期刊
CELL METABOLISM
卷 31, 期 3, 页码 580-+出版社
CELL PRESS
DOI: 10.1016/j.cmet.2020.01.009
关键词
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资金
- NIH [R01DK 117481, R01DK101885, R01AG063404, R01AG 063389, DP1HD087988, R01Al124491]
- National Institute of Food and Agriculture
- France-Berkeley Fund
- Glenn/AFAR Scholarship
- James C.Y. Soong Fellowship
- Government Scholarship for Study Abroad (GSSA) from Taiwan
- ITO Scholarship
- Honjo International Scholarship
It is well documented that the rate of aging can be slowed, but it remains unclear to which extent aging-associated conditions can be reversed. How the interface of immunity and metabolism impinges upon the diabetes pandemic is largely unknown. Here, we show that NLRP3, a pattern recognition receptor, is modified by acetylation in macrophages and is deacetylated by SIRT2, an NAD(+)-dependent deacetylase and a metabolic sensor. We have developed a cell-based system that models aging-associated inflammation, a defined co-culture system that simulates the effects of inflammatory milieu on insulin resistance in metabolic tissues during aging, and aging mouse models; and demonstrate that SIRT2 and NLRP3 deacetylation prevent, and can be targeted to reverse, aging-associated inflammation and insulin resistance. These results establish the dysregulation of the acetylation switch of the NLRP3 inflammasome as an origin of aging-associated chronic inflammation and highlight the reversibility of aging-associated chronic inflammation and insulin resistance.
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