Toward a comparative endocrinology of aging: insights from insects

Insulin-like signaling modulates aging and lifespan in insects. Here, we discuss a novel view of this control: insulin hormone in the adult regulates the production of the sesquiterpenoid juvenile hormone (JH) that in turn acts as the systemic regulator of aging and lifespan. Work in Drosophila establishes that insulin signaling is allatotropic - it stimulates the production and secretion of JH from the corpora allata. JH then exerts systemic effects on adult survival through its control of specific proteins, translation and proteostasis. The interdependent functions of insulin and JH allow reproduction and longevity to be coupled in many insects or decoupled in social insects with long-lived queens and in some long-lived genetic mutants of Drosophila. Features of these insulin-regulated life history syndromes are also found in the nematode Caenorhabditis elegans. Recognizing the systemic role of JH in aging provides grounds to search for analogous systems in mammals that might modulate human lifespan.