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 the control of aging and life span in invertebrates. Major extension of life span in growth hormone receptor knock out (GHR-KO) mice that are GH resistant, and subsequently, IGF-I-deficient indicates that similar mechanisms may operate in mammals. This conclusion is supported by association of reduced IGF-I levels and delayed aging in three different GH-deficient mutant mice and in animals subjected to caloric restriction, but is difficult to reconcile with neuroprotective effects of IGF-I and with the suspected role of declining GH levels during aging. We suggest that the role of IGF in the regulation of growth and adult body size is important in mediating the effects of longevity genes on aging and life span. Suspected mechanisms of IGF-I action in aging also include reduced insulin signaling, enhanced sensitivity to insulin, and reduced thermogenesis with diminished oxidative damage of macromolecules being the likely final common pathway of these effects. We suspect that IGF-I is important in evolutionarily conserved mechanisms that link life history, including development, reproduction, and aging with availability of energy resources.