Theorizing on Thrifty Genes and Overnutrition

An open access paper: "Nearly 50 years ago geneticist James Neel famously proposed that 'thrifty genes' were important contributors to the rising prevalence of diabetes. Such genes promote efficient use and conservation of food energy, he theorized, and thus were favored by natural selection to help our ancient ancestors cope with famines. Now widespread in various populations, they predispose to obesity and diabetes, abetting a tendency to prepare for famines that never come. ... Here I propose an extension of this reproduction-centered version of Neel's theory that bears on aging. One of my key premises is that many windows of opportunity for reproductive booms occurred during the Holocene as agricultural innovations spread, periodically increasing food availability between times of nutritional stress. The periods of plenty selected for genotypes capable of rapidly ramping up fecundity as food intake increased. ... I believe the boom times' selection of genotypes prone to nutrition-cued accelerated development is having an especially problematic effect today because of widespread childhood overnutrition. Accelerated development, which enhanced reproductive success in the past, now has a pro-aging effect with rapidly growing costs. Indeed, when viewed through the lens of the antagonistic pleiotropy theory of aging, this effect seems anything but thrifty: It predisposes toward what might be called the spendthrift phenotype, characterized by chronic activation of pro-growth pathways - notably those involving mTOR, insulin, and insulin-like growth factor-1 - that support rapid development and sexual maturation but that also underlie later senescence. The modern fallout encompasses a much broader array of age-associated ills than the diabetes that prompted Neel's original hypothesis. Indeed, the spendthrift phenotype may well increase the age-associated risks of most if not all diseases of aging, like the ruinous adult legacy of flush, fast-living youth."

Link: http://www.impactaging.com/papers/v3/n2/full/100286.html

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