Hormetic nutrient stress promotes longevity by orchestrating histone acetylation on key lipid catabolism and antioxidant defense genes.

ABSTRACT: Exposure to low levels of environmental challenges, known as hormetic stress, such as nutrient deprivation and heat shock, fosters subsequent stress resistance and promotes healthy aging in later life. However, specific mechanisms governing transcriptional reprogramming upon hormetic nutrient stress remain elusive. In this study, we identified histone H3 lysine 27 acetylation (H3K27ac) as a crucial driver of transcriptomic adaptation to hormetic fasting. Beyond its immediate function of enhancing lipid catabolism for alternative energy sources, stress-induced H3K27ac activates lifelong antioxidant defenses, thereby reducing reactive oxygen species (ROS) produced by stress-induced fatty acid oxidation and their accumulation during aging. The increase in H3K27ac, mediated by pioneer factor P

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC12424834 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature