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Intrinsic capacity, a crucial concept in healthy ageing, is defined by WHO as “the composite of all the physical and mental capacities that an individual can draw on at any point in time”. Vitality capacity is considered the underlying physiological determinant of intrinsic capacity. To advance the measurement and monitoring of vitality capacity, a working group of WHO staff members and twenty experts representing six WHO regions was convened to discuss and clarify the attributes of vitality capacity and to develop a clear working definition of the concept. Potential biomarkers to measure vitality capacity were identified, and the following consensual working definition was developed: vitality capacity is a physiological state (due to normal or accelerated biological ageing processes) resulting from the interaction between multiple physiological systems, reflected in (the level of) energy and metabolism, neuromuscular function, and immune and stress response functions of the body.

Introduction: Reference values to define cognitive impairment in individuals aged 90 years and older are lacking. We systematically reviewed the literature to determine the level of cognitive functioning of individuals aged 90 years and older without dementia. Methods: The search identified 3972 articles of which 20 articles were included in the review. We calculated mean cognitive test scores and cut-off scores for cognitive tests published in two or more articles. Results: The mean cognitive test scores (SD)/cut-off scores for individuals aged 90 years and older without dementia of the five most commonly used cognitive tests were: MMSE: 26.6 (2.6)/23.3 points, Digit Span forward: 5.9 (1.8)/3.6 digits, Digit Span backward: 4.4 (1.6)/2.4 digits, TMT-A: 85.8 (42.5)/140.2 s and TMT-B: 220.3 (99.2)/347.3 s. Discussion: We provided mean cognitive test scores and cut-off scores that will improve the diagnostic process of cognitive impairment in individuals aged 90 years and older. (C) 2017 Elsevier B.V. All rights reserved.

Long-term implications of the exposure to traumatizing experiences during childhood or adolescence, such as sexual abuse, or cancer, have been documented, namely the subjects' response to an acute stress in adulthood. Several indicators of the stress response have been considered (e.g. cortisol, heart rate). Oxytocin (OT) response to an acute stress of individuals exposed to trauma has not been documented. Eighty subjects (n=26 women who had experienced episodes of child abuse, n=25 men and women healthy survivors of cancer in childhood or adolescence, and 29 controls) have been submitted to a laboratory session involving an experimental stress challenge, the Trier social stress test. Overall, there was a clear OT response to the psychosocial challenge. Subjects having experienced a childhood/adolescence life-threatening illness had higher mean levels of OT than both abused and control subjects. There was a moderate negative relationship between OT and salivary cortisol. It is suggested that an acute stress stimulates OT secretion, and that the exposure to enduring life-threatening experiences in childhood/adolescence has long-lasting consequences regarding the stress system and connected functions, namely the activation of OT secretion. Better knowledge of such long-term implications is important so that to prevent dysregulations of the stress responses, which have been shown to be associated to the individual's mental health.

Udgivelsesdato: 2009-Jan-9 Insulin exocytosis is regulated in pancreatic ss-cells by a cascade of intracellular signals translating glucose levels into corresponding secretory responses. The mitochondrial enzyme glutamate dehydrogenase (GDH) is regarded as a major player in this process, although its abrogation has not been tested yet in animal models. Here, we generated transgenic mice, named betaGlud1(-/-), with ss-cell-specific GDH deletion. Our results show that GDH plays an essential role in the full development of the insulin secretory response. In situ pancreatic perfusion revealed that glucose-stimulated insulin secretion was reduced by 37% in betaGlud1(-/-). Furthermore, isolated islets with either constitutive or acute adenovirus-mediated knock-out of GDH showed a 49 and 38% reduction in glucose-induced insulin release, respectively. Adenovirus-mediated re-expression of GDH in betaGlud1(-/-) islets fully restored glucose-induced insulin release. Thus, GDH appears to account for about 40% of glucose-stimulated insulin secretion and to lack redundant mechanisms. In betaGlud1(-/-) mice, the reduced secretory capacity resulted in lower plasma insulin levels in response to both feeding and glucose load, while body weight gain was preserved. The results demonstrate that GDH is essential for the full development of the secretory response in beta-cells. However, maximal secretory capacity is not required for maintenance of glucose homeostasis in normo-caloric conditions.

Summary Background Cross-sectional data have shown that sarcopenia and fat accumulation are associated with aging and can be limited by structured physical training. However, it is often difficult to maintain a long-term compliance to training programs. It is not clear whether leisure-time physical activity is effective in preventing sarcopenia and fat accumulation. Objectives (i) To investigate longitudinal body composition changes in a population of elderly people in good apparent health. (ii) To evaluate the impact of leisure-time physical activity on muscle mass and characteristic as reflected by total body potassium per fat-free soft tissue (TBK/FFST), and on fat accumulation. Design Longitudinal evaluation over 3 years, of body composition changes in 74 healthy men and 66 women, over 65 years old. Body fat and FFST were analyzed by dual-energy X-ray absorptiometry and TBK by whole-body 40K counter. Physical activity was analyzed by a specific questionnaire. Results Despite a stable total body weight, FFST and appendicular skeletal muscle mass slightly decreased (−0.3±1.4 and −0.2±2.2 kg, P 0.0 1 , respectively) as well as the TBK/FFST (−4.1±6.3 mmol/kg, P 0.0 0 1 ), over the 3-year period. Body fat increased significantly (0.6±2.2 kg, P 0.0 0 0 1 ), and it accumulated mainly in the abdomen (0.4±1.5 kg, P 0.0 1 ). Multiple regression analysis showed that body composition changes were related mainly to body weight changes. Nevertheless, positive linear correlations were observed between the degree of engagement in leisure-time physical activity and FFST ( P 0.0 1 ), appendicular skeletal muscle mass ( P 0.0 5 ), TBK/FFST ( P 0.0 5 ), whereas negative correlation was observed with total and truncal fat ( P 0.0 1 ). Conclusions Mild but significant decline in muscle mass and its TBK content, and body fat accumulation were observed over a 3-year period in healthy elderly subject: leisure-time physical activity does not seem to prevent them. However, a higher level of physical activity is associated with higher muscle mass and TBK content, and less total and truncal fat.

Background: In a previous study, scanning electron microscopy (SEM) showed agerelated changes in the rat retina. We carried out a study to evaluate age-related changes in the human retina. Methods: Samples of fresh retinal tissue obtained from younger (age 22 years or less) and older (age 66 years or more) donors were studied by means of traditional histologic methods and by SEM. Eight retinas were obtained from four donors whose corneas had been used for transplantation, and four retinas were obtained from four subjects whose eyes had been enucleated owing to injury. All morphologic results were subjected to quantitative analysis of images. The concentration of cytoplasmic (free) and structural (tissue-associated) protein in retinal tissue homogenates was determined by means of biochemical methods. Results: There was a decrease in all features studied with the exception of structural protein concentration.The mean retinal thickness (and standard error of the mean) was 426 (34.2) μm in the younger subjects and 261 (18.9) μm in the older subjects. The mean numbers of ganglion cells (and standard error of the mean) were 413.5/mm 2 (32.3/mm 2 ) and 256.2/mm 2 (26.8/mm 2 ) respectively, of capillaries 3.6/mm 2 (1.4/mm 2 ) and 1.8/mm 2 (1.2/mm 2 ) respectively, of synaptic bodies 122.4 (4.9) conventional units (CU)/area observed and 38.5 (1.6) CU/area observed respectively, of cellular processes 82.3 (3.1) CU/area observed and 13.1 (1.5) CU/area observed respectively, and of intercellular connections 36.4 (2.5) CU/area observed and 14.3 (1.4) CU/area observed respectively. The mean concentration of total protein per milligram of fresh tissue (and standard error of the mean) was 92.1 (1.8) μg in the younger subjects and 78.7 (1.3) μg in the older subjects; the corresponding values for cytoplasmic protein were 27.6 (1.3) μg and 11.8 (0.8) μg, and for structural protein, 64.4 (1.6) μg and 86.9 (1.4) μg. All differences between the younger and older subjects were significant ( p μ 0.001) with the exception of mean concentration of cytoplasmic and of structural protein. Interpretation: The human retina undergoes specific changes with aging. SEM provides new morphometric information regarding age-related changes in photoreceptor cells, bipolar cells and ganglion cells that increases our understanding of this topic. Our results may be adopted as a model or as normal values when studying other changes that may occur in the human retina in pathological conditions.

We developed several techniques that provide data on body elemental composition from in vivo measurements in rats. These methods include total body potassium by whole-body counting of endogenous 40K; total body calcium (TBCa), sodium and chloride by in vivo neutron activation analysis and total body phosphorus (TBP) and nitrogen (TBN) by photon activation analysis. These elements provide information on total body fat, total body protein and skeletal mass. Measurements were made in 6-, 12- and 24-month-old rats. TBN increased slightly between 6 and 12 months but was significantly lower by 24 months, indicating a substantial loss in total body protein. Working at the National Synchrotron Light Source, we studied rat femurs by computed microtomography (CMT), and the elemental profile of the femur cortex by synchrotron-radiation induced X-ray emission (SRIXE). Although there were no significant changes in TBCa and TBP, indices of skeletal mass, CMT revealed a marked increase in the size and number of cavities in the endosteal region of the femur cortex with increasing age. The SRIXE analysis of this cortical bone revealed a parallel decrease in the endosteal Ca/P ratio. Thus, there are major alterations in bone morphology and regional elemental composition despite only modest changes in total skeletal mass. J Nutr

Normal human fibroblasts have a limited replicative potential in culture and eventually reach a state of irreversible growth arrest, termed senescence. In a previous study aiming to identify genes that are differentially regulated during cellular senescence we have cloned clusterin/apolipoprotein J (Apo J), a 80 kDa secreted glycoprotein. In the current report we pursue our studies and show that senescence of human diploid fibroblasts is accompanied by up-regulation of both Apo J mRNA and protein levels, but with no altered biogenesis, binding partner profile or intracellular distribution of the two Apo J forms detected. To analyze the causal relationship between senescence and Apo J protein accumulation, we stably overexpressed the Apo J gene in primary as well as in SV40 T antigen-immortalized human fibroblasts and we showed no alteration of the proliferative capacity of the transduced cells. Despite previous reports on tumor-derived cell lines, overexpression of Apo J in human fibroblasts did not provide protection against apoptosis or growth arrest induced by hydrogen peroxide. Overall, our results suggest that Apo J overexpression does not induce senescence but it is rather a secondary consequence of the senescence phenotype. To our knowledge this is the first report that provides a functional analysis of human Apo J during replicative senescence. FEBS Lett

Numerous aspects of mammalian physiology exhibit cyclic daily patterns, known as circadian rhythms. However, studies in aged humans and animals indicate that these physiological rhythms are not consistent throughout the life span. The simultaneous development of disrupted circadian rhythms and age-related impairments suggests a shared mechanism which may be amenable to therapeutic intervention. Recently, the endocannabinoid system has emerged as a complex signaling network which regulates numerous aspects of circadian physiology relevant to the neurobiology of aging. Agonists of cannabinoid receptor-1 (CB1) have consistently been shown to decrease neuronal activity, core body temperature, locomotion, and cognitive function. Paradoxically, several lines of evidence now suggest that very low doses of cannabinoids are beneficial in advanced age. One potential explanation for this phenomenon is that these drugs exhibit hormesis - a biphasic dose-response wherein low doses produce the opposite effects of higher doses. Therefore, it is important to determine the dose-, age-, and time-dependent effects of these substances on the regulation of circadian rhythms and other processes dysregulated in aging. This review highlights three fields - biological aging, circadian rhythms, and endocannabinoid signaling - to critically assess the therapeutic potential of endocannabinoid modulation in aged individuals. If the hormetic properties of exogenous cannabinoids are confirmed, we conclude that precise administration of these compounds may bidirectionally entrain central and peripheral circadian clocks and benefit multiple aspects of aging physiology.

Although many genetic factors and lifestyle interventions are known to affect the mean lifespan of animal populations, the physiological variation displayed by individuals across their lifespans remains largely uncharacterized. Here, we use a custom culture apparatus to continuously monitor five aspects of aging physiology across hundreds of isolated Caenorhabditis elegans individuals kept in a constant environment from hatching until death. Aggregating these measurements into an overall estimate of senescence, we find two chief differences between longer- and shorter-lived individuals. First, though long- and short-lived individuals are physiologically equivalent in early adulthood, longer-lived individuals experience a lower rate of physiological decline throughout life. Second, and counter-intuitively, long-lived individuals have a disproportionately extended “twilight” period of low physiological function. While longer-lived individuals experience more overall days of good health, their proportion of good to bad health, and thus their average quality of life, is systematically lower than that of shorter-lived individuals. We conclude that within a homogeneous population reared under constant conditions, the period of early-life good health is comparatively uniform and the most plastic period in the aging process is end-of-life senescence.

The increased prevalence of dizziness with advancing age is the result of specific disease processes superimposed on normal aging physiology. The first step in evaluating dizziness in older persons is a careful clinical history, focusing on the type, temporal pattern, onset, associated symptoms, and the patient's overall physical health. Common dizziness problems in this age group are postural dizziness without postural hypotension, positional vertigo, cerebrovascular disease, a variety of acute and recurrent labyrinthine problems, neck problems, physical deconditioning, and medications. Often, multiple problems coexist, and secondary psychologic disability results. Treatment should aim at identifying and managing remediable problems.

This issue of Clinics in Geriatric Medicine, devoted to Medical Implications of Elder Abuse and Neglect, is edited by Drs. Lisa Gibbs and Laura Mosqueda. Articles in this issue include: Aging: Physiology, Disease, and Abuse; Understanding the Medical Markers of Elder Abuse and Neglect: Physical Examination Findings; Medical and Laboratory Indicators of Elder Abuse and Neglect; Common Presentations of Elder Abuse in Health Care Settings; Prevention and Early Identification of Elder Abuse; Elder Physical Abuse; Elder Neglect; Case Series of Sexual Assault in Older Persons; Medical Implications of Elder Abuse: Self-Neglect; Evaluating Abuse in the Patient with Dementia; Mental Health/Psychiatric Issues in Elder Abuse and Neglect; The Role of Capacity Assessments in Elder Abuse Investigations and Guardianships; Care of the Victim; and Health Professionals' Roles and Relationships with Other Agencies.

This annotated bibliography provides selected references to journal articles addressing general issues of the care of elderly patients in the emergency department. The bibliography was compiled by the Society for Academic Emergency Medicine Geriatric Emergency Medicine Task Force. Because the literature pertinent to geriatrics has continued to grow rapidly, only key articles of general interest to the clinician and academician are included in the bibliography. Preference is given to recent publications; most references date from the past five years. The articles cited are primarily concerned with the delivery of emergency care to geriatric patients; economic, legal, ethical, and sociological topics receive limited coverage. Some articles were selected to highlight current controversies or changes in viewpoint. Aging physiology, atypical characteristics of illness, and disease processes have been addressed elsewhere (J Am Geriatr Soc 1989;37:894-910).

This article reviews the current data on mortality rates of elderly patients undergoing major thoracic and abdominal surgery, those procedures most applicable to cancer surgery. The major morbidity of surgery is discussed in relation to normal aging physiology of the heart, lungs, and kidneys. Preoperative risk assessment is discussed in relation to clinical assessment, laboratory and radiologic assessment, and the use of indexes developed to estimate surgical risk. General recommendations important in the perioperative period are given as well as specific recommendations for patients with cardiac disease, cerebrovascular disease, hypertension, thromboembolic disease, diabetes mellitus, and renal disease.