SRT1720-induced activation of SIRT1 alleviates vascular smooth muscle cell senescence through PKA-dependent phosphorylation of AMPKα at Ser485

FEBS Open Bio. 2020 Jul;10(7):1316-1325. doi: 10.1002/2211-5463.12895. Epub 2020 Jun 5.


Aging is a major risk factor for hypertension and atherosclerosis, and vascular smooth muscle cell (VSMC) senescence can promote aging-related vascular diseases. Sirtuin-1 (SIRT1) and AMP-activated protein kinase (AMPK) were previously reported to modulate vascular senescence; however, its effects have not been well characterized. To determine the nature of the interaction between SIRT1 and AMPK in VSMC senescence, we investigated the effects of SRT1720 on its downstream targets of SIRT1 and the phosphorylation of AMPKα at Ser485. During Adriamycin-induced VSMC senescence, SRT1720 increased the activity of SIRT1 and AMPKα phosphorylation at Ser485 via the cAMP-protein kinase A (PKA) pathway. Telomere length and telomerase reverse transcriptase expression were increased by SIRT1 activation with SRT1720. Taken together, these data show that activation of the SIRT1/cAMP-PKA/p-AMPKα (Ser485) pathway may be an effective antisenescence mechanism for VSMCs.

Keywords: SIRT1; SRT1720; VSMC senescence; p-AMPK (Ser485); telomere length.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / antagonists & inhibitors*
  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Cells, Cultured
  • Cellular Senescence / drug effects
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Heterocyclic Compounds, 4 or More Rings / pharmacology*
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Phosphorylation / drug effects
  • Rats
  • Serine / antagonists & inhibitors*
  • Serine / metabolism
  • Sirtuin 1 / metabolism*


  • Heterocyclic Compounds, 4 or More Rings
  • SRT1720
  • Serine
  • Cyclic AMP-Dependent Protein Kinases
  • AMP-Activated Protein Kinases
  • Sirt1 protein, rat
  • Sirtuin 1