Molecular Mechanisms Determining Lifespan in Short- and Long-Lived Species

Aging is a global decline of physiological functions, leading to an increased susceptibility to diseases and ultimately death. Maximum lifespans differ up to 200-fold between mammalian species. Although considerable progress has been achieved in identifying conserved pathways that regulate individual lifespan within model organisms, whether the same pathways are responsible for the interspecies differences in longevity remains to be determined. Recent cross-species studies have begun to identify pathways responsible for interspecies differences in lifespan. Here, we review the evidence supporting the role of anticancer mechanisms, DNA repair machinery, insulin/insulin-like growth factor 1 signaling, and proteostasis in defining species lifespans. Understanding the mechanisms responsible for the dramatic differences in lifespan between species will have a transformative effect on developing interventions to improve human health and longevity.