Abstract
Linking Nutrition, Maturation and Aging: From Thrifty Genes to the Spendthrift Phenotype
Highlights
50 years ago geneticist James Neel famously proposed that "thrifty genes" were important contributors to the rising prevalence of diabetes [1]. Such genes promote efficient use and conservation of food energy, he theorized, and were favored by natural selection to help our ancient ancestors cope with famines
Widespread in various populations, they predispose to obesity and diabetes, abetting a tendency to prepare for famines that never come
Neel’s proposal that past famines reduced survival of individuals lacking thrifty genotypes has been invoked to explain, among other things, epidemic rates of type 2 diabetes that developed among various new-world populations after their adoption of western diets and lifestyles, such as the Central Pacific's Nauru Islanders [8,9]
Summary
50 years ago geneticist James Neel famously proposed that "thrifty genes" were important contributors to the rising prevalence of diabetes [1]. Such genes promote efficient use and conservation of food energy, he theorized, and were favored by natural selection to help our ancient ancestors cope with famines. When viewed through the lens of the antagonistic pleiotropy theory of aging [6], 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 underlie later senescence [7]. 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
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