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. Author manuscript; available in PMC: 2009 Jun 8.
Published in final edited form as: Nat Rev Neurosci. 2008 Sep 4;9(10):759–767. doi: 10.1038/nrn2474

Figure 3. Optimal-IIS-rate model.

Figure 3

a | Each organism and each tissue has an optimal insulin/insulin-like growth factor 1 (IGF1) signalling (IIS) level that ensures maximal health and longevity. IIS rates that are either lower or higher than optimal will cause disease and reduce lifespan. b | The natural IIS rate of well-fed Caenorhabditis elegans is tuned to be at the high zone. Thus, feeding them with bacteria that knock down their daf-2 RNA through RNA interference (RNAi) reduces the rate of IIS and extends their health and lifespan. Mutated daf-2 alleles further reduce IIS and provide maximal longevity, whereas daf-2 inactivation or over-reduction causes lethality. c | In mice that harbour only one copy of Igf1r, the reduction in brain IIS provides stress resistance and extends lifespan. Similarly, the optimal IIS model proposes that IGF1 infusion activates feedback loops that reduce IIS in the brain, leading to similar outcomes. Igf1r-null mice are embryonic lethal.