Insulin-like growth factor 1 (IGF-1) and aging: Controversies and new insights

Insulin/insulin-like growth factor(IGF) signaling plays a major role in thecontrol of aging and life span ininvertebrates. Major extension of life span ingrowth hormone receptor knock out (GHR-KO) micethat are GH resistant, and subsequently, IGF-I-deficient indicates that similar mechanisms mayoperate in mammals. This conclusion issupported by association of reduced IGF-Ilevels and delayed aging in three different GH-deficient mutant mice and in animals subjectedto caloric restriction, but is difficult toreconcile with neuroprotective effects of IGF-Iand with the suspected role of declining GHlevels during aging. We suggest that the roleof IGF in the regulation of growth and adultbody size is important in mediating the effectsof longevity genes on aging and life span. Suspected mechanisms of IGF-I action in agingalso include reduced insulin signaling,enhanced sensitivity to insulin, and reducedthermogenesis with diminished oxidative damageof macromolecules being the likely final commonpathway of these effects. We suspect thatIGF-I is important in evolutionarily conservedmechanisms that link life history, includingdevelopment, reproduction, and aging withavailability of energy resources.