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Age (Dordrecht, Netherlands) Jun 2016We have reported telomere attrition in β and α cells of the pancreas in elderly patients with type 2 diabetes, but it has not been explored how the telomere lengths of...
We have reported telomere attrition in β and α cells of the pancreas in elderly patients with type 2 diabetes, but it has not been explored how the telomere lengths of these islet cells change according to age in normal subjects. To examine the telomere lengths of β and α cells in individuals without diabetes across a wide range of ages, we conducted measurement of the telomere lengths of human pancreatic β and α cells obtained from 104 autopsied subjects without diabetes ranging in age from 0 to 100 years. As an index of telomere lengths, the normalized telomere-centromere ratio (NTCR) was determined for β (NTCRβ) and α (NTCRα) cells by quantitative fluorescence in situ hybridization (Q-FISH). We found NTCRβ and NTCRα showed almost the same levels and both decreased according to age (p < 0.001 for both). NTCRs decreased more rapidly with age and were more widely distributed (p = 0.036 for NTCRβ, p < 0.001 for NTCRα) in subjects under 18 years of age than in subjects over 18 years. There was a positive correlation between NTCRβ and NTCRα only among adult subjects (p < 0.001). In conclusion, the telomeres of β and α cells become shortened with normal aging process.
Topics: Adult; Aged; Aging; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glucagon-Secreting Cells; Humans; In Situ Hybridization, Fluorescence; Insulin-Secreting Cells; Male; Middle Aged; Retrospective Studies; Telomere
PubMed: 27216158
DOI: 10.1007/s11357-016-9923-0 -
Age Apr 1999Model systems implementing various approaches to immortalize cells have led toward further understanding of replicative senescence and carcinogenesis. Human diploid...
Model systems implementing various approaches to immortalize cells have led toward further understanding of replicative senescence and carcinogenesis. Human diploid cells have a limited life span, termed replicative senescence. Because cells are terminally growth arrested during replicative senescence, it has been suggested that it acts as a tumor suppression mechanism as tumor cells exhibit an indefinite life span and are immortal. The generation of immortal cells lines, by the introduction of SV40 and human papillomavirus (HPV) sequences into cells, has provided invaluable tools to dissect the mechanisms of immortalization. We have developed matched sets of nonimmortal and immortal SV40 cell lines which have been useful in the identification of novel growth suppressor genes (SEN6) as well as providing a model system for the study of processes such as cellular aging, apoptosis, and telomere stabilization. Thus, their continued use is anticipated to lead to insights into other processes, which are effected by the altered expression of oncogenes and growth suppressors.
PubMed: 23604398
DOI: 10.1007/s11357-999-0008-1 -
Age (Dordrecht, Netherlands) Oct 2012The immune system must overcome daily challenges from pathogens to protect the body from infection. The success of the immune response to infection relies on the ability... (Review)
Review
The immune system must overcome daily challenges from pathogens to protect the body from infection. The success of the immune response to infection relies on the ability to sense and evaluate microbial threats and organize their elimination, while limiting damage to host tissues. This delicate balance is achieved through coordinated action of the innate and adaptive arms of the immune system. Aging results in several structural and functional changes in the immune system, often described under the umbrella term "immune senescence". Age-related changes affect both the innate and adaptive arms of the immune system and are believed to result in increased susceptibility and severity of infectious diseases, which is further exacerbated by reduced vaccine efficacy in the elderly. Therefore, multiple strategies to improve immune function in the aged are being investigated. Traditionally, studies on immune senescence are conducted using inbred specific pathogen free (SPF) rodents. This animal model has provided invaluable insight into the mechanisms of aging. However, the limited genetic heterogeneity and the SPF status of this model restrict the successful transfer of immunological discoveries between murine models and the clinical setting. More recently, nonhuman primates (NHPs) have emerged as a leading translational model to investigate immune senescence and to test interventions aimed at delaying/reversing age-related changes in immune function. In this article, we review and summarize advances in immuno-restorative approaches investigated in the NHP model system and discuss where the NHP model can support the development of novel therapeutics.
Topics: Adaptation, Physiological; Aging; Animals; Disease Models, Animal; Immune System; Infections; Primates
PubMed: 22180097
DOI: 10.1007/s11357-011-9353-y -
Age (Dordrecht, Netherlands) Feb 2016We hypothesize that the time when age-related changes in autonomic functioning and in sleep structure occur are different and that autonomic functioning modulates sleep...
We hypothesize that the time when age-related changes in autonomic functioning and in sleep structure occur are different and that autonomic functioning modulates sleep architecture differently before and after 50 years of age. Sixty-eight healthy subjects (aged 20 to 79 years old, 49 of them women) were enrolled. Correlation analysis revealed that wake after sleep onset, the absolute and relative value of stage 1 (S1; S1%), and relative value of stage 2 (S2) were positively correlated with age; however, sleep efficiency, stage 3 (S3), S3%, and rapid-eye-movement latency (REML) were negatively correlated with age. Significant degenerations of sleep during normal aging were occurred after 50 years of age; however, significant declines of autonomic activity were showed before 50 years of age. Before 50 years of age, vagal function during sleep was negatively correlated with arousal index; however, after 50 years of age, it was positively correlated with S1 and S1%. In addition, sympathetic activity during wake stage was positively related to S2% only after 50 years of age. Our results imply that the age-related changes in autonomic functioning decline promptly as individuals leave the younger part of their adult life span and that age-related changes in sleep slowly develop as individuals enter the older part of their adult life span. Furthermore, while various aspects of sleep architecture are modulated by both the sympathetic and vagal nervous systems during adult life span, the sleep quality is mainly correlated with the sympathetic division after 50 years of age.
Topics: Adult; Aged; Aging; Autonomic Nervous System; Electrocardiography; Electroencephalography; Electromyography; Female; Follow-Up Studies; Healthy Volunteers; Heart Rate; Humans; Male; Middle Aged; Signal Processing, Computer-Assisted; Sleep; Young Adult
PubMed: 26728397
DOI: 10.1007/s11357-015-9863-0 -
Age (Dordrecht, Netherlands) Oct 2015Walking speed is a key vital sign in older people. Given the implications of slower gait speed, a large literature has identified health-related, behavioral, cognitive,...
Walking speed is a key vital sign in older people. Given the implications of slower gait speed, a large literature has identified health-related, behavioral, cognitive, and biological factors that moderate age-related decline in mobility. The present study aims to contribute to existing knowledge by examining whether subjective age, how old or young individuals experience themselves to be relative to their chronological age, contributes to walking speed. Participants were drawn from the 2008 and 2012 waves of the Health and Retirement Study (HRS, N = 2970) and the 2011 and 2013 waves of the National Health and Aging Trends Study (NHATS, N = 5423). In both the HRS and the NHATS, linear regression analysis revealed that a younger subjective age was associated with faster walking speed at baseline and with less decline over time, controlling for age, sex, education, and race. These associations were partly accounted for by depressive symptoms, disease burden, physical activity, cognition, body mass index, and smoking. Additional analysis revealed that feeling younger than one's age was associated with a reduced risk of walking slower than the frailty-related threshold of 0.6 m/s at follow-up in the HRS. The present study provides novel and consistent evidence across two large prospective studies for an association between the subjective experience of age and walking speed of older adults. Subjective age may help identify individuals at risk for mobility limitations in old age and may be a target for interventions designed to mitigate functional decline.
Topics: Age Factors; Aged; Aging; Body Mass Index; Cognition; Female; Gait; Humans; Male; Mobility Limitation; Prospective Studies; Walking
PubMed: 26296609
DOI: 10.1007/s11357-015-9830-9 -
Age (Dordrecht, Netherlands) Jun 2012Alzheimer's disease (AD) is an age-related progressive neurodegenerative disease commonly found among elderly. In addition to cognitive and behavioral deficits, vision... (Review)
Review
Alzheimer's disease (AD) is an age-related progressive neurodegenerative disease commonly found among elderly. In addition to cognitive and behavioral deficits, vision abnormalities are prevalent in AD patients. Recent studies investigating retinal changes in AD double-transgenic mice have shown altered processing of amyloid precursor protein and accumulation of β-amyloid peptides in neurons of retinal ganglion cell layer (RGCL) and inner nuclear layer (INL). Apoptotic cells were also detected in the RGCL. Thus, the pathophysiological changes of retinas in AD patients are possibly resembled by AD transgenic models. The retina is a simple model of the brain in the sense that some pathological changes and therapeutic strategies from the retina may be observed or applicable to the brain. Furthermore, it is also possible to advance our understanding of pathological mechanisms in other retinal degenerative diseases. Therefore, studying AD-related retinal degeneration is a promising way for the investigation on (1) AD pathologies and therapies that would eventually benefit the brain and (2) cellular mechanisms in other retinal degenerations such as glaucoma and age-related macular degeneration. This review will highlight the efforts on retinal degenerative research using AD transgenic mouse models.
Topics: Aging; Alzheimer Disease; Animals; Apoptosis; Disease Models, Animal; Disease Progression; Mice; Mice, Transgenic; Retina; Retinal Degeneration; Retinal Ganglion Cells
PubMed: 21559868
DOI: 10.1007/s11357-011-9260-2 -
Age (Dordrecht, Netherlands) Oct 2012Many environmental conditions show rhythmic changes across the 24-h day; these include changes in light intensity, ambient temperature, food availability, and presence... (Review)
Review
Many environmental conditions show rhythmic changes across the 24-h day; these include changes in light intensity, ambient temperature, food availability, and presence or absence of predators. Consequently, many organisms have developed corresponding adaptations, which ensure that specific physiological and behavioral events occur at an appropriate time of the day. In mammals, the underlying mechanism responsible for synchronizing internal biochemical processes with circadian environmental cues has been well studied and is thought to comprise three major components: (1) photoreception by the retina and transmission of neural signals along the retinohypothalamic tract, (2) integration of photoperiodic information with an internal reference circadian pacemaker located in the suprachiasmatic nucleus, and (3) dissemination of circadian information to target organs, via the autonomic nervous system and through humoral pathways. Given the importance that neuroendocrine rhythms play in coordinating normal circadian physiology and behavior, it is plausible that their perturbation during aging contributes to the etiology of age-related pathologies. This mini-review highlights some of the most dramatic rhythmic neuroendocrine changes that occur in primates during aging, focusing primarily on data from the male rhesus macaques (Macaca mulatta). In addition to the age-associated attenuation of hormone levels and reduction of humoral circadian signaling, there are also significant age-related changes in intracrine processing enzymes and hormone receptors which may further affect the functional efficacy of these hormones. Rhesus macaques, like humans, are large diurnal primates and show many of the same physiological and behavioral circadian changes during aging. Consequently, they represent an ideal translational animal model in which to study the causes and consequences of age-associated internal circadian disruption and in which to evaluate novel therapies.
Topics: Aging; Animals; Brain; Circadian Rhythm; Macaca mulatta; Neurosecretory Systems
PubMed: 22198672
DOI: 10.1007/s11357-011-9352-z -
Age Jul 1998Heme oxygenase (HO) performs the rate limiting step in heme degradation and is induced by cell injury or stress. We wished to determine if dietary fatty acid...
Heme oxygenase (HO) performs the rate limiting step in heme degradation and is induced by cell injury or stress. We wished to determine if dietary fatty acid composition, increased age and/or an induced oxidative stress would alter the expression of HO-1 (constitutive and inducible isozyme) or of HO-2 (constitutive isozyme), in mouse liver, spleen and brain. Six-and 24-month-old male B6C3F1 mice were fed AIN-76A diets containing either 5% corn oil (CO, moderately unsaturated, n=5 per age group) or 19% menhaden fish oil plus 1% corn oil (FO, highly polyunsaturated, n=20 per age group). After 2 weeks, 5 CO and 5 FO fed mice in each age group were sacrificed. The remaining FO diet mice (n=15 per age group) were then challenged with a systemic oxidative stress by intraperitoneal injection of 125 mg iron/kg body weight as iron dextran. Five stressed mice from each age group were sacrificed 1, 5, and 24 hours post injection; liver, spleen and brain were removed. Part of each tissue was fixed in formalin, and microsomal protein isolated from the remaining tissue. HO-1 and HO-2 were detected by immunoblot of microsomal protein and by immunohistochemical staining of fixed tissue in the liver and spleen, but only HO-2 was detected in the brain. There was no significant difference in HO-1 or HO-2 expression due to diet. The liver of old unstressed mice had significantly more HO-1 than young mice. However, HO-1 was significantly induced in the livers of young mice, but not of old mice, following oxidative stress. Spleen HO-1 expression was not significantly altered by age or oxidative stress. HO-2 expression was not significantly altered by age or induced oxidative stress in any tissue examined. Age-related alterations in liver HO-1 isozyme expression and inducibility may contribute to increased susceptibility to exogenous stress and disease.
PubMed: 23604370
DOI: 10.1007/s11357-998-0019-3 -
Age (Dordrecht, Netherlands) 2014Age-related muscle loss, termed sarcopenia, has been linked to functional deficits and an increased risk of falling. Such risk is of alarming concern due to the high...
Age-related muscle loss, termed sarcopenia, has been linked to functional deficits and an increased risk of falling. Such risk is of alarming concern due to the high disability and mortality rates associated with falling in older adults. Our laboratory recently developed a prediction model for fat-free mass index (FFMI) and, subsequently, sarcopenia within a community-dwelling older adult population using functional measures that are easily accessible to clinicians. The purpose of this study was to (1) determine how our prediction model performed in an older and less mobile assisted-living population, and if performance of the model was poor; (2) to improve and modify our previous prediction model using data acquired from this unique population. Forty assisted-living older adults (10 males) aged 86.1 ± 6.2 years participated in the study. Each completed four questionnaires to examine their mental and physical health status and anxiety levels related to falling. Anthropometric, balance, strength, and gait tests were conducted. Fat-free mass values, determined by bioelectrical impedance analysis, were normalized by height to obtain FFMI. Using an algorithm proposed by the European Working Group on Sarcopenia in Older People, FFMI along with grip strength and gait speed were used to identify sarcopenic individuals. FFMI was significantly correlated with sex, body mass index (BMI), circumference measures, handgrip strength, gait velocity, and measures of gait variability. The percentage of the variable variation explained by our previous model was reduced for a population of assisted-living older adults (R(2) of 0.6744 compared to the reported R(2) of 0.9272 for community-dwelling older adults; McIntosh et al. Age (Dordrecht, Netherlands), 2013). The prediction equation that accounted for the greatest variability of FFMI for the assisted living group included the independent variables of forearm circumference, BMI, handgrip strength, and variability of the double support time during gait (adjusted R(2) = 0.7950). This prediction model could be used by clinicians working in an assisted-living facility to identify individuals with reduced muscle mass and, once identified, aid with the planning and implementation of appropriate intervention strategies to attenuate the progression of additional muscle loss and improve quality of life.
Topics: Age Factors; Aged, 80 and over; Aging; Assisted Living Facilities; Body Mass Index; Female; Follow-Up Studies; Gait; Geriatric Assessment; Health Status; Humans; Male; Muscle Strength; Muscle, Skeletal; Ontario; Prevalence; Prognosis; Quality of Life; Sarcopenia; Surveys and Questionnaires
PubMed: 24994536
DOI: 10.1007/s11357-014-9674-8 -
Age (Dordrecht, Netherlands) Jun 2013Ageing is accompanied with a decline in respiratory function. It is hypothesised that this may be attenuated by high physical activity levels. We performed spirometry in... (Comparative Study)
Comparative Study
Ageing is accompanied with a decline in respiratory function. It is hypothesised that this may be attenuated by high physical activity levels. We performed spirometry in master athletes (71 women; 84 men; 35-86 years) and sedentary people (39 women; 45 men; 24-82 years), and calculated the predicted lung age (PLA). The negative associations of age with forced expiratory volume in 1 s (FEV1; 34 mL·year(-1)) and other ventilatory parameters were similar in controls and master athletes. FEV1pred was 9 % higher (P < 0.005) and PLA 15 % lower (P = 0.013) in athletes than controls. There were no significant differences between endurance and power athletes and sedentary people in maximal inspiratory and expiratory pressure. Neither age-graded performance nor weekly training hours were significantly related to lung age. Life-long exercise does not appear to attenuate the age-related decrease in ventilatory function. The better respiratory function in master athletes than age-matched sedentary people might be due to self-selection and attrition bias.
Topics: Adult; Aged; Aged, 80 and over; Aging; Athletes; Athletic Performance; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Middle Aged; Mouth; Peak Expiratory Flow Rate; Pressure; Reference Values; Retrospective Studies; Spirometry; Young Adult
PubMed: 22544616
DOI: 10.1007/s11357-012-9409-7