Systematic profiling reveals betaine as an exercise mimetic for geroprotection
Cell, 2025
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 Z., Fu X., Zhang X., Zhao G., Izpisua Belmonte J., Wang S., Song M., Zhang W., Qu J., Liu G.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Wellness Studies Aging | Pathophysiology | Plasma |  Olink Target 96 |
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.