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Very Old Subjects (very + old_subject)
Selected AbstractsMetabolic age modelling: the lesson from centenariansEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2000G. Paolisso Evolutionary theories of ageing, and data emerging from cellular and molecular biology of ageing, suggested that animals and humans capable of reaching an age close to the extreme limit of the life span should be equipped with a very efficient network of anti-ageing mechanisms. Indeed several evidences have demonstrated that starting from young to very old subjects, ageing is associated with a progressive remodelling. Thus, a new paradigm, the remodelling theory of age, was proposed. This theory, focusing on the human immune system, suggested that immunosenescence is the net result of the continuous adaptation of the body to the deteriorative changes occurring over time. According to this hypothesis, body resources are continuously optimized, and immunosenescence must be considered a very dynamic process including both loss and gain. Whether the metabolic pathways and the endocrine functions are also part of the age remodelling is not investigated. The aim of this review is to focus on the age-related changes in metabolic pathways and endocrine functions and to demonstrate that healthy centenarians (HC) represent the best living example of successful age-remodelling in whom the age remodelling has occurred without problems. In order to design the clinical picture of such successful ageing, anthropometric, endocrine and metabolic characteristics of healthy centenarians (HC), compared with aged subject, have been outlined. [source] Human NK cells display major phenotypic and functional changes over the life spanAGING CELL, Issue 4 2010Magali Le Garff-Tavernier Summary Aging is generally associated with an increased predisposition to infectious diseases and cancers, related in part to the development of immune senescence, a process that affects all cell compartments of the immune system. Although many studies have investigated the effects of age on natural killer (NK) cells, their conclusions remain controversial because the diverse health status of study subjects resulted in discordant findings. To clarify this situation, we conducted the first extensive phenotypic and functional analysis of NK cells from healthy subjects, comparing NK cells derived from newborn (cord blood), middle-aged (18,60 years), old (60,80 years), and very old (80,100 years) subjects. We found that NK cells in cord blood displayed specific features associated with immaturity, including poor expression of KIR and LIR-1/ILT-2 and high expression of both NKG2A and IFN-,. NK cells from older subjects, on the other hand, preserved their major phenotypic and functional characteristics, but with their mature features accentuated. These include a profound decline of the CD56bright subset, a specific increase in LIR-1/ILT-2, and a perfect recovering of NK-cell function following IL2-activation in very old subjects. We conclude that the preservation of NK cell features until very advanced age may contribute to longevity and successful aging. [source] Stress-induced responses of human skin fibroblasts in vitro reflect human longevityAGING CELL, Issue 5 2009Pim Dekker Summary Unlike various model organisms, cellular responses to stress have not been related to human longevity. We investigated cellular responses to stress in skin fibroblasts that were isolated from young and very old subjects, and from offspring of nonagenarian siblings and their partners, representatives of the general population. Fibroblasts were exposed to rotenone and hyperglycemia and assessed for senescence-associated ,-galactosidase (SA-,-gal) activity by flow cytometry. Apoptosis/cell death was measured with the Annexin-V/PI assay and cell-cycle analysis (Sub-G1 content) and growth potential was determined by the colony formation assay. Compared with fibroblasts from young subjects, baseline SA-,-gal activity was higher in fibroblasts from old subjects (P = 0.004) as were stress-induced increases (rotenone: P < 0.001, hyperglycemia: P = 0.027). For measures of apoptosis/cell death, fibroblasts from old subjects showed higher baseline levels (Annexin V+/PI+ cells: P = 0.040, Sub-G1: P = 0.014) and lower stress-induced increases (Sub-G1: P = 0.018) than fibroblasts from young subjects. Numbers and total size of colonies under nonstressed conditions were higher for fibroblasts from young subjects (P = 0.017 and 0.006, respectively). Baseline levels of SA-,-gal activity and apoptosis/cell death were not different between fibroblasts from offspring and partner. Stress-induced increases were lower for SA-,-gal activity (rotenone: P = 0.064, hyperglycemia: P < 0.001) and higher for apoptosis/cell death (Annexin V+/PI, cells: P = 0.041, Annexin V+/PI+ cells: P = 0.008). Numbers and total size of colonies under nonstressed conditions were higher for fibroblasts from offspring (P = 0.001 and 0.024, respectively) whereas rotenone-induced decreases were lower (P = 0.008 and 0.004, respectively). These data provide strong support for the hypothesis that in vitro cellular responses to stress reflect the propensity for human longevity. [source] Prevalence, incidence and persistence of antipsychotic drug prescribing in the Italian general population: retrospective database analysis, 1999,2002,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 6 2006Mersia Mirandola StatD Abstract Purpose To investigate the prevalence, incidence and persistence with antipsychotic drug therapy in a large and geographically defined catchment area of Italian general population. Methods All antipsychotic drug prescriptions dispensed during 1999, 2000, 2001 and 2002 were extracted from an administrative prescription database covering a population of 2,640,379 individuals. Antipsychotic drug users were defined as patients who had at least one recorded prescription in the current year. New users were defined as patients receiving a first prescription without any recorded antipsychotic drug treatment in the previous 12 months. Prevalence data were calculated by dividing users by the total number of male and female residents in each age group. Incidence data were calculated as the number of new users divided by the person-time free from antipsychotic drugs in the current year. The cumulative persistence of each medication was calculated by dividing the total prescribed amount of antipsychotic drug by the recommended daily dose, according to each agent's defined daily dose (DDD). Results A progressive rise in prevalence and incidence rates was observed during the 4-year period. In each census year, the prevalence and incidence of prescribing was higher in females than males, and progressively rose with age, with the highest rates in old and very old subjects. The analysis of persistence with therapy revealed that 3176 individuals (78.5%) were occasional antipsychotic drug users, and that occasional use was more frequent among individuals receiving conventional antipsychotic drugs than among individuals receiving novel antipsychotic drugs. This difference was not explained by differences in the occurrence of neurologic adverse reactions, as shown by the concurrent prescribing of anticholinergic drugs, which was fairly similar between the two groups of new drug users. Additionally, we found that conventioal antipsychotic drugs were more often used in older individuals, where occasional use is very frequent, while novel antipsychotic drugs were more often prescribed in young and adult individuals, where regular use is more frequent. Conclusions An epidemiologically relevant proportion of everyday individuals is annually exposed to antipsychotic drugs. The distribution of prevalence and incidence rates by age highlighted an emerging public health issue related to the adverse and beneficial consequences of antipsychotic drug exposure in the elderly. The finding that persistence with therapy was longer in new users of novel antipsychotic drugs compared with new users of conventional agents might be explained by the different demographic and clinical characteristics of individuals receiving these two drug classes and not by the different tolerability profile of these two drug classes. Copyright © 2005 John Wiley & Sons, Ltd. [source] | ||||||||||