SIRT1 suppresses cellular senescence and inflammatory cytokine release in human dermal fibroblasts by promoting the deacetylation of NF-κB and activating autophagy.

Abstract

Skin aging is a complex process and involves extrinsic and intrinsic processes with distinct characteristics. Understanding skin aging requires knowledge of the senescence of human dermal fibroblasts (HDFs) and the biological mechanisms involved in this process. However, the molecular mechanism responsible for the aging of HDFs is still not clear. Therefore, we investigated mechanisms of autophagy, inflammation, and cellular senescence by Western blotting, immunofluorescence, real-time PCR, and senescence-associated β-galactosidase (SA-β-gal) staining in senescent HDFs. We found SRT1720 inhibited the inductions of inflammatory cytokines and cellular senescence by deacetylating acetyl-NF-κB levels and enhancing levels of autophagy-associated proteins and SIRT1 in senescent HDFs. However, the NF-κB activator prostratin attenuated signals associated with autophagy, such as those of LC3-II and Beclin-1, but increased inflammatory cytokine levels and cellular senescence. Notably, the expression levels of SIRT1 and autophagy-associated proteins were higher in aged mice administered SRT1720 than in old mice, and SRT1720 also decreased levels of acetyl-NF-κB, inflammatory cytokines, and senescence markers, which was in accord with in vitro results. These findings support that SRT1720 acts as an anti-aging agent and inhibits the inductions of inflammatory cytokines and senescence by regulating the SIRT1/acetyl-NF-κB signaling pathway and activating autophagy in senescent HDFs.

• Authors: Jin Young Sung, Seul Gi Kim, Jae-Ryong Kim, Hyoung Chul Choi
• Journal: Experimental gerontology (Exp Gerontol) Vol. 150 Pg. 111394 (07 15 2021) ISSN: 1873-6815 [Electronic] England
• PMID: 33965557 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Cytokines
• NF-kappa B
• SIRT1 protein, human
• Sirt1 protein, mouse
• Sirtuin 1

Topics

• Animals
• Autophagy
• Cells, Cultured
• Cellular Senescence
• Cytokines
• Fibroblasts
• Humans
• Mice
• NF-kappa B
• Sirtuin 1