The oocyte-enriched metabolite serotonin alleviates cellular senescence and aging phenotypes in the mouse
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.
Authors
- Xufeng Liao
- Lidan Hu (ORCID: https://orcid.org/0000-0002-1145-2745)
- Jin Zhang (ORCID: https://orcid.org/0000-0003-0197-3624)
- Yuyan Xu (ORCID: https://orcid.org/0000-0001-5567-0958)
- Mengchen Wu (ORCID: https://orcid.org/0000-0001-7222-9187)
- Bing Yang (ORCID: https://orcid.org/0000-0001-6739-2932)
- Li Zhang (ORCID: https://orcid.org/0000-0003-0633-8881)
- Jingjing Wang (ORCID: https://orcid.org/0000-0003-3170-8952)
- Jinjie Zhong
- Ling Zhang (ORCID: https://orcid.org/0009-0001-4193-5908)
- Yuhang Fan (ORCID: https://orcid.org/0009-0005-5654-0764)
- Enze Li
- Jing Zhao
- Rouyi Shao
- Jia Zhang
- Min Zhang
- Jianhua Mao
- Limeng Cai
- Hailing Zhang (ORCID: https://orcid.org/0009-0009-1171-4416)
- Gang Wang
- Wenjie Wang
- Qixin Wu
Institutions
- Nanjing General Hospital of Nanjing Military Command (CN)
- Gene Therapy Laboratory (FR)
- Children's Hospital of Zhejiang University (CN)
- First Affiliated Hospital Zhejiang University (CN)
- Zhejiang University (CN)
- Nanjing University (CN)
Publication Details
- Journal
- The EMBO Journal
- Published
- 2026-06-16
- DOI
- https://doi.org/10.1038/s44318-026-00832-x
- Primary Topic
- Reproductive Biology and Fertility
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Jiangsu Province
- Natural Science Foundation of Zhejiang Province
- Key Research and Development Program of Zhejiang Province