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

Area of Science:

• Gerontology
• Cardiovascular Biology
• Molecular Biology

Background:

• Aging is a major risk factor for numerous diseases, including cardiovascular disease (CVD).
• Young blood has shown potential in mitigating age-associated pathologies, but the specific factors responsible are largely unknown.
• The apelinergic system's role in aging has not been fully elucidated.

Purpose of the Study:

• To investigate the role of the apelinergic axis in mammalian aging.
• To identify apelin as a potential anti-aging factor.
• To determine if restoring apelinergic signaling can reverse age-related decline.

Main Methods:

• Assessed age-dependent expression of apelin (apln) and its receptor (aplnr) in multiple organs.
• Studied mice with genetic deficiencies in aplnr or apln.
• Utilized genetic and pharmacological methods to abrogate or restore apln signaling.
• Evaluated physiological and behavioral phenotypes in aged mice with restored apln signaling.

Main Results:

• Apelin and aplnr expression decline with age in various organs.
• Genetic deficiency in aplnr or apln accelerated cardiovascular, renal, and reproductive aging.
• Reduced apln signaling induced cellular senescence.
• Restoration of apln in aged mice reduced cardiac hypertrophy and exercise-induced hypertension.
• Apelin restoration enhanced vigor and rejuvenated behavioral and circadian phenotypes.

Conclusions:

• A declining apelinergic axis promotes aging and age-associated diseases.
• Restoration of the apelinergic axis can extend healthspan and reverse aging phenotypes in mice.
• Apelin is identified as a key anti-aging factor within the apelinergic system.