Multitasking Roles for Poly(ADP-ribosyl)ation in Aging and Longevity

Abstract

Aging is a multifactorial process that depends on diverse molecular and cellular mechanisms, such as genome instability, epigenetic and transcriptional changes, loss of proteostasis, cell death and senescence, metabolic dysfunction, and inflammation. Enzymes of the family of poly(ADP-ribose) polymerases (PARPs) catalyze the synthesis of the biopolymer poly(ADP-ribose) (PAR), a drastic posttranslational modification that plays significant roles in all of these processes. On the one hand, poly(ADP-ribosyl)ation (PARylation) contributes to genome and proteome homeostasis, as it participates in chromatin remodeling, genome maintenance, cell cycle control, and the regulation of the ubiquitin-proteasome system. On the other hand, PARPs and PARylation interfere with cellular and organismic energy metabolism, and act as mediators of inflammation, senescence and cell death. Therefore, PARylation is discussed both as a longevity assurance factor on the one hand and an aging-promoting factor on the other hand. Here we highlight the mechanisms underlying the various roles of PARylation in longevity and aging with a focus on molecular and cellular mechanisms.