Apelin/APJ system: A novel promising target for anti-aging intervention

Apelin, an endogenous ligand for the G protein-coupled receptor APJ, is widely expressed in various organs. Recent research has indicated that the Apelin/APJ system plays an important role in aging. Apelin and APJ receptor expression are down-regulated with increasing age. In murine models, Apelin and APJ knockouts exhibit accelerated senescence whereas Apelin-restoration results in enhanced vigor and rejuvenated behavioral and circadian phenotypes. Furthermore, aged Apelin knockout mice develop progressive impairment of cardiac contractility associated with systolic dysfunction. Apelin is crucial to maintain cardiac contractility in aging. Moreover, the Apelin/APJ system appears to be involved in regulation of renin-angiotensin-aldosterone system (RAAS), apoptosis, inflammation and oxidative stress which promotes aging. Likewise, the Apelin/APJ system regulates autophagy, stem cells and the sirtuin family thus contributing to anti-aging. In this review, we describe the relationship between Apelin/APJ system and aging. We elaborate on the role of the Apelin/APJ system in aging stimulators, aging inhibitors and age-related diseases such as obesity, diabetes and cardiovascular disease. We conclude that Apelin/APJ system might become a novel promising therapeutic target for anti-aging.