The mechanisms whereby insulin/IGF-1 signaling regulates aging and longevity
Ueki, K.
Nihon Rinsho. Japanese Journal of Clinical Medicine 67(7): 1315-1320
2009
ISSN/ISBN: 0047-1852 PMID: 19591278 Document Number: 630980
There is a conserved mechanism in all living organisms whereby overnutrition negatively regulates lifespan, while loss of function mutations in the genes encoding insulin/IGF-1 signaling molecules also independently shorten lifespan in worms and flies. However, in mammals, same mutations sometimes result in severe metabolic disorders and shorter lifespan, although knockout mice with disruption of some insulin/IGF-1 signaling molecules display prolonged lifespan. Moreover, obesity-induced diabetes and metabolic syndrome are also associated with shorter lifespan despite the decreased insulin signaling in liver and skeletal muscle. This is presumably because hyperinsulinemia in obese animals and humans enhances insulin signaling in particular tissues which determine aging and longevity. It is also likely that overnutrition suppresses AMP kinase and increase mTOR activity, contributing to the shorter lifespan in obese subjects.