Systematic profiling reveals betaine as an exercise mimetic for geroprotection

Murph

Senior Member (Voting Rights)
This is a detailed study on the proteomics of acute and sustained exercise in the healthy, it is paywalled but definitely the sort of paper that can help establish norms against which we can measure PwME. It also hints at a supplement that I'm about to check and see if we have any forum posts on!


Article: https://www.eurekalert.org/news-releases/1089007

June 25, 2025 —A Cell-published study led by Chinese Academy of Sciences and Xuanwu Hospital Capital Medical University reveals how exercise systemically counters aging and identifies betaine—a kidney-derived metabolite—as an oral compound mimicking exercise’s rejuvenating effects.

The exercise paradox was decoded as follows: Acute exercise triggered inflammatory "metabolic chaos," while sustained training rebuilt homeostasis. Chronic exercise modulated gut microbiomes, enhanced antioxidant defenses by upregulating antioxidant enzymes, and reversed T-cell aging by stabilizing DNA integrity and modulating epigenetic marks through the repression of transcription factor ETS1 expression, rejuvenating the immune system.

Long-term exercise boosted kidney betaine production partially via mitochondrial enzyme CHDH. Strikingly, betaine supplementation alone replicated many of exercise’s benefits, such as alleviating cellular aging in human kidney, vascular, and immune cells, enhancing metabolism, kidney function, coordination, cognition, and reducing depressive-like behaviors in aged mice, and slashing inflammation systemically.



Paper: Systematic profiling reveals betaine as an exercise mimetic for geroprotection

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.
 
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