten healthy young adults to reach to a remembered 3D location presented in an immersive virtual environment. A multi-phase learning paradigm was used having four conditions: baseline, initial learning, reversal learning and aftereffect. In initial learning, the computer altered the position of a simulated arm endpoint used for movement feedback by shifting its apparent location diagonally, requiring thereby both horizontal and vertical compensations. This visual distortion forced subjects to learn new coordinations between what they saw in the virtual environment and the actual position of their limbs, which they had to derive from proprioceptive information (or efference copy). In reversal learning, the sign of the distortion was reversed. Both elderly subjects and PD patients showed learning phase-dependent difficulties. First, elderly controls were slower than young subjects when learning both dimensions of the initial biaxial discordance. However, their performance improved during reversal learning and as a result elderly and young controls showed similar adaptation rates during reversal learning. Second, in striking contrast to healthy elderly subjects, PD patients were more profoundly impaired during the reversal phase of learning. PD patients were able to learn the initial biaxial discordance but were on average slower than age-matched controls

  19. Disentangling normal aging from Alzheimer's disease in structural magnetic resonance images.

    PubMed

    Lorenzi, Marco; Pennec, Xavier; Frisoni, Giovanni B; Ayache, Nicholas

    2015-01-01

    The morphology observed in the brains of patients affected by Alzheimer's disease (AD) is a combination of different biological processes, such as normal aging and the pathological matter loss specific to AD. The ability to differentiate between these biological factors is fundamental to reliably evaluate pathological AD-related structural changes, especially in the earliest phase of the disease, at prodromal and preclinical stages. Here we propose a method based on non-linear image registration to estimate and analyze from observed brain morphologies the relative contributions from aging and pathology. In particular, we first define a longitudinal model of the brain's normal aging process from serial T1-weight magnetic resonance imaging scans of 65 healthy participants. The longitudinal model is then used as a reference for the cross-sectional analysis. Given a new brain image, we then estimate its anatomical age relative to the aging model; this is defined as a morphological age shift with respect to the average age of the healthy population at baseline. Finally, we define the specific morphological process as the remainder of the observed anatomy after the removal of the estimated normal aging process. Experimental results from 105 healthy participants, 110 subjects with mild cognitive impairment (MCI), 86 with MCI converted to AD, and 134 AD patients provide a novel description of the anatomical changes observed across the AD time span: normal aging, normal aging at risk, conversion to MCI, and the latest stages of AD. More advanced AD stages are associated with an increased morphological age shift in the brain and with strong disease-specific morphological changes affecting mainly ventricles, temporal poles, the entorhinal cortex, and hippocampi. Our model shows that AD is characterized by localized disease-specific brain changes as well as by an accelerated global aging process. This method may thus represent a more precise instrument to identify potential

  20. Mitochondria in Ageing and Diseases: The Super Trouper of the Cell.

    PubMed

    Coppotelli, Giuseppe; Ross, Jaime M

    2016-01-01

    The past decade has witnessed an explosion of knowledge regarding how mitochondrial dysfunction may translate into ageing and disease phenotypes, as well as how it is modulated by genetic and lifestyle factors.[...]. PMID:27187361

  1. Metabolic Syndrome As an Underlying Disease Entity and Its Relationship to Subclinical Atherosclerosis in Andean Hispanics

    PubMed Central

    Medina-Lezama, Josefina; Arguelles, William; Goldberg, Ronald; Schneiderman, Neil; Khan, Zubair; Morey, Oscar O.; Raja, Muhammad Waheed; Paz, Roberto; Chirinos, Julio A.; Llabre, Maria M.

    2014-01-01

    Abstract Background: The question of whether the metabolic syndrome truly reflects a single disease entity with a common underlying pathology remains unclear. In this study, we assess whether metabolic syndrome represents an underlying disease construct in a large population-based sample of Andean Hispanic adults and examine its relationship to subclinical atherosclerosis. Methods: The study sample was comprised of 2513 participants. Confirmatory factor analysis (CFA) was used to identify a metabolic syndrome latent factor using waist circumference, systolic and diastolic blood pressure, high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), and glucose levels as indicators. The relationship with subclinical atherosclerosis, measured by carotid intima media thickness (cIMT), was assessed using structural equation modeling. Results: Results supported the proposed structure of the metabolic syndrome latent factor evidenced by adequate fit indexes. HDL-C did not significantly load on the metabolic syndrome latent factor (standardized factor loading=0.01, P=0.88). The metabolic syndrome latent factor was significantly associated with cIMT in women (B=0.007, P<0.001) and men (B=0.008, P<0.001) after controlling for age, low-density lipoprotein cholesterol and smoking. Conclusions: Our findings suggest that metabolic syndrome components, such as waist circumference, blood pressure, TGs, and glucose levels, but not HDL-C, share a common underlying pathophysiology that may contribute to the progression of atherosclerosis in Andean Hispanics. Its longitudinal association with cardiovascular disease should be the focus of future research. PMID:24206171

  2. From cellular senescence to age-associated diseases: the miRNA connection

    PubMed Central

    2012-01-01

    Cellular senescence has evolved from an in-vitro model system to study aging in vitro to a multifaceted phenomenon of in-vivo importance as senescent cells in vivo have been identified and their removal delays the onset of age-associated diseases in a mouse model system. From the large emerging class of non-coding RNAs, miRNAs have only recently been functionally implied in the regulatory networks that are modified during the aging process. Here we summarize examples of similarities between the differential expression of miRNAs during senescence and age-associated diseases and suggest that these similarities might emphasize the importance of senescence for the pathogenesis of age-associated diseases. Understanding such a connection on the level of miRNAs might offer valuable opportunities for designing novel diagnostic and therapeutic strategies. PMID:24472232

  3. Potential Therapeutical Contributions of the Endocannabinoid System towards Aging and Alzheimer’s Disease

    PubMed Central

    Bonnet, Amandine E; Marchalant, Yannick

    2015-01-01

    Aging can lead to decline in cognition, notably due to neurodegenerative processes overwhelming the brain over time. As people live longer, numerous concerns are rightfully raised toward long-term slowly incapacitating diseases with no cure, such as Alzheimer’s disease. Since the early 2000’s, the role of neuroinflammation has been scrutinized for its potential role in the development of diverse neurodegenerative diseases notably because of its slow onset and chronic nature in aging. Despite the lack of success yet, treatment of chronic neuroinflammation could help alleviate process implicated in neurodegenerative disease. A growing number of studies including our own have aimed at the endocannabinoid system and unfolded unique effects of this system on neuroinflammation, neurogenesis and hallmarks of Alzheimer’s disease and made it a reasonable target in the context of normal and pathological brain aging. PMID:26425394

  4. Impact of Air Pollutants on Oxidative Stress in Common Autophagy-Mediated Aging Diseases

    PubMed Central

    Numan, Mohamed Saber; Brown, Jacques P.; Michou, Laëtitia

    2015-01-01

    Atmospheric pollution-induced cellular oxidative stress is probably one of the pathogenic mechanisms involved in most of the common autophagy-mediated aging diseases, including neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer’s, disease, as well as Paget’s disease of bone with or without frontotemporal dementia and inclusion body myopathy. Oxidative stress has serious damaging effects on the cellular contents: DNA, RNA, cellular proteins, and cellular organelles. Autophagy has a pivotal role in recycling these damaged non-functional organelles and misfolded or unfolded proteins. In this paper, we highlight, through a narrative review of the literature, that when autophagy processes are impaired during aging, in presence of cumulative air pollution-induced cellular oxidative stress and due to a direct effect on air pollutant, autophagy-mediated aging diseases may occur. PMID:25690002

  5. [Bolsa Família: food and nutrition insecurity of children under five years of age].

    PubMed

    Monteiro, Flávia; Schmidt, Suely Teresinha; da Costa, Islandia Bezerra; Almeida, Claudia Choma Bettega; Matuda, Nívea da Silva

    2014-05-01

    This is a descriptive cross-sectional study of the population base conducted in the town of Colombo in the state of Paraná. The objectives were to identify the prevalence of food insecurity in families that are beneficiaries of the Bolsa Família Program and the factors related to this condition, and describe the nutritional status of children under five years of age. Analyses of association were performed using Fisher's exact test. The sample included 442 families, of which 168 have children under five years of age. The Brazilian Food Insecurity Scale was applied to evaluate food insecurity and the nutritional status of the 199 children evaluated was determined by the height-for-age, weight-for-age and body mass-for-age indices in accordance with the WHO reference values for 2006. The prevalence of food insecurity was 81.6%. Overweight and stunting among children coexisted. Food insecurity was found to be associated with the height-for-age index among children under two years of age. The per capita income and food deficits influenced the situation of food insecurity significantly.

  6. Effect of Aging on Periodontal Inflammation, Microbial Colonization, and Disease Susceptibility.

    PubMed

    Wu, Y; Dong, G; Xiao, W; Xiao, E; Miao, F; Syverson, A; Missaghian, N; Vafa, R; Cabrera-Ortega, A A; Rossa, C; Graves, D T

    2016-04-01

    Periodontitis is a chronic inflammatory disease induced by a biofilm that forms on the tooth surface. Increased periodontal disease is associated with aging. We investigated the effect of aging on challenge by oral pathogens, examining the host response, colonization, and osteoclast numbers in aged versus young mice. We also compared the results with mice with lineage-specific deletion of the transcription factor FOXO1, which reduces dendritic cell (DC) function. Periodontitis was induced by oral inoculation of Porphyromonas gingivalis and Fusobacterium nucleatum in young (4 to 5 mo) and aged (14 to 15 mo) mice. Aged mice as well as mice with reduced DC function had decreased numbers of DCs in lymph nodes, indicative of a diminished host response. In vitro studies suggest that reduced DC numbers in lymph nodes of aged mice may involve the effect of advanced glycation end products on DC migration. Surprisingly, aged mice but not mice with genetically altered DC function had greater production of antibody to P. gingivalis, greater IL-12 expression, and more plasma cells in lymph nodes following oral inoculation as compared with young mice. The greater adaptive immune response in aged versus young mice was linked to enhanced levels of P. gingivalis and reduced bacterial diversity. Thus, reduced bacterial diversity in aged mice may contribute to increased P. gingivalis colonization following inoculation and increased periodontal disease susceptibility, reflected by higher TNF levels and osteoclast numbers in the periodontium of aged versus young mice. PMID:26762510

  7. Longitudinal Cerebrospinal Fluid Biomarker Changes in Preclinical Alzheimer Disease During Middle Age

    PubMed Central

    Sutphen, Courtney L.; Jasielec, Mateusz S.; Shah, Aarti R.; Macy, Elizabeth M.; Xiong, Chengjie; Vlassenko, Andrei G.; Benzinger, Tammie L. S.; Stoops, Erik E. J.; Vanderstichele, Hugo M. J.; Brix, Britta; Darby, Heather D.; Vandijck, Manu L. J.; Ladenson, Jack H.; Morris, John C.; Holtzman, David M.; Fagan, Anne M.

    2015-01-01

    IMPORTANCE Individuals in the presymptomatic stage of Alzheimer disease (AD) are increasingly being targeted for AD secondary prevention trials. How early during the normal life span underlying AD pathologies begin to develop, their patterns of change over time, and their relationship with future cognitive decline remain to be determined. OBJECTIVE To characterize the within-person trajectories of cerebrospinal fluid (CSF) biomarkers of AD over time and their association with changes in brain amyloid deposition and cognitive decline in cognitively normal middle-aged individuals. DESIGN, SETTING, AND PARTICIPANTS As part of a cohort study, cognitively normal (Clinical Dementia Rating [CDR] of 0) middle-aged research volunteers (n = 169) enrolled in the Adult Children Study at Washington University, St Louis, Missouri, had undergone serial CSF collection and longitudinal clinical assessment (mean, 6 years; range, 0.91–11.3 years) at 3-year intervals at the time of analysis, between January 2003 and November 2013. A subset (n = 74) had also undergone longitudinal amyloid positron emission tomographic imaging with Pittsburgh compound B (PiB) in the same period. Serial CSF samples were analyzed for β-amyloid 40 (Aβ40), Aβ42, total tau, tau phosphorylated at threonine 181 (P-tau181), visinin-like protein 1 (VILIP-1), and chitinase-3-like protein 1 (YKL-40). Within-person measures were plotted according to age and AD risk defined by APOE genotype (ε4 carriers vs noncarriers). Linear mixed models were used to compare estimated biomarker slopes among middle-age bins at baseline (early, 45–54 years; mid, 55–64 years; late, 65–74 years) and between risk groups. Within-person changes in CSF biomarkers were also compared with changes in cortical PiB binding and progression to a CDR higher than 0 at follow-up. MAIN OUTCOMES AND MEASURES Changes in Aβ40, Aβ42, total tau, P-tau181, VILIP-1, and YKL-40 and, in a subset of participants, changes in cortical PiB binding

  8. Interest of active posturography to detect age-related and early Parkinson's disease-related impairments in mediolateral postural control.

    PubMed

    Bonnet, Cédrick T; Delval, Arnaud; Defebvre, Luc

    2014-11-15

    Patients with Parkinson's disease display impairments of postural control most particularly in active, challenging conditions. The objective of the present study was to analyze early signs of disease-related and also age-related impairments in mediolateral body extension and postural control. Fifty-five participants (18 Hoehn and Yahr stage 2 patients in the off-drug condition, 18 healthy elderly control subjects, and 19 young adults) were included in the study. The participants performed a quiet stance task and two active tasks that analyzed the performance in mediolateral body motion: a limit of stability and a rhythmic weight shift task. As expected, the patients displayed significantly lower and slower body displacement (head, neck, lower back, center of pressure) than elderly control subjects when performing the two body excursion tasks. However, the behavioral variability in both tasks was similar between the groups. Under these active conditions, the patients showed significantly lower contribution of the hip postural control mechanisms compared with the elderly control subjects. Overall, the patients seemed to lower their performance in order to prevent a mediolateral postural instability. However, these patients, at an early stage of their disease, were not unstable in quiet stance. Complementarily, elderly control subjects displayed slower body performance than young adults, which therefore showed an additional age-related impairment in mediolateral postural control. Overall, the study illustrated markers of age-related and Parkinson's disease impairments in mediolateral postural control that may constrain everyday activities in elderly adults and even more in patients with Parkinson's disease.

  9. Rejuvenation of senescent cells-the road to postponing human aging and age-related disease?

    PubMed

    Sikora, Ewa

    2013-07-01

    Cellular senescence is the state of permanent inhibition of cell proliferation. Replicative senescence occurs due to the end replication problem and shortening telomeres with each cell division leading to DNA damage response (DDR). The number of short telomeres increases with age and age-related pathologies. Stress induced senescence, although not accompanied by attrition of telomeres, is also attributed to the DDR induced by irreparable DNA lesions in telomeric DNA. Senescent cells characterized by the presence of γH2AX, the common marker of double DNA strand breaks, and other senescence markers including activity of SA-β-gal, accumulate in tissues of aged animals and humans as well as at sites of pathology. It is believed that cellular senescence evolved as a cancer barrier since non-proliferating senescent cells cannot be transformed to neoplastic cells. On the other hand senescent cells favor cancer development, just like other age-related pathologies, by creating a low grade inflammatory state due to senescence associated secretory phenotype (SASP). Reversal/inhibition of cellular senescence could prolong healthy life span, thus many attempts have been undertaken to influence cellular senescence. The two main approaches are genetic and pharmacological/nutritional modifications of cell fate. The first one concerns cell reprogramming by induced pluripotent stem cells (iPSCs), which in vitro is effective even in cells undergoing senescence, or derived from very old or progeroid patients. The second approach concerns modification of senescence signaling pathways just like TOR-induced by pharmacological or with natural agents. However, knowing that aging is unavoidable we cannot expect its elimination, but prolonging healthy life span is a goal worth serious consideration. PMID:23064316

  10. Mesenchymal stem cells: a revolution in therapeutic strategies of age-related diseases.

    PubMed

    Peng, Yan; Huang, Sha; Cheng, Biao; Nie, Xiaohu; Enhe, Jirigala; Feng, Changjiang; Fu, Xiaobing

    2013-01-01

    The great evolutionary biologist Theodosius Dobzhansky once said: "Nothing in biology makes sense except in the light of evolution". Aging is a complex biological phenomenon and the factors governing the process of aging and age-related diseases are only beginning to be understood, oxidative stress, telomere shortening in DNA components and genetic changes were shown to be the mainly regulating mechanisms during the recent decades. Although a considerable amount of both animal and clinical data that demonstrate the extensive and safe use of mesenchymal stromal cells (MSCs) is available, the precise summarization and identification of MSCs in age-related diseases remains a challenge. Along this line, this review discussed several typical age-related diseases for which MSCs have been proved to confer protection and put forward a hypothesis for the association among MSCs and age-related diseases from an evolutionary perspective. Above all, we hope further and more research efforts could be aroused to elucidate the role and mechanisms that MSCs involved in the age-related diseases.

  11. Survey of Canadian chiropractors’ involvement in the treatment of patients under the age of 18

    PubMed Central

    Verhoef, Marja J; Papadopoulos, Costa

    1999-01-01

    Background: There is limited information about the degree of Canadian chiropractors’ involvement in treating patients under the age of 18. Study Objective: To determine how frequently and for what reasons chiropractors treat patients under the age of 18. Methods: A cross-sectional survey of a random sample of 1,200 Canadian chiropractors. In addition to completing a questionnaire, chiropractors were asked to keep a diary for one month indicating how many children under the age of 18 they had seen and for what reason. Results: Fifty-nine percent completed the questionnaire and 48% the diaries. Almost all chiropractors were involved in treating patients under the age of 18. The older the patients, the more likely chiropractors were to treat them. The diary data show consistently lower involvement in treating patients under age 18 than the questionnaires. Differences were smaller, the older the patient. Questionnaire and diary data show that chiropractors see these patients mostly for musculoskeletal conditions. However, chiropractors overestimated the frequency of treating children with colic, menstrual complaints and immune system conditions on the questionnaire. Major geographic differences were found. Eighty-six percent of chiropractors expressed interest in more training in this field. Conclusion: These data provide important baseline data for further studies and suggest the importance of further training.

  12. Impaired Word Recognition in Alzheimer's Disease: The Role of Age of Acquisition

    ERIC Educational Resources Information Center

    Cuetos, Fernando; Herrera, Elena; Ellis, Andrew W.

    2010-01-01

    Studies of word production in patients with Alzheimer's disease have identified the age of acquisition of words as an important predictor of retention or loss, with early acquired words remaining accessible for longer than later acquired words. If, as proposed by current theories, effects of age of acquisition reflect the involvement of semantic…

  13. Human iPSC-based Modeling of Late-Onset Disease via Progerin-induced Aging

    PubMed Central

    Miller, Justine D.; Ganat, Yosif M.; Kishinevsky, Sarah; Bowman, Robert L.; Liu, Becky; Tu, Edmund Y.; Mandal, Pankaj; Vera, Elsa; Shim, Jae-won; Kriks, Sonja; Taldone, Tony; Fusaki, Noemi; Tomishima, Mark J.; Krainc, Dimitri; Milner, Teresa A.; Rossi, Derrick J.; Studer, Lorenz

    2014-01-01

    Summary Reprogramming somatic cells to induced pluripotent stem cells (iPSCs), resets their identity back to an embryonic age, and thus presents a significant hurdle for modeling late-onset disorders. In this study, we describe a strategy for inducing aging-related features in human iPSC-derived lineages and apply it to the modeling of Parkinson’s disease (PD). Our approach involves expression of progerin, a truncated form of lamin A associated with premature aging. We found that expression of progerin in iPSC-derived fibroblasts and neurons induces multiple aging-related markers and characteristics, including dopamine-specific phenotypes such as neuromelanin accumulation. Induced aging in PD-iPSC-derived dopamine neurons revealed disease phenotypes that require both aging and genetic susceptibility, such as pronounced dendrite degeneration, progressive loss of tyrosine-hydroxylase (TH) expression and enlarged mitochondria or Lewy body-precursor inclusions. Thus, our study suggests that progerin-induced aging can be used to reveal late-onset age-related disease features in hiPSC-based disease models. PMID:24315443

  14. "I'm Not Going to Die from the AIDS": Resilience in Aging with HIV Disease

    ERIC Educational Resources Information Center

    Emlet, Charles A.; Tozay, Shakima; Raveis, Victoria H.

    2011-01-01

    Purpose: Adults aging with HIV/AIDS can experience resilience in spite of the deleterious affects of the disease. This study seeks to examine the lived experiences of older adults with HIV/AIDS as it relates to strengths and resilience in dealing with this devastating disease. Design and methods: Semistructured in-depth interviews were conducted…

  15. A mutation in APP protects against Alzheimer's disease and age-related cognitive decline.

    PubMed

    Jonsson, Thorlakur; Atwal, Jasvinder K; Steinberg, Stacy; Snaedal, Jon; Jonsson, Palmi V; Bjornsson, Sigurbjorn; Stefansson, Hreinn; Sulem, Patrick; Gudbjartsson, Daniel; Maloney, Janice; Hoyte, Kwame; Gustafson, Amy; Liu, Yichin; Lu, Yanmei; Bhangale, Tushar; Graham, Robert R; Huttenlocher, Johanna; Bjornsdottir, Gyda; Andreassen, Ole A; Jönsson, Erik G; Palotie, Aarno; Behrens, Timothy W; Magnusson, Olafur T; Kong, Augustine; Thorsteinsdottir, Unnur; Watts, Ryan J; Stefansson, Kari

    2012-08-01

    The prevalence of dementia in the Western world in people over the age of 60 has been estimated to be greater than 5%, about two-thirds of which are due to Alzheimer's disease. The age-specific prevalence of Alzheimer's disease nearly doubles every 5 years after age 65, leading to a prevalence of greater than 25% in those over the age of 90 (ref. 3). Here, to search for low-frequency variants in the amyloid-β precursor protein (APP) gene with a significant effect on the risk of Alzheimer's disease, we studied coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. We found a coding mutation (A673T) in the APP gene that protects against Alzheimer's disease and cognitive decline in the elderly without Alzheimer's disease. This substitution is adjacent to the aspartyl protease β-site in APP, and results in an approximately 40% reduction in the formation of amyloidogenic peptides in vitro. The strong protective effect of the A673T substitution against Alzheimer's disease provides proof of principle for the hypothesis that reducing the β-cleavage of APP may protect against the disease. Furthermore, as the A673T allele also protects against cognitive decline in the elderly without Alzheimer's disease, the two may be mediated through the same or similar mechanisms.

  16. The emerging role of Notch pathway in ageing: Focus on the related mechanisms in age-related diseases.

    PubMed

    Balistreri, Carmela Rita; Madonna, Rosalinda; Melino, Gerry; Caruso, Calogero

    2016-08-01

    Notch signaling is an evolutionarily conserved pathway, which is fundamental for the development of all tissues, organs and systems of human body. Recently, a considerable and still growing number of studies have highlighted the contribution of Notch signaling in various pathological processes of the adult life, such as age-related diseases. In particular, the Notch pathway has emerged as major player in the maintenance of tissue specific homeostasis, through the control of proliferation, migration, phenotypes and functions of tissue cells, as well as in the cross-talk between inflammatory cells and the innate immune system, and in onset of inflammatory age-related diseases. However, until now there is a confounding evidence about the related mechanisms. Here, we discuss mechanisms through which Notch signaling acts in a very complex network of pathways, where it seems to have the crucial role of hub. Thus, we stress the possibility to use Notch pathway, the related molecules and pathways constituting this network, both as innovative (predictive, diagnostic and prognostic) biomarkers and targets for personalised treatments for age-related diseases. PMID:27328278

  17. [Epidemiology of arbovirus diseases: use and value of physiologic age determination of female mosquito vectors].

    PubMed

    Mondet, B

    1996-01-01

    The physiological age of Yellow Fever Aedes females in Africa was studied during four years, from 1988 to 1992. We used a method, according to Polovodova's method, which looks for the "yellow body" under natural light. Those yellow bodies exist in the old females, the "parous" ones, and not in the young females, the "nulliparous" ones. We present some results to illustrate the interest of studying the physiological age of mosquitoes in the epidemiology of the arboviral diseases. The transmission risk, in relation with abundance and parity rate was illustrated, in particular for Aedes africanus and Aedes luteocephalus, which is useful to compare species, or with a given species, to compare periods. The parity rate of Aedes furcifer females was studied on 6 points along a transect between a forest and a village. The rate and the abundance of the females caught on human bates are inversely proportional. The parity rate is minimum in the canopy forest (about 50%) and maximum inside a house (100%). The rains have different consequences on the species, according to the period of fall. At the beginning of the dry season, they bring about hatching, but not at the end of the dry season. Massive hatching, will occur just at the beginning of the rainy season, some weeks later. Studying the physiological age of Ae. africanus females, the number of nulliparous is not related to the rain. That means a possibility of "natural" hatching for part of the eggs. Among the female of the dry season, young females are found, which is important for the transmission capacity. The method, described herein, to determine the physiological age is perfectly applicable to the Yellow Fever vector Haemagogus janthinomys in Southern America. But for the Dengue vectors Aedes aegypti and probably Aedes albopictus, the Detinova's method seems better. Actually, it seems important to study the physiological age of the vectors Ae. aegypti and Ae. albopictus, as well as the evolution of the physiological

  18. Effect of age on geriatric depression scale performance in Parkinson's disease.

    PubMed

    Weintraub, Daniel; Saboe, Kirsten; Stern, Matthew B

    2007-07-15

    The purpose of this study was to compare the validity of the 15-item Geriatric Depression Scale (GDS-15) in nonelderly (<65 years), young-elderly (age, 65-75), and old-elderly (>75 years) patients with Parkinson's disease (PD). 57 nonelderly, 88 young-elderly, and 81 old-elderly PD patients were administered the GDS-15 and the Structured Clinical Interview for DSM-IV depression module. Receiver-operating characteristic (ROC) curves were plotted for GDS-15 scores against a DSM-IV diagnosis of major or minor depression. The discriminant validity of the GDS-15 was high for nonelderly, young-elderly, and old-elderly subjects (ROC area under curve = 0.92, 0.91, and 0.95, respectively), with optimal dichotomization at a cut-off of 4/5 (85% sensitivity and 84% specificity in nonelderly; 89% sensitivity and 82% specificity in young-elderly) and 5/6 (90% sensitivity and 90% specificity in old-elderly). In conclusion, the GDS-15 has comparable validity in younger and older PD patients, suggesting its appropriateness as a depression screening instrument in PD patients of all ages.

  19. The Potential of Chitosan and Its Derivatives in Prevention and Treatment of Age-Related Diseases

    PubMed Central

    Kerch, Garry

    2015-01-01

    Age-related, diet-related and protein conformational diseases, such as atherosclerosis, diabetes mellitus, cancer, hypercholesterolemia, cardiovascular and neurodegenerative diseases are common in the elderly population. The potential of chitosan, chitooligosaccharides and their derivatives in prevention and treatment of age-related dysfunctions is reviewed and discussed in this paper. The influence of oxidative stress, low density lipoprotein oxidation, increase of tissue stiffness, protein conformational changes, aging-associated chronic inflammation and their pathobiological significance have been considered. The chitosan-based functional food also has been reviewed. PMID:25871293

  20. The potential of chitosan and its derivatives in prevention and treatment of age-related diseases.

    PubMed

    Kerch, Garry

    2015-04-01

    Age-related, diet-related and protein conformational diseases, such as atherosclerosis, diabetes mellitus, cancer, hypercholesterolemia, cardiovascular and neurodegenerative diseases are common in the elderly population. The potential of chitosan, chitooligosaccharides and their derivatives in prevention and treatment of age-related dysfunctions is reviewed and discussed in this paper. The influence of oxidative stress, low density lipoprotein oxidation, increase of tissue stiffness, protein conformational changes, aging-associated chronic inflammation and their pathobiological significance have been considered. The chitosan-based functional food also has been reviewed.

  1. Common cell biologic and biochemical changes in aging and age-related diseases of the eye: Toward new therapeutic approaches to age-related ocular diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reviews of information about age related macular degeneration (AMD), cataract, and glaucoma make it apparent that while each eye tissue has its own characteristic metabolism, structure and function, there are common perturbations to homeostasis that are associated with age-related dysfunction. The c...

  2. An evaluation of the Aberrant Behavior Checklist for children under age 5.

    PubMed

    Schmidt, Jonathan D; Huete, John M; Fodstad, Jill C; Chin, Michelle D; Kurtz, Patricia F

    2013-04-01

    Severe problem behaviors such as self-injury and aggression are frequently observed in young children under age 5 with intellectual and developmental disabilities (IDD). Although early identification of problem behavior is critical to effective intervention, there are few standardized measures available that identify severe problem behavior in this population. The Aberrant Behavior Checklist-Community (ABC-C; Aman & Singh, 1994) is a rating scale that measures the severity of a range of problem behaviors commonly observed in individuals with IDD. While it has been used with children under 5, investigations into the fit of the ABC-C for this population are sparse. The purpose of the present study was to report on ABC-C scores in a sample of 97 children under age 5 with problem behavior. Analyses included evaluating differences in scores between age groups, comparing sample norms to established norms for older children, and conducting a confirmatory factor analysis. Results indicated differences in mean scores based on age with younger children generally scoring higher on some subscales of the ABC-C. Furthermore, the original 5-factor structure of the ABC-C was not fully supported. In general, the ABC-C may over- or underestimate behavior problems in younger children; therefore more extensive investigation into the utility of the ABC-C for children under age 5 is warranted.

  3. Hair trace elementary profiles in aging rodents and primates: links to altered cell homeodynamics and disease.

    PubMed

    Ambeskovic, Mirela; Fuchs, Eberhard; Beaumier, Pierre; Gerken, Michael; Metz, Gerlinde A

    2013-10-01

    Aging is associated with an increased incidence of pathological conditions such as neurodegeneration, cardiovascular and renal disease, and cancer. These conditions are believed to be linked to a disruption in cell homeodynamics, which is regulated by essential trace elements. In this study we used hair elementary analysis by inductively coupled plasma mass spectrometry (ICPMS) to examine age-related profiles of 47 elements in both rats and common marmoset monkeys. Hair was collected from young adult (6 months) and aged (18 months) Long-Evans male rats, and young adult (2 years), middle-aged (4 years) and aged (>8 years) marmosets. The results revealed that aging reduces content levels of cobalt, potassium and selenium while content levels of aluminium, arsenic, boron, mercury, molybdenum, and titanium were elevated in aged rats. Similarly, aged marmosets showed reduced levels of cobalt and elevated levels of aluminium. Case studies in aged rats revealed that myocardial infarction was associated with elevated levels of sodium, potassium and cadmium and reduced zinc, while renal failure was linked to elevated content of potassium, chloride and boron and reduced contents of manganese. Carcinoma was linked to elevated arsenic and reduced selenium levels. These findings indicate that hair elementary profiles in healthy aging and age-related diseases reflect altered cell and organ metabolic functions. Cobalt and aluminium in particular may serve as biomarkers of aging in animal models. Thus, elementary deposition in hair may have predictive and diagnostic value in age-related pathological conditions, including cardiovascular and kidney disease and cancer. PMID:24057279

  4. Music and Memory in Alzheimer's Disease and The Potential Underlying Mechanisms.

    PubMed

    Peck, Katlyn J; Girard, Todd A; Russo, Frank A; Fiocco, Alexandra J

    2016-01-01

    With population aging and a projected exponential expansion of persons diagnosed with Alzheimer's disease (AD), the development of treatment and prevention programs has become a fervent area of research and discovery. A growing body of evidence suggests that music exposure can enhance memory and emotional function in persons with AD. However, there is a paucity of research that aims to identify specific underlying neural mechanisms associated with music's beneficial effects in this particular population. As such, this paper reviews existing anecdotal and empirical evidence related to the enhancing effects of music exposure on cognitive function and further provides a discussion on the potential underlying mechanisms that may explain music's beneficial effect. Specifically, this paper will outline the potential role of the dopaminergic system, the autonomic nervous system, and the default network in explaining how music may enhance memory function in persons with AD. PMID:26967216

  5. Music and Memory in Alzheimer's Disease and The Potential Underlying Mechanisms.

    PubMed

    Peck, Katlyn J; Girard, Todd A; Russo, Frank A; Fiocco, Alexandra J

    2016-01-01

    With population aging and a projected exponential expansion of persons diagnosed with Alzheimer's disease (AD), the development of treatment and prevention programs has become a fervent area of research and discovery. A growing body of evidence suggests that music exposure can enhance memory and emotional function in persons with AD. However, there is a paucity of research that aims to identify specific underlying neural mechanisms associated with music's beneficial effects in this particular population. As such, this paper reviews existing anecdotal and empirical evidence related to the enhancing effects of music exposure on cognitive function and further provides a discussion on the potential underlying mechanisms that may explain music's beneficial effect. Specifically, this paper will outline the potential role of the dopaminergic system, the autonomic nervous system, and the default network in explaining how music may enhance memory function in persons with AD.

  6. Developmental mechanisms underlying variation in craniofacial disease and evolution.

    PubMed

    Fish, Jennifer L

    2016-07-15

    Craniofacial disease phenotypes exhibit significant variation in penetrance and severity. Although many genetic contributions to phenotypic variation have been identified, genotype-phenotype correlations remain imprecise. Recent work in evolutionary developmental biology has exposed intriguing developmental mechanisms that potentially explain incongruities in genotype-phenotype relationships. This review focuses on two observations from work in comparative and experimental animal model systems that highlight how development structures variation. First, multiple genetic inputs converge on relatively few developmental processes. Investigation of when and how variation in developmental processes occurs may therefore help predict potential genetic interactions and phenotypic outcomes. Second, genetic mutation is typically associated with an increase in phenotypic variance. Several models outlining developmental mechanisms underlying mutational increases in phenotypic variance are discussed using Satb2-mediated variation in jaw size as an example. These data highlight development as a critical mediator of genotype-phenotype correlations. Future research in evolutionary developmental biology focusing on tissue-level processes may help elucidate the "black box" between genotype and phenotype, potentially leading to novel treatment, earlier diagnoses, and better clinical consultations for individuals affected by craniofacial anomalies. PMID:26724698

  7. Systems medicine approaches for the definition of complex phenotypes in chronic diseases and ageing. From concept to implementation and policies.

    PubMed

    Bousquet, Jean; Jorgensen, Christian; Dauzat, Michel; Cesario, Alfredo; Camuzat, Thierry; Bourret, Rodolphe; Best, Nicolas; Anto, Josep M; Abecassis, Frederic; Aubas, Pierre; Avignon, Antoine; Badin, Melanie; Bedbrook, Anna; Blain, Hubert; Bourdin, Arnaud; Bringer, Jacques; Camu, William; Cayla, Guilhaume; Costa, David J; Courtet, Philippe; Cristol, Jean-Paul; Demoly, Pascal; de la Coussaye, Jean-Emmanuel; Fesler, Pierre; Gouzi, Fares; Gris, Jean-Christophe; Guillot, Bernard; Hayot, Maurice; Jeandel, Claude; Jonquet, Olivier; Journot, Laurent; Lehmann, Sylvain; Mathieu, Gwenaelle; Morel, Jacques; Ninot, Gregory; Pelissier, Jacques; Picot, Marie-Christine; Radier-Pontal, Francoise; Robine, Jean-Marie; Rodier, Michel; Roubille, Francois; Sultan, Ariane; Wojtusciszyn, Anne; Auffray, Charles; Balling, Rudi; Barbara, Cristina; Cambon-Thomsen, Anne; Chavannes, Niels H; Chuchalin, Alexander; Crooks, George; Dedeu, Antoni; Fabbri, Leonardo M; Garcia-Aymerich, Judith; Hajjam, Jawad; Melo Gomes, Elisabete; Palkonen, Susana; Piette, Francois; Pison, Christophe; Price, David; Samolinski, Boleslaw; Schunemann, Holger J; Sterk, Peter J; Yiallouros, Panayiotis; Roca, Josep; Van de Perre, Philippe; Mercier, Jacques

    2014-01-01

    Chronic diseases are diseases of long duration and slow progression. Major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases, diabetes, rheumatologic diseases and mental health) represent the predominant health problem of the Century. The prevention and control of NCDs are the priority of the World Health Organization 2008 Action Plan, the United Nations 2010 Resolution and the European Union 2010 Council. The novel trend for the management of NCDs is evolving towards integrative, holistic approaches. NCDs are intertwined with ageing. The European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) has prioritised NCDs. To tackle them in their totality in order to reduce their burden and societal impact, it is proposed that NCDs should be considered as a single expression of disease with different risk factors and entities. An innovative integrated health system built around systems medicine and strategic partnerships is proposed to combat NCDs. It includes (i) understanding the social, economic, environmental, genetic determinants, as well as the molecular and cellular mechanisms underlying NCDs; (ii) primary care and practice-based interprofessional collaboration; (iii) carefully phenotyped patients; (iv) development of unbiased and accurate biomarkers for comorbidities, severity and follow up of patients; (v) socio-economic science; (vi) development of guidelines; (vii) training; and (viii) policy decisions. The results could be applicable to all countries and adapted to local needs, economy and health systems. This paper reviews the complexity of NCDs intertwined with ageing. It gives an overview of the problem and proposes two practical examples of systems medicine (MeDALL) applied to allergy and to NCD co-morbidities (MACVIA-LR, Reference Site of the European Innovation Partnership on Active and Healthy Ageing).

  8. Systems medicine approaches for the definition of complex phenotypes in chronic diseases and ageing. From concept to implementation and policies.

    PubMed

    Bousquet, Jean; Jorgensen, Christian; Dauzat, Michel; Cesario, Alfredo; Camuzat, Thierry; Bourret, Rodolphe; Best, Nicolas; Anto, Josep M; Abecassis, Frederic; Aubas, Pierre; Avignon, Antoine; Badin, Melanie; Bedbrook, Anna; Blain, Hubert; Bourdin, Arnaud; Bringer, Jacques; Camu, William; Cayla, Guilhaume; Costa, David J; Courtet, Philippe; Cristol, Jean-Paul; Demoly, Pascal; de la Coussaye, Jean-Emmanuel; Fesler, Pierre; Gouzi, Fares; Gris, Jean-Christophe; Guillot, Bernard; Hayot, Maurice; Jeandel, Claude; Jonquet, Olivier; Journot, Laurent; Lehmann, Sylvain; Mathieu, Gwenaelle; Morel, Jacques; Ninot, Gregory; Pelissier, Jacques; Picot, Marie-Christine; Radier-Pontal, Francoise; Robine, Jean-Marie; Rodier, Michel; Roubille, Francois; Sultan, Ariane; Wojtusciszyn, Anne; Auffray, Charles; Balling, Rudi; Barbara, Cristina; Cambon-Thomsen, Anne; Chavannes, Niels H; Chuchalin, Alexander; Crooks, George; Dedeu, Antoni; Fabbri, Leonardo M; Garcia-Aymerich, Judith; Hajjam, Jawad; Melo Gomes, Elisabete; Palkonen, Susana; Piette, Francois; Pison, Christophe; Price, David; Samolinski, Boleslaw; Schunemann, Holger J; Sterk, Peter J; Yiallouros, Panayiotis; Roca, Josep; Van de Perre, Philippe; Mercier, Jacques

    2014-01-01

    Chronic diseases are diseases of long duration and slow progression. Major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases, diabetes, rheumatologic diseases and mental health) represent the predominant health problem of the Century. The prevention and control of NCDs are the priority of the World Health Organization 2008 Action Plan, the United Nations 2010 Resolution and the European Union 2010 Council. The novel trend for the management of NCDs is evolving towards integrative, holistic approaches. NCDs are intertwined with ageing. The European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) has prioritised NCDs. To tackle them in their totality in order to reduce their burden and societal impact, it is proposed that NCDs should be considered as a single expression of disease with different risk factors and entities. An innovative integrated health system built around systems medicine and strategic partnerships is proposed to combat NCDs. It includes (i) understanding the social, economic, environmental, genetic determinants, as well as the molecular and cellular mechanisms underlying NCDs; (ii) primary care and practice-based interprofessional collaboration; (iii) carefully phenotyped patients; (iv) development of unbiased and accurate biomarkers for comorbidities, severity and follow up of patients; (v) socio-economic science; (vi) development of guidelines; (vii) training; and (viii) policy decisions. The results could be applicable to all countries and adapted to local needs, economy and health systems. This paper reviews the complexity of NCDs intertwined with ageing. It gives an overview of the problem and proposes two practical examples of systems medicine (MeDALL) applied to allergy and to NCD co-morbidities (MACVIA-LR, Reference Site of the European Innovation Partnership on Active and Healthy Ageing). PMID:24641234

  9. UPS Activation in the Battle Against Aging and Aggregation-Related Diseases: An Extended Review.

    PubMed

    Papaevgeniou, Nikoletta; Chondrogianni, Niki

    2016-01-01

    Aging is a biological process accompanied by gradual increase of damage in all cellular macromolecules, i.e., nucleic acids, lipids, and proteins. When the proteostasis network (chaperones and proteolytic systems) cannot reverse the damage load due to its excess as compared to cellular repair/regeneration capacity, failure of homeostasis is established. This failure is a major hallmark of aging and/or aggregation-related diseases. Dysfunction of the major cellular proteolytic machineries, namely the proteasome and the lysosome, has been reported during the progression of aging and aggregation-prone diseases. Therefore, activation of these pathways is considered as a possible preventive or therapeutic approach against the progression of these processes. This chapter focuses on UPS activation studies in cellular and organismal models and the effects of such activation on aging, longevity and disease prevention or reversal. PMID:27613027

  10. Younger age at onset of sporadic Parkinson's disease among subjects occupationally exposed to metals and pesticides

    PubMed Central

    Farb, David H.; Ozer, Josef; Feldman, Robert G.; Durso, Raymon

    2014-01-01

    An earlier age at onset of Parkinson's disease (PD) has been reported to be associated with occupational exposures to manganese and hydrocarbon solvents suggesting that exposure to neurotoxic chemicals may hasten the progression of idiopathic PD. In this study the role of occupational exposure to metals and pesticides in the progression of idiopathic PD was assessed by looking at age at disease onset. The effects of heritable genetic risk factors, which may also influence age at onset, was minimized by including only sporadic cases of PD with no family history of the disease (n=58). Independent samples Student t-test revealed that subjects with occupational exposure to metals and/or pesticides (n=36) were significantly (p=0.013) younger than unexposed controls (n=22). These subjects were then divided into three groups [high (n=18), low (n=18), and unexposed (n=22)] to ascertain if duration of exposure further influenced age at onset of PD. One-way ANOVA revealed that subjects in the high exposure group were significantly (p=0.0121) younger (mean age: 50.33 years) than unexposed subjects (mean age: 60.45 years). Subjects were also stratified by exposure type (metals vs. pesticides). These results suggest that chronic exposure to metals and pesticides is associated with a younger age at onset of PD among patients with no family history of the disease and that duration of exposure is a factor in the magnitude of this effect. PMID:26109889

  11. Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection.

    PubMed

    Blackburn, Elizabeth H; Epel, Elissa S; Lin, Jue

    2015-12-01

    Telomeres are the protective end-complexes at the termini of eukaryotic chromosomes. Telomere attrition can lead to potentially maladaptive cellular changes, block cell division, and interfere with tissue replenishment. Recent advances in the understanding of human disease processes have clarified the roles of telomere biology, especially in diseases of human aging and in some aging-related processes. Greater overall telomere attrition predicts mortality and aging-related diseases in inherited telomere syndrome patients, and also in general human cohorts. However, genetically caused variations in telomere maintenance either raise or lower risks and progression of cancers, in a highly cancer type-specific fashion. Telomere maintenance is determined by genetic factors and is also cumulatively shaped by nongenetic influences throughout human life; both can interact. These and other recent findings highlight both causal and potentiating roles for telomere attrition in human diseases.

  12. Age at onset of Alzheimer's disease: clue to the relative importance of etiologic factors

    SciTech Connect

    Horner, R.D.

    1987-09-01

    Clues to the relative importance of possible etiologic factors for dementia of the Alzheimer type may be gained by examining the fit of case series to Sartwell's model of the distribution of incubation periods. If age at disease onset is used as the incubation period of this disease, a genetic or environmental factor acting during the prenatal period is suggested if the distribution of these ages fits the lognormal curve; otherwise, environmental factors acting after birth are implicated. Case series were identified from the literature. Four case series were found which contained sufficiently detailed data to permit this secondary analysis; only one case series was population-based. The distribution of age at disease onset for each series was graphically and statistically assessed for fit to the logarithmic normal distribution. Each case series fit the lognormal curve well. This suggests that research into the etiology of dementia of the Alzheimer type should focus on the prenatal experiences of patients with this disease.

  13. Neuropathology and apolipoprotein E profile of aged chimpanzees: implications for Alzheimer disease.

    PubMed Central

    Gearing, M; Rebeck, G W; Hyman, B T; Tigges, J; Mirra, S S

    1994-01-01

    Neuropathological findings in three aged chimpanzees were compared with those in rhesus monkeys and individuals with Alzheimer disease. Senile plaques and blood vessels were immunoreactive for amyloid beta-protein and apolipoprotein E (apoE) in the nonhuman primates, recapitulating findings in human aging and Alzheimer disease. Neurofibrillary tangles, another hallmark of Alzheimer disease, were absent. PCR/restriction-enzyme analysis in chimpanzees revealed an APOE profile similar to the human APOE type 4 allele associated with an increased risk of Alzheimer disease. These findings militate against the hypothesis that the absence of APOE type 3 allele predisposes to neurofibrillary tangle formation and support the value of aged primates for exploring mechanisms of amyloid processing and the role of apoE. Images PMID:7937774

  14. Menopausal Hormone Therapy, Age, and Chronic Diseases: Perspectives on Statistical Trends

    PubMed Central

    2016-01-01

    The release of the Women’s Health Initiative (WHI) study in 2002 was a shock to the medical community. Hormone therapy (HT) had generally been considered to be highly beneficial for postmenopausal women since it was the gold standard for relief of menopausal symptoms (hot flashes, night sweats, vaginal atrophy) and it was thought to protect women from osteoporosis, heart disease, and cognitive decline and to generally improve quality of life. However, WHI showed a statistically significant increase in a number of disease states, including breast cancer, cardiovascular disease, and stroke. One problem with the WHI study was that the average age of women in the study was 63, which is considerably older than the age at which most women enter menopause (about 51). The timing hypothesis attempts to rationalize the effect of age on response to HT and risk of various diseases. The data suggests that younger women (50–60) may be protected from heart disease with only a slight increase in breast cancer risk. In contrast, older women (>65) are more susceptible to breast cancer and heart disease and should avoid HT. This Perspective on Statistical Trends evaluates the current data on HT and risk for chronic diseases as a function of age. PMID:27636306

  15. Adverse Childhood Experiences and Adult Risk Factors for Age-Related Disease

    PubMed Central

    Danese, Andrea; Moffitt, Terrie E.; Harrington, HonaLee; Milne, Barry J.; Polanczyk, Guilherme; Pariante, Carmine M.; Poulton, Richie; Caspi, Avshalom

    2013-01-01

    Objective To understand why children exposed to adverse psychosocial experiences are at elevated risk for age-related disease, such as cardiovascular disease, by testing whether adverse childhood experiences predict enduring abnormalities in stress-sensitive biological systems, namely, the nervous, immune, and endocrine/metabolic systems. Design A 32-year prospective longitudinal study of a representative birth cohort. Setting New Zealand. Participants A total of 1037 members of the Dunedin Multidisciplinary Health and Development Study. Main Exposures During their first decade of life, study members were assessed for exposure to 3 adverse psychosocial experiences: socioeconomic disadvantage, maltreatment, and social isolation. Main Outcome Measures At age 32 years, study members were assessed for the presence of 3 age-related-disease risks: major depression, high inflammation levels (high-sensitivity C-reactive protein level >3 mg/L), and the clustering of metabolic risk biomarkers (overweight, high blood pressure, high total cholesterol, low high-density lipoprotein cholesterol, high glycated hemoglobin, and low maximum oxygen consumption levels. Results Children exposed to adverse psychosocial experiences were at elevated risk of depression, high inflammation levels, and clustering of metabolic risk markers. Children who had experienced socioeconomic disadvantage (incidence rate ratio, 1.89; 95% confidence interval, 1.36–2.62), maltreatment (1.81; 1.38–2.38), or social isolation (1.87; 1.38–2.51) had elevated age-related-disease risks in adulthood. The effects of adverse childhood experiences on age-related-disease risks in adulthood were nonredundant, cumulative, and independent of the influence of established developmental and concurrent risk factors. Conclusions Children exposed to adverse psychosocial experiences have enduring emotional, immune, and metabolic abnormalities that contribute to explaining their elevated risk for age-related disease. The

  16. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels

    PubMed Central

    Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F.; Eszes, Marika; Faull, Richard L.M.; Curtis, Maurice A.; Waldvogel, Henry J.; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V.; Coppola, Giovanni; Yang, X. William

    2016-01-01

    Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=−0.41, p=5.5×10−8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels. PMID:27479945

  17. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels.

    PubMed

    Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F; Eszes, Marika; Faull, Richard L M; Curtis, Maurice A; Waldvogel, Henry J; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V; Coppola, Giovanni; Yang, X William

    2016-07-01

    Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=-0.41, p=5.5×10-8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels. PMID:27479945

  18. Neuronal amyloid-β accumulation within cholinergic basal forebrain in ageing and Alzheimer's disease.

    PubMed

    Baker-Nigh, Alaina; Vahedi, Shahrooz; Davis, Elena Goetz; Weintraub, Sandra; Bigio, Eileen H; Klein, William L; Geula, Changiz

    2015-06-01

    The mechanisms that contribute to selective vulnerability of the magnocellular basal forebrain cholinergic neurons in neurodegenerative diseases, such as Alzheimer's disease, are not fully understood. Because age is the primary risk factor for Alzheimer's disease, mechanisms of interest must include age-related alterations in protein expression, cell type-specific markers and pathology. The present study explored the extent and characteristics of intraneuronal amyloid-β accumulation, particularly of the fibrillogenic 42-amino acid isoform, within basal forebrain cholinergic neurons in normal young, normal aged and Alzheimer's disease brains as a potential contributor to the selective vulnerability of these neurons using immunohistochemistry and western blot analysis. Amyloid-β1-42 immunoreactivity was observed in the entire cholinergic neuronal population regardless of age or Alzheimer's disease diagnosis. The magnitude of this accumulation as revealed by optical density measures was significantly greater than that in cortical pyramidal neurons, and magnocellular neurons in the globus pallidus did not demonstrate a similar extent of amyloid immunoreactivity. Immunoblot analysis with a panel of amyloid-β antibodies confirmed accumulation of high concentration of amyloid-β in basal forebrain early in adult life. There was no age- or Alzheimer-related alteration in total amyloid-β content within this region. In contrast, an increase in the large molecular weight soluble oligomer species was observed with a highly oligomer-specific antibody in aged and Alzheimer brains when compared with the young. Similarly, intermediate molecular weight oligomeric species displayed an increase in aged and Alzheimer brains when compared with the young using two amyloid-β42 antibodies. Compared to cortical homogenates, small molecular weight oligomeric species were lower and intermediate species were enriched in basal forebrain in ageing and Alzheimer's disease. Regional and age

  19. Paternal aging and increased risk of congenital disease, psychiatric disorders, and cancer.

    PubMed

    Conti, Simon L; Eisenberg, Michael L

    2016-01-01

    As couples are increasingly delaying parenthood, the effect of the aging men and women on reproductive outcomes has been an area of increased interest. Advanced paternal age has been shown to independently affect the entire spectrum of male fertility as assessed by reductions in sperm quality and fertilization (both assisted and unassisted). Moreover, epidemiological data suggest that paternal age can lead to higher rates of adverse birth outcomes and congenital anomalies. Mounting evidence also suggests increased risk of specific pediatric and adult disease states ranging from cancer to behavioral traits. While disease states associated with advancing paternal age have been well described, consensus recommendations for neonatal screening have not been as widely implemented as have been with advanced maternal age. PMID:26975491

  20. Paternal aging and increased risk of congenital disease, psychiatric disorders, and cancer

    PubMed Central

    Conti, Simon L; Eisenberg, Michael L

    2016-01-01

    As couples are increasingly delaying parenthood, the effect of the aging men and women on reproductive outcomes has been an area of increased interest. Advanced paternal age has been shown to independently affect the entire spectrum of male fertility as assessed by reductions in sperm quality and fertilization (both assisted and unassisted). Moreover, epidemiological data suggest that paternal age can lead to higher rates of adverse birth outcomes and congenital anomalies. Mounting evidence also suggests increased risk of specific pediatric and adult disease states ranging from cancer to behavioral traits. While disease states associated with advancing paternal age have been well described, consensus recommendations for neonatal screening have not been as widely implemented as have been with advanced maternal age. PMID:26975491

  1. Paternal aging and increased risk of congenital disease, psychiatric disorders, and cancer.

    PubMed

    Conti, Simon L; Eisenberg, Michael L

    2016-01-01

    As couples are increasingly delaying parenthood, the effect of the aging men and women on reproductive outcomes has been an area of increased interest. Advanced paternal age has been shown to independently affect the entire spectrum of male fertility as assessed by reductions in sperm quality and fertilization (both assisted and unassisted). Moreover, epidemiological data suggest that paternal age can lead to higher rates of adverse birth outcomes and congenital anomalies. Mounting evidence also suggests increased risk of specific pediatric and adult disease states ranging from cancer to behavioral traits. While disease states associated with advancing paternal age have been well described, consensus recommendations for neonatal screening have not been as widely implemented as have been with advanced maternal age.

  2. The impact of base excision DNA repair in age-related neurodegenerative diseases.

    PubMed

    Leandro, Giovana S; Sykora, Peter; Bohr, Vilhelm A

    2015-06-01

    The aging process and several age-related neurodegenerative disorders have been linked to elevated levels of DNA damage induced by ROS and deficiency in DNA repair mechanisms. DNA damage induced by ROS is a byproduct of cellular respiration and accumulation of damage over time, is a fundamental aspect of a main theory of aging. Mitochondria have a pivotal role in generating cellular oxidative stress, and mitochondrial dysfunction has been associated with several diseases. DNA base excision repair is considered the major pathway for repair of oxidized bases in DNA both in the nuclei and in mitochondria, and in neurons this mechanism is particularly important because non-diving cells have limited back-up DNA repair mechanisms. An association between elevated oxidative stress and a decrease in BER is strongly related to the aging process and has special relevance in age-related neurodegenerative diseases. Here, we review the role of DNA repair in aging, focusing on the implications of the DNA base excision repair pathways and how alterations in expression of these DNA repair proteins are related to the aging process and to age-related neurodegenerative diseases.

  3. Parkinson disease male-to-female ratios increase with age: French nationwide study and meta-analysis

    PubMed Central

    Moisan, Frédéric; Kab, Sofiane; Mohamed, Fatima; Canonico, Marianne; Le Guern, Morgane; Quintin, Cécile; Carcaillon, Laure; Nicolau, Javier; Duport, Nicolas; Singh-Manoux, Archana; Boussac-Zarebska, Marjorie; Elbaz, Alexis

    2016-01-01

    Background Parkinson’s disease (PD) is 1.5 times more frequent in men than women. Whether age modifies this ratio is unclear. We examined whether male-to-female (M–F) ratios change with age through a French nationwide prevalence/incidence study (2010) and a meta-analysis of incidence studies. Methods We used French national drug claims databases to identify PD cases using a validated algorithm. We computed M–F prevalence/incidence ratios overall and by age using Poisson regression. Ratios were regressed on age to estimate their annual change. We identified all PD incidence studies with age/sex-specific data, and performed a meta-analysis of M–F ratios. Results On the basis of 149 672 prevalent (50% women) and 25 438 incident (49% women) cases, age-standardised rates were higher in men (prevalence=2.865/1000; incidence=0.490/1000 person-years) than women (prevalence=1.934/1000; incidence=0.328/1000 person-years). The overall M–F ratio was 1.48 for prevalence and 1.49 for incidence. Prevalence and incidence M–F ratios increased by 0.05 and 0.14, respectively, per 10 years of age. Incidence was similar in men and women under 50 years (M–F ratio <1.2, p>0.20), and over 1.6 (p<0.001) times higher in men than women above 80 years (p trend <0.001). A meta-analysis of 22 incidence studies (14 126 cases, 46% women) confirmed that M– F ratios increased with age (0.26 per 10 years, p trend=0.005). Conclusions Age-increasing M–F ratios suggest that PD aetiology changes with age. Sex-related risk/protective factors may play a different role across the continuum of age at onset. This finding may inform aetiological PD research. PMID:26701996

  4. Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease.

    PubMed

    Moskalev, Alexey; Chernyagina, Elizaveta; de Magalhães, João Pedro; Barardo, Diogo; Thoppil, Harikrishnan; Shaposhnikov, Mikhail; Budovsky, Arie; Fraifeld, Vadim E; Garazha, Andrew; Tsvetkov, Vasily; Bronovitsky, Evgeny; Bogomolov, Vladislav; Scerbacov, Alexei; Kuryan, Oleg; Gurinovich, Roman; Jellen, Leslie C; Kennedy, Brian; Mamoshina, Polina; Dobrovolskaya, Evgeniya; Aliper, Alex; Kaminsky, Dmitry; Zhavoronkov, Alex

    2015-09-01

    As the level of interest in aging research increases, there is a growing number of geroprotectors, or therapeutic interventions that aim to extend the healthy lifespan and repair or reduce aging-related damage in model organisms and, eventually, in humans. There is a clear need for a manually-curated database of geroprotectors to compile and index their effects on aging and age-related diseases and link these effects to relevant studies and multiple biochemical and drug databases. Here, we introduce the first such resource, Geroprotectors (http://geroprotectors.org). Geroprotectors is a public, rapidly explorable database that catalogs over 250 experiments involving over 200 known or candidate geroprotectors that extend lifespan in model organisms. Each compound has a comprehensive profile complete with biochemistry, mechanisms, and lifespan effects in various model organisms, along with information ranging from chemical structure, side effects, and toxicity to FDA drug status. These are presented in a visually intuitive, efficient framework fit for casual browsing or in-depth research alike. Data are linked to the source studies or databases, providing quick and convenient access to original data. The Geroprotectors database facilitates cross-study, cross-organism, and cross-discipline analysis and saves countless hours of inefficient literature and web searching. Geroprotectors is a one-stop, knowledge-sharing, time-saving resource for researchers seeking healthy aging solutions. PMID:26342919

  5. Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease.

    PubMed

    Moskalev, Alexey; Chernyagina, Elizaveta; de Magalhães, João Pedro; Barardo, Diogo; Thoppil, Harikrishnan; Shaposhnikov, Mikhail; Budovsky, Arie; Fraifeld, Vadim E; Garazha, Andrew; Tsvetkov, Vasily; Bronovitsky, Evgeny; Bogomolov, Vladislav; Scerbacov, Alexei; Kuryan, Oleg; Gurinovich, Roman; Jellen, Leslie C; Kennedy, Brian; Mamoshina, Polina; Dobrovolskaya, Evgeniya; Aliper, Alex; Kaminsky, Dmitry; Zhavoronkov, Alex

    2015-09-01

    As the level of interest in aging research increases, there is a growing number of geroprotectors, or therapeutic interventions that aim to extend the healthy lifespan and repair or reduce aging-related damage in model organisms and, eventually, in humans. There is a clear need for a manually-curated database of geroprotectors to compile and index their effects on aging and age-related diseases and link these effects to relevant studies and multiple biochemical and drug databases. Here, we introduce the first such resource, Geroprotectors (http://geroprotectors.org). Geroprotectors is a public, rapidly explorable database that catalogs over 250 experiments involving over 200 known or candidate geroprotectors that extend lifespan in model organisms. Each compound has a comprehensive profile complete with biochemistry, mechanisms, and lifespan effects in various model organisms, along with information ranging from chemical structure, side effects, and toxicity to FDA drug status. These are presented in a visually intuitive, efficient framework fit for casual browsing or in-depth research alike. Data are linked to the source studies or databases, providing quick and convenient access to original data. The Geroprotectors database facilitates cross-study, cross-organism, and cross-discipline analysis and saves countless hours of inefficient literature and web searching. Geroprotectors is a one-stop, knowledge-sharing, time-saving resource for researchers seeking healthy aging solutions.

  6. Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease

    PubMed Central

    Moskalev, Alexey; Chernyagina, Elizaveta; de Magalhães, João Pedro; Barardo, Diogo; Thoppil, Harikrishnan; Shaposhnikov, Mikhail; Budovsky, Arie; Fraifeld, Vadim E.; Garazha, Andrew; Tsvetkov, Vasily; Bronovitsky, Evgeny; Bogomolov, Vladislav; Scerbacov, Alexei; Kuryan, Oleg; Gurinovich, Roman; Jellen, Leslie C.; Kennedy, Brian; Mamoshina, Polina; Dobrovolskaya, Evgeniya; Aliper, Alex; Kaminsky, Dmitry; Zhavoronkov, Alex

    2015-01-01

    As the level of interest in aging research increases, there is a growing number of geroprotectors, or therapeutic interventions that aim to extend the healthy lifespan and repair or reduce aging-related damage in model organisms and, eventually, in humans. There is a clear need for a manually-curated database of geroprotectors to compile and index their effects on aging and age-related diseases and link these effects to relevant studies and multiple biochemical and drug databases. Here, we introduce the first such resource, Geroprotectors (http://geroprotectors.org). Geroprotectors is a public, rapidly explorable database that catalogs over 250 experiments involving over 200 known or candidate geroprotectors that extend lifespan in model organisms. Each compound has a comprehensive profile complete with biochemistry, mechanisms, and lifespan effects in various model organisms, along with information ranging from chemical structure, side effects, and toxicity to FDA drug status. These are presented in a visually intuitive, efficient framework fit for casual browsing or in-depth research alike. Data are linked to the source studies or databases, providing quick and convenient access to original data. The Geroprotectors database facilitates cross-study, cross-organism, and cross-discipline analysis and saves countless hours of inefficient literature and web searching. Geroprotectors is a one-stop, knowledge-sharing, time-saving resource for researchers seeking healthy aging solutions. PMID:26342919

  7. Interaction between Streptococcus pneumoniae and Staphylococcus aureus in paediatric patients suffering from an underlying chronic disease.

    PubMed

    Esposito, Susanna; Marseglia, Gian Luigi; Colombo, Carla; Iughetti, Lorenzo; Terranova, Leonardo; Ierardi, Valentina; Gambino, Monia; Principi, Nicola

    2015-12-01

    Little is known about the interaction between Streptococcus pneumoniae and Staphylococcus aureus in school-age children and adolescents suffering from an underlying chronic disease. To increase our knowledge in this regard, an oropharyngeal swab was obtained from school-age children and adolescents suffering from asthma (n = 423), cystic fibrosis (CF) (n = 212) and type 1 diabetes mellitus (DM1) (n = 296). S. pneumoniae detection and serotyping were performed using a real-time polymerase chain reaction, and S. aureus detection was performed using the RIDAGENE MRSA system. Among asthmatic, CF and DM1 patients, both pathogens were identified in 65/423 (15.4%), 21/212 (9.9%) and 62/296 (20.9%) children, respectively; S. pneumoniae alone was identified in 127/434 (30.0%), 21/212 (9.9%) and 86/296 (29.1%), respectively; S. aureus alone was identified in 58/434 (13.7%), 78/212 (36.8%) and 49/296 (16.6%), respectively. S. pneumoniae colonisation rates were higher in younger children and declined with age, whereas the frequency of S. aureus colonisation was quite similar in the different age groups. Among asthmatic and CF patients aged 6-9 years, S. aureus carriage was significantly higher in children who were positive for S. pneumoniae (P <0.05). No significant association emerged between S. aureus carriage and carriage of S. pneumoniae serotypes included in the pneumococcal conjugate vaccines (PCVs). This study shows for the first time that school-age children and adolescents with asthma, CF and DM1 are frequently colonised by S. pneumoniae and S. aureus and that no negative relationship seems to exist between these pathogens. Moreover, the supposed protection offered by PCV administration against S. aureus colonisation was not demonstrated.

  8. Notch signaling deficiency underlies age-dependent depletion of satellite cells in muscular dystrophy.

    PubMed

    Jiang, Chunhui; Wen, Yefei; Kuroda, Kazuki; Hannon, Kevin; Rudnicki, Michael A; Kuang, Shihuan

    2014-08-01

    Duchenne muscular dystrophy (DMD) is a devastating disease characterized by muscle wasting, loss of mobility and death in early adulthood. Satellite cells are muscle-resident stem cells responsible for the repair and regeneration of damaged muscles. One pathological feature of DMD is the progressive depletion of satellite cells, leading to the failure of muscle repair. Here, we attempted to explore the molecular mechanisms underlying satellite cell ablation in the dystrophin mutant mdx mouse, a well-established model for DMD. Initial muscle degeneration activates satellite cells, resulting in increased satellite cell number in young mdx mice. This is followed by rapid loss of satellite cells with age due to the reduced self-renewal ability of mdx satellite cells. In addition, satellite cell composition is altered even in young mdx mice, with significant reductions in the abundance of non-committed (Pax7+ and Myf5-) satellite cells. Using a Notch-reporter mouse, we found that the mdx satellite cells have reduced activation of Notch signaling, which has been shown to be necessary to maintain satellite cell quiescence and self-renewal. Concomitantly, the expression of Notch1, Notch3, Jag1, Hey1 and HeyL are reduced in the mdx primary myoblast. Finally, we established a mouse model to constitutively activate Notch signaling in satellite cells, and show that Notch activation is sufficient to rescue the self-renewal deficiencies of mdx satellite cells. These results demonstrate that Notch signaling is essential for maintaining the satellite cell pool and that its deficiency leads to depletion of satellite cells in DMD.

  9. Alzheimer’s disease as homeostatic responses to age-related myelin breakdown

    PubMed Central

    Bartzokis, George

    2011-01-01

    The amyloid hypothesis (AH) of Alzheimer’s disease (AD) posits that the fundamental cause of AD is the accumulation of the peptide amyloid beta (Aβ) in the brain. This hypothesis has been supported by observations that genetic defects in amyloid precursor protein (APP) and presenilin increase Aβ production and cause familial AD (FAD). The AH is widely accepted but does not account for important phenomena including recent failures of clinical trials to impact dementia in humans even after successfully reducing Aβ deposits. Herein, the AH is viewed from the broader overarching perspective of the myelin model of the human brain that focuses on functioning brain circuits and encompasses white matter and myelin in addition to neurons and synapses. The model proposes that the recently evolved and extensive myelination of the human brain underlies both our unique abilities and susceptibility to highly prevalent age-related neuropsychiatric disorders such as late onset AD (LOAD). It regards oligodendrocytes and the myelin they produce as being both critical for circuit function and uniquely vulnerable to damage. This perspective reframes key observations such as axonal transport disruptions, formation of axonal swellings/sphenoids and neuritic plaques, and proteinaceous deposits such as Aβ and tau as by-products of homeostatic myelin repair processes. It delineates empirically testable mechanisms of action for genes underlying FAD and LOAD and provides “upstream” treatment targets. Such interventions could potentially treat multiple degenerative brain disorders by mitigating the effects of aging and associated changes in iron, cholesterol, and free radicals on oligodendrocytes and their myelin. PMID:19775776

  10. Epigenetic Control of Stem Cell Potential During Homeostasis, Aging, and Disease

    PubMed Central

    Beerman, Isabel; Rossi, Derrick J.

    2015-01-01

    Stem cell decline is an important cellular driver of aging-associated pathophysiology in multiple tissues. Epigenetic regulation is central to establishing and maintaining stem cell function, and emerging evidence indicates that epigenetic dysregulation contributes to the altered potential of stem cells during aging. Unlike terminally differentiated cells, the impact of epigenetic dysregulation in stem cells is propagated beyond self; alterations can be heritably transmitted to differentiated progeny, in addition to being perpetuated and amplified within the stem cell pool through self-renewal divisions. This review focuses on recent studies examining epigenetic regulation of tissue-specific stem cells in homeostasis, aging, and aging-related disease. PMID:26046761

  11. Dysregulated TGF-β Production Underlies the Age-Related Vulnerability to Chikungunya Virus

    PubMed Central

    Uhrlaub, Jennifer L.; Pulko, Vesna; DeFilippis, Victor R.; Streblow, Daniel N.; Coleman, Gary D.; Lindo, John F.; Vickers, Ivan; Anzinger, Joshua J.; Nikolich-Žugich, Janko

    2016-01-01

    Chikungunya virus (CHIKV) is a re-emerging global pathogen with pandemic potential, which causes fever, rash and debilitating arthralgia. Older adults over 65 years are particularly susceptible to severe and chronic CHIKV disease (CHIKVD), accounting for >90% of all CHIKV-related deaths. There are currently no approved vaccines or antiviral treatments available to limit chronic CHIKVD. Here we show that in old mice excessive, dysregulated TGFβ production during acute infection leads to a reduced immune response and subsequent chronic disease. Humans suffering from CHIKV infection also exhibited high TGFβ levels and a pronounced age-related defect in neutralizing anti-CHIKV antibody production. In vivo reduction of TGFβ levels minimized acute joint swelling, restored neutralizing antibody production and diminished chronic joint pathology in old mice. This study identifies increased and dysregulated TGFβ secretion as one key mechanism contributing to the age-related loss of protective anti-CHIKV-immunity leading to chronic CHIKVD. PMID:27736984

  12. Stress-Activated Cap’n’collar Transcription Factors in Aging and Human Disease

    PubMed Central

    Sykiotis, Gerasimos P.; Bohmann, Dirk

    2010-01-01

    Cap’n’collar (Cnc) transcription factors are conserved in metazoans and have important developmental and homeostatic functions. The vertebrate Nrf1, Nrf2, and Nrf3, the Caenorhabditis elegans SKN-1, and the Drosophila CncC comprise a subgroup of Cnc factors that mediate adaptive responses to cellular stress. The most studied stress-activated Cnc factor is Nrf2, which orchestrates the transcriptional response of cells to oxidative stressors and electrophilic xenobiotics. In rodent models, signaling by Nrf2 defends against oxidative stress and aging-associated disorders, such as neurodegeneration, respiratory diseases, and cancer. In humans, polymorphisms that decrease Nrf2 abundance have been associated with various pathologies of the skin, respiratory system, and digestive tract. In addition to preventing disease in rodents and humans, Cnc factors have lifespan-extending and anti-aging functions in invertebrates. However, despite the pro-longevity and antioxidant roles of stress-activated Cnc factors, their activity paradoxically declines in aging model organisms and in humans suffering from progressing respiratory disease or neurodegeneration. We review the roles and regulation of stress-activated Cnc factors across species, present all reported instances in which their activity is paradoxically decreased in aging and disease, and discuss the possibility that the pharmacological restoration of Nrf2 signaling may be useful in the prevention and treatment of age-related diseases. PMID:20215646

  13. Mass spectrometric analysis of protein tyrosine nitration in aging and neurodegenerative diseases.

    PubMed

    Yeo, Woon-Seok; Kim, Young Jun; Kabir, Mohammad Humayun; Kang, Jeong Won; Ahsan-Ul-Bari, Md; Kim, Kwang Pyo

    2015-01-01

    This review highlights the significance of protein tyrosine nitration (PTN) in signal transduction pathways, the progress achieved in analytical methods, and the implication of nitration in the cellular pathophysiology of aging and age-related neurodegenerative diseases. Although mass spectrometry of nitrated peptides has become a powerful tool for the characterization of nitrated peptides, the low stoichiometry of this modification clearly necessitates the use of affinity chromatography to enrich modified peptides. Analysis of nitropeptides involves identification of endogenous, intact modification as well as chemical conversion of the nitro group to a chemically reactive amine group and further modifications that enable affinity capture and enhance detectability by altering molecular properties. In this review, we focus on the recent progress in chemical derivatization of nitropeptides for enrichment and mass analysis, and for detection and quantification using various analytical tools. PTN participates in physiological processes, such as aging and neurodegenerative diseases. Accumulation of 3-nitrotyrosine has been found to occur during the aging process; this was identified through mass spectrometry. Further, there are several studies implicating the presence of nitrated tyrosine in age-related diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. PMID:24889964

  14. Neurofunctional (Re)Organization Underlying Narrative Discourse Processing in Aging: Evidence from fNIRS

    ERIC Educational Resources Information Center

    Scherer, Lilian Cristine; Fonseca, Rochele Paz; Giroux, Francine; Senhadji, Noureddine; Marcotte, Karine; Tomitch, Leda Maria Braga; Benali, Habib; Lesage, Frederic; Ska, Bernadette; Joanette, Yves

    2012-01-01

    Relatively few studies have analyzed the mechanisms underlying the cognitive changes that affect language in the elderly, and fewer have done so for narrative discourse. The goal of this study was to explore the neurofunctional changes associated with aging for different components of narrative discourse. Functional near-infrared spectroscopy…

  15. Alcohol Use by Persons under the Legal Drinking Age of 21. The NHSDA Report.

    ERIC Educational Resources Information Center

    Substance Abuse and Mental Health Services Administration (DHHS/PHS), Rockville, MD. Office of Applied Studies.

    This report presents findings on underage alcohol use (i.e., alcohol use among persons under the age of 21) from the National Household Survey on Drug Abuse (NHSDA). The NHSDA asks respondents about the quantity and frequency of their alcohol use in the past month. The NHSDA also asks about problems or behaviors associated with their alcohol use…

  16. An Evaluation of the Aberrant Behavior Checklist for Children under Age 5

    ERIC Educational Resources Information Center

    Schmidt, Jonathan D.; Huete, John M.; Fodstad, Jill C.; Chin, Michelle D.; Kurtz, Patricia F.

    2013-01-01

    Severe problem behaviors such as self-injury and aggression are frequently observed in young children under age 5 with intellectual and developmental disabilities (IDD). Although early identification of problem behavior is critical to effective intervention, there are few standardized measures available that identify severe problem behavior in…

  17. Age-Related Declines and Disease-Associated Variation in Immune Cell Telomere Length in a Wild Mammal

    PubMed Central

    Beirne, Christopher; Delahay, Richard; Hares, Michelle; Young, Andrew

    2014-01-01

    Immunosenescence, the deterioration of immune system capability with age, may play a key role in mediating age-related declines in whole-organism performance, but the mechanisms that underpin immunosenescence are poorly understood. Biomedical research on humans and laboratory models has documented age and disease related declines in the telomere lengths of leukocytes (‘immune cells’), stimulating interest their having a potentially general role in the emergence of immunosenescent phenotypes. However, it is unknown whether such observations generalise to the immune cell populations of wild vertebrates living under ecologically realistic conditions. Here we examine longitudinal changes in the mean telomere lengths of immune cells in wild European badgers (Meles meles). Our findings provide the first evidence of within-individual age-related declines in immune cell telomere lengths in a wild vertebrate. That the rate of age-related decline in telomere length appears to be steeper within individuals than at the overall population level raises the possibility that individuals with short immune cell telomeres and/or higher rates of immune cell telomere attrition may be selectively lost from this population. We also report evidence suggestive of associations between immune cell telomere length and bovine tuberculosis infection status, with individuals detected at the most advanced stage of infection tending to have shorter immune cell telomeres than disease positive individuals. While male European badgers are larger and show higher rates of annual mortality than females, we found no evidence of a sex difference in either mean telomere length or the average rate of within-individual telomere attrition with age. Our findings lend support to the view that age-related declines in the telomere lengths of immune cells may provide one potentially general mechanism underpinning age-related declines in immunocompetence in natural populations. PMID:25268841

  18. Age-related declines and disease-associated variation in immune cell telomere length in a wild mammal.

    PubMed

    Beirne, Christopher; Delahay, Richard; Hares, Michelle; Young, Andrew

    2014-01-01

    Immunosenescence, the deterioration of immune system capability with age, may play a key role in mediating age-related declines in whole-organism performance, but the mechanisms that underpin immunosenescence are poorly understood. Biomedical research on humans and laboratory models has documented age and disease related declines in the telomere lengths of leukocytes ('immune cells'), stimulating interest their having a potentially general role in the emergence of immunosenescent phenotypes. However, it is unknown whether such observations generalise to the immune cell populations of wild vertebrates living under ecologically realistic conditions. Here we examine longitudinal changes in the mean telomere lengths of immune cells in wild European badgers (Meles meles). Our findings provide the first evidence of within-individual age-related declines in immune cell telomere lengths in a wild vertebrate. That the rate of age-related decline in telomere length appears to be steeper within individuals than at the overall population level raises the possibility that individuals with short immune cell telomeres and/or higher rates of immune cell telomere attrition may be selectively lost from this population. We also report evidence suggestive of associations between immune cell telomere length and bovine tuberculosis infection status, with individuals detected at the most advanced stage of infection tending to have shorter immune cell telomeres than disease positive individuals. While male European badgers are larger and show higher rates of annual mortality than females, we found no evidence of a sex difference in either mean telomere length or the average rate of within-individual telomere attrition with age. Our findings lend support to the view that age-related declines in the telomere lengths of immune cells may provide one potentially general mechanism underpinning age-related declines in immunocompetence in natural populations. PMID:25268841

  19. Maremar, prevalence of chronic kidney disease, how to avoid over-diagnosis and under-diagnosis.

    PubMed

    De Broe, Marc E; Gharbi, Mohammed Benghanem; Elseviers, Monique

    2016-04-01

    Chronic kidney disease is considered as a major public health problem. Recent studies mention a prevalence rate between 8%-12%. Several editorials, comments, short reviews described the weaknesses (lack of confirmation of proteinuria, and of chronicity of decreased estimated glomerular filtration rate) of a substantial number of studies and the irrational of using a single arbitrary set point, i.e. diagnosis of chronic kidney disease whenever the estimated glomerular filtration rate is less than 60mL/min/1.73m(2). Maremar (Maladies rénales chroniques au Maroc) is a prevalence study of chronic kidney disease, hypertension, diabetes and obesity in a randomized, representative, high response rate (85%), sample of the adult population of Morocco, strictly applying the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Compared to the vast majority of the available studies, Maremar has a low prevalence of chronic kidney disease (2.9% adjusted to the actual adult population of Morocco). The population pyramid, and particularly the confirmation of proteinuria and "chronicity" of the decreased estimated glomerular filtration rate are the main reasons for this low prevalence of chronic kidney disease. The choice of arbitrary single threshold of estimated glomerular filtration rate for classifying stage 3-5 chronic kidney disease inevitably leads to "over-diagnosis" (false positives) of the disease in the elderly, particularly those without proteinuria, hematuria or hypertension, and to "under-diagnosed" (false negatives) in younger individuals with an estimated glomerular filtration rate above 60mL/min/1.73m(2) and below the 3rd percentile of their age/gender category. There is an urgent need for quality studies using in a correct way the recent KDIGO guidelines when investigating the prevalence of chronic kidney disease, in order to avoid a 50 to 100% overestimation of a disease state with potential dramatic consequences. The combination of the general population

  20. Epidemiology of the spread of viral diseases under aquaculture.

    PubMed

    Murray, Alexander G

    2013-02-01

    Aquaculture production is increasing rapidly worldwide. However, production has been associated with the emergence of several novel diseases, including viral diseases, that have caused serious problems for producers. Using examples largely from salmon farming in Scotland I review briefly the factors that allow transmission to occur in aquaculture. These include transmission through the water, which is relatively local to the infected farm, and anthropogenic transports (such as transport of fish between sites) that may occur over very long distances. A Disease Management Area (DMA) approach, as developed in Scotland to fight infectious salmon anaemia, can be effective at reducing pathogen transmission and hence disease emergence.

  1. Recent Developments in Understanding Brain Aging: Implications for Alzheimer's Disease and Vascular Cognitive Impairment.

    PubMed

    Deak, Ferenc; Freeman, Willard M; Ungvari, Zoltan; Csiszar, Anna; Sonntag, William E

    2016-01-01

    As the population of the Western world is aging, there is increasing awareness of age-related impairments in cognitive function and a rising interest in finding novel approaches to preserve cerebral health. A special collection of articles in The Journals of Gerontology: Biological Sciences and Medical Sciences brings together information of different aspects of brain aging, from latest developments in the field of neurodegenerative disorders to cerebral microvascular mechanisms of cognitive decline. It is emphasized that although the cellular changes that occur within aging neurons have been widely studied, more research is required as new signaling pathways are discovered that can potentially protect cells. New avenues for research targeting cellular senescence, epigenetics, and endocrine mechanisms of brain aging are also discussed. Based on the current literature it is clear that understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal function. Thus, comprehensive approaches need to be developed that address the multiple, interrelated mechanisms of brain aging. Attention is brought to the importance of maintenance of cerebromicrovascular health, restoring neuroendocrine balance, and the pressing need for funding more innovative research into the interactions of neuronal, neuroendocrine, inflammatory and microvascular mechanisms of cognitive impairment, and Alzheimer's disease. PMID:26590911

  2. Recent Developments in Understanding Brain Aging: Implications for Alzheimer's Disease and Vascular Cognitive Impairment.

    PubMed

    Deak, Ferenc; Freeman, Willard M; Ungvari, Zoltan; Csiszar, Anna; Sonntag, William E

    2016-01-01

    As the population of the Western world is aging, there is increasing awareness of age-related impairments in cognitive function and a rising interest in finding novel approaches to preserve cerebral health. A special collection of articles in The Journals of Gerontology: Biological Sciences and Medical Sciences brings together information of different aspects of brain aging, from latest developments in the field of neurodegenerative disorders to cerebral microvascular mechanisms of cognitive decline. It is emphasized that although the cellular changes that occur within aging neurons have been widely studied, more research is required as new signaling pathways are discovered that can potentially protect cells. New avenues for research targeting cellular senescence, epigenetics, and endocrine mechanisms of brain aging are also discussed. Based on the current literature it is clear that understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal function. Thus, comprehensive approaches need to be developed that address the multiple, interrelated mechanisms of brain aging. Attention is brought to the importance of maintenance of cerebromicrovascular health, restoring neuroendocrine balance, and the pressing need for funding more innovative research into the interactions of neuronal, neuroendocrine, inflammatory and microvascular mechanisms of cognitive impairment, and Alzheimer's disease.

  3. A novel diagnostic tool reveals mitochondrial pathology in human diseases and aging.

    PubMed

    Scheibye-Knudsen, Morten; Scheibye-Alsing, Karsten; Canugovi, Chandrika; Croteau, Deborah L; Bohr, Vilhelm A

    2013-03-01

    The inherent complex and pleiotropic phenotype of mitochondrial diseases poses a significant diagnostic challenge for clinicians as well as an analytical barrier for scientists. To overcome these obstacles we compiled a novel database, www.mitodb.com, containing the clinical features of primary mitochondrial diseases. Based on this we developed a number of qualitative and quantitative measures, enabling us to determine whether a disorder can be characterized as mitochondrial. These included a clustering algorithm, a disease network, a mitochondrial barcode and two scoring algorithms. Using these tools we detected mitochondrial involvement in a number of diseases not previously recorded as mitochondrial. As a proof of principle Cockayne syndrome, ataxia with oculomotor apraxia 1 (AOA1), spinocerebellar ataxia with axonal neuropathy 1 (SCAN1) and ataxia-telangiectasia have recently been shown to have mitochondrial dysfunction and those diseases showed strong association with mitochondrial disorders. We next evaluated mitochondrial involvement in aging and detected two distinct categories of accelerated aging disorders, one of them being associated with mitochondrial dysfunction. Normal aging seemed to associate stronger with the mitochondrial diseases than the non-mitochondrial partially supporting a mitochondrial theory of aging.

  4. Physical ageing of polyethylene terephthalate under natural sunlight: correlation study between crystallinity and mechanical properties

    NASA Astrophysics Data System (ADS)

    Aljoumaa, Khaled; Abboudi, Maher

    2016-01-01

    Semi-crystalline polyethylene terephthalate (PET) was aged under the effect of natural UV exposure and outdoor temperature during 670 days. The variation in the mechanical and thermal properties beside to the morphology was tracked by applying different analytical techniques, including scanning electron microscopy, infrared spectroscopy, differential scanning calorimetry and wide angle X-ray diffraction, in addition to tensile strength and hardness measurements. It has been confirmed that the ageing process is the results of physical trend only. The aged PET showed a decrease in both tensile strength and strain with an increase in the degree of crystallinity of aged PET samples during the whole period. These changes in crystallinity were examined by various analysis methods: density, calorimetric and infrared spectroscopy. New peaks in FTIR analysis at 1115 and 1090 cm-1 were characterized and proved that this technique is considered to be an easy tool to track the change in the surface crystallinity of aged PET samples directly. The results of this study showed that an augmentation in the degree of crystallinity of outdoor aged PET samples from 18 to 36 %, accompanied with a decrease in tensile strength from 167.9 to 133.7 MPa. Moreover, a good exponential correlation was found between the degree of crystallinity and the mechanical properties of the aged PET.

  5. Age and gender as independent predictors of violence under the influence of alcohol in Zurich, Switzerland.

    PubMed

    Mica, Ladislav; Oesterle, Linda; Werner, Clément M L; Simmen, Hans-Peter

    2015-04-01

    Violent behaviour associated with alcohol consumption is frequently reported by different media. Clinical data analysing the correlation between alcohol intoxication, age, gender and violence are scarce. The aim of this study was to evaluate the influence of age, gender and blood alcohol content on violent behaviour under the influence of alcohol under central European conditions. Three hundred patients admitted to the emergency department were included into this study in the time period from January 01. to December 31. 2009. The inclusion criteria were a blood alcohol content (BAC) of ≥10 mmol/l, any traumatic injury and an age ≥16 years. Violence was defined as an evitable act committed by others leading to patient's hospitalisation. The data were compared with Wilcoxon and χ2-test for proportions. The data were considered as significant if p<0,05. Predictive quality was evaluated by using receiver operating characteristic (ROC) curve. Independent predictors were analyzed by logistic regression analysis. The average age was 36,9±16,9 years (range: 16-84 years), 259 (86%) males and 41 (24%) females. There was a significant difference in gender (odds ratio for gender male 2,88; CI 95%: 1,24-6,67; p<0,001) and age dependent (odds ratio for each year of age 0,94; CI 95%: 0,93-0,96; p<0,0001) violence with no correlation to blood alcohol content found. Logistic regression analysis revealed male gender and young age as an independent predictor for violence. These results clarify the relationship between alcohol, age, gender and violence and have important implications for municipal-level alcohol policies.

  6. Infectious disease burden and cognitive function in young to middle-aged adults.

    PubMed

    Gale, Shawn D; Erickson, Lance D; Berrett, Andrew; Brown, Bruce L; Hedges, Dawson W

    2016-02-01

    Prior research has suggested an association between exposure to infectious disease and neurocognitive function in humans. While most of these studies have explored individual viral, bacterial, and even parasitic sources of infection, few have considered the potential neurocognitive burden associated with multiple infections. In this study, we utilized publically available data from a large dataset produced by the Centers for Disease Control and Prevention that included measures of neurocognitive function, sociodemographic variables, and serum antibody data for several infectious diseases. Specifically, immunoglobulin G antibodies for toxocariasis, toxoplasmosis, hepatitis A, hepatitis B, and hepatitis C, cytomegalovirus, and herpes 1 and 2 were available in 5662 subjects. We calculated an overall index of infectious-disease burden to determine if an aggregate measure of exposure to infectious disease would be associated with neurocognitive function in adults aged 20-59 years. The index predicted processing speed and learning and memory but not reaction time after controlling for age, sex, race-ethnicity, immigration status, education, and the poverty-to-income ratio. Interactions between the infectious-disease index and some sociodemographic variables were also associated with neurocognitive function. In summary, an index aggregating exposure to several infectious diseases was associated with neurocognitive function in young- to middle-aged adults. PMID:26598104

  7. Perspectives of aging among persons living with chronic obstructive pulmonary disease.

    PubMed

    Low, Gail; Ross, Carolyn; Stickland, Michael; Wilson, Donna; Wong, Eric

    2013-08-01

    Among pulmonary rehabilitation attendees, we explored their tendency to downplay versus acknowledge physical and psychosocial health limitations, and the subsequent impact either strategy had on how they perceive their own aging process. Participants (N = 87) were 44 to 82 years of age, and diagnosed with chronic obstructive pulmonary disease (COPD). The St. George's Respiratory Questionnaire measured their health limitations. The Attitudes to Aging Questionnaire captured their perspectives of aging. Participants downplayed their symptoms and psychosocial impact, and remained most positive about psychosocial loss and carefully reserved about psychological growth. Acknowledged activity impairment had negative consequences, however, for their perspectives of physical change. These findings signify a balanced identity and perspective of aging that supports the Identity Process Theory. We encourage nurses and other practitioners, and researchers in pulmonary rehabilitation setting, to use this theory to better understand how people with COPD adapt to aging.

  8. Forecasting and Analyzing the Disease Burden of Aged Population in China, Based on the 2010 Global Burden of Disease Study

    PubMed Central

    Bao, Chengzhen; Mayila, Mamat; Ye, Zhenhua; Wang, Jianbing; Jin, Mingjuan; He, Wenjiong; Chen, Kun

    2015-01-01

    Background: Forecasting the disease burden of the elderly will contribute to make a comprehensive assessment about physical and mental status of the elderly in China and provide a basis for reducing the negative consequences of aging society to a minimum. Methods: This study collected data from a public database online provided by Global Burden of Disease Study 2010. Grey model GM (1, 1) was used to forecast all-cause and disease-specific rates of disability adjusted life years (DALYs) in 2015 and 2020. Results: After cross-sectional and longitudinal analysis, we found that non-communicable diseases (NCDs) were still the greatest threats in the elderly, followed by injuries. As for 136 predicted causes, more than half of NCDs increased obviously with age, less than a quarter of communicable, material, neonatal, and nutritional disorders or injuries had uptrend. Conclusions: The findings display the health condition of the Chinese elderly in the future, which will provide critical information for scientific and sociological researches on preventing and reducing the risks of aging society. PMID:26121188

  9. Beyond and behind the fingerprints of oxidative stress in age-related diseases: Secrets of successful aging.

    PubMed

    Polidori, M Cristina; Scholtes, Marlies

    2016-04-01

    Several years after the first publication of the definition of oxidative stress by Helmut Sies, this topic is still focus of a large body of attention and research in the field of aging, neurodegeneration and disease prevention. The conduction of clinical and epidemiological research without a solid biochemical rationale has led to largely frustrating results without being able to disprove the oxidative stress hypothesis. The present work is dedicated to Helmut Sies and describes the successful scientific approach to bench-to-bedside (-to-behavior) oxidative stress clinical research. PMID:27095215

  10. A culture-brain link: Negative age stereotypes predict Alzheimer's disease biomarkers.

    PubMed

    Levy, Becca R; Ferrucci, Luigi; Zonderman, Alan B; Slade, Martin D; Troncoso, Juan; Resnick, Susan M

    2016-02-01

    Although negative age stereotypes have been found to predict adverse outcomes among older individuals, it was unknown whether the influence of stereotypes extends to brain changes associated with Alzheimer's disease. To consider this possibility, we drew on dementia-free participants, in the Baltimore Longitudinal Study of Aging, whose age stereotypes were assessed decades before yearly magnetic resonance images and brain autopsies were performed. Those holding more-negative age stereotypes earlier in life had significantly steeper hippocampal-volume loss and significantly greater accumulation of neurofibrillary tangles and amyloid plaques, adjusting for relevant covariates. These findings suggest a new pathway to identifying mechanisms and potential interventions related to the pathology of Alzheimer's disease.

  11. Age-at-Onset in Late Onset Alzheimer Disease is Modified by Multiple Genetic Loci

    PubMed Central

    Naj, Adam C.; Jun, Gyungah; Reitz, Christiane; Kunkle, Brian W.; Perry, William; Park, YoSon; Beecham, Gary W.; Rajbhandary, Ruchita A.; Hamilton-Nelson, Kara L.; Wang, Li-San; Kauwe, John S.K.; Huentelman, Matthew J.; Myers, Amanda J.; Bird, Thomas D.; Boeve, Bradley F.; Baldwin, Clinton T.; Jarvik, Gail P.; Crane, Paul K.; Rogaeva, Ekaterina; Barmada, Michael M.; Demirci, F. Yesim; Cruchaga, Carlos; Kramer, Patricia; Ertekin-Taner, Nilufer; Hardy, John; Graff-Radford, Neill R.; Green, Robert C.; Larson, Eric B.; St George-Hyslop, Peter; Buxbaum, Joseph D.; Evans, Denis; Schneider, Julie A.; Lunetta, Kathryn L.; Kamboh, M. Ilyas; Saykin, Andrew J.; Reiman, Eric M.; De Jager, Philip L.; Bennett, David A.; Morris, John C.; Montine, Thomas J.; Goate, Alison M.; Blacker, Deborah; Tsuang, Debby W.; Hakonarson, Hakon; Kukull, Walter A.; Foroud, Tatiana M.; Martin, Eden R.; Haines, Jonathan L.; Mayeux, Richard; Farrer, Lindsay A.; Schellenberg, Gerard D.; Pericak-Vance, Margaret A.

    2015-01-01

    Importance As APOE locus variants contribute to both risk of late-onset Alzheimer disease and differences in age-at-onset, it is important to know if other established late-onset Alzheimer disease risk loci also affect age-at-onset in cases. Objectives To investigate the effects of known Alzheimer disease risk loci in modifying age-at-onset, and to estimate their cumulative effect on age-at-onset variation, using data from genome-wide association studies in the Alzheimer’s Disease Genetics Consortium (ADGC). Design, Setting and Participants The ADGC comprises 14 case-control, prospective, and family-based datasets with data on 9,162 Caucasian participants with Alzheimer’s occurring after age 60 who also had complete age-at-onset information, gathered between 1989 and 2011 at multiple sites by participating studies. Data on genotyped or imputed single nucleotide polymorphisms (SNPs) most significantly associated with risk at ten confirmed LOAD loci were examined in linear modeling of AAO, and individual dataset results were combined using a random effects, inverse variance-weighted meta-analysis approach to determine if they contribute to variation in age-at-onset. Aggregate effects of all risk loci on AAO were examined in a burden analysis using genotype scores weighted by risk effect sizes. Main Outcomes and Measures Age at disease onset abstracted from medical records among participants with late-onset Alzheimer disease diagnosed per standard criteria. Results Analysis confirmed association of APOE with age-at-onset (rs6857, P=3.30×10−96), with associations in CR1 (rs6701713, P=7.17×10−4), BIN1 (rs7561528, P=4.78×10−4), and PICALM (rs561655, P=2.23×10−3) reaching statistical significance (P<0.005). Risk alleles individually reduced age-at-onset by 3-6 months. Burden analyses demonstrated that APOE contributes to 3.9% of variation in age-at-onset (R2=0.220) over baseline (R2=0.189) whereas the other nine loci together contribute to 1.1% of

  12. Genetic Architecture of Context Processing in Late Middle Age: More Than One Underlying Mechanism

    PubMed Central

    Kremen, William S.; Panizzon, Matthew S.; Xian, Hong; Barch, Deanna M.; Franz, Carol E.; Grant, Michael D.; Toomey, Rosemary; Lyons, Michael J.

    2011-01-01

    Studies comparing young and older adults suggest a deficit in processing context information as a key mechanism underlying cognitive aging. However, the genetic architecture of context processing has not been examined. Consistent with previous results, we found evidence of functionally dissociable components of context processing accuracy in 1127 late middle-aged twins ages 51–60. One component emphasizes use of context cues to prepare responses (proactive cognitive control); the other emphasizes adjustment of responses after probes are presented (reactive control). Approximately one-quarter of the variance in each component was accounted for by genes. Multivariate twin analysis indicated that genetic factors underlying two important components of context processing were independent of one another, thus implicating more than one underlying mechanism. Slower reaction time (RT) on non-context processing trials was positively correlated with errors on the strongly proactive control component on which young adults outperform older adults, but RT was negatively correlated with errors on the strongly reactive control component on which older adults perform better. Although this RT measure was uncorrelated with chronological age in our age-homogeneous sample, slower RT was associated with performance patterns that were more like older adults. However, this did not generalize to other processing speed measures. Genetic correlations, which reflect shared genetic variance, paralleled the phenotypic correlations. There was also a positive genetic correlation between general cognitive ability and accuracy on the proactive control component, but there were still mostly distinct genetic influences underlying these measures. In contrast, the reactive control component was unrelated to general cognitive ability. PMID:21875218

  13. [Relationship between educational level and dementia: social factor and age-related chronic disease].

    PubMed

    Dartigues, J-F; Foubert-Samier, A; Helmer, C

    2013-08-01

    Dementia is an age-related chronic syndrome, whose the first cause is a neurodegenerative disease: Alzheimer's disease (AD). In spite of some controversies, educational level is now considered as a major risk factor for dementia and AD. The protective effect of a high level of education could be related to a preservation of cognitive reserve and a reinforcement of brain reserve. Moreover, subjects with a high level of education have a better access to health care and a better management of vascular risk factors. With the general improvement of the educational level, the age-related incidence of AD and dementia should decrease in the future.

  14. Influence of age and disease state in nonsteroidal antiinflammatory drug associated gastric bleeding.

    PubMed

    Llewellyn, J G; Pritchard, M H

    1988-04-01

    In our study of 552 acute admissions for gastrointestinal hemorrhage, 18% were found to be taking nonsteroidal antiinflammatory drugs (NSAID) at the time of the bleed; 49% of these were found at endoscopy to have a gastric or prepyloric lesion, compared with 20% of the non-NSAID control group. Prescription data was used to calculate the risk added by age and disease state to the NSAID associated bleeding. We found that patients with chronic inflammatory disease had 2-3 times the expected bleeding incidence, but while there was a definite trend towards an age related risk in older patients, this was not statistically significant.

  15. Polyphenol Stilbenes: Molecular Mechanisms of Defence against Oxidative Stress and Aging-Related Diseases

    PubMed Central

    Reinisalo, Mika; Kårlund, Anna; Koskela, Ali; Kaarniranta, Kai; Karjalainen, Reijo O.

    2015-01-01

    Numerous studies have highlighted the key roles of oxidative stress and inflammation in aging-related diseases such as obesity, type 2 diabetes, age-related macular degeneration (AMD), and Alzheimer's disease (AD). In aging cells, the natural antioxidant capacity decreases and the overall efficiency of reparative systems against cell damage becomes impaired. There is convincing data that stilbene compounds, a diverse group of natural defence phenolics, abundant in grapes, berries, and conifer bark waste, may confer a protective effect against aging-related diseases. This review highlights recent data helping to clarify the molecular mechanisms involved in the stilbene-mediated protection against oxidative stress. The impact of stilbenes on the nuclear factor-erythroid-2-related factor-2 (Nrf2) mediated cellular defence against oxidative stress as well as the potential roles of SQSTM1/p62 protein in Nrf2/Keap1 signaling and autophagy will be summarized. The therapeutic potential of stilbene compounds against the most common aging-related diseases is discussed. PMID:26180583

  16. Age-related changes in the rate of disease transmission: implications for the design of vaccination programmes.

    PubMed Central

    Anderson, R. M.; May, R. M.

    1985-01-01

    Mathematical models are developed to aid in the investigation of the implications of heterogeneity in contact with infection within a community, on the design of mass vaccination programmes for the control of childhood viral and bacterial infections in developed countries. Analyses are focused on age-dependency in the rate at which individuals acquire infection, the question of 'who acquires infection from whom', and the implications of genetic variability in susceptibility to infection. Throughout, theoretical predictions are based on parameter estimates obtained from epidemiological studies and are compared with observed temporal trends in disease incidence and age-stratified serological profiles. Analysis of case notification records and serological data suggest that the rate at which individuals acquire many common infections changes from medium to high and then to low levels in the infant, child and teenage plus adult age groups respectively. Such apparent age-dependency in attack rate acts to reduce slightly the predicted levels of herd immunity required for the eradication of infections such as measles, when compared with the predictions of models based on age-independent transmission. The action of maternally derived immunity in prohibiting vaccination in infants, and the broad span of age classes over which vaccination currently takes place in the U.K., however, argue that levels of herd immunity of between 90 and 94% would be required to eliminate measles. Problems surrounding the interpretation of apparent age-related trends in the acquisition of infection and their relevance to the design of vaccination programmes, are discussed in relation to the possible role of genetically based variation in susceptibility to infection and observations on epidemics in 'virgin' populations. Heterogeneous mixing models provide predictions of changes in serology and disease incidence under the impact of mass vaccination which well mirror observed trends in England and

  17. The Possible Mechanism of Advanced Glycation End Products (AGEs) for Alzheimer’s Disease

    PubMed Central

    Ko, Shun-Yao; Ko, Hshin-An; Chu, Kuo-Hsiung; Shieh, Tzong-Ming; Chi, Tzong-Cherng; Chen, Hong-I; Chang, Weng-Cheng; Chang, Shu-Shing

    2015-01-01

    Amyloid precursor protein (APP) has been modified by β and γ-secretase that cause amyloid deposits (plaques) in neuronal cells. Glyceraldhyde-derived AGEs has been identified as a major source of neurotoxicity in Alzheimer’s disease (AD). In a previous study, we demonstrated that glyceraldehyde-derived AGEs increase APP and Aβ via ROS. Furthermore, the combination of AGEs and Aβ has been shown to enhance neurotoxicity. In mice, APP expression is increased by tail vein injection of AGEs. This evidence suggests a correlation between AGEs and the development of AD. However, the role played by AGEs in the pathogenesis of AD remains unclear. In this report, we demonstrate that AGEs up-regulate APP processing protein (BACE and PS1) and Sirt1 expression via ROS, but do not affect the expression of downstream antioxidant genes HO-1 and NQO-1. Moreover, we found that AGEs increase GRP78 expression and enhance the cell death-related pathway p53, bcl-2/bax ratio, caspase 3. These results indicate that AGEs impair the neuroprotective effects of Sirt1 and lead to neuronal cell death via ER stress. Our findings suggest that AGEs increase ROS production, which stimulates downstream pathways related to APP processing, Aβ production, Sirt1, and GRP78, resulting in the up-regulation of cell death related pathway. This in-turn enhances neuronal cell death, which leads to the development of AD. PMID:26587989

  18. [Advances on pharmacokinetics of traditional Chinese medicine under disease states].

    PubMed

    Gong, Zi-peng; Chen, Ying; Zhang, Rui-jie; Yang, Qing; Zhu, Xiao-xin

    2015-01-01

    In recent years, more and more research shows that the pharmacokinetic parameter of traditional Chinese medicine can be affected by the disease states. It's possible that drug metabolic enzymes, transporters, cell membrane permeability and the change of microbes group could be interfered with physiological and pathological changes, which enables the pharmacokinetics of traditional Chinese medicine in the body to be altered, including the process of absorption, distribution, metabolism and excretion, and then the pharmacokinetic parameters of traditional chinese medicine are altered. It's found that investigating the pharmacokinetic of traditional Chinese medicine in the pathological state is more useful than that of in normal state because the great part of traditional Chinese medicine is mainly used to treat disease. This article reflects the latest research on the pharmacokinetic of traditional Chinese medicine in the disease state such as diabete, cerebral ischemia, liver injury, inflammatory disease, nervous system disorders and fever in order to provide certain reference for clinicians designing reasonable administration dose.

  19. Neural stem cells could serve as a therapeutic material for age-related neurodegenerative diseases.

    PubMed

    Suksuphew, Sarawut; Noisa, Parinya

    2015-03-26

    Progressively loss of neural and glial cells is the key event that leads to nervous system dysfunctions and diseases. Several neurodegenerative diseases, for instance Alzheimer's disease, Parkinson's disease, and Huntington's disease, are associated to aging and suggested to be a consequence of deficiency of neural stem cell pool in the affected brain regions. Endogenous neural stem cells exist throughout life and are found in specific niches of human brain. These neural stem cells are responsible for the regeneration of new neurons to restore, in the normal circumstance, the functions of the brain. Endogenous neural stem cells can be isolated, propagated, and, notably, differentiated to most cell types of the brain. On the other hand, other types of stem cells, such as mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells can also serve as a source for neural stem cell production, that hold a great promise for regeneration of the brain. The replacement of neural stem cells, either endogenous or stem cell-derived neural stem cells, into impaired brain is highly expected as a possible therapeutic mean for neurodegenerative diseases. In this review, clinical features and current routinely treatments of age-related neurodegenerative diseases are documented. Noteworthy, we presented the promising evidence of neural stem cells and their derivatives in curing such diseases, together with the remaining challenges to achieve the best outcome for patients.

  20. Age-related differences in celiac disease: Specific characteristics of adult presentation

    PubMed Central

    Vivas, Santiago; Vaquero, Luis; Rodríguez-Martín, Laura; Caminero, Alberto

    2015-01-01

    Celiac disease may appear both in early childhood and in elderly subjects. Current knowledge of the disease has revealed some differences associated to the age of presentation. Furthermore, monitoring and prognosis of celiac subjects can vary depending on the pediatric or adult stage. The main objective of this review is to provide guidance for the adult diagnostic and follow-up processes, which must be tailored specifically for adults and be different from pediatric patients. PMID:26558154

  1. BrainAGE in Mild Cognitive Impaired Patients: Predicting the Conversion to Alzheimer’s Disease

    PubMed Central

    Klöppel, Stefan; Koutsouleris, Nikolaos; Sauer, Heinrich

    2013-01-01

    Alzheimer’s disease (AD), the most common form of dementia, shares many aspects of abnormal brain aging. We present a novel magnetic resonance imaging (MRI)-based biomarker that predicts the individual progression of mild cognitive impairment (MCI) to AD on the basis of pathological brain aging patterns. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE) score indicates accelerated atrophy and is considered a risk factor for conversion to AD. Here, the BrainAGE framework was applied to predict the individual brain ages of 195 subjects with MCI at baseline, of which a total of 133 developed AD during 36 months of follow-up (corresponding to a pre-test probability of 68%). The ability of the BrainAGE framework to correctly identify MCI-converters was compared with the performance of commonly used cognitive scales, hippocampus volume, and state-of-the-art biomarkers derived from cerebrospinal fluid (CSF). With accuracy rates of up to 81%, BrainAGE outperformed all cognitive scales and CSF biomarkers in predicting conversion of MCI to AD within 3 years of follow-up. Each additional year in the BrainAGE score was associated with a 10% greater risk of developing AD (hazard rate: 1.10 [CI: 1.07–1.13]). Furthermore, the post-test probability was increased to 90% when using baseline BrainAGE scores to predict conversion to AD. The presented framework allows an accurate prediction even with multicenter data. Its fast and fully automated nature facilitates the integration into the clinical workflow. It can be exploited as a tool for screening as well as for monitoring treatment options. PMID:23826273

  2. Ageing and inflammation - A central role for mitochondria in brain health and disease.

    PubMed

    Currais, Antonio

    2015-05-01

    To develop successful therapies that prevent or treat neurodegenerative diseases requires an understanding of the upstream events. Ageing is by far the greatest risk factor for most of these diseases, and to clarify their causes will require an understanding of the process of ageing itself. Starting with the question Why do we age as individual organisms, but the line of pluripotent embryonic stem cells and germ cells carried by individuals and transmitted to descendants is immortal? this review discusses how the process of cellular differentiation leads to the accumulation of biological imperfections with ageing, and how these imperfections may be the cause of chronic inflammatory responses to stress that undermine cellular function. Both differentiation and inflammation involve drastic metabolic changes associated with alterations in mitochondrial dynamics that shift the balance between aerobic glycolysis and oxidative phosphorylation. With ageing, mitochondrial dysfunction can be both the cause and consequence of inflammatory processes and elicit metabolic adaptations that might be either protective or become progressively detrimental. It is argued here that an understanding of the relationship between metabolism, differentiation and inflammation is essential to understand the pathological mechanisms governing brain health and disease during ageing.

  3. The maternal-age-associated risk of congenital heart disease is modifiable.

    PubMed

    Schulkey, Claire E; Regmi, Suk D; Magnan, Rachel A; Danzo, Megan T; Luther, Herman; Hutchinson, Alayna K; Panzer, Adam A; Grady, Mary M; Wilson, David B; Jay, Patrick Y

    2015-04-01

    Maternal age is a risk factor for congenital heart disease even in the absence of any chromosomal abnormality in the newborn. Whether the basis of this risk resides with the mother or oocyte is unknown. The impact of maternal age on congenital heart disease can be modelled in mouse pups that harbour a mutation of the cardiac transcription factor gene Nkx2-5 (ref. 8). Here, reciprocal ovarian transplants between young and old mothers establish a maternal basis for the age-associated risk in mice. A high-fat diet does not accelerate the effect of maternal ageing, so hyperglycaemia and obesity do not simply explain the mechanism. The age-associated risk varies with the mother's strain background, making it a quantitative genetic trait. Most remarkably, voluntary exercise, whether begun by mothers at a young age or later in life, can mitigate the risk when they are older. Thus, even when the offspring carry a causal mutation, an intervention aimed at the mother can meaningfully reduce their risk of congenital heart disease.

  4. Complement system in dermatological diseases - fire under the skin.

    PubMed

    Panelius, Jaana; Meri, Seppo

    2015-01-01

    The complement system plays a key role in several dermatological diseases. Overactivation, deficiency, or abnormality of the control proteins are often related to a skin disease. Autoimmune mechanisms with autoantibodies and a cytotoxic effect of the complement membrane attack complex on epidermal or vascular cells can cause direct tissue damage and inflammation, e.g., in systemic lupus erythematosus (SLE), phospholipid antibody syndrome, and bullous skin diseases like pemphigoid. By evading complement attack, some microbes like Borrelia spirochetes and staphylococci can persist in the skin and cause prolonged symptoms. In this review, we present the most important skin diseases connected to abnormalities in the function of the complement system. Drugs having an effect on the complement system are also briefly described. On one hand, drugs with free hydroxyl on amino groups (e.g., hydralazine, procainamide) could interact with C4A, C4B, or C3 and cause an SLE-like disease. On the other hand, progress in studies on complement has led to novel anti-complement drugs (recombinant C1-inhibitor and anti-C5 antibody, eculizumab) that could alleviate symptoms in diseases associated with excessive complement activation. The main theme of the manuscript is to show how relevant the complement system is as an immune effector system in contributing to tissue injury and inflammation in a broad range of skin disorders.

  5. Complement System in Dermatological Diseases – Fire Under the Skin

    PubMed Central

    Panelius, Jaana; Meri, Seppo

    2015-01-01

    The complement system plays a key role in several dermatological diseases. Overactivation, deficiency, or abnormality of the control proteins are often related to a skin disease. Autoimmune mechanisms with autoantibodies and a cytotoxic effect of the complement membrane attack complex on epidermal or vascular cells can cause direct tissue damage and inflammation, e.g., in systemic lupus erythematosus (SLE), phospholipid antibody syndrome, and bullous skin diseases like pemphigoid. By evading complement attack, some microbes like Borrelia spirochetes and staphylococci can persist in the skin and cause prolonged symptoms. In this review, we present the most important skin diseases connected to abnormalities in the function of the complement system. Drugs having an effect on the complement system are also briefly described. On one hand, drugs with free hydroxyl on amino groups (e.g., hydralazine, procainamide) could interact with C4A, C4B, or C3 and cause an SLE-like disease. On the other hand, progress in studies on complement has led to novel anti-complement drugs (recombinant C1-inhibitor and anti-C5 antibody, eculizumab) that could alleviate symptoms in diseases associated with excessive complement activation. The main theme of the manuscript is to show how relevant the complement system is as an immune effector system in contributing to tissue injury and inflammation in a broad range of skin disorders. PMID:25688346

  6. Evidence of subclinical prion disease in aged mice following exposure to bovine spongiform encephalopathy.

    PubMed

    Brown, Karen L; Mabbott, Neil A

    2014-01-01

    The occurrence of variant Creutzfeldt-Jakob (vCJD) disease in humans was almost certainly the result of consumption of food contaminated with bovine spongiform encephalopathy (BSE) prions. Despite probable widespread exposure of the UK population to BSE-contaminated food in the 1980s, vCJD has been identified predominantly in young individuals, and there have been fewer cases of clinical disease than anticipated. The reasons for this are uncertain. Following peripheral exposure, many prions replicate within the lymphoid tissues before infecting the central nervous system. We have shown that the effects of host age on the microarchitecture of the spleen significantly impair susceptibility to mouse-adapted prions after peripheral exposure. The transmission of prions between different mammalian species is considered to be limited by the 'species barrier', which is dependent on several factors, including an intact immune system. Thus, cross-species prion transmission may be much less efficient in aged individuals. To test this hypothesis, we compared prion pathogenesis in groups of young (6-8 weeks old) and aged (600 days old) mice injected with primary BSE brain homogenate. We showed that prion pathogenesis was impaired dramatically in aged mice when compared with young animals. Whereas most young mice succumbed to clinical prion disease, all aged mice failed to develop clinical disease during their lifespans. However, the demonstration that prion accumulation was detected in the lymphoid tissues of some aged mice after injection with primary BSE brain homogenate, in the absence of clinical signs of prion disease, has important implications for human health.

  7. Prediction of Alzheimer's Disease Dementia: Data from the GuidAge Prevention Trial.

    PubMed

    Di Stefano, Francesca; Epelbaum, Stephane; Coley, Nicola; Cantet, Christelle; Ousset, Pierre-Jean; Hampel, Harald; Bakardjian, Hovagim; Lista, Simone; Vellas, Bruno; Dubois, Bruno; Andrieu, Sandrine

    2015-01-01

    In therapeutic trials, it is crucial to identify Alzheimer's disease (AD) at its prodromal stage. We assessed the accuracy of the free and cued selective reminding test (FCSRT) compared to other cognitive tests to predict AD dementia in subjects with subjective cognitive decline or mild cognitive impairment. Subjects from the placebo group of the GuidAge trial over 70 years old and without clinical signs of dementia at baseline who completed the 5-year follow-up free of dementia (n = 840) or developed AD dementia (n = 73) were included in our study. Among all the tests, the sum of the 3 free recall of the FCSRT (FCSRT-FR) and the sum of free and cued recall (FCSRT-TR) yielded the best results to predict AD dementia occurrence (all p values <0.05 for comparison of FCSRT-FR ROC and MMSE, CDRsb, and CVF ROCs). FCSRT-FR had an area under the ROC curve of 0.799 (95% CI 0.738-0.85) and the optimal cut-off was 20 (se 68.06% , sp 81.43% , PPV 23.90% , NPV 96,75%). Concerning FCSRT-TR, the AUC was 0.776 and the optimal cut-off was 42 (se 62.5% , sp 82.26% , PPV 23.20% and NPV 96.24%). This study sets the framework for implementing the FCSRT in clinical and therapeutic trials for efficient subject selection. PMID:26402073

  8. Epigenetics of Aging and Alzheimer’s Disease: Implications for Pharmacogenomics and Drug Response

    PubMed Central

    Cacabelos, Ramón; Torrellas, Clara

    2015-01-01

    Epigenetic variability (DNA methylation/demethylation, histone modifications, microRNA regulation) is common in physiological and pathological conditions. Epigenetic alterations are present in different tissues along the aging process and in neurodegenerative disorders, such as Alzheimer’s disease (AD). Epigenetics affect life span and longevity. AD-related genes exhibit epigenetic changes, indicating that epigenetics might exert a pathogenic role in dementia. Epigenetic modifications are reversible and can potentially be targeted by pharmacological intervention. Epigenetic drugs may be useful for the treatment of major problems of health (e.g., cancer, cardiovascular disorders, brain disorders). The efficacy and safety of these and other medications depend upon the efficiency of the pharmacogenetic process in which different clusters of genes (pathogenic, mechanistic, metabolic, transporter, pleiotropic) are involved. Most of these genes are also under the influence of the epigenetic machinery. The information available on the pharmacoepigenomics of most drugs is very limited; however, growing evidence indicates that epigenetic changes are determinant in the pathogenesis of many medical conditions and in drug response and drug resistance. Consequently, pharmacoepigenetic studies should be incorporated in drug development and personalized treatments. PMID:26703582

  9. Prediction of Alzheimer's Disease Dementia: Data from the GuidAge Prevention Trial.

    PubMed

    Di Stefano, Francesca; Epelbaum, Stephane; Coley, Nicola; Cantet, Christelle; Ousset, Pierre-Jean; Hampel, Harald; Bakardjian, Hovagim; Lista, Simone; Vellas, Bruno; Dubois, Bruno; Andrieu, Sandrine

    2015-01-01

    In therapeutic trials, it is crucial to identify Alzheimer's disease (AD) at its prodromal stage. We assessed the accuracy of the free and cued selective reminding test (FCSRT) compared to other cognitive tests to predict AD dementia in subjects with subjective cognitive decline or mild cognitive impairment. Subjects from the placebo group of the GuidAge trial over 70 years old and without clinical signs of dementia at baseline who completed the 5-year follow-up free of dementia (n = 840) or developed AD dementia (n = 73) were included in our study. Among all the tests, the sum of the 3 free recall of the FCSRT (FCSRT-FR) and the sum of free and cued recall (FCSRT-TR) yielded the best results to predict AD dementia occurrence (all p values <0.05 for comparison of FCSRT-FR ROC and MMSE, CDRsb, and CVF ROCs). FCSRT-FR had an area under the ROC curve of 0.799 (95% CI 0.738-0.85) and the optimal cut-off was 20 (se 68.06% , sp 81.43% , PPV 23.90% , NPV 96,75%). Concerning FCSRT-TR, the AUC was 0.776 and the optimal cut-off was 42 (se 62.5% , sp 82.26% , PPV 23.20% and NPV 96.24%). This study sets the framework for implementing the FCSRT in clinical and therapeutic trials for efficient subject selection.

  10. Creep and aging of hard-sphere glasses under constant stress.

    PubMed

    Ballesta, P; Petekidis, G

    2016-04-01

    We investigate the aging behavior of glassy suspensions of nearly hard-sphere colloids submitted to a constant shear stress. For low stresses, below the yield stress, the system is subject to creep motion. As the sample ages, the shear rate exhibits a power-law decrease with time with exponents that depend on the sample age. We use a combination of rheological experiments with time-resolved photon correlation spectroscopy to investigate the time evolution of the sample dynamics under shear on various time and length scales. Long-time light-scattering experiments reveal the occurrence of microscopic rearrangement events that are linked with the macroscopic strain deformation of the sample. Dynamic time sweep experiments indicate that while the internal microscopic dynamics slow down continuously with waiting time, the storage and loss moduli are almost constant after a fast, weak decrease, resembling the behavior of quenched systems with partially frozen-in stresses. PMID:27176358

  11. New insights into brain BDNF function in normal aging and Alzheimer disease.

    PubMed

    Tapia-Arancibia, Lucia; Aliaga, Esteban; Silhol, Michelle; Arancibia, Sandor

    2008-11-01

    The decline observed during aging involves multiple factors that influence several systems. It is the case for learning and memory processes which are severely reduced with aging. It is admitted that these cognitive effects result from impaired neuronal plasticity, which is altered in normal aging but mainly in Alzheimer disease. Neurotrophins and their receptors, notably BDNF, are expressed in brain areas exhibiting a high degree of plasticity (i.e. the hippocampus, cerebral cortex) and are considered as genuine molecular mediators of functional and morphological synaptic plasticity. Modification of BDNF and/or the expression of its receptors (TrkB.FL, TrkB.T1 and TrkB.T2) have been described during normal aging and Alzheimer disease. Interestingly, recent findings show that some physiologic or pathologic age-associated changes in the central nervous system could be offset by administration of exogenous BDNF and/or by stimulating its receptor expression. These molecules may thus represent a physiological reserve which could determine physiological or pathological aging. These data suggest that boosting the expression or activity of these endogenous protective systems may be a promising therapeutic alternative to enhance healthy aging.

  12. National Lung Screening Trial Findings by Age: Medicare-Eligible Versus Under-65 Population

    PubMed Central

    Pinsky, Paul F.; Gierada, David S.; Hocking, William; Patz, Edward F.; Kramer, Barnett S.

    2015-01-01

    Background The NLST (National Lung Screening Trial) showed reduced lung cancer mortality in high-risk participants (smoking history of ≥30 pack-years) aged 55 to 74 years who were randomly assigned to screening with low-dose computed tomography (LDCT) versus those assigned to chest radiography. An advisory panel recently expressed reservations about Medicare coverage of LDCT screening because of concerns about performance in the Medicare-aged population, which accounted for only 25% of the NLST participants. Objective To examine the results of the NLST LDCT group by age (Medicare-eligible vs. <65 years). Design Secondary analysis of a group from a randomized trial (NCT00047385). Setting 33 U.S. screening centers. Patients 19 612 participants aged 55 to 64 years (under-65 cohort) and 7110 participants aged 65 to 74 years (65+ cohort) at randomization. Intervention 3 annual rounds of LDCT screening. Measurements Demographics, smoking and medical history, screening examination adherence and results, diagnostic follow-up procedures and complications, lung cancer diagnoses, treatment, survival, and mortality. Results The aggregate false-positive rate was higher in the 65+ cohort than in the under-65 cohort (27.7% vs. 22.0%; P < 0.001). Invasive diagnostic procedures after false-positive screening results were modestly more frequent in the older cohort (3.3% vs. 2.7%; P = 0.039). Complications from invasive procedures were low in both groups (9.8% in the under-65 cohort vs. 8.5% in the 65+ cohort). Prevalence and positive predictive value (PPV) were higher in the 65+ cohort (PPV, 4.9% vs. 3.0%). Resection rates for screen-detected cancer were similar (75.6% in the under-65 cohort vs. 73.2% in the 65+ cohort). Five-year all-cause survival was lower in the 65+ cohort (55.1% vs. 64.1%; P = 0.018). Limitation The oldest screened patient was aged 76 years. Conclusion NLST participants aged 65 years or older had a higher rate of false-positive screening results than those

  13. [Thoracoscopic management of suspected thoraco-pulmonary malignant diseases in pediatric age].

    PubMed

    Lima, M; Bertozzi, M; Dòmini, M; Pession, A; Ruggeri, G; Libri, M; Antonellini, C; Pelusi, G; Messina, P; Fae, M

    2004-01-01

    Recent improvements and miniaturization of instruments have encouraged a wider use of thoracoscopy and laparoscopy as a modality for diagnostic and operative procedures in pediatric age. The utility of thoracoscopy in pediatric patients with suspected thoracopulmonary oncological diseases is shown by diagnostic accuracy and, if necessary, the possibility to perform at the meantime a mininvasive surgery. We report the experience of our Institution in 16 patients with suspected thoraco-pulmonary oncological diseases and treated for this reason with thoracoscopy. Thoracoscopic is indicated in cases of suspected oncological diseases in children both for diagnosis and treatment.

  14. "...Rewritten in the skin": clues to skin biology and aging from inherited disease.

    PubMed

    Monnat, Raymond J

    2015-06-01

    The growing diversity of heritable skin diseases, a practical challenge to clinicians and dermato-nosologists alike, has nonetheless served as a rich source of insight into skin biology and disease mechanisms. I summarize below some key insights from the recent gene-driven phase of research on Werner syndrome, a heritable adult progeroid syndrome with prominent dermatologic features, constitutional genomic instability, and an elevated risk of cancer. I also indicate how new insights into skin biology, disease, and aging may come from unexpected sources.

  15. A review of creatine supplementation in age-related diseases: more than a supplement for athletes.

    PubMed

    Smith, Rachel N; Agharkar, Amruta S; Gonzales, Eric B

    2014-01-01

    Creatine is an endogenous compound synthesized from arginine, glycine and methionine. This dietary supplement can be acquired from food sources such as meat and fish, along with athlete supplement powders. Since the majority of creatine is stored in skeletal muscle, dietary creatine supplementation has traditionally been important for athletes and bodybuilders to increase the power, strength, and mass of the skeletal muscle. However, new uses for creatine have emerged suggesting that it may be important in preventing or delaying the onset of neurodegenerative diseases associated with aging. On average, 30% of muscle mass is lost by age 80, while muscular weakness remains a vital cause for loss of independence in the elderly population. In light of these new roles of creatine, the dietary supplement's usage has been studied to determine its efficacy in treating congestive heart failure, gyrate atrophy, insulin insensitivity, cancer, and high cholesterol. In relation to the brain, creatine has been shown to have antioxidant properties, reduce mental fatigue, protect the brain from neurotoxicity, and improve facets/components of neurological disorders like depression and bipolar disorder. The combination of these benefits has made creatine a leading candidate in the fight against age-related diseases, such as Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, long-term memory impairments associated with the progression of Alzheimer's disease, and stroke. In this review, we explore the normal mechanisms by which creatine is produced and its necessary physiology, while paying special attention to the importance of creatine supplementation in improving diseases and disorders associated with brain aging and outlining the clinical trials involving creatine to treat these diseases.

  16. Differences in selected medical care parameters in rheumatic disease ward patients of different ages of life

    PubMed Central

    Pobrotyn, Piotr; Susło, Robert; Milczanowski, Piotr; Drobnik, Jarosław

    2016-01-01

    Introduction Rheumatic diseases are becoming more and more common in Poland with the ageing of the population. Nearly 18% of the total hospital admissions in Poland result from rheumatic diseases, which was equivalent to 350 thousand cases in the year 2008. These diseases tend to last for many decades, decreasing both the quality of life and income of the patients as well as increasing the medical institutions’ workload and society's financial burden. The aim of the study was to determine whether the medical care parameters in a rheumatic disease hospital ward show any significant differences among different patient age groups – especially such that would support taking them into account as a basis for adjusting the financial coverage level of medical services. Material and methods Data on hospitalizations at the Rheumatic Diseases Ward of Wroclaw University Hospital in Wroclaw in the years 2009–2015 were analyzed, taking into account the age groups, number of hospital admissions, their duration and causes. Relevant statistical data analysis was performed. Discussion The study revealed that the number of old patients hospitalized at the rheumatic diseases ward increased over the last 6 years and that such statistically significant differences do exist: on average the old patients not only tend to stay much longer at the hospital, but also suffer from a different and more diverse spectrum of diseases in comparison to their younger counterparts. Conclusions The detected differences in medical care parameters support the need for more individualized medical care and increased cost of the hospital stay in the case of older patients. Consequently, those factors justify the necessity to increase the value of medical services in the case of old patients, possibly also taking into account the variation between age subgroups. PMID:27407280

  17. Ocular Surface Disease and Dacryoadenitis in Aging C57BL/6 Mice

    PubMed Central

    McClellan, Andrew J.; Volpe, Eugene A.; Zhang, Xiaobo; Darlington, Gretchen J.; Li, De-Quan; Pflugfelder, Stephen C.; de Paiva, Cintia S.

    2015-01-01

    Dry eye in humans displays increased prevalence in the aged and in women. Here, we investigated the ocular surfaces and lacrimal glands of aged mice of both sexes. We surveyed three different ages [young, middle-aged (6 to 9 months), and elderly] by investigating severity markers of dry eye disease (DED). We observed an age-dependent dry eye phenotype as early as 6 to 9 months: increased corneal surface irregularity, increased corneal barrier disruption, conjunctival CD4+ T-cell infiltration, and loss of mucin-filled goblet cells. Expression of interferon-γ, IL-17 mRNA transcripts was increased in the conjunctiva and IL-17A, matrix metallopeptidase 9, and chemokine ligand 20 in the corneas of elderly mice. Elderly male mice develop more of a skewed response of type 1 T helper cell, whereas female mice have a bias toward type 17 T helper cell in the conjunctiva. In the lacrimal gland, an increase in CD4+ and CD8+ T cells and B cells and a decrease in activated dendritic cells were observed. Adoptive transfer of CD4+ T cells isolated from elderly mice transferred DED into young immunodeficient recipients, which was more pronounced from male donors. Our findings show the development of DED in aging mice. Pathogenic CD4+ T cells that develop with aging are capable of transferring DED from older mice to naive immunodeficient recipients. Taken together, our results indicate that age-related autoimmunity contributes to development of DED with aging. PMID:24389165

  18. Mechanical Properties of Anisotropic Conductive Adhesive Film Under Hygrothermal Aging and Thermal Cycling

    NASA Astrophysics Data System (ADS)

    Gao, Li-Lan; Chen, Xu; Gao, Hong

    2012-07-01

    Mechanical properties of anisotropic conductive adhesive film (ACF) were investigated experimentally under various environmental conditions. The temperature sweep test was conducted to investigate the effects of temperature on dynamical mechanical properties of the ACF. The ACF exhibited transitions to the glass state, viscoelastic state, and rubber state with increasing temperature, and its glass-transition temperature ( T g) was determined to be 149°C. The creep-recovery behaviors of the ACF were investigated, and it was found that the initial strains, instantaneous strains, and creep or recovery rates increased with increasing temperature. No obvious creep phenomenon was observed at low temperatures (≤0°C). The creep strain and creep rates at any time decreased with increasing hygrothermal aging time. The uniaxial tensile behaviors of the ACF were also investigated under hygrothermal aging and thermal cycling. The results show that the Young's modulus and tensile strength of the ACF decrease with increasing hygrothermal aging time; however, they increase at first and then decrease with increasing thermal cycling time. T g decreases slightly for the ACF after hygrothermal aging; however, it increases after thermal cycling.

  19. Age-related declines in car following performance under simulated fog conditions.

    PubMed

    Ni, Rui; Kang, Julie J; Andersen, George J

    2010-05-01

    The present study examined age-related differences in car following performance when contrast of the driving scene was reduced by simulated fog. Older (mean age of 72.6) and younger (mean age of 21.1) drivers were presented with a car following scenario in a simulator in which a lead vehicle (LV) varied speed according to a sum of three sine wave functions. Drivers were shown an initial following distance of 18 m and were asked to maintain headway distance by controlling speed to match changes in LV speed. Five simulated fog conditions were examined ranging from a no fog condition (contrast of 0.55) to a high fog condition (contrast of 0.03). Average LV speed varied across trials (40, 60, or 80 km/h). The results indicated age-related declines in car following performance for both headway distance and RMS (root mean square) error in matching speed. The greatest decline occurred at moderate speeds under the highest fog density condition, with older drivers maintaining a headway distance that was 21% closer than younger drivers. At higher speeds older drivers maintained a greater headway distance than younger drivers. These results suggest that older drivers may be at greater risk for a collision under high fog density and moderate speeds.

  20. Differences in duration of Huntington's disease based on age at onset

    PubMed Central

    Foroud, T.; Gray, J.; Ivashina, J.; Conneally, P

    1999-01-01

    OBJECTIVES—Data from a sample of 2494 patients affected with Huntington's disease (HD), collected as part of the National Research Roster for Huntington Disease Patients and Families, were examined to determine if there was a relation between age at onset and duration of illness.
METHODS—Sufficient data for inclusion in analysis was available from 2068 patients, of whom 828 were deceased and 1240 were living. The median duration of disease was 21.4 years with a range of 1.2 to 40.8 years. Patients were categorised into one of four groups based on their age at onset.
RESULTS—Significant differences in duration based on the age at onset were found (p<0.025), with juvenile and late onset patients with HD having shorter duration of illness compared with those with an onset between 20-49 years.
CONCLUSIONS—Duration of disease is influenced by the age at symptom onset with juvenile and late onset patients having the shortest duration.

 PMID:9886451

  1. Age-associated B vitamin deficiency as a determinant of chronic diseases.

    PubMed

    Brachet, Patrick; Chanson, Aurélie; Demigné, Christian; Batifoulier, Frédérique; Alexandre-Gouabau, Marie-Cécile; Tyssandier, Viviane; Rock, Edmond

    2004-06-01

    The number of elderly individuals is growing rapidly worldwide and degenerative diseases constitute an increasing problem in terms of both public health and cost. Nutrition plays a role in the ageing process and there has been intensive research during the last decade on B vitamin-related risk factors in vascular and neurological diseases and cancers. Data from epidemiological studies indicate that subclinical deficiency in most water-soluble B vitamins may occur gradually during ageing, possibly due to environmental, metabolic, genetic, nutritional and pathological determinants, as well as to lifestyle, gender and drug consumption. Older adults have distinct absorption, cell transport and metabolism characteristics that may alter B vitamin bioavailability. Case-control and longitudinal studies have shown that, concurrent with an insufficient status of certain B vitamins, hyperhomocysteinaemia and impaired methylation reactions may be some of the mechanisms involved before a degenerative pathology becomes evident. The question that arises is whether B vitamin inadequacies contribute to the development of degenerative diseases or result from ageing and disease. The present paper aims to give an overview of these issues at the epidemiological, clinical and molecular levels and to discuss possible strategies to prevent B vitamin deficiency during ageing.

  2. Psychosocial Factors Associated with Risk Perceptions for Chronic Diseases in Younger and Middle-Aged Women

    PubMed Central

    Hamilton, Jada G.; Lobel, Marci

    2016-01-01

    Perceptions of disease risk play an important role in motivating people to adopt healthy behaviors. However, little is known about psychosocial factors that influence women’s perceived risk for developing disease. The present study investigated the extent to which individual traits, social influences, objective risk factors, and demographic characteristics were associated with women’s risk perceptions for cardiovascular disease, breast cancer, and lung cancer. Using structural equation modeling, we examined hypothesized associations among 452 younger (ages 18-25 years) and 167 middle-aged (ages 40-64 years) women. A greater number and variety of factors were associated with middle-aged women’s risk perceptions compared to younger women. For both groups, some objective risk factors were associated with risk perceptions; yet, associations also existed between multiple psychosocial variables (optimism, health locus of control, social exposure to disease, perceived stigma) and risk perceptions. Results suggested that women may base their risk estimates on factors beyond those considered important by healthcare providers. PMID:26110993

  3. Can Neglected Tropical Diseases Compromise Human Wellbeing in Sex-, Age-, and Trait-Specific Ways?

    PubMed Central

    Geary, David C.

    2016-01-01

    Traits that facilitate competition for reproductive resources or that influence mate choice have evolved to signal resilience to infectious disease and other stressors. As a result, the dynamics of competition and choice can, in theory, be used to generate predictions about sex-, age-, and trait-specific vulnerabilities for any sexually reproducing species, including humans. These dynamics and associated vulnerabilities are reviewed for nonhuman species, focusing on traits that are compromised by exposure to parasites. Using the same approach, sex-, age-, and trait-specific vulnerabilities to parasitic disease are illustrated for children’s and adolescent’s physical growth and fitness. Suggestions are then provided for widening the assessment of human vulnerabilities to include age-appropriate measures of behavioral (e.g., children’s play) and cognitive (e.g., language fluency) traits. These are traits that are likely to be compromised by infection in age- and sex-specific ways. Inclusion of these types of measures in studies of neglected tropic diseases has the potential to provide a more nuanced understanding of how these diseases undermine human wellbeing and may provide a useful means to study the efficacy of associated treatments. PMID:27077746

  4. Cerebral glucose metabolic patterns in Alzheimer's disease. Effect of gender and age at dementia onset

    SciTech Connect

    Small, G.W.; Kuhl, D.E.; Riege, W.H.; Fujikawa, D.G.; Ashford, J.W.; Metter, E.J.; Mazziotta, J.C.

    1989-06-01

    No previous study of Alzheimer's disease has, to our knowledge, assessed the effect of both age at dementia onset and gender on cerebral glucose metabolic patterns. To this end, we used positron emission tomography (fludeoxyglucose F 18 method) to study 24 patients with clinical diagnoses of probable Alzheimer's disease. Comparisons of the 13 patients with early-onset dementia (less than 65 years of age) with the 11 patients with late-onset dementia (greater than 65 years of age) revealed significantly lower left parietal metabolic ratios (left posterior parietal region divided by the hemispheric average) in the early-onset group. The metabolic ratio of posterior parietal cortex divided by the relatively disease-stable average of caudate and thalamus also separated patients with early-onset dementia from those with late-onset dementia, but not men from women. Further comparisons between sexes showed that, in all brain regions studied, the 9 postmenopausal women had higher nonweighted mean metabolic rates than the 15 men from the same age group, with hemispheric sex differences of 9% on the right and 7% on the left. These results demonstrate decreased parietal ratios in early-onset dementia of Alzheimer's disease, independent of a gender effect.

  5. Can Neglected Tropical Diseases Compromise Human Wellbeing in Sex-, Age-, and Trait-Specific Ways?

    PubMed

    Geary, David C

    2016-04-01

    Traits that facilitate competition for reproductive resources or that influence mate choice have evolved to signal resilience to infectious disease and other stressors. As a result, the dynamics of competition and choice can, in theory, be used to generate predictions about sex-, age-, and trait-specific vulnerabilities for any sexually reproducing species, including humans. These dynamics and associated vulnerabilities are reviewed for nonhuman species, focusing on traits that are compromised by exposure to parasites. Using the same approach, sex-, age-, and trait-specific vulnerabilities to parasitic disease are illustrated for children's and adolescent's physical growth and fitness. Suggestions are then provided for widening the assessment of human vulnerabilities to include age-appropriate measures of behavioral (e.g., children's play) and cognitive (e.g., language fluency) traits. These are traits that are likely to be compromised by infection in age- and sex-specific ways. Inclusion of these types of measures in studies of neglected tropic diseases has the potential to provide a more nuanced understanding of how these diseases undermine human wellbeing and may provide a useful means to study the efficacy of associated treatments. PMID:27077746

  6. The influence of age at disease onset on disease activity and disability: results from the Ontario Best Practices Research Initiative.

    PubMed

    Ruban, T N; Jacob, B; Pope, J E; Keystone, E C; Bombardier, C; Kuriya, B

    2016-03-01

    This study aims to compare characteristics between late-onset rheumatoid arthritis (RA) and young-onset RA and determine the association between age at disease onset and disease severity. We cross-sectionally studied 971 patients at the time of entry into the Ontario Best Practices Research Initiative, a registry of RA patients followed up in routine care. We restricted patients to ≤5 years of disease duration. Late-onset RA was defined as an onset ≥60 years of age and young-onset RA <60 years. Group differences were compared, and multivariate linear regression models were used to test the influence of age at onset on Disease Activity Score in 28 Joints with erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), and Health Assessment Questionnaire (HAQ) scores. The swollen joint count (6.2 vs. 5.3), acute phase reactants (C-reactive protein (CRP) 17.4 vs. 11.8 mg/L, ESR 30.6 vs. 21.5 mm/h), and comorbidity burden were higher in late-onset RA compared to young-onset RA (p < 0.01). Mean DAS28-ESR (4.6 vs. 4.3) and HAQ (1.2 vs. 1.1) scores were higher in late-onset RA patients (p < 0.05). Late-onset RA patients received more initial disease-modifying antirheumatic drug (DMARD) monotherapy and corticosteroids in comparison to greater DMARD/biologic combination therapy in young-onset RA patients (p < 0.05). Adjusted multivariate analyses showed that late-onset RA was independently associated with higher mean DAS28-ESR and HAQ scores, but not CDAI. Late-onset RA patients have greater disease activity that may contribute to disability early in the disease course. Despite this, initial treatment consists of less combination DMARD and biologic use in late-onset RA patients. This may have implications for future response to therapy and development of joint damage, disability, and comorbidities in this group.

  7. Chronic and progressive Parkinson's disease MPTP model in adult and aged mice.

    PubMed

    Muñoz-Manchado, Ana B; Villadiego, Javier; Romo-Madero, Sonia; Suárez-Luna, Nela; Bermejo-Navas, Alfonso; Rodríguez-Gómez, José A; Garrido-Gil, Pablo; Labandeira-García, José L; Echevarría, Miriam; López-Barneo, José; Toledo-Aral, Juan J

    2016-01-01

    Despite the different animal models of Parkinson's disease developed during the last years, they still present limitations modelling the slow and progressive process of neurodegeneration. Here, we undertook a histological, neurochemical and behavioural analysis of a new chronic parkinsonian mouse model generated by the subcutaneous administration of low doses of MPTP (20 mg/kg, 3 times per week) for 3 months, using both young adult and aged mice. The MPTP-induced nigrostriatal neurodegeneration was progressive and was accompanied by a decrease in striatal dopamine levels and motor impairment. We also demonstrated the characteristic neuroinflammatory changes (microglial activation and astrogliosis) associated with the neurodegenerative process. Aged animals showed both a faster time course of neurodegeneration and an altered neuroinflammatory response. The long-term systemic application of low MPTP doses did not induce any increase in mortality in either young adult or aged mice and better resembles the slow evolution of the neurodegenerative process. This treatment could be useful to model different stages of Parkinson's disease, providing a better understanding of the pathophysiology of the disease and facilitating the testing of both protective and restorative treatments. Here, we show a new chronic and progressive parkinsonian mouse model, in young and aged mice. This model produces a stable degeneration of the dopaminergic nigrostriatal pathway, continuous neuroinflammatory reaction and motor deficits. Aged animals showed a faster neurodegeneration and an altered neuroinflammatory response. This treatment could be useful to model different stages of PD and to test both protective and restorative therapeutic approaches.

  8. iPSCs as a major opportunity to understand and cure age-related diseases.

    PubMed

    Lemey, Camille; Milhavet, Ollivier; Lemaitre, Jean-Marc

    2015-08-01

    Cellular senescence plays an important role in the process of aging and is often associated with age-related diseases. Senescence was originally considered as a barrier to cell reprogramming, however we developed a strategy to overcome this hurdle and derive induced pluripotent stem cells (iPSCs) from senescent cells and cells from centenarians. Furthermore we showed that the newly generated iPSCs could be re-differentiated into fully rejuvenated cells. That has increased the known beneficial properties of iPSCs to include them as a tool to model age-related diseases or even to cure them through cell therapy. In this review, we describe the hallmarks of cellular senescence before presenting how we reprogrammed aged and senescent cells into iPSCs and obtained rejuvenated re-differentiated cells. Finally, we take an interest in the way iPSCs can be used to understand and cure age-related diseases and we present their advantages for patient-specific therapy.

  9. Evaluating Health Span in Preclinical Models of Aging and Disease: Guidelines, Challenges, and Opportunities for Geroscience

    PubMed Central

    Huffman, Derek M.; Justice, Jamie N.; Stout, Michael B.; Kirkland, James L.; Barzilai, Nir

    2016-01-01

    Life extension is no longer considered sufficient evidence of delayed aging in research animals. It must also be demonstrated that a broad swathe of health indicators have been extended. During a retreat of the Geroscience Network, a consortium of basic and clinical aging researchers, potential measures of mouse health were considered for their potential as easily standardized, highly informative metrics. Major health domains considered were neuromuscular, cognitive, cardiovascular, metabolic, and inflammatory functions as well as body composition and energetics and a multitude of assays interrogating these domains. A particularly sensitive metric of health is the ability to respond to, and recover, from stress. Therefore, the Network also considered stresses of human relevance that could be implemented in mouse models to assess frailty and resilience. Mouse models already exist for responses to forced immobility, cancer chemotherapy, infectious diseases, dietary challenges, and surgical stress, and it was felt that these could be employed to determine whether putative senescence-retarding interventions increased and extended organismal robustness. The Network discussed challenges in modeling age-related human chronic diseases and concluded that more attention needs to be paid to developing disease models with later age of onset, models of co- and multimorbidity, diversifying the strains and sexes commonly used in aging research, and considering additional species. PMID:27535967

  10. Towards a better monitoring of seed ageing under ex situ seed conservation

    PubMed Central

    Fu, Yong-Bi; Ahmed, Zaheer; Diederichsen, Axel

    2015-01-01

    Long-term conservation of 7.4 million ex situ seed accessions held in agricultural genebanks and botanic gardens worldwide is a challenging mission for human food security and ecosystem services. Recent advances in seed biology and genomics may have opened new opportunities for effective management of seed germplasm under long-term storage. Here, we review the current development of tools for assessing seed ageing and research advances in seed biology and genomics, with a focus on exploring their potential as better tools for monitoring of seed ageing. Seed ageing is found to be associated with the changes reflected in reactive oxygen species and mitochondria-triggered programmed cell deaths, expression of antioxidative genes and DNA and protein repair genes, chromosome telomere lengths, epigenetic regulation of related genes (microRNA and methylation) and altered organelle and nuclear genomes. Among these changes, the signals from mitochondrial and nuclear genomes may show the most promise for use in the development of tools to predict seed ageing. Non-destructive and non-invasive analyses of stored seeds through calorimetry or imaging techniques are also promising. It is clear that research into developing advanced tools for monitoring seed ageing to supplement traditional germination tests will be fruitful for effective conservation of ex situ seed germplasm. PMID:27293711

  11. Surface and interface properties of carbon fiber composites under cyclical aging

    NASA Astrophysics Data System (ADS)

    Lv, Xinying; Wang, Rongguo; Liu, Wenbo; Jiang, Long

    2011-10-01

    Carbon fiber-reinforced BMI composites have been subjected to combination accelerated aging comprising a hygrothermal process, a thermal-oxidative process, and a freezing process in order to simulate their responses under complicated service environments. This cyclical condition, including the freezing process, has not been investigated by other researchers so far. The effects of this combination accelerated aging on the mechanical properties have been characterized by FTIR, SEM/EDXA, XRD, and moisture-uptake determination. The results indicated that combination accelerated aging had great effects on the mechanical properties of the composite, the network structure of the BMI matrix, and the moisture uptake by the composite. After a third cycle of accelerated aging, moisture reached the center layer of the composite and as a result led to an obvious decrease in ILSS due to deterioration of the carbon fiber-BMI interface. Sufficient moisture absorption on the composite surface made the network structure of the BMI matrix more open, which facilitated stress relaxation and the creation of micro-cracks, with a consequent obvious decrease in flexural strength. With increasing number of combined-action accelerated aging cycles, ever more moisture was absorbed during each hygrothermal process due to the plasticizing effect of water, and micro-cracks propagated as a result of internal stresses caused by the hygrothermal process, the thermal-oxidative process, and the freezing process of each cycle. XRD analysis indicated that moisture penetrated through the amorphous region of the BMI matrix.

  12. Digit span changes from puberty to old age under different levels of education.

    PubMed

    Karakaş, Sirel; Yalin, Ayşe; Irak, Metehan; Erzengin, O Utku

    2002-01-01

    The goal of this study is to demonstrate the age-related changes in multimodality digit span under a research design in which level of education is controlled. Volunteer participants (n = 1183) were distributed over levels of age (13-98 years) and education (5-8, 9-11, and 12+ years). Digit span was measured through 11 scores of the Visual Aural Digit Span Test-Revised on aural or visual stimulation and oral or written response execution, thus allowing for the measurement of intra- and intersensory integration. The increase in digit span scores reversed to a decrease with early adulthood. The slope of the regression line was small but significant. A 4 x 3 x 2 multivariate analysis of variance showed a significant effect of age and education on a combined score comprising the 11 digit span scores. Differences of age and education were predicted by the auditory and visual input scores. The article discusses the cognitive correlates and the age-related changes in digit span from the biological standpoint.

  13. Mechanical Testing of TR-55 Rubber Thermally Aged Under Tensile Strain

    SciTech Connect

    Small IV, W; Alviso, C T; Wilson, T S; Chinn, S C; Maxwell, R S

    2009-03-10

    TR-55 rubber specimens were previously subjected to an aging process consisting of the application of a tensile strain of approximately 67%, 100%, 133%, or 167% elongation for 4, 8, 12, or 16 h at either 250 C or room temperature. Control specimens at the same temperatures/durations were not subjected to tensile strain. The specimens were allowed to recover at room temperature without external stimuli for over 100 days before tensile testing. A single dog bone was cut from each specimen and a stress-strain curve was obtained. The elastic modulus of each specimen was calculated. Specimens aged under tensile strain exhibited rubber-like behavior dependent on the aging elongation and duration. This behavior was not evident in the unstrained controls. For the unstrained controls, exposure to 250 C resulted in an increase in modulus relative to the unheated material independent of the heating duration. The tensile strain applied during the aging process caused a reduction in modulus relative to the controls; lower moduli were observed for the shorter aging durations. Slippage of the specimens in the grips prevented determination of ultimate strength, as all specimens either slipped completely out of the grip before failure or failed at the original grip edge after slipping.

  14. What is role of sex and age differences in marital conflict and stress of patients under Cardiac Rehabilitation Program?

    PubMed Central

    Komasi, Saeid; Saeidi, Mozhgan

    2016-01-01

    BACKGROUND To investigate the role of sex and age differences in marital conflict and stress of patients who were under cardiac rehabilitation (CR) program. METHODS The data of this cross-sectional study were collected from the database of the CR Department of Imam Ali Hospital, Kermanshah, Iran. The demographics and medical data of 683 persons were collected from January 2003 and January 2010 using medical records, the Beck Anxiety Inventory, the Beck Depression Inventory, the Hudson’s Index of Marital Stress, and the Structured Clinical Interview for axis I disorders. Data were analyzed through Analysis of Covariance and Bonferroni test. RESULTS About 74.8% of the subjects were male. After adjustment for age, educational level, anxiety, and depression-the findings showed that women in CR program had a higher level of marital stress compared to men (54.75 ± 2.52 vs. 49.30 ± 0.89; P = 0.042). Furthermore, it was revealed that women who aged 56-65 years and more experienced higher level of marital stress compared to younger patients (P < 0.050); however, no significant difference was observed between different age groups in male patients (P > 0.050). CONCLUSION Marital conflict and stress threaten healthiness of women who aged 56-65 years more prominently than does in males or younger patients. Regarding the effect of marital stress on recurrence of the disease and cardiac-related morbidity and mortality in women, providing effective education and interventions to this group of patients, especially older women and even their spouses could be one of the useful objectives of CR programs. PMID:27752271

  15. Effect of energy density on color stability in dental resin composites under accelerated aging.

    PubMed

    Zamarripa, Eliezer; Ancona, Adriana L; D'Accorso, Norma B; Macchi, Ricardo L; Abate, Pablo F

    2008-01-01

    The effects of the energy density that is used for polymerization on properties of dental resin composites are well known. However, few studies relate color stability to this factor. The aim of this study was to assess color changes (deltaE*), in vitro, in terms of accelerated aging under UV exposure of specimens prepared with different energy densities. Four commercial dental resin composites were included in the study. Thirty six specimens were prepared for each one of them, following the procedure established by ISO 4049 Standard, and assigned to three groups: A (3.75 J/cm2), B (9 J/cm2), C (24 J/cm2). Each group was further subdivided into four subgroups: 1 (no aging), 2 (500 hours aging), 3 (1000 hours aging) and 4 (1500 hours aging). The results were analyzed by means of ANOVA and Tukey's test (alpha = 0.05) to determine the effect of the factors. Correlation was performed in order to determine the possible relationship among variables. Energy density is not a significant factor in color stability. However aging is directly proportional to color changes. deltaE* depends on filler size; hybrid material presented deltaE* of 2.1(0.5), 2.4(0.6) and 3.3(0.3) at 500, 1000 and 1500 hours of accelerated aging respectively, and nanofilled material showed deltaE* of 3.0(0.6), 4.5(1.2) and 5.9(0.6) at the same times respectively. It can be concluded that deltaE* does not depend on energy density; however other factors are involved in color change. Further studies in this area are warranted.

  16. Well-Being and Chronic Disease Incidence: The English Longitudinal Study of Ageing

    PubMed Central

    Okely, Judith A.; Gale, Catharine R.

    2016-01-01

    ABSTRACT Background Previous research suggests that greater well-being may protect against onset of chronic disease. However, it is unclear whether this association is similar across different types of disease. Method We used Cox proportional hazards regression to examine the prospective relationship between well-being (measured using the CASP-19 quality of life questionnaire) and incidence of arthritis, cancer, stroke, diabetes, myocardial infarction, and chronic lung disease over 8 years. The sample consisted of 8182 participants 50 years or older from the English Longitudinal Study of Ageing. Results After adjustments for established risk factors, a standard deviation increase in CASP-19 score was associated with a decrease in arthritis risk (hazard ratio [HR] = 0.89, 95% confidence interval [CI] = 0.83–0.96) and, in those younger than 65 years, a decrease in diabetes risk (HR = 0.82, 95% CI = 0.70–0.95) and chronic lung disease risk (HR = 0.80, 95% CI = 0.66–0.97). Higher CASP-19 scores were associated with reduced risk for stroke and myocardial infarction; however, these associations were no longer significant after adjustments for established risk factors. No association was observed for cancer incidence. An age interaction was observed for diabetes, myocardial infarction, and chronic lung disease, with a stronger association between CASP-19 score and disease incidence at younger ages. Conclusions The extent of association between well-being and incident disease risk is not consistent across different chronic diseases. Future studies should examine the cause of this variation. PMID:26569542

  17. Synchronizing an aging brain: can entraining circadian clocks by food slow Alzheimer's disease?

    PubMed

    Kent, Brianne A

    2014-01-01

    Alzheimer's disease (AD) is a global epidemic. Unfortunately, we are still without effective treatments or a cure for this disease, which is having devastating consequences for patients, their families, and societies around the world. Until effective treatments are developed, promoting overall health may hold potential for delaying the onset or preventing neurodegenerative diseases such as AD. In particular, chronobiological concepts may provide a useful framework for identifying the earliest signs of age-related disease as well as inexpensive and noninvasive methods for promoting health. It is well reported that AD is associated with disrupted circadian functioning to a greater extent than normal aging. However, it is unclear if the central circadian clock (i.e., the suprachiasmatic nucleus) is dysfunctioning, or whether the synchrony between the central and peripheral clocks that control behavior and metabolic processes are becoming uncoupled. Desynchrony of rhythms can negatively affect health, increasing morbidity and mortality in both animal models and humans. If the uncoupling of rhythms is contributing to AD progression or exacerbating symptoms, then it may be possible to draw from the food-entrainment literature to identify mechanisms for re-synchronizing rhythms to improve overall health and reduce the severity of symptoms. The following review will briefly summarize the circadian system, its potential role in AD, and propose using a feeding-related neuropeptide, such as ghrelin, to synchronize uncoupled rhythms. Synchronizing rhythms may be an inexpensive way to promote healthy aging and delay the onset of neurodegenerative disease such as AD. PMID:25225484

  18. Aging, Neurodegenerative Disease, and Traumatic Brain Injury: The Role of Neuroimaging

    PubMed Central

    Levine, Brian

    2015-01-01

    Abstract Traumatic brain injury (TBI) is a highly prevalent condition with significant effects on cognition and behavior. While the acute and sub-acute effects of TBI recover over time, relatively little is known about the long-term effects of TBI in relation to neurodegenerative disease. This issue has recently garnered a great deal of attention due to publicity surrounding chronic traumatic encephalopathy (CTE) in professional athletes, although CTE is but one of several neurodegenerative disorders associated with a history of TBI. Here, we review the literative on neurodegenerative disorders linked to remote TBI. We also review the evidence for neuroimaging changes associated with unhealthy brain aging in the context of remote TBI. We conclude that neuroimaging biomarkers have significant potential to increase understanding of the mechanisms of unhealthy brain aging and neurodegeneration following TBI, with potential for identifying those at risk for unhealthy brain aging prior to the clinical manifestation of neurodegenerative disease. PMID:25192426

  19. New areas of focus at workshop on human diseases involving DNA repair deficiency and premature aging.

    PubMed

    Kraemer, Kenneth H; Sander, Miriam; Bohr, Vilhelm A

    2007-02-01

    Researchers and clinicians interested in human diseases of DNA repair deficiency and premature aging gathered at the National Conference Center in Lansdowne, Virginia on 5-8 September 2006 to attend a workshop co-organized by Vilhelm Bohr (National Institute of Aging) and Kenneth Kraemer (National Cancer Institute). An important feature of this workshop was the participation of representatives from xeroderma pigmentosum (XP), Cockayne Syndrome (CS) and trichothiodystrophy (TTD) family support groups. Studies presented at the workshop described important new insights into the phenotypic complexity of XP, CS and TTD, renewed focus on the neurological manifestations of each of these diseases, as well as keen interest in the role of oxidative stress and mitochondrial dysfunction in neurodegenerative processes and normal and/or premature aging. This workshop report summarizes some of the presentations and outcomes of the workshop.

  20. When aging-onset diabetes is coming across with Alzheimer disease: comparable pathogenesis and therapy.

    PubMed

    Tang, Jun; Pei, Yijin; Zhou, Guangji

    2013-08-01

    Diabetes mellitus is a metabolic disorder that is characterized by high blood glucose because of the insulin-resistance and insulin-deficiency in Type 2, while the insulin deficiency due to destruction of islet cells in the pancreas in Type 1. The development of Type 2 diabetes is caused by a combination of lifestyle and genetic factors. Aging patients with diabetes are at increased risk of developing cognitive and memory dysfunctions, which is one of the significant symptoms of Alzheimer disease (AD). Also, over 2/3 of AD patients were clinically indentified with impairment of glucose. Cognitive dysfunction would be associated with poor self-care ability in diabetes patients. This review will briefly summarize the current knowledge of the pathogenesis of these two diseases and highlight similarities in their pathophysiologies. Furthermore, we will shortly discuss recent progress in the insulin-targeted strategy, aiming to explore the inner linkage between these two diseases in aging populations.

  1. Adult Hippocampal Neurogenesis, Aging and Neurodegenerative Diseases: Possible Strategies to Prevent Cognitive Impairment.

    PubMed

    Vivar, Carmen

    2015-01-01

    The adult brain of humans and other mammals continuously generates new neurons throughout life. However, this neurogenic capacity is limited to two brain areas, the dentate gyrus (DG of the hippocampus and the subventricular zone (SVZ of the lateral ventricle. Although the DG generates new neurons, its neurogenic capacity declines with age and neurodegenerative diseases such as Alzheimer's disease (AD and Huntington's disease (HD. This review focuses on the role of newly-born neurons in cognitive processes, and discusses some of the strategies proposed in humans and animals to enhance neurogenesis and counteract age-related cognitive deficits, such as physical exercise and intake of natural products like omega-3 fatty acids, curcumin and flavanols. PMID:26059358

  2. Pathology supported genetic testing and treatment of cardiovascular disease in middle age for prevention of Alzheimer's disease.

    PubMed

    Kotze, Maritha J; van Rensburg, Susan J

    2012-09-01

    Chronic, multi-factorial conditions caused by a complex interaction between genetic and environmental risk factors frequently share common disease mechanisms, as evidenced by an overlap between genetic risk factors for cardiovascular disease (CVD) and Alzheimer's disease (AD). Single nucleotide polymorphisms (SNPs) in several genes including ApoE, MTHFR, HFE and FTO are known to increase the risk of both conditions. The E4 allele of the ApoE polymorphism is the most extensively studied risk factor for AD and increases the risk of coronary heart disease by approximately 40%. It furthermore displays differential therapeutic responses with use of cholesterol-lowering statins and acetylcholinesterase inhibitors, which may also be due to variation in the CYP2D6 gene in some patients. Disease expression may be triggered by gene-environment interaction causing conversion of minor metabolic abnormalities into major brain disease due to cumulative risk. A growing body of evidence supports the assessment and treatment of CVD risk factors in midlife as a preventable cause of cognitive decline, morbidity and mortality in old age. In this review, the concept of pathology supported genetic testing (PSGT) for CVD is described in this context. PSGT combines DNA testing with biochemical measurements to determine gene expression and to monitor response to treatment. The aim is to diagnose treatable disease subtypes of complex disorders, facilitate prevention of cumulative risk and formulate intervention strategies guided from the genetic background. CVD provides a model to address the lifestyle link in most chronic diseases with a genetic component. Similar preventative measures would apply for optimisation of heart and brain health.

  3. Electroencephalographic Fractal Dimension in Healthy Ageing and Alzheimer’s Disease

    PubMed Central

    Cottone, Carlo; Cancelli, Andrea; Rossini, Paolo Maria; Tecchio, Franca

    2016-01-01

    Brain activity is complex; a reflection of its structural and functional organization. Among other measures of complexity, the fractal dimension is emerging as being sensitive to neuronal damage secondary to neurological and psychiatric diseases. Here, we calculated Higuchi’s fractal dimension (HFD) in resting-state eyes-closed electroencephalography (EEG) recordings from 41 healthy controls (age: 20–89 years) and 67 Alzheimer’s Disease (AD) patients (age: 50–88 years), to investigate whether HFD is sensitive to brain activity changes typical in healthy aging and in AD. Additionally, we considered whether AD-accelerating effects of the copper fraction not bound to ceruloplasmin (also called “free” copper) are reflected in HFD fluctuations. The HFD measure showed an inverted U-shaped relationship with age in healthy people (R2 = .575, p < .001). Onset of HFD decline appeared around the age of 60, and was most evident in central-parietal regions. In this region, HFD decreased with aging stronger in the right than in the left hemisphere (p = .006). AD patients demonstrated reduced HFD compared to age- and education-matched healthy controls, especially in temporal-occipital regions. This was associated with decreasing cognitive status as assessed by mini-mental state examination, and with higher levels of non-ceruloplasmin copper. Taken together, our findings show that resting-state EEG complexity increases from youth to maturity and declines in healthy, aging individuals. In AD, brain activity complexity is further reduced in correlation with cognitive impairment. In addition, elevated levels of non-ceruloplasmin copper appear to accelerate the reduction of neural activity complexity. Overall, HDF appears to be a proper indicator for monitoring EEG-derived brain activity complexity in healthy and pathological aging. PMID:26872349

  4. Abnormal brain aging as a radical-related disease: A new target for nuclear medicine

    SciTech Connect

    Fujibayashi, Y.; Yamamoto, S.; Waki, A. |

    1996-05-01

    DNA damages caused by endogenously produced radicals are closely correlated with aging. Among them, mitochondrial DNA (mtDNA) deletions have been reported as a memory of DNA damage by oxygen radicals. In fact, clinical as well as experimental studies indicated the accumulation of deleted mtDNA in the brain, myocardium and son on, in aged subjects. In our previous work, radioiodinated radical trapping agent, p-iodophenyl-N-t-butylnitrone, and hypoxia imaging agent, Cu-62 diacetyl-bis-N-4-methyl-thiosemicarbazone have been developed for the diagnosis of radical-related diseases, such as ischemic, inflammation, cancer or aging. The aim of the present work was to evaluate these agents for brain aging studies. In our university, an unique animal model, a senescence accelerated model mouse (SAM), has been established. Among the various substrains, SAMP8 showing memory deterioration in its young age ({approximately}3 month) was basically evaluated as an abnormal brain aging model with mtDNA deletion. As controls, SAMR1 showing normal aging and ddY mice were used. MtDNA deletion n the brain was analyzed with polymerase-chain reaction (PCR) method, and relationship between mtDNA deletion and brain uptake of IPBN or Cu-62-ATSM was studied. In 1-3 month old SAMP8 brain, multiple mtDNa deletions were already found and their content was significantly higher than that of SAMR1 or age-matched ddY control. Thus, it was cleared that SAMP8 brain has high tendency to be attacked by endogenously produced oxygen radicals, possibly from its birth. Both IPBN and Cu-ATSM showed significantly higher accumulation in the SAMP8 brain than in the SAMR1 brain, indicating that these agents have high possibility for the early detection of abnormal brain aging as a radical-related disease.

  5. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease

    PubMed Central

    Allison, Beth J.; Kaandorp, Joepe J.; Kane, Andrew D.; Camm, Emily J.; Lusby, Ciara; Cross, Christine M.; Nevin-Dolan, Rhianon; Thakor, Avnesh S.; Derks, Jan B.; Tarry-Adkins, Jane L.; Ozanne, Susan E.; Giussani, Dino A.

    2016-01-01

    Aging and developmental programming are both associated with oxidative stress and endothelial dysfunction, suggesting common mechanistic origins. However, their interrelationship has been little explored. In a rodent model of programmed cardiovascular dysfunction we determined endothelial function and vascular telomere length in young (4 mo) and aged (15 mo) adult offspring of normoxic or hypoxic pregnancy with or without maternal antioxidant treatment. We show loss of endothelial function [maximal arterial relaxation to acetylcholine (71 ± 3 vs. 55 ± 3%) and increased vascular short telomere abundance (4.2–1.3 kb) 43.0 ± 1.5 vs. 55.1 ± 3.8%) in aged vs. young offspring of normoxic pregnancy (P < 0.05). Hypoxic pregnancy in young offspring accelerated endothelial dysfunction (maximal arterial relaxation to acetylcholine: 42 ± 1%, P < 0.05) but this was dissociated from increased vascular short telomere length abundance. Maternal allopurinol rescued maximal arterial relaxation to acetylcholine in aged offspring of normoxic or hypoxic pregnancy but not in young offspring of hypoxic pregnancy. Aged offspring of hypoxic allopurinol pregnancy compared with aged offspring of untreated hypoxic pregnancy had lower levels of short telomeres (vascular short telomere length abundance 35.1 ± 2.5 vs. 48.2 ± 2.6%) and of plasma proinflammatory chemokine (24.6 ± 2.8 vs. 36.8 ± 5.5 pg/ml, P < 0.05). These data provide evidence for divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease, and aging being decelerated by antioxidants even prior to birth.—Allison, B. J., Kaandorp, J. J., Kane, A. D., Camm, E. J., Lusby, C., Cross, C. M., Nevin-Dolan, R., Thakor, A. S., Derks, J. B., Tarry-Adkins, J. L., Ozanne, S. E., Giussani, D. A. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease. PMID:26932929

  6. Prevention of mutation, cancer, and other age-associated diseases by optimizing micronutrient intake.

    PubMed

    Ames, Bruce N

    2010-01-01

    I review three of our research efforts which suggest that optimizing micronutrient intake will in turn optimize metabolism, resulting in decreased DNA damage and less cancer as well as other degenerative diseases of aging. (1) Research on delay of the mitochondrial decay of aging, including release of mutagenic oxidants, by supplementing rats with lipoic acid and acetyl carnitine. (2) The triage theory, which posits that modest micronutrient deficiencies (common in much of the population) accelerate molecular aging, including DNA damage, mitochondrial decay, and supportive evidence for the theory, including an in-depth analysis of vitamin K that suggests the importance of achieving optimal micronutrient intake for longevity. (3) The finding that decreased enzyme binding constants (increased Km) for coenzymes (or substrates) can result from protein deformation and loss of function due to an age-related decline in membrane fluidity, or to polymorphisms or mutation. The loss of enzyme function can be compensated by a high dietary intake of any of the B vitamins, which increases the level of the vitamin-derived coenzyme. This dietary remediation illustrates the importance of understanding the effects of age and polymorphisms on optimal micronutrient requirements. Optimizing micronutrient intake could have a major effect on the prevention of cancer and other degenerative diseases of aging.

  7. Vascular aging: Chronic oxidative stress and impairment of redox signaling—consequences for vascular homeostasis and disease

    PubMed Central

    Bachschmid, Markus M.; Schildknecht, Stefan; Matsui, Reiko; Zee, Rebecca; Haeussler, Dagmar; Cohen, Richard A.; Pimental, David; van der Loo, Bernd

    2013-01-01

    Characteristic morphological and molecular alterations such as vessel wall thickening and reduction of nitric oxide occur in the aging vasculature leading to the gradual loss of vascular homeostasis. Consequently, the risk of developing acute and chronic cardiovascular diseases increases with age. Current research of the underlying molecular mechanisms of endothelial function demonstrates a duality of reactive oxygen and nitrogen species in contributing to vascular homeostasis or leading to detrimental effects when formed in excess. Furthermore, changes in function and redox status of vascular smooth muscle cells contribute to age-related vascular remodeling. The age-dependent increase in free radical formation causes deterioration of the nitric oxide signaling cascade, alters and activates prostaglandin metabolism, and promotes novel oxidative posttranslational protein modifications that interfere with vascular and cell signaling pathways. As a result, vascular dysfunction manifests. Compensatory mechanisms are initially activated to cope with age-induced oxidative stress, but become futile, which results in irreversible oxidative modifications of biological macromolecules. These findings support the ‘free radical theory of aging’ but also show that reactive oxygen and nitrogen species are essential signaling molecules, regulating vascular homeostasis. PMID:22380696

  8. Increased epigenetic age and granulocyte counts in the blood of Parkinson's disease patients.

    PubMed

    Horvath, Steve; Ritz, Beate R

    2015-12-01

    It has been a long standing hypothesis that blood tissue of PD Parkinson's disease (PD) patients may exhibit signs of accelerated aging. Here we use DNA methylation based biomarkers of aging ("epigenetic clock") to assess the aging rate of blood in two ethnically distinct case-control data sets. Using n=508 Caucasian and n=84 Hispanic blood samples, we assess a) the intrinsic epigenetic age acceleration of blood (IEAA), which is independent of blood cell counts, and b) the extrinsic epigenetic age acceleration rate of blood (EEAA) which is associated with age dependent changes in blood cell counts. Blood of PD subjects exhibits increased age acceleration according to both IEAA (p=0.019) and EEAA (p=6.1 x 10(-3)). We find striking differences in imputed blood cell counts between PD cases and controls. Compared to control subjects, PD subjects contains more granulocytes (p=1.0 x 10(-9) in Caucasians, p=0.00066 in Hispanics) but fewer T helper cells (p=1.4 x 10(-6) in Caucasians, p=0.0024 in Hispanics) and fewer B cells (p=1.6 x 10(-5) in Caucasians, p=4.5 x 10(-5) in Hispanics). Overall, this study shows that the epigenetic age of the immune system is significantly increased in PD patients and that granulocytes play a significant role. PMID:26655927

  9. Age effects on the control of dynamic balance during step adjustments under temporal constraints.

    PubMed

    Nakano, Wataru; Fukaya, Takashi; Kobayashi, Satomi; Ohashi, Yukari

    2016-06-01

    This study investigated the age effects on the control of dynamic balance during step adjustments under temporal constraints. Fifteen young adults and 14 older adults avoided a virtual white planar obstacle by lengthening or shortening their steps under free or constrained conditions. In the anterior-posterior direction, older adults demonstrated significantly decreased center of mass velocity at the swing foot contact under temporal constraints. Additionally, the distances between the 'extrapolated center of mass' position and base of support at the swing foot contact were greater in older adults than young adults. In the mediolateral direction, center of mass displacement was significantly increased in older adults compared with young adults. Consequently, older adults showed a significantly increased step width at the swing foot contact in the constraint condition. Overall, these data suggest that older adults demonstrate a conservative strategy to maintain anterior-posterior stability. By contrast, although older adults are able to modulate their step width to maintain mediolateral dynamic balance, age-related changes in mediolateral balance control under temporal constraints may increase the risk of falls in the lateral direction during obstacle negotiation.

  10. Hardness and Young's modulus of transparent dentin associated with aging and carious disease.

    PubMed

    Zheng, Lei; Nakajima, Masatoshi; Higashi, Takashi; Foxton, Richard M; Tagami, Junji

    2005-12-01

    This study investigated the changes in hardness and Young's modulus of the transparent layer of dentin associated with aging and the carious process. Eighteen extracted human molars with or without coronal caries were used in this study. The normal teeth were divided into two groups by age, and the carious teeth were divided into two groups of active or arrested caries. After polishing the specimens parallel to the long axis of the tooth, both hardness and Young's modulus were measured using a nanoindentation tester. The hardness and Young's modulus of the transparent layer in aged dentin were higher than the other portions of aged dentin. The transparent layer under carious lesions had a significantly lower hardness than the underlying normal dentin, whereas its Young's modulus was not significantly reduced. The hardness and Young's modulus of the transparent layer in active carious lesions were lower than those in arrested carious lesions.

  11. Huntington’s disease: underlying molecular mechanisms and emerging concepts

    PubMed Central

    Labbadia, John; Morimoto, Richard I.

    2013-01-01

    Huntington’s disease (HD) is a progressive neurodegenerative disorder for which no disease modifying treatments exist. Many molecular changes and cellular consequences that underlie HD are observed in other neurological disorders suggesting that common pathological mechanisms and pathways may exist. Recent findings have enhanced our understanding of the way cells regulate and respond to expanded polyglutamine proteins such as mutant huntingtin. These studies demonstrate that in addition to effects on folding, aggregation, and clearance pathways, a general transcriptional mechanism also dictates the expression of polyglutamine proteins. Here we summarize the key pathways and networks that are important in HD in the context of recent therapeutic advances and highlight how their interplay may be of relevance to other protein folding disorders. PMID:23768628

  12. Anemia in inflammatory bowel disease: an under-estimated problem?

    PubMed

    Rogler, Gerhard; Vavricka, Stephan

    2014-01-01

    Anemia is one of the most frequent complications and/or extraintestinal manifestations of inflammatory bowel disease (IBD). Iron deficiency is the most important cause of anemia in Crohn's disease and ulcerative colitis patients. Iron deficiency even without anemia may impact the quality of life of our IBD patients. In the last 10 years, the understanding of the pathology of iron-deficiency anemia and "anemia of chronic diseases" has increased; new diagnostic tools have been developed and new therapeutic strategies have been discussed. Hepcidin has been identified to be a central regulator of iron absorption from the intestine and of iron plasma levels. Hepcidin is regulated by iron deficiency but also as an acute phase protein by pro-inflammatory mediators such as interleukin-6. Innovative diagnostic tools have not been introduced in clinical routine or are not available for routine diagnostics. As iron substitution therapy is easy these days with a preference for intravenous substitution, the impact of differential diagnosis of anemia in IBD patients is underestimated. PMID:25646159

  13. Aging modulates the oscillatory dynamics underlying successful working memory encoding and maintenance.

    PubMed

    Proskovec, Amy L; Heinrichs-Graham, Elizabeth; Wilson, Tony W

    2016-06-01

    Working memory is central to the execution of many daily functions and is typically divided into three phases: encoding, maintenance, and retrieval. While working memory performance has been repeatedly shown to decline with age, less is known regarding the underlying neural processes. We examined age-related differences in the neural dynamics that serve working memory by recording high-density magnetoencephalography (MEG) in younger and older adults while they performed a modified, high-load Sternberg working memory task with letters as stimuli. MEG data were evaluated in the time-frequency domain and significant oscillatory responses were imaged using a beamformer. A hierarchical regression was performed to investigate whether age moderated the relationship between oscillatory activity and accuracy on the working memory task. Our results indicated that the spatiotemporal dynamics of oscillatory activity in language-related areas of the left fronto-temporal cortices were similar across groups. Age-related differences emerged during early encoding in the right-hemispheric homologue of Wernicke's area. Slightly later, group differences emerged in the homologue of Broca's area and these persisted throughout memory maintenance. Additionally, occipital alpha activity during maintenance was stronger, occurred earlier, and involved more cortical tissue in older adults. Finally, age significantly moderated the relationship between accuracy and neural activity in the prefrontal cortices. In younger adults, as prefrontal activity decreased, accuracy tended to increase. Our results are consistent with predictions of the compensation-related utilization of neural circuits hypothesis (CRUNCH). Such differences in the oscillatory dynamics could reflect compensatory mechanisms, which would aid working memory performance in older age. Hum Brain Mapp 37:2348-2361, 2016. © 2016 Wiley Periodicals, Inc. PMID:26991358

  14. The Circadian Timing System: A Recent Addition in the Physiological Mechanisms Underlying Pathological and Aging Processes

    PubMed Central

    Arellanes-Licea, Elvira; Caldelas, Ivette; De Ita-Pérez, Dalia; Díaz-Muñoz, Mauricio

    2014-01-01

    Experimental findings and clinical observations have strengthened the association between physio-pathologic aspects of several diseases, as well as aging process, with the occurrence and control of circadian rhythms. The circadian system is composed by a principal pacemaker in the suprachiasmatic nucleus (SNC) which is in coordination with a number of peripheral circadian oscillators. Many pathological entities such as metabolic syndrome, cancer and cardiovascular events are strongly connected with a disruptive condition of the circadian cycle. Inadequate circadian physiology can be elicited by genetic defects (mutations in clock genes or circadian control genes) or physiological deficiencies (desynchronization between SCN and peripheral oscillators). In this review, we focus on the most recent experimental findings regarding molecular defects in the molecular circadian clock and the altered coordination in the circadian system that are related with clinical conditions such as metabolic diseases, cancer predisposition and physiological deficiencies associated to jet-lag and shiftwork schedules. Implications in the aging process will be also reviewed. PMID:25489492

  15. AMPA receptor trafficking and the mechanisms underlying synaptic plasticity and cognitive aging.

    PubMed

    Henley, Jeremy M; Wilkinson, Kevin A

    2013-03-01

    Even in healthy individuals there is an inexorable agerelated decline in cognitive function. This is due, in large part, to reduced synaptic plasticity caused by changes in the molecular composition of the postsynaptic membrane. AMPA receptors (AMPARs) are glutamate-gated cation channels that mediate the overwhelming majority of fast excitatory transmission in the brain. Changes in AMPAR number and/or function are a core feature of synaptic plasticity and age-related cognitive decline, AMPARs are highly dynamic proteins that are subject to highly controlled trafficking, recycling, and/or degradation and replacement. This active regulation of AMPAR synthesis, targeting, synaptic dwell time, and degradation is fundamentally important for memory formation and storage. Further, aberrant AMPAR trafficking and consequent detrimental changes in synapses are strongly implicated in many brain diseases, which represent a vast social and economic burden. The purpose of this article is to provide an overview of the molecular and cellular AMPA receptor trafficking events that control synaptic responsiveness and plasticity, and highlight what is known currently known about how these processes change with age and disease.

  16. AMPA receptor trafficking and the mechanisms underlying synaptic plasticity and cognitive aging

    PubMed Central

    Henley, Jeremy M.; Wilkinson, Kevin A.

    2013-01-01

    Even in healthy individuals there is an inexorable agerelated decline in cognitive function. This is due, in large part, to reduced synaptic plasticity caused by changes in the molecular composition of the postsynaptic membrane. AMPA receptors (AMPARs) are glutamate-gated cation channels that mediate the overwhelming majority of fast excitatory transmission in the brain. Changes in AMPAR number and/or function are a core feature of synaptic plasticity and age-related cognitive decline, AMPARs are highly dynamic proteins that are subject to highly controlled trafficking, recycling, and/or degradation and replacement. This active regulation of AMPAR synthesis, targeting, synaptic dwell time, and degradation is fundamentally important for memory formation and storage. Further, aberrant AMPAR trafficking and consequent detrimental changes in synapses are strongly implicated in many brain diseases, which represent a vast social and economic burden. The purpose of this article is to provide an overview of the molecular and cellular AMPA receptor trafficking events that control synaptic responsiveness and plasticity, and highlight what is known currently known about how these processes change with age and disease. PMID:23576886

  17. Selective Vulnerability of Neurons in Layer II of the Entorhinal Cortex during Aging and Alzheimer's Disease

    PubMed Central

    Stranahan, Alexis M.; Mattson, Mark P.

    2010-01-01

    All neurons are not created equal. Certain cell populations in specific brain regions are more susceptible to age-related changes that initiate regional and system-level dysfunction. In this respect, neurons in layer II of the entorhinal cortex are selectively vulnerable in aging and Alzheimer's disease (AD). This paper will cover several hypotheses that attempt to account for age-related alterations among this cell population. We consider whether specific developmental, anatomical, or biochemical features of neurons in layer II of the entorhinal cortex contribute to their particular sensitivity to aging and AD. The entorhinal cortex is a functionally heterogeneous environment, and we will also review data suggesting that, within the entorhinal cortex, there is subregional specificity for molecular alterations that may initiate cognitive decline. Taken together, the existing data point to a regional cascade in which entorhinal cortical alterations directly contribute to downstream changes in its primary afferent region, the hippocampus. PMID:21331296

  18. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases.

    PubMed

    Franceschi, Claudio; Campisi, Judith

    2014-06-01

    Human aging is characterized by a chronic, low-grade inflammation, and this phenomenon has been termed as "inflammaging." Inflammaging is a highly significant risk factor for both morbidity and mortality in the elderly people, as most if not all age-related diseases share an inflammatory pathogenesis. Nevertheless, the precise etiology of inflammaging and its potential causal role in contributing to adverse health outcomes remain largely unknown. The identification of pathways that control age-related inflammation across multiple systems is therefore important in order to understand whether treatments that modulate inflammaging may be beneficial in old people. The session on inflammation of the Advances in Gerosciences meeting held at the National Institutes of Health/National Institute on Aging in Bethesda on October 30 and 31, 2013 was aimed at defining these important unanswered questions about inflammaging. This article reports the main outcomes of this session.

  19. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases.

    PubMed

    Franceschi, Claudio; Campisi, Judith

    2014-06-01

    Human aging is characterized by a chronic, low-grade inflammation, and this phenomenon has been termed as "inflammaging." Inflammaging is a highly significant risk factor for both morbidity and mortality in the elderly people, as most if not all age-related diseases share an inflammatory pathogenesis. Nevertheless, the precise etiology of inflammaging and its potential causal role in contributing to adverse health outcomes remain largely unknown. The identification of pathways that control age-related inflammation across multiple systems is therefore important in order to understand whether treatments that modulate inflammaging may be beneficial in old people. The session on inflammation of the Advances in Gerosciences meeting held at the National Institutes of Health/National Institute on Aging in Bethesda on October 30 and 31, 2013 was aimed at defining these important unanswered questions about inflammaging. This article reports the main outcomes of this session. PMID:24833586

  20. The impact of health insurance for children under age 6 in Vietnam: A regression discontinuity approach.

    PubMed

    Palmer, Michael; Mitra, Sophie; Mont, Daniel; Groce, Nora

    2015-11-01

    Accessing health services at an early age is important to future health and life outcomes. Yet, little is currently known on the role of health insurance in facilitating access to care for children. Exploiting a regression discontinuity design made possible through a policy to provide health insurance to pre-school aged children in Vietnam, this paper evaluates the impact of health insurance on the health care utilization outcomes of children at the eligibility threshold of six years. Using three rounds of the Vietnam Household Living Standards Survey, the study finds a positive impact on inpatient and outpatient visits and no significant impact on expenditures per visit at public facilities. We find moderately high use of private outpatient services and no evidence of a switch from private to covered public facilities under insurance. Results suggest that adopting public health insurance programs for children under age 6 may be an important vehicle to improving service utilization in a low- and middle-income country context. Challenges remain in providing adequate protections from the costs and other barriers to care.

  1. Neurodevelopment and brain growth in classic Menkes disease is influenced by age and symptomatology at initiation of copper treatment.

    PubMed

    Kaler, Stephen G

    2014-10-01

    Menkes disease is an X-linked recessive disorder of brain copper metabolism caused by mutations in an essential mammalian copper transport gene, ATP7A. Untreated affected individuals suffer failure to thrive and neurodevelopmental delays that usually commence at 6-8 weeks of age. Death by age three years is typical. While provision of working copies of ATP7A to the brain by viral vectors is a promising strategy under development, the only treatment currently available is subcutaneous copper injections. These can normalize circulating blood levels and may replete brain copper depending on the molecular context, e.g., the severity of ATP7A mutation and potential presence of mosaicism. In this paper, we summarize somatic growth and neurodevelopmental outcomes for 60 subjects enrolled in a recently concluded phase I/II clinical trial of copper histidine for Menkes disease (ClinicalTrials.gov Identifier: NCT00001262). Primary outcomes indicate highly statistically significant improvements in gross motor, fine motor/adaptive, personal-social, and language neurodevelopment in the cohort of subjects who received early treatment prior to onset of symptoms (n=35). Correlating with these findings, quantitative parameters of somatic growth indicated statistically significant greater growth in head circumference for the initially asymptomatic group, whereas weight and height/length at age three years (or at time of death) did not differ significantly. Mortality at age 3 was higher (50%) in subjects older and symptomatic when treatment commenced compared to the asymptomatic group (28.6%). We conclude that early copper histidine for Menkes disease is safe and efficacious, with treatment outcomes influenced by the timing of intervention, and ATP7A mutation. PMID:25281031

  2. Analyzing aging under oscillatory strain field through the soft glassy rheology model.

    PubMed

    Kaushal, Manish; Joshi, Yogesh M

    2016-06-28

    In this work, we solve the Soft Glassy Rheology (SGR) model under application of oscillatory deformation field with varying magnitudes of strain as well as frequency for different noise temperatures. In the glassy domain, the SGR model undergoes time evolution of elastic modulus. Increase in strain magnitude beyond the linear regime is observed to enhance the rate of aging as manifested by a faster evolution of elastic modulus with increase in strain amplitude due to overaging. However at higher strain magnitudes, the rejuvenation effect starts dominating over the aging, thereby reducing the rate at which elastic modulus evolves. We also plot the aging phase diagram describing an occurrence of the linear, the overaging, and the rejuvenation regimes as a function of strain and frequency for different noise temperatures. The aging phase diagram suggests that while the linear regime remains unaffected by the changes in frequency and noise temperature, the width of the overaging regime increases with increase in frequency and noise temperature. We also study the time evolution of the shapes of relaxation time spectra as a function of strain amplitude, which renders further insight into the overaging and the rejuvenation behavior. While the phenomenon of overaging is observed to be an inherent character of the SGR model, experimentally not all the materials demonstrate overaging. Such a discrepancy suggests that the energy well depths before and after a yielding event may not be completely uncorrelated as assumed in the SGR formalism. PMID:27369524

  3. Preservation of Cognitive Performance with Age during Exertional Heat Stress under Low and High Air Velocity

    PubMed Central

    Wright Beatty, Heather E.; Keillor, Jocelyn M.; Hardcastle, Stephen G.; Boulay, Pierre; Kenny, Glen P.

    2015-01-01

    Older adults may be at greater risk for occupational injuries given their reduced capacity to dissipate heat, leading to greater thermal strain and potentially cognitive decrements. Purpose. To examine the effects of age and increased air velocity, during exercise in humid heat, on information processing and attention. Methods. Nine young (24 ± 1 years) and 9 older (59 ± 1 years) males cycled 4 × 15 min (separated by 15 min rest) at a fixed rate of heat production (400 W) in humid heat (35°C, 60% relative humidity) under 0.5 (low) and 3.0 (high) m·s−1 air velocity wearing coveralls. At rest, immediately following exercise (end exercise), and after the final recovery, participants performed an abbreviated paced auditory serial addition task (PASAT, 2 sec pace). Results. PASAT numbers of correct responses at end exercise were similar for young (low = 49 ± 3; high = 51 ± 3) and older (low = 46 ± 5; high = 47 ± 4) males and across air velocity conditions, and when scored relative to age norms. Psychological sweating, or an increased sweat rate with the administration of the PASAT, was observed in both age groups in the high condition. Conclusion. No significant decrements in attention and speeded information processing were observed, with age or altered air velocity, following intermittent exercise in humid heat. PMID:25874223

  4. Visceral Leishmaniasis in China: an Endemic Disease under Control

    PubMed Central

    Wu, Ming-Shui; Chen, Yun-Fu; Wang, Jun-Yun; Zhou, Xiao-Nong; Liao, Li-Fu; Chen, Jian-Ping; Chow, Larry M. C.

    2015-01-01

    SUMMARY Visceral leishmaniasis (VL) caused by Leishmania spp. is an important vector-borne and largely zoonotic disease. In China, three epidemiological types of VL have been described: anthroponotic VL (AVL), mountain-type zoonotic VL (MT-ZVL), and desert-type ZVL (DT-ZVL). These are transmitted by four different sand fly species: Phlebotomus chinensis, P. longiductus, P. wui, and P. alexandri. In 1951, a detailed survey of VL showed that it was rampant in the vast rural areas west, northwest, and north of the Yangtze River. Control programs were designed and implemented stringently by the government at all administrative levels, resulting in elimination of the disease from most areas of endemicity, except the western and northwestern regions. The control programs consisted of (i) diagnosis and chemotherapy of patients, (ii) identification, isolation, and disposal of infected dogs, and (iii) residual insecticide indoor spraying for vector control. The success of the control programs is attributable to massive and effective mobilization of the general public and health workers to the cause. Nationally, the annual incidence is now very low, i.e., only 0.03/100,000 according to the available 2011 official record. The overwhelming majority of cases are reported from sites of endemicity in the western and northwestern regions. Here, we describe in some depth and breadth the current status of epidemiology, diagnosis, treatment, and prevention of the disease, with particular reference to the control programs. Pertinent information has been assembled from scattered literature of the past decades in different languages that are not readily accessible to the scientific community. The information provided constitutes an integral part of our knowledge on leishmaniasis in the global context and will be of special value to those interested in control programs. PMID:26354822

  5. Neuropsychology of cognitive ageing, minimal cognitive impairment, Alzheimer's disease, and vascular cognitive impairment.

    PubMed

    Lindeboom, Jaap; Weinstein, Henry

    2004-04-19

    In this review, the neuropsychological symptoms of different diseases in the elderly are described. After a brief explanation of relevant principles in the neuropsychological assessment of older individuals, a summary of the complex relation between ageing and cognition is presented. It may be concluded that cognitive decline is not an inevitable outcome of ageing, and may well be the result of unrecognised pathology. The term mild cognitive impairment is reserved for patients whose impairment is objectively demonstrable but is not pronounced in more than one domain of cognition and does not seriously affect activities of daily living. The initial phase of Alzheimer's disease is marked by a progressive deterioration of episodic memory. When the process advances, the impairment spreads to other functions, such as semantic memory, language and visuo-spatial ability. Vascular dementia is the second most common type of dementia; however, it is increasingly being recognised that vascular dementia is actually a heterogeneous syndrome and that several vascular pathologies can lead to cognitive deterioration. In contrast to the striking deficits produced by cortical infarcts, lesions of the subcortical white matter are mainly associated with a non-specific slowing of behaviour. Cerebrovascular disease also plays an important role in forms of cognitive decline other than dementia, and as such, it appears to be no less prevalent in old age than Alzheimer's disease. Neuropsychology is an important asset to the study and treatment of cognitive decline, but must be embedded in a multi-disciplinary context.

  6. Common Alzheimer's Disease Research Ontology: National Institute on Aging and Alzheimer's Association collaborative project.

    PubMed

    Refolo, Lorenzo M; Snyder, Heather; Liggins, Charlene; Ryan, Laurie; Silverberg, Nina; Petanceska, Suzana; Carrillo, Maria C

    2012-07-01

    Alzheimer's disease is recognized as a public health crisis worldwide. As public and private funding agencies around the world enhance and expand their support of Alzheimer's disease research, there is an urgent need to coordinate funding strategies and leverage resources to maximize the impact on public health and avoid duplication of effort and inefficiency. Such coordination requires a comprehensive assessment of the current landscape of Alzheimer's disease research in the United States and internationally. To this end, the National Institute on Aging at the National Institutes of Health and the Alzheimer's Association developed the Common Alzheimer's Disease Research Ontology (CADRO) as a dynamic portfolio analysis tool that can be used by funding agencies worldwide for strategic planning and coordination.

  7. Age-related changes of protein SUMOylation balance in the AβPP Tg2576 mouse model of Alzheimer's disease

    PubMed Central

    Nisticò, Robert; Ferraina, Caterina; Marconi, Veronica; Blandini, Fabio; Negri, Lucia; Egebjerg, Jan; Feligioni, Marco

    2014-01-01

    Alzheimer's disease (AD) is a complex disorder that affects the central nervous system causing a severe neurodegeneration. This pathology affects an increasing number of people worldwide due to the overall aging of the human population. In recent years SUMO protein modification has emerged as a possible cellular mechanism involved in AD. Some of the proteins engaged in the physiopathological process of AD, like BACE1, GSK3-β tau, AβPP, and JNK, are in fact subject to protein SUMO modifications or interactions. Here, we have investigated the SUMO/deSUMOylation balance and SUMO-related proteins during the onset and progression of the pathology in the Tg2576 mouse model of AD. We examined four age-stages (1.5, 3, 6, 17 months old) and observed shows an increase in SUMO-1 protein conjugation at 3 and 6 months in transgenic mice with respect to WT in both cortex and hippocampus. Interestingly this is paralleled by increased expression levels of Ubc9 and SENP1 in both brain regions. At 6 months of age also the SUMO-1 mRNA resulted augmented. SUMO-2-ylation was surprisingly decreased in old transgenic mice and was unaltered in the other time windows. The fact that alterations in SUMO/deSUMOylation equilibrium occur from the early phases of AD suggests that global posttranslational modifications may play an important role in the mechanisms underlying disease pathogenesis, thus providing potential targets for pharmacological interventions. PMID:24778618

  8. Altered connexin 43 expression underlies age dependent decrease of Treg cell suppressor function in NOD mice

    PubMed Central

    Kuczma, Michal; Wang, Cong-Yi; Ignatowicz, Leszek; Gourdie, Robert; Kraj, Piotr

    2015-01-01

    Type I diabetes (T1D) is one of the most extensively studied autoimmune diseases but the cellular and molecular mechanisms leading to T cell-mediated destruction of insulin-producing β-cells are still not well understood. Here we show that Treg cells in NOD mice undergo age-dependent loss of suppressor functions exacerbated by the decreased ability of activated effector T cells to upregulate Foxp3 and generate Treg cells in the peripheral organs. This age-dependent loss is associated with reduced intercellular communication mediated by gap junctions, which is caused by impaired upregulation and decreased expression of connexin 43. Regulatory functions can be corrected, even in T cells isolated from aged, diabetic mice, by a synergistic activity of retinoic acid, TGF-β, and IL-2, which enhance connexin 43 and Foxp3 expression in Treg cells and restore the ability of conventional CD4+ T cells to upregulate Foxp3 and generate peripherally derived Treg cells. Moreover, we demonstrate that suppression mediated by Treg cells from diabetic mice is enhanced by a novel reagent, which facilitates gap junction aggregation. In summary, our report identifies gap junction-mediated intercellular communication as an important component of the Treg cell suppression mechanism compromised in NOD mice and suggests how Treg mediated immune regulation can be improved. PMID:25911751

  9. The influence of age and mild cognitive impairment on associative memory performance and underlying brain networks.

    PubMed

    Oedekoven, Christiane S H; Jansen, Andreas; Keidel, James L; Kircher, Tilo; Leube, Dirk

    2015-12-01

    Associative memory is essential to everyday activities, such as the binding of faces and corresponding names to form single bits of information. However, this ability often becomes impaired with increasing age. The most important neural substrate of associative memory is the hi