The role of Sirt1 in renal rejuvenation and resistance to stress

Abstract

This issue of the JCI includes studies demonstrating that sirtuin 1 (Sirt1), a NAD+-dependent deacetylase, slows renal senescence and safeguards cells in the renal medulla. Kume et al. demonstrated that caloric restriction protected the aging kidney by preserving renal Sirt1 expression, the latter deacetylating forkhead box O3a (FOXO3a), inducing Bnip 3, and promoting mitochondrial autophagy. Sirt1 expression, as shown by He et al., enabled interstitial cells to withstand the oxidizing medullary environment and exerted antiapoptotic and antifibrotic effects in the obstructed kidney. Sirt1 is thus an important participant in renal cytoprotective responses to aging and stress.

Figure 1. Sirt1 plays an important role in renal cytoprotective responses to aging and stress.

In this issue of the JCI, Kume et al. (3) demonstrated that in aged mice maintained on ad libitum feeding, the kidney exhibited cortical hypoxia and decreased expression of Sirt1; caloric restriction prevented the reduction in Sirt1 but did not alleviate cortical hypoxia. Transcriptional targets of acetylated FOXO3a include Bim1, while those of deacetylated FOXO3a include Bnip3 and p27. In the medulla, as reported by He et al. in this issue (15), interstitial cells expressed Sirt1; Sirt1 conferred resistance to urinary tract obstruction–induced (UTO-induced) apoptosis and fibrosis and to ROS, in part, through the expression of COX2 and PGE₂ (15).