SIRT2 and NAD+ Boosting Broadly Suppress Aging-Associated Inflammation

  • Aging Cell. 2025 Sep;24(9):e70162. doi: 10.1111/acel.70162.
Marine Barthez  1 Zehan Song  1  2 Yufan Feng  1 Yifei Wang  1  2 Chih-Ling Wang  1 Danica Chen  1
Affiliations
  • 1. Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California, USA.
  • 2. Metabolic Biology Graduate Program, University of California, Berkeley, California, USA.
Abstract

Aging leads to chronic inflammation that is linked to aging-associated conditions and diseases. Multiple immune pathways become activated during aging, posing a challenge to effectively reduce aging-associated inflammation. SIRT2, an NAD+-dependent deacetylase, suppresses several immune pathways that become activated during aging and may represent an attractive target to broadly dampen aging-associated inflammation. Here, we show that SIRT2 deficiency leads to increased inflammation governed by multiple immune pathways and tissue function decline at an old age, while NAD+ boosting with 78c suppresses aging-associated inflammation and improves tissue function. These findings highlight SIRT2 as a master regulator of aging-associated inflammation and support NAD+ boosting as an effective strategy to counteract aging-associated inflammation and tissue function decline.

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