脂肪酸氧化通过调节自噬-SIRT1轴调节细胞衰老

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
BMB Reports Pub Date : 2023-12-01
Seungyeon Yang, Subin Moon, Soojung Claire Hur, Seung Min Jeong
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引用次数: 0

摘要

衰老是一个细胞过程,通过这一过程,受损或功能失调的细胞抑制了细胞周期,从而导致衰老或与年龄相关的功能衰退。细胞新陈代谢与衰老过程密切相关,人们普遍认为新陈代谢的变化是衰老导致细胞改变的基础。在这里,我们报告了脂肪酸氧化(FAO)是细胞衰老的关键调节因子,并揭示了抑制 FAO 诱导衰老的内在机制。药物或基因消减 FAO 会导致 p53 依赖性诱导人成纤维细胞衰老,而增强 FAO 则会抑制复制性衰老。我们发现,抑制 FAO 可通过乙酰-CoA 促进细胞衰老,而与能量耗竭无关。从机理上讲,抑制 FAO 后自噬体的形成增加,导致 SIRT1 蛋白水平降低,从而诱导衰老。最后,我们发现抑制自噬或加强 SIRT1 的表达可以挽救 FAO 抑制导致的衰老诱导。总之,我们的研究揭示了FAO-自噬-SIRT1轴在细胞衰老调控中的独特作用。[BMB Reports 2023; 56(12): 651-656]。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Fatty acid oxidation regulates cellular senescence by modulating the autophagy-SIRT1 axis.

Senescence, a cellular process through which damaged or dysfunctional cells suppress the cell cycle, contributes to aging or age-related functional decline. Cell metabolism has been closely correlated with aging processes, and it has been widely recognized that metabolic changes underlie the cellular alterations that occur with aging. Here, we report that fatty acid oxidation (FAO) serves as a critical regulator of cellular senescence and uncover the underlying mechanism by which FAO inhibition induces senescence. Pharmacological or genetic ablation of FAO results in a p53-dependent induction of cellular senescence in human fibroblasts, whereas enhancing FAO suppresses replicative senescence. We found that FAO inhibition promotes cellular senescence through acetyl-CoA, independent of energy depletion. Mechanistically, increased formation of autophagosomes following FAO inhibition leads to a reduction in SIRT1 protein levels, thereby contributing to senescence induction. Finally, we found that inhibition of autophagy or enforced expression of SIRT1 can rescue the induction of senescence as a result of FAO inhibition. Collectively, our study reveals a distinctive role for the FAO-autophagy-SIRT1 axis in the regulation of cellular senescence. [BMB Reports 2023; 56(12): 651-656].

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来源期刊
BMB Reports
BMB Reports 生物-生化与分子生物学
CiteScore
5.10
自引率
7.90%
发文量
141
审稿时长
1 months
期刊介绍: The BMB Reports (BMB Rep, established in 1968) is published at the end of every month by Korean Society for Biochemistry and Molecular Biology. Copyright is reserved by the Society. The journal publishes short articles and mini reviews. We expect that the BMB Reports will deliver the new scientific findings and knowledge to our readers in fast and timely manner.
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