Role of SIRT1 on regulation of senescence-associated secretory phenotype during senescence

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590369
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: National Center for Geriatrics and Gerontology
• Principal Investigator: MOTOYAMA NOBORU 独立行政法人国立長寿医療研究センター, 加齢健康脳科学研究部, 室長 (50277282)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 細胞老化 / SIRT1 / エピジェネティクス / アセチル化

Outline of Final Research Achievements

Senescent cells develop a pro-inflammatory response termed the senescence-associated secretory phenotype (SASP). It has been thought that SASP may be a key phenomenon in linking cellular senescence with individual aging. SIRT1 is an NAD+-dependent protein deacetylase, which regulates a diverse set of biological processes. We showed that SIRT1 suppressed the expression of SASP factors. SIRT1 bound to the promoter regions of SASP components, but dissociated from them during cellular senescence. In SIRT1-depleted cells, the acetylation levels of these regions were already higher than those in control cells in the pre-senescent stage. Moreover, these acetylation levels in SIRT1-depleted cells were significantly higher than those in control cells during cellular senescence. These results suggest that SIRT1 repressed the expression of SASP factors through the deacetylation of histones in their promoter regions.

Free Research Field

分子細胞生物学