An Yongpan, Wang Qian, Qiao Panshuang, Liu Jihan, Ma Ang, Chen Yutong, Yang Daqian, Ying Yi, Li Nannan, Lu Feng, Zhang Hang, Chen Guoqiang, Zhu Yinhua, Yang Baoxue, Xie Zhengwei
Peking University International Cancer Institute, Health Science Center, Peking University, 38 Xueyuan Lu, Haidian District, Beijing 100191, China.
Department of Pharmacology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Lu, Haidian District, Beijing 100191, China.
Nutrients. 2025 May 12;17(10):1647. doi: 10.3390/nu17101647.
BACKGROUND/OBJECTIVE: Aging is a significant risk factor for chronic diseases and disability, yet effective anti-aging interventions remain elusive. We explored the potential of 3-hydroxybutyrate (3HB), an endogenous metabolite with established safety, to modulate longevity in mice.
In this study, we employed 2BS and WI-38 cell models, a yeast model, and naturally aging mouse models to investigate the effects of 3HB on aging in various systems. Additionally, we utilized RNA sequencing and metabolomics technologies to explore the potential mechanisms underlying the action of 3HB.
Our findings demonstrate that 3HB supplementation effectively delays cellular senescence, extending yeast lifespan by 51.3% and the median lifespan of naturally senescent mice by 21.0%. Notably, 3HB prolonged healthy lifespan in mice while mitigating age-related tissue morphology changes and organ senescence. Mechanistically, we identified that 3HB's anti-aging properties are mediated through its ability to delay cellular senescence and metabolic reprogramming, while promoting the production of beneficial metabolites like trigoneline and isoguvacine.
These findings highlight the promising therapeutic potential of 3HB as an anti-aging intervention and provide novel insights into its underlying mechanisms.
背景/目的：衰老 是慢性疾病和残疾的一个重要风险因素，但有效的抗衰老干预措施仍然难以捉摸。我们探讨了3-羟基丁酸（3HB）（一种安全性已得到确证的内源性代谢物）调节小鼠寿命的潜力。
在本研究中，我们采用2BS和WI-38细胞模型、酵母模型以及自然衰老小鼠模型来研究3HB对各个系统衰老的影响。此外，我们利用RNA测序和代谢组学技术来探究3HB作用的潜在机制。
我们的研究结果表明，补充3HB可有效延缓细胞衰老，使酵母寿命延长51.3%，使自然衰老小鼠的中位寿命延长21.0%。值得注意的是，3HB延长了小鼠的健康寿命，同时减轻了与年龄相关的组织形态变化和器官衰老。从机制上来说，我们发现3HB的抗衰老特性是通过其延缓细胞衰老和代谢重编程的能力介导的，同时促进了诸如胡芦巴碱和异古豆碱等有益代谢物的产生。
这些发现凸显了3HB作为一种抗衰老干预措施的广阔治疗潜力，并为其潜在机制提供了新的见解。
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