Senolytics Enhance the Longevity of Caenorhabditis elegans by Altering Betaine Metabolism

作者：Wenning Lan, Xiaolian Xiao, Jingjing Nian, Ziran Wang, Xiaojing Zhang, Yajiao Wu, Dongcheng Zhang, Junkun Chen, Wenqiang Bao, Chutao Li, Yun Zhang, An Zhu, Fangrong Zhang · 发表于：The Journals of Gerontology Series A · 年份：2024 · DOI：10.1093/gerona/glae221 · 被引用次数：13 · 研究领域：Genetics, Aging, and Longevity in Model Organisms、Circadian rhythm and melatonin、Telomeres, Telomerase, and Senescence

Aging triggers physiological changes in organisms that are tightly linked to metabolic changes. Senolytics targeting many fundamental aging processes are currently being developed. However, the host metabolic response to natural senescence and the molecular mechanism underlying the antiaging benefits of senolytics remain poorly understood. In this study, we investigated metabolic changes during natural senescence based on the Caenorhabditis elegans model and pinpointed potential biomarkers linked to the benefits of senolytics. These results suggest that age-dependent metabolic changes during natural aging occur in C elegans. Betaine was identified as a crucial metabolite in the natural aging process. We explored the metabolic effects of aging interventions by administering 3 antiaging drugs-metformin, quercetin, and minocycline-to nematodes. Notably, betaine expression significantly increased under the 3 antiaging drug treatments. Our findings demonstrated that betaine supplementation extends lifespan, primarily through pathways associated with the forkhead box transcription factor (FoxO) signaling pathway, the p38-mitogen-activated protein kinase (MAPK) signaling pathway, autophagy, the longevity regulating pathway, and the target of rapamycin (mTOR) signaling pathway. In addition, autophagy and free radicals are altered in betaine-treated nematodes. Overall, we found that betaine is a critical metabolite during natural aging and that senolytics extend the lifespan of nemato...