Sirtuins and the circadian clock interplay in cardioprotection: focus on sirtuin 1

Cell Mol Life Sci. 2021 Mar;78(6):2503-2515. doi: 10.1007/s00018-020-03713-6. Epub 2021 Jan 3.


Chronic disruption of circadian rhythms which include intricate molecular transcription-translation feedback loops of evolutionarily conserved clock genes has serious health consequences and negatively affects cardiovascular physiology. Sirtuins (SIRTs) are nuclear, cytoplasmic and mitochondrial histone deacetylases that influence the circadian clock with clock-controlled oscillatory protein, NAMPT, and its metabolite NAD+. Sirtuins are linked to the multi-organ protective role of melatonin, particularly in acute kidney injury and in cardiovascular diseases, where melatonin, via upregulation of SIRT1 expression, inhibits the apoptotic pathway. This review focuses on SIRT1, an NAD+-dependent class III histone deacetylase which counterbalances the intrinsic histone acetyltransferase activity of one of the clock genes, CLOCK. SIRT1 is involved in the development of cardiomyocytes, regulation of voltage-gated cardiac sodium ion channels via deacetylation, prevention of atherosclerotic plaque formation in the cardiovascular system, protection against oxidative damage and anti-thrombotic actions. Overall, SIRT1 has a see-saw effect on cardioprotection, with low levels being cardioprotective and higher levels leading to cardiac hypertrophy.

Keywords: Circadian rhythms; Clock genes; Heart; Melatonin; Sirtuins.

Publication types

  • Review

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • CLOCK Proteins / metabolism
  • Calcium / metabolism
  • Circadian Clocks / drug effects
  • Circadian Clocks / physiology*
  • Heart / physiology*
  • Humans
  • Melatonin / metabolism
  • Melatonin / pharmacology
  • Sirtuin 1 / metabolism*
  • Sirtuins / metabolism


  • Basic Helix-Loop-Helix Transcription Factors
  • CLOCK Proteins
  • Sirtuin 1
  • Sirtuins
  • Melatonin
  • Calcium