Cell Reports
Volume 21, Issue 6, 7 November 2017, Pages 1471-1480
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Downregulation of the Apelinergic Axis Accelerates Aging, whereas Its Systemic Restoration Improves the Mammalian Healthspan

https://doi.org/10.1016/j.celrep.2017.10.057Get rights and content
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Highlights

  • Senescence downregulates the endogenous apelinergic axis

  • Aplnr−/− and apln−/− mice and aplnkd cells exhibit accelerated senescence

  • Apln reduces cardiac hypertrophy and exercise-induced BP in 15-month-old mice

Summary

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

Keywords

apelin
aplnr
APJ
aging
senescence

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