Caloric restriction (CR) without malnutrition delays aging and extends lifespan in diverse species; however, its effect on resistance to illness and mortality in primates is not clearly established. We report findings of a 20-year longitudinal adult-onset CR study in rhesus monkeys aimed at filling this critical gap in aging research. In a population of rhesus macaques maintained at the Wisconsin National Primate Research Center, moderate CR lowered the incidence of aging-related deaths. At the time point reported 50% of control fed animals survived compared with 80% survival of CR animals. Further, CR delayed the onset of age-associated pathologies. Specifically, CR reduced the incidence of diabetes, cancer, cardiovascular disease, and brain atrophy. These data demonstrate that CR slows aging in a primate species.
Forecasts of life expectancy are an important component of public policy that influence age-based entitlement programs such as Social Security and Medicare. Although the Social Security Administration recently raised its estimates of how long Americans are going to live in the 21st century, current trends in obesity in the United States suggest that these estimates may not be accurate. From our analysis of the effect of obesity on longevity, we conclude that the steady rise in life expectancy during the past two centuries may soon come to an end.
Physical function declines in old age, portending disability, increased health expenditures, and mortality. Cellular senescence, leading to tissue dysfunction, may contribute to these consequences of aging, but whether senescence can directly drive age-related pathology and be therapeutically targeted is still unclear. Here we demonstrate that transplanting relatively small numbers of senescent cells into young mice is sufficient to cause persistent physical dysfunction, as well as to spread cellular senescence to host tissues. Transplanting even fewer senescent cells had the same effect in older recipients and was accompanied by reduced survival, indicating the potency of senescent cells in shortening health- and lifespan. The senolytic cocktail, dasatinib plus quercetin, which causes selective elimination of senescent cells, decreased the number of naturally occurring senescent cells and their secretion of frailty-related proinflammatory cytokines in explants of human adipose tissue. Moreover, intermittent oral administration of senolytics to both senescent cell-transplanted young mice and naturally aged mice alleviated physical dysfunction and increased post-treatment survival by 36% while reducing mortality hazard to 65%. Our study provides proof-of-concept evidence that senescent cells can cause physical dysfunction and decreased survival even in young mice, while senolytics can enhance remaining health- and lifespan in old mice.
In just a few years, microarrays have gone from obscurity to being almost ubiquitous in biological research. At the same time, the statistical methodology for microarray analysis has progressed from simple visual assessments of results to a weekly deluge of papers that describe purportedly novel algorithms for analysing changes in gene expression. Although the many procedures that are available might be bewildering to biologists who wish to apply them, statistical geneticists are recognizing commonalities among the different methods. Many are special cases of more general models, and points of consensus are emerging about the general approaches that warrant use and elaboration.
The estimated number of annual deaths attributable to obesity among US adults is approximately 280000 based on HRs from all subjects and 325000 based on HRs from only nonsmokers and never-smokers.
Life extension by calorie restriction (CR) has been widely reported in a variety of species and remains on the forefront of anti-aging intervention studies. We report healthspan and survival effects of CR from a 23-year study in rhesus macaques conducted at the National Institute on Aging (NIA). CR initiated at older ages did not increase survival relative to Controls; however, CR monkeys demonstrated an improved metabolic profile and may have less oxidative stress as indicated by plasma isoprostane levels. When initiated in young monkeys, there was a trend (p=0.06) for a delay in age-associated disease onset in CR monkeys; but again, survival curves were not improved, in contrast to another study reported in the literature. This suggests that the effects of CR in a long-lived animal are complex and likely dependent on a variety of environmental, nutritional, and genetic factors.
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