Growth Hormone and IGF-1 Axis in Aging and Longevity

Abstract

The growth hormone (GH)-IGF-1 axis, which regulates postnatal growth and metabolism, progressively declines after puberty. This decline causes alterations in body composition and thus physical frailty in aging animals. By contrast, attenuation of the GH-IGF-1 axis consistently increases lifespan in a range of animals. Studies using mutant animals reveal key molecules for longevity in cytoplasmic IGF-1 signaling, including mechanistic target of rapamycin (mTOR) and forkhead box, subgroup O (FoxO) transcription factors. Dietary calorie restriction, a robust experimental intervention to extend lifespan in animals, also inhibits the GH-IGF-1 axis. Studies in human dwarf cohorts report lower incidences of cancers and cardiovascular diseases, though there is no scientific evidence of extended lifespan in these people. Genome-wide studies in long-lived people indicate an association between longevity and minor alleles of genes that lead to a reduction in IGF-1 signaling. Evolutionary views suggest a trade-off relation between growth and longevity. Therefore, it is rational to conclude that the GH-IGF-1 axis is the central pathway that regulates lifespan and thus aging in animals.