辅酶A与年龄相关的下降通过扰乱铁稳态导致肠道干细胞功能障碍。
Age-associated decline of Coenzyme A leads to intestinal stem cells dysfunction via disturbing iron homeostasis.
作者信息
Liu Zhiming, Du Gang, Chen Yi, Chen Haiyang
机构信息
West China Centre of Excellence for Pancreatitis, and Laboratory of Metabolism and Aging, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America.
出版信息
PLoS Genet. 2025 May 30;21(6):e1011704. doi: 10.1371/journal.pgen.1011704. eCollection 2025 Jun.
The decline in adult stem cell performance is closely linked to tissue malfunction and the rising incidence of age-related diseases. To investigate the molecular basis of these impairments, our screening strategy identified reduced activity in the pantothenate/coenzyme A (CoA) pathway within aged ISCs. Furthermore, exogenous CoA supplementation restructured ISC metabolic pathways, reversing age-induced hyperproliferation and intestinal dysfunction, and thus extending Drosophila lifespan by curbing excessive iron accumulation in ISCs. These findings uncover a new mechanism of stem cell aging and propose that pantothenate and CoA could be potential therapeutic targets for treating age-related diseases and enhancing healthy aging in humans.
成体干细胞性能的下降与组织功能障碍以及与年龄相关疾病发病率的上升密切相关。为了研究这些损伤的分子基础，我们的筛选策略发现老年肠干细胞中泛酸盐/辅酶A（CoA）途径的活性降低。此外，外源性CoA补充可重塑肠干细胞代谢途径，逆转年龄诱导的过度增殖和肠道功能障碍，从而通过抑制肠干细胞中过量铁的积累来延长果蝇的寿命。这些发现揭示了干细胞衰老的一种新机制，并提出泛酸盐和CoA可能是治疗与年龄相关疾病和促进人类健康衰老的潜在治疗靶点。
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