[PDF][PDF] An acetylation switch of the NLRP3 inflammasome regulates aging-associated chronic inflammation and insulin resistance
Cell metabolism, 2020•cell.com
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 …
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 …
Summary
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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