Downregulation of the Apelinergic Axis Accelerates Aging, whereas Its Systemic Restoration Improves the Mammalian Healthspan

• DOI: 10.1016/j.celrep.2017.10.057
• Publication Date: 2017-11-07T12:17:37Z
• Authors: Rahul Rai; Asish K. Ghosh; Mesut Eren; Alexander R. Mackie; Daniel C. Levine; So-Youn Kim; Jonathan Cedernaes; Veronica Ramirez; Daniele Procissi; Layton H. Smith; Teresa K. Woodruff; Joseph Bass; Douglas E. Vaughan
• Keywords: Apelin; Senescence; Homeostasis; Premature aging

Aging drives the occurrence of numerous diseases, including cardiovascular disease (CVD). Recent studies indicate that blood from young mice reduces age-associated pathologies. However, "anti-aging" factors in juvenile circulation remain poorly identified. Here, we characterize role apelinergic axis mammalian aging and identify apelin as an anti-aging factor. The expression (apln) its receptor (aplnr) exhibits age-dependent decline multiple organs. Reduced apln signaling perturbs organismal homeostasis; harboring genetic deficiency aplnr or exhibit enhanced cardiovascular, renal, reproductive aging. Genetic pharmacological abrogation also induces cellular senescence mediated, part, by activation senescence-promoting transcription factors. Conversely, restoration 15-month-old wild-type cardiac hypertrophy exercise-induced hypertensive response. Additionally, apln-restored vigor rejuvenated behavioral circadian phenotypes. Hence, a declining promotes aging, whereas extends murine healthspan.