An Introduction to DAF-16 and FOXO in the Context of Aging and Longevity

In the early 1990s Cynthia Kenyon and others produced the first C. elegans nematode worms to exhibit significantly extended longevity through a single gene mutation, in daf-2, the nematode version of the insulin-like growth factor 1 (IGF-1) receptor, and went on to map the relevant nearby biochemical landscape of these mutants. It is perhaps overly simplistic to mark this as the dividing line between a research mainstream whose members believed aging to be an intractably complex process, and a research mainstream increasingly interested in slowing aging through adjustment of metabolism, but that is the story as it is commonly told these days. The mechanisms of longevity enhancement in daf-2 mutants depend on daf-16, a FOXO family transcription factor. The roles of these and other related proteins have been studied intensively in nematodes and other species since the first discoveries. Insulin metabolism - involving insulin, IGF-1, growth hormone, and their cell surface receptors - has emerged as one of the more influential means by which cellular mechanisms determine variations in longevity, both in response to circumstances for individuals within the same species, and to some degree between species. The record for mouse longevity is still held by growth hormone receptor loss of function mutants, for example. These proteins and their relationships are tied to cell growth, nutrient sensing, the calorie restriction response, temperature regulation, autophagy, and many ot...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs