The oocyte-enriched metabolite serotonin alleviates cellular senescence and aging phenotypes in the mouse.

Yuyan Xu, Ling Zhang, Xufeng Liao, Yuhang Fan, Rouyi Shao, Mengchen Wu, Li Zhang, Min Zhang, Gang Wang, Hailing Zhang, Enze Li, Qixin Wu, Jing Zhao, Jia Zhang, Wenjie Wang, Limeng Cai, Jinjie Zhong, Lidan Hu, Jingjing Wang, Jianhua Mao, Bing Yang, Jin Zhang

Bone Marrow Transplantation Center of the First Affiliated Hospital, and Center for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China.Bone Marrow Transplantation Center of the First Affiliated Hospital, and Center for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China. · pubmed

Paper

Abstract

Whether metabolites enriched at early developmental stages affect cellular and organismal aging remains unclear. In this study, we comprehensively profiled the metabolic landscape of mouse oocytes in comparison to cleavage-stage embryos. Our analysis revealed that oocytes display accumulation of reductive metabolites that diminish following fertilization. Notably, we identified serotonin (5-hydroxytryptamine, 5-HT) as an oocyte-enriched metabolite with protective roles in aging. The underlying mechanisms operate through dual pathways: (i) in a canonical pathway serotonin acts via its receptor 5HTR1B to modulate mitochondrial function, and (ii) in a non-canonical pathway serotonin promotes serotonylation of HSP90β, which effectively reduces endoplasmic reticulum stress. Overall, our study demonstrates that oocyte-enriched metabolites including serotonin can alleviate aging-related cellular and systemic phenotypes, suggesting new avenues for anti-aging strategies.

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Research summary

The study claims that the oocyte-enriched metabolite serotonin alleviates cellular senescence and aging phenotypes in mice by modulating mitochondrial function and reducing ER stress via HSP90β serotonylation. This work is relevant as it identifies a specific metabolic mechanism for aging intervention, but the impact is limited because serotonin is a well-known, non-novel compound with established safety profiles, representing an incremental mechanistic exploration rather than a transformative breakthrough in longevity science.

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