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. 2025 Sep 18;188(19):5403-5425.e33.
doi: 10.1016/j.cell.2025.06.001. Epub 2025 Jun 25.

Systematic profiling reveals betaine as an exercise mimetic for geroprotection

Lingling Geng  1 , Jiale Ping  2 , Ruochen Wu  3 , Haoteng Yan  1 , Hui Zhang  4 , Yuan Zhuang  5 , Taixin Ning  1 , Jun Wang  6 , Chuqian Liang  3 , Jiachen Zhang  1 , Qingqing Chu  4 , Jing Zhang  1 , Yifan Wen  3 , Yaobin Jing  7 , Shuhui Sun  4 , Qin Qiao  8 , Qian Zhao  1 , Qianzhao Ji  9 , Shuai Ma  10 , Yusheng Cai  9 , Yandong Zheng  11 , Zhiran Zou  3 , Zhiqing Diao  3 , Mingheng Li  3 , Hao Zhang  3 , Jianli Hu  2 , Liangzheng Fu  3 , Wang Kang  2 , Ruijun Bai  12 , Hongkai Zhao  3 , Sheng Zhang  3 , Yingjie Ding  2 , Jinghui Lei  1 , Wei Wang  3 , Yun Ji  3 , Bo Gou  3 , Guoqiang Sun  3 , Jian Yin  3 , Pengze Yan  3 , Hao Li  2 , Zehua Wang  3 , Shikun Ma  12 , Zunpeng Liu  3 , Hezhen Shan  12 , Qiaoran Wang  2 , Tianling Cao  3 , Shanshan Yang  1 , Cui Wang  2 , Ping Yang  3 , Yanling Fan  8 , Yanxia Ye  9 , Jinghao Hu  1 , Mengmeng Jiang  9 , Ye Wang  13 , Kan Liu  13 , Yujing Li  3 , Yuanxiang Li  3 , Jingyi Li  14 , Weimin Ci  13 , Zi-Bing Jin  15 , Xiaobing Fu  16 , Xu Zhang  13 , Guoguang Zhao  17 , Juan Carlos Izpisua Belmonte  18 , Si Wang  19 , Moshi Song  20 , Weiqi Zhang  21 , Jing Qu  22 , Guang-Hui Liu  23
Affiliations

Systematic profiling reveals betaine as an exercise mimetic for geroprotection

Lingling Geng et al. Cell. .

Erratum in

  • Systematic profiling reveals betaine as an exercise mimetic for geroprotection.
    Geng L, Ping J, Wu R, Yan H, Zhang H, Zhuang Y, Ning T, Wang J, Liang C, Zhang J, Chu Q, Zhang J, Wen Y, Jing Y, Sun S, Qiao Q, Zhao Q, Ji Q, Ma S, Cai Y, Zheng Y, Zou Z, Diao Z, Li M, Zhang H, Hu J, Fu L, Kang W, Bai R, Zhao H, Zhang S, Ding Y, Lei J, Wang W, Ji Y, Gou B, Sun G, Yin J, Yan P, Li H, Wang Z, Ma S, Liu Z, Shan H, Wang Q, Cao T, Yang S, Wang C, Yang P, Fan Y, Ye Y, Hu J, Jiang M, Wang Y, Liu K, Li Y, Li Y, Li J, Ci W, Jin ZB, Fu X, Zhang X, Zhao G, Izpisua Belmonte JC, Wang S, Song M, Zhang W, Qu J, Liu GH. Geng L, et al. Cell. 2025 Sep 18;188(19):5426-5428. doi: 10.1016/j.cell.2025.07.030. Epub 2025 Aug 12. Cell. 2025. PMID: 40803320 No abstract available.

Abstract

Exercise has well-established health benefits, yet its molecular underpinnings remain incompletely understood. We conducted an integrated multi-omics analysis to compare the effects of acute vs. long-term exercise in healthy males. Acute exercise induced transient responses, whereas repeated exercise triggered adaptive changes, notably reducing cellular senescence and inflammation and enhancing betaine metabolism. Exercise-driven betaine enrichment, partly mediated by renal biosynthesis, exerts geroprotective effects and rescues age-related health decline in mice. Betaine binds to and inhibits TANK-binding kinase 1 (TBK1), retarding the kinetics of aging. These findings systematically elucidate the molecular benefits of exercise and position betaine as an exercise mimetic for healthy aging.

Keywords: ETS1; TBK1; aging; betaine; exercise; exercise immunology; exercise metabolism; inflammation; kidney; senescence.

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Conflict of interest statement

Declaration of interests J.C.I.B. is an employee of Altos Labs.

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