Read More at Fight Aging!
Within a species, variations in the operation of metabolism correlate with later life health and life span. Insulin metabolism is one of the more prominent and well studied examples. Much of this may stem from the lifestyle choices that epidemiology shows explain the majority of the variation in human life expectancy. Become sedentary or overweight and this pushes metabolism into a less optimal, more harmful state. The consequences to health and risk of mortality accrue over a long period of time, but are no less real for it.
The study of aging has long been linked with the study of metabolism, as early theories pointed to the rate of metabolism and by-products of metabolism as drivers of aging processes. The earliest recognized interventions that caused life span extension in model organisms targeted nutritional and metabolic pathways. A more nuanced view of aging mechanisms has since emerged that identifies dysregulated metabolism as one of many hallmarks of aging.
Epidemiologic studies of the oldest old humans, centenarians, strive to identify unifying lifestyle elements, nutritional patterns, and genetic or metabolomic signatures that clearly underlie longevity. Certainly, the female sex confers a longevity advantage, as centenarians are disproportionately female. This pattern of increased female longevity is seen across species; however, its underpinnings are incompletely understood. Social engagement, diet composition, and fasting patterns have been identified as factors that may confer longevity on a population level. Indeed, caloric restriction is known to promote longevity and delay the onset of age-related disease in multiple species. The people of Okinawa, who before the influence of a Western diet ate only 83% of the average calories consumed by the mainland Japanese population, were observed to have a longer life span and lower mortality from coronary artery disease and cancer than mainland Japanese or American people.
Long-lived humans may have some advantage in glucose handling. In one study, human centenarians (older than 100 years of age) had better insulin sensitivity than did younger controls older than 75 years of age. Insulin sensitivity is associated with healthy aging across species, and in fact modifications in glucose signaling pathways were some of the first interventions to lead to life span extension in model systems including yeast and Caenorhabditis elegans. Similarly, inhibition of the growth hormone (GH) axis is associated with longevity in model systems. However, lifelong GH deficiency is also accompanied by smaller body size, which in humans may confer undesirable effects such as adipose tissue accumulation and intellectual deficiency. Body size is typically inversely correlated with longevity (such as in dogs), but this does not seem to be the case in humans.