Mechanisms of spermidine-induced autophagy and geroprotection

Aging involves the systemic deterioration of all known cell types in most eukaryotes. Several recently discovered compounds that extend the healthspan and lifespan of model organisms decelerate pathways that govern the aging process. Among these geroprotectors, spermidine, a natural polyamine ubiquitously found in organisms from all kingdoms, prolongs the lifespan of fungi, nematodes, insects and rodents. In mice, it also postpones the manifestation of various age-associated disorders such as cardiovascular disease and neurodegeneration. The specific features of spermidine, including its presence in common food items, make it an interesting candidate for translational aging research. Here, we review novel insights into the geroprotective mode of action of spermidine at the molecular level, as we discuss strategies for elucidating its clinical potential. Spermidine is a naturally occurring polyamine that elicits geroprotection and autophagy induction across species. This Review delineates its molecular targets, effects on the hallmarks of aging, and recent insights from epidemiological and clinical studies.