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

Rahul Rai | Zendy; Asish K. Ghosh | Zendy; Mesut Eren | Zendy; Alexander R Mackie | Zendy; Daniel C. Levine | Zendy; SoYoun Kim | Zendy; Jonathan Cedernaes | Zendy; Veronica Ramirez | Zendy; Daniele Procissi | Zendy; Layton H. Smith | Zendy; Teresa K. Woodruff | Zendy; Joseph Bass | Zendy; Douglas E. Vaughan | Zendy

Open Access

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

Author(s) -

Rahul Rai,

Asish K. Ghosh,

Mesut Eren,

Alexander R Mackie,

Daniel C. Levine,

SoYoun Kim,

Jonathan Cedernaes,

Veronica Ramirez,

Daniele Procissi,

Layton H. Smith,

Teresa K. Woodruff,

Joseph Bass,

Douglas E. Vaughan

Publication year - 2017

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2017.10.057

Subject(s) - apelin , senescence , downregulation and upregulation , biology , phenotype , transcription factor , endocrinology , medicine , muscle hypertrophy , homeostasis , premature aging , microbiology and biotechnology , disease , receptor , physiology , genetics , gene

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.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research