Deregulated nutrient sensing: mTOR, IGF, FOXO and aging

• daf-2 mutant C.elegans live longer (if daf-16 is intact)

• Daf-2 in mammals: insulin receptor

• Daf-16 in mammals: FOXO

• Igf1r mutant mice live longer

• homozygous GH mutants are smaller

• GH overexpressing mice are bigger

• longevity is probably independent from size

• increase expression of NAD+ dependent protein deacetylases

• are activated by caloric restriction

• activity increases lifespan

• are required for lifespan extension under caloric restriction

• have many functions in many tissues

mTOR is always active!

• induction can prolong longevity

• can be induced by spermidine or other polyamines