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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 nematodes by increasing betaine levels and promoting autophagy and antioxidant activity. This finding suggests that betaine could be a novel therapeutic target for promoting longevity., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: The healthy human urine sediment proteome and metaproteome are investigated, to shed light on the variations of urine sediment proteins and metaproteins associated with sex and age., Experimental Design: Urine sediment samples are collected from 19 healthy subjects. Protein identification and quantification are performed by liquid chromatography coupled high-resolution mass spectrometry., Results: A total of 2736 human proteins were identified, which were primarily associated with inflammatory response and energy metabolism. For the metaproteome, 65 genera were identified that were primarily involved in translation and carbohydrate metabolic processes. The median biological coefficient variation of the proteome/metaproteome of human urine sediment was 0.5/0.72, similar to the proteome of human urine supernatant. In addition, sex and age were observed to affect the proteome and metaproteome of healthy human urine sediment., Conclusion and Clinical Relevance: The healthy human urine sediment were characterized, indicating that urine sediment might represent an alternative resource for disease research in addition to urine supernatant, but the influence of sex and age must be considered in the study design process., (© 2021 Wiley-VCH GmbH.)