The Nuclear-Mitochondrial Crosstalk in Aging: From Mechanisms to Therapeutics.

IF 7.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Free Radical Biology and Medicine Pub Date : 2025-03-12 DOI:10.1016/j.freeradbiomed.2025.03.012
Yifei Feng, Yan Lu
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Abstract

Aging is a complex physiological process characterized by an irreversible decline in tissue and cellular functions, accompanied by an increased risk of age-related diseases, including neurodegenerative, cardiovascular, and metabolic disorders. Central to this process are epigenetic modifications, particularly DNA methylation, which regulate gene expression and contribute to aging-related epigenetic drift. This drift is characterized by global hypomethylation and localized hypermethylation, impacting genomic stability and cellular homeostasis. Simultaneously, mitochondrial dysfunction, a hallmark of aging, manifests as impaired oxidative phosphorylation, excessive reactive oxygen species production, and mitochondrial DNA mutations, driving oxidative stress and cellular senescence. Emerging evidence highlights a bidirectional interplay between epigenetics and mitochondrial function. DNA methylation modulates the expression of nuclear genes governing mitochondrial biogenesis and quality control, while mitochondrial metabolites, such as acetyl-CoA and S-adenosylmethionine, reciprocally influence epigenetic landscapes. This review delves into the intricate nuclear-mitochondrial crosstalk, emphasizing its role in aging-related diseases and exploring therapeutic avenues targeting these interconnected pathways to counteract aging and promote health span extension.

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衰老是一个复杂的生理过程,其特点是组织和细胞功能不可逆转地衰退,同时与衰老相关的疾病风险增加,包括神经退行性疾病、心血管疾病和代谢紊乱。这一过程的核心是表观遗传修饰,尤其是 DNA 甲基化,它调控基因表达并导致与衰老相关的表观遗传漂移。这种漂移的特点是全局低甲基化和局部高甲基化,影响基因组稳定性和细胞稳态。同时,作为衰老标志的线粒体功能障碍表现为氧化磷酸化受损、活性氧生成过多和线粒体 DNA 变异,从而导致氧化应激和细胞衰老。新出现的证据强调了表观遗传学与线粒体功能之间的双向相互作用。DNA 甲基化会调节管理线粒体生物生成和质量控制的核基因的表达,而线粒体代谢产物(如乙酰-CoA 和 S-腺苷蛋氨酸)会对表观遗传学景观产生相互影响。这篇综述深入探讨了核-线粒体之间错综复杂的相互作用,强调了它在衰老相关疾病中的作用,并探讨了针对这些相互关联的途径的治疗方法,以对抗衰老并促进健康寿命的延长。
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来源期刊
Free Radical Biology and Medicine
Free Radical Biology and Medicine 医学-内分泌学与代谢
CiteScore
14.00
自引率
4.10%
发文量
850
审稿时长
22 days
期刊介绍: Free Radical Biology and Medicine is a leading journal in the field of redox biology, which is the study of the role of reactive oxygen species (ROS) and other oxidizing agents in biological systems. The journal serves as a premier forum for publishing innovative and groundbreaking research that explores the redox biology of health and disease, covering a wide range of topics and disciplines. Free Radical Biology and Medicine also commissions Special Issues that highlight recent advances in both basic and clinical research, with a particular emphasis on the mechanisms underlying altered metabolism and redox signaling. These Special Issues aim to provide a focused platform for the latest research in the field, fostering collaboration and knowledge exchange among researchers and clinicians.
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