Aerobic exercise restores aging-associated reductions in arterial adropin levels and improves adropin-induced nitric oxide-dependent vasorelaxation

Shumpei Fujie, Natsuki Hasegawa, Naoki Horii, Masataka Uchida, Kiyoshi Sanada, Takafumi Hamaoka, Jaume Padilla, Luis A. Martinez-Lemus, Seiji Maeda, Motoyuki Iemitsu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


BACKGROUND: Adropin is a peptide hormone that promotes nitric oxide (NO) production via activation of endothelial NO syn-thase (eNOS) in endothelial cells. Its circulating levels are reduced with aging and increased with aerobic exercise training (AT). Using a mouse model, we hypothesized that AT restores aging-associated reductions in arterial and circulating adropin and improves adropin-induced NO-dependent vasorelaxation. Further, we hypothesized these findings would be consistent with data obtained in elderly humans. METHODS AND RESULTS: In the animal study, 50-week-old SAMP1 male mice that underwent 12 weeks of voluntary wheel running, or kept sedentary, were studied. A separate cohort of 25-week-old SAMP1 male mice were used as a mature adult sedentary group. In the human study, 14 healthy elderly subjects completed an 8-week AT program consisting of 45 minutes of cycling 3 days/week. In mice, we show that advanced age is associated with a decline in arterial and circulating levels of adropin along with deterioration of endothelial function, arterial NO production, and adropin-induced vasodilation. All these defects were restored by AT. Moreover, AT-induced increases in arterial adropin were correlated with increases in arterial eNOS phosphorylation and NO production. Consistently with these findings in mice, AT in elderly subjects enhanced circulating adropin levels and these effects were correlated with increases in circulating nitrite/nitrate (NOx) and endothelial function. CONCLUSIONS: Changes in arterial adropin that occur with age or AT relate to alterations in endothelial function and NO produc-tion, supporting the notion that adropin should be considered a therapeutic target for vascular aging.

Original languageEnglish
Article numbere020641
JournalJournal of the American Heart Association
Issue number10
Publication statusPublished - 2021
Externally publishedYes


  • Adropin
  • Aging
  • Exercise training
  • Nitric oxide
  • Vasodilation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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