miRNAs regulate SIRT1 expression during mouse embryonic stem cell differentiation and in adult mouse tissues

Aging (Albany NY). 2010 Jul;2(7):415-31. doi: 10.18632/aging.100176.


SIRT1 is increasingly recognized as a critical regulator of stress responses, replicative senescence, inflammation, metabolism, and aging. SIRT1 expression is regulated transcriptionally and post-transcriptionally, and its enzymatic activity is controlled by NAD+ levels and interacting proteins. We found that SIRT1 protein levels were much higher in mouse embryonic stem cells (mESCs) than in differentiated tissues. miRNAs post-transcriptionally downregulated SIRT1 during mESC differentiation and maintained low levels of SIRT1 expression in differentiated tissues. Specifically, miR-181a and b, miR-9, miR-204, miR-199b, and miR-135a suppressed SIRT1 protein expression. Inhibition of mir-9, the SIRT1-targeting miRNA induced earliest during mESC differentiation, prevented SIRT1 downregulation. Conversely, SIRT1 protein levels were upregulated post-transcriptionally during the reprogramming of mouse embryonic fibroblasts (MEFs) into induced pluripotent stem (iPS) cells. The regulation of SIRT1 protein levels by miRNAs might provide new opportunities for therapeutic tissue-specific modulation of SIRT1 expression and for reprogramming of somatic cells into iPS cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation* / genetics
  • Cellular Senescence / physiology
  • Down-Regulation / physiology
  • Drug Design
  • Embryonic Stem Cells* / physiology
  • Genomic Instability / physiology
  • Mice
  • MicroRNAs* / physiology
  • Organ Specificity
  • Protein Biosynthesis / physiology*
  • RNA Processing, Post-Transcriptional
  • Sirtuin 1* / antagonists & inhibitors
  • Sirtuin 1* / physiology


  • MicroRNAs
  • Sirt1 protein, mouse
  • Sirtuin 1