Turning off the Wnt—a dietary restriction switch for healthy aging

Dietary restriction (DR) with adequate nutrition (i.e., undernutrition without malnutrition) extends lifespan and improves healthspan in diverse model organisms, ranging from yeast to mammals. The molecular mechanisms by which a reduced nutrient uptake extends lifespan and delays the onset of pathologies associated with aging are only partly understood. In this issue of EMBO reports, Xu et al identify a conserved microRNA named mir-235, that is induced by DR and is required for DR-induced longevity in Caenorhabditis elegans. mir-235 inhibits a highly conserved developmental pathway—the Wnt signaling pathway. Consistent with the developmental roles of the Wnt pathway, the mir-235 interferes with its activity at the onset of adulthood, and not at the embryo stage, therefore protecting the embryo from putative developmental defects due to precocious inactivation of the Wnt pathway. Understanding the impacts of such signals, which are induced by DR and mitigate the antagonistic activity of pleiotropic genes, could guide the design of treatments that mimic DR-related consequences without the need for a restricted diet, to delay age-related diseases in humans.