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Human Lifespan (human + lifespan)
Selected AbstractsTargeting Alzheimer's disease: Is there a light at the end of the tunnel?DRUG DEVELOPMENT RESEARCH, Issue 2 2002David Gurwitz Abstract The prevalence of Alzheimer's disease (AD) is on the rise in developed nations as a consequence of longer human lifespan. Current costs to society are alarming, and are projected to become even more demanding on future health budgets. Considering the relative success of Parkinson's disease pharmacotherapy, the success of AD therapy has been disappointing. Quite a few novel and promising AD drug targets are presented in this special issue of Drug Development Research. These are built on countless research studies, by many bright minds, carried out over the last several decades. However, the answer to the growing AD threat must include reliable and accurate tools, presently lacking, for its early diagnosis in at-risk individuals. Drug Dev. Res. 56:45,48, 2002. © 2002 Wiley-Liss, Inc. [source] Ten-Year Echo/Doppler Determination of the Benefits of Aerobic Exercise after the Age of 65 YearsECHOCARDIOGRAPHY, Issue 1 2010Alexander J. Muster M.D. As the human lifespan becomes progressively extended, potential health-related effects of intense aerobic exercise after age 65 need evaluation. This study evaluates the cardiovascular (CV), pulmonary, and metabolic effects of competitive distance running on age-related deterioration in men between 69 (±3) and 77 (±2) years (mean ± SD). Twelve elderly competitive distance runners (ER) underwent oxygen consumption and echo/Doppler treadmill stress testing (Balke protocol) for up to 10 years. Twelve age-matched sedentary controls (SC) with no history of CV disease were similarly tested and the results compared for the initial three series of the study. CV data clearly separated the ER from SC. At entry, resting and maximal heart rate, systolic/diastolic blood pressure, peak oxygen consumption (VO2max), and E/A ratio of mitral inflow were better in the ER (P < 0.05 vs. SC). With aging, ER had a less deterioration of multiple health parameters. Exceptions were VO2max and left ventricular diastolic function (E/A, AFF, IVRT) that decreased (P < 0.05, Year 10 vs. Year 1). Health advantages of high-level aerobic exercise were demonstrated in the ER when compared to SC. Importantly, data collected in ER over 10 years confirm the benefit of intensive exercise for slowing several negative effects of aging. However, the normative drop of exercise capacity in the seventh and eighth decades reduces the potential athleticism plays in prevention of CV events. (Echocardiography 2010;27:5-10) [source] Age-related changes in human meniscal glycosaminoglycansINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2004Gareth Blackburn Introduction With an increased human lifespan, a major challenge is now to ensure a concomitant increase in healthspan. Meniscal damage and degradation are common and are strongly correlated with subsequent osteoarthritis. Indeed, meniscal damage has been identified in about 60% of people over 60. Markers of pathology will facilitate intervention but first require normal age-related changes to be established. Methods Undamaged vascular and avascular regions of medial and lateral human menisci were comminuted and the tissue extracted into 4- m GuHCl and subject to associative CsCl density gradient centrifugation. Aggrecan and the small leucine rich PGs (SLRPs) were isolated and their GAG profiles examined by HPAEC fingerprinting, following enzyme depolymerization, and by an NMR spectroscopy. Results and discussion Analysis of aggrecan and the SLRPs show that there is a complex and dynamic pattern of KS, CS and DS abundance and distribution within human menisci, which changes with age. The abundance of SLRPs is higher in the avascular than vascular tissues, however, this is not reflected in the abundance of aggrecan which is present at similar levels in both tissue regions. The data show no other significant differences between medial and lateral and between vascular and avascular tissue regions. Analysis of the sulfation pattern of CS following digestion by ACII lyase, shows that in both aggrecan and SLRPs the 4-sulfation level falls with age from 20 to 35% in young tissues to 10,20% in older. Subsequent analyses following ABC lyase depolymerization, to include DS, shows very significant change with age from CS + DS 4-sulfation levels of ca. 40,55% in young tissue to ca. 15,30% in older. The difference between these datasets represents the contribution made by 4-sulfated DS. Thus, analysis of the difference suggests that DS makes a decreasing contribution to the CS/DS profile with age. Indeed, this is confirmed by an NMR analysis of these samples. Analysis of the resonances in the region 1.95,2.2 p.p.m. (ref to TSP) allows the estimation of the contribution made by DS, CS and KS. These data show that, in aggrecan, the contribution made by DS chains falls from ca. 10% in younger tissues to ca. 2,4% in older tissues. NMR analysis also shows that KS levels fall with age from ca. 15,20% in younger tissues to 5,10% in older tissues. Analysis of the structure of the KS chains shows chains with a structure similar to that of in articular cartilage but that at all ages there are very low levels of fucosylation (ca. 1,5%). Previous studies of age-related changes in CS/DS and KS structures have shown significant changes in the first 17 years of life, with only modest nonpathological changes after that time. These data from meniscal tissues do not show such a dramatic halting of normal age-related changes. Indeed, the data show gradual age-related changes in DS, CS and KS abundance and structure throughout life. These baseline age-related changes data will now allow the analysis of pathology-related changes. [source] HRAS1 and LASS1 with APOE are associated with human longevity and healthy agingAGING CELL, Issue 5 2010S. Michal Jazwinski Summary The search for longevity-determining genes in human has largely neglected the operation of genetic interactions. We have identified a novel combination of common variants of three genes that has a marked association with human lifespan and healthy aging. Subjects were recruited and stratified according to their genetically inferred ethnic affiliation to account for population structure. Haplotype analysis was performed in three candidate genes, and the haplotype combinations were tested for association with exceptional longevity. An HRAS1 haplotype enhanced the effect of an APOE haplotype on exceptional survival, and a LASS1 haplotype further augmented its magnitude. These results were replicated in a second population. A profile of healthy aging was developed using a deficit accumulation index, which showed that this combination of gene variants is associated with healthy aging. The variation in LASS1 is functional, causing enhanced expression of the gene, and it contributes to healthy aging and greater survival in the tenth decade of life. Thus, rare gene variants need not be invoked to explain complex traits such as aging; instead rare congruence of common gene variants readily fulfills this role. The interaction between the three genes described here suggests new models for cellular and molecular mechanisms underlying exceptional survival and healthy aging that involve lipotoxicity. [source] Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevityAGING CELL, Issue 4 2009Ludmila Pawlikowska Summary The insulin/IGF1 signaling pathways affect lifespan in several model organisms, including worms, flies and mice. To investigate whether common genetic variation in this pathway influences lifespan in humans, we genotyped 291 common variants in 30 genes encoding proteins in the insulin/IGF1 signaling pathway in a cohort of elderly Caucasian women selected from the Study of Osteoporotic Fractures (SOF). The cohort included 293 long-lived cases (lifespan , 92 years (y), mean ± standard deviation (SD) = 95.3 ± 2.2y) and 603 average-lifespan controls (lifespan , 79y, mean = 75.7 ± 2.6y). Variants were selected for genotyping using a haplotype-tagging approach. We found a modest excess of variants nominally associated with longevity. Nominally significant variants were then replicated in two additional Caucasian cohorts including both males and females: the Cardiovascular Health Study and Ashkenazi Jewish Centenarians. An intronic single nucleotide polymorphism in AKT1, rs3803304, was significantly associated with lifespan in a meta-analysis across the three cohorts (OR = 0.78 95%CI = 0.68,0.89, adjusted P = 0.043); two intronic single nucleotide polymorphisms in FOXO3A demonstrated a significant lifespan association among women only (rs1935949, OR = 1.35, 95%CI = 1.15,1.57, adjusted P = 0.0093). These results demonstrate that common variants in several genes in the insulin/IGF1 pathway are associated with human lifespan. [source] Waddling and toddling: The biomechanical effects of an immature gaitAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 1 2010Libby W. Cowgill Abstract Femoral shape changes during the course of human growth, transitioning from a subcircular tube to a teardrop-shaped diaphysis with a posterior pilaster. Differences between immature and mature bipedalism and body shape may generate different loads, which, in turn, may influence femoral modeling and remodeling during the course of the human lifespan. This study uses two different approaches to evaluate the hypotheses that differences in gait between young and mature walkers result in differences in ground reaction forces (GRFs) and that the differences in loading regimes between young children and adults will be reflected in the geometric structure of the midshaft femur. The results of this analysis indicate that GRFs differ between young walkers and adults in that normalized mediolateral (ML) forces are significantly higher in younger age groups. In addition, these differences between children and adults in the relative level of ML bending force are reflected in changes in femoral geometry during growth. During the earlier stages of human development, immature femoral diaphyses are heavily reinforced in approximately ML plane. The differences in gait between mature and immature walkers, and hence the differences in femoral shape, are likely partially a product of a minimal bicondylar angle and relatively broad body in young children. Am J Phys Anthropol 143:52,61, 2010. © 2010 Wiley-Liss, Inc. [source] | |||||||||||||