Regulation of SIRT1 by microRNAs.

Abstract

Sirtuin 1 (SIRT1) is an NAD(+)-dependent deacetylase that connects cellular energy levels to homeostatic responses by deacetylating and modulating the activities of many transcriptional regulators. Discovered as a longevity protein in yeast, the mammalian SIRT1 has been intensively studied because of its great potential as a therapeutic target to benefit human health by preventing and improving many age-related diseases. There has been, therefore, substantial interest in developing agents that upregulate SIRT1 expression and activity. SIRT1 is regulated at multiple levels, including post-transcriptionally by microRNAs (miRs), powerful regulators of diverse biological pathways. Here we discuss how expression and activity of SIRT1 and other sirtuins are inhibited by miRs and further discuss the therapeutic potential of targeting miRs for age-related diseases that involve SIRT1 dysfunction, focusing on obesityrelated diseases.