Early-life exercise induces immunometabolic epigenetic modification enhancing anti-inflammatory immunity in middle-aged male mice

This study demonstrates that early-life regular exercise enhances anti-inflammatory immunity in middle-aged male mice through epigenetic immunometabolic modulation. Swimming training starting at one month of age significantly reduced cytokine responses and sepsis severity upon lipopolysaccharide (LPS) challenge, even after a prolonged detraining period. Pipecolic acid, a non-encoded amino acid, was identified as a key metabolite upregulated by exercise, reducing inflammation and sepsis via mTORC1 inhibition. Early-life exercise increased histone 3 lysine 4 trimethylation (H3K4me3) at the Crym promoter in the liver, an enzyme crucial for pipecolic acid production. Liver-specific Crym knockdown abolished the protective effects of early-life exercise. These findings highlight the long-term immunomodulatory benefits of early-life exercise.

Nini Zhang, Xinpei Wang, Mengya Feng, Min Li, Jing Wang, Hongyan Yang, Siyu He, Ziqi Xia, Lei Shang, Xun Jiang, Mao Sun, Yuanming Wu, Chaoxue Ren, Xing Zhang, Jia Li, Feng Gao