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衰老和疾病中细胞衰老的特征与机制

Hallmarks and mechanisms of cellular senescence in aging and disease.

作者信息

Ajoolabady Amir, Pratico Domenico, Bahijri Suhad, Eldakhakhny Basmah, Tuomilehto Jaakko, Wu Feng, Ren Jun

机构信息

National Clinical Research Center for Interventional Medicine, Shanghai, 200032, China.

State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

出版信息

Cell Death Discov. 2025 Aug 4;11(1):364. doi: 10.1038/s41420-025-02655-x.


DOI:10.1038/s41420-025-02655-x
PMID:40759632
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12322153/
Abstract

Cellular senescence, often referred to simply as "senescence", is a complex intracellular process with diverse biological, physiological, and pathological roles. Biologically, it is essential for embryogenesis and development. Physiologically, senescence acts as a safeguard against tumorigenesis by preventing the proliferation of damaged or defective cells. However, persistent activation of senescence can contribute to various pathological conditions, particularly those associated with aging, cancer, and other chronic diseases such as liver and pulmonary diseases. Growing evidence links aging to heightened activation of cellular senescence, leading to the accumulation of senescent cells. Here in this perspective, we aim to decipher the latest molecular mechanisms and regulatory pathways of cellular senescence in the context of aging and aging-related diseases. Additionally, we discuss emerging research directions, highlighting current limitations and gaps in the field. Addressing these challenges may not only advance our understanding of senescence but also uncover new therapeutic opportunities.

摘要

细胞衰老,通常简称为“衰老”,是一个复杂的细胞内过程,具有多种生物学、生理学和病理学作用。在生物学上,它对胚胎发生和发育至关重要。在生理学上,衰老通过阻止受损或有缺陷的细胞增殖,起到防止肿瘤发生的作用。然而,衰老的持续激活会导致各种病理状况,特别是那些与衰老、癌症以及其他慢性疾病(如肝脏和肺部疾病)相关的病理状况。越来越多的证据表明衰老与细胞衰老的激活增强有关,导致衰老细胞的积累。在此观点中,我们旨在解读衰老及衰老相关疾病背景下细胞衰老的最新分子机制和调控途径。此外,我们讨论新兴的研究方向,突出该领域当前的局限性和差距。应对这些挑战不仅可能增进我们对衰老的理解,还可能发现新的治疗机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c0/12322153/04042fbbaa23/41420_2025_2655_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c0/12322153/e18345ab4fc5/41420_2025_2655_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c0/12322153/9c1552f0eff3/41420_2025_2655_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c0/12322153/04042fbbaa23/41420_2025_2655_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c0/12322153/e18345ab4fc5/41420_2025_2655_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c0/12322153/9c1552f0eff3/41420_2025_2655_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c0/12322153/04042fbbaa23/41420_2025_2655_Fig3_HTML.jpg

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本文引用的文献

[1]
Mettl1-dependent mG tRNA modification is essential for maintaining spermatogenesis and fertility in Drosophila melanogaster.

Nat Commun. 2024-9-24

[2]
RHNO1: at the crossroads of DNA replication stress, DNA repair, and cancer.

Oncogene. 2024-8

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TIPE2 gene transfer ameliorates aging-associated osteoarthritis in a progeria mouse model by reducing inflammation and cellular senescence.

Mol Ther. 2024-9-4

[4]
Perturbation of METTL1-mediated tRNA N- methylguanosine modification induces senescence and aging.

Nat Commun. 2024-7-8

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mA Reader YTHDC1 Impairs Respiratory Syncytial Virus Infection by Downregulating Membrane CX3CR1 Expression.

Viruses. 2024-5-14

[6]
Cellular senescence, DNA damage, and neuroinflammation in the aging brain.

Trends Neurosci. 2024-6

[7]
Beyond the Anticodon: tRNA Core Modifications and Their Impact on Structure, Translation and Stress Adaptation.

Genes (Basel). 2024-3-19

[8]
WTAP Mediated N6-methyladenosine RNA Modification of ELF3 Drives Cellular Senescence by Upregulating IRF8.

Int J Biol Sci. 2024

[9]
Type 2 cytokine signaling in macrophages protects from cellular senescence and organismal aging.

Immunity. 2024-3-12

[10]
The Versatile Attributes of MGMT: Its Repair Mechanism, Crosstalk with Other DNA Repair Pathways, and Its Role in Cancer.

Cancers (Basel). 2024-1-11

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