Multi-omics strategies to decode the molecular landscape of cellular senescence

IF 12.4 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews Pub Date : 2025-07-05 DOI:10.1016/j.arr.2025.102824

Manuela Giovanna Basilicata , Eduardo Sommella , Lucia Scisciola , Giovanni Tortorella , Marco Malavolta , Chiara Giordani , Michelangela Barbieri , Pietro Campiglia , Giuseppe Paolisso

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引用次数: 0

Abstract

Cellular senescence is a conserved cellular program characterized by a permanent cell cycle arrest triggered by a variety of stressors. Originally described as a tumor-suppressive mechanism, it is now recognized to exert pleiotropic and context-dependent functions, contributing to key physiological processes such as embryogenesis and tissue repair, as well as to processes associated with aging and the development of age-related diseases. Unlike normal cells, senescent cells remain metabolically active despite their non-dividing state. They significantly impact their environment through the Senescence-Associated Secretory Phenotype (SASP), a complex mix of cytokines, growth factors, and proteases. This secretory profile can promote tissue repair and regeneration but, if persistent, contributes to chronic inflammation, fibrosis, and tissue dysfunction. Two major pathways primarily regulate senescence: the p53/p21 and p16^INK4a^/Rb axes. These respond to stress signals like DNA damage, oxidative stress, and oncogenic activation, enforcing stable cell cycle arrest to prevent uncontrolled proliferation. However, as senescent cells accumulate over time, their ongoing SASP activity disrupts tissue homeostasis, driving inflammation and age-related diseases. Recent advances in multi-omics technologies, including metabolomics, proteomics, and lipidomics, have provided deeper insights into the complex molecular changes within senescent cells, revealing new biomarkers and potential therapeutic targets. These approaches offer a comprehensive understanding of cellular senescence, but challenges remain in distinguishing the causal relationships within these data and translating findings into clinical applications. This review integrates recent multi-omics discoveries, highlighting their potential to refine our understanding of senescence and support the development of targeted interventions to extend healthspan and combat age-related pathologies.

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多组学策略解码细胞衰老的分子景观。

细胞衰老是一种保守的细胞程序，其特征是由各种应激源引发的永久性细胞周期停滞。它最初被描述为一种肿瘤抑制机制，现在被认为具有多效性和环境依赖性功能，有助于关键的生理过程，如胚胎发生和组织修复，以及与衰老和年龄相关疾病的发展相关的过程。与正常细胞不同，衰老细胞尽管处于非分裂状态，但仍保持代谢活性。它们通过衰老相关分泌表型（SASP）显著影响环境，SASP是细胞因子、生长因子和蛋白酶的复杂组合。这种分泌特征可以促进组织修复和再生，但如果持续，会导致慢性炎症、纤维化和组织功能障碍。两个主要的途径主要调控衰老：p53/p21和p16^INK4a^/Rb轴。这些细胞对DNA损伤、氧化应激和致癌激活等应激信号作出反应，强制稳定的细胞周期阻滞以防止不受控制的增殖。然而，随着衰老细胞的积累，它们持续的SASP活性会破坏组织稳态，导致炎症和与年龄相关的疾病。包括代谢组学、蛋白质组学和脂质组学在内的多组学技术的最新进展，为衰老细胞内复杂的分子变化提供了更深入的了解，揭示了新的生物标志物和潜在的治疗靶点。这些方法提供了对细胞衰老的全面理解，但在区分这些数据中的因果关系并将研究结果转化为临床应用方面仍然存在挑战。这篇综述整合了最近的多组学发现，强调了它们的潜力，以完善我们对衰老的理解，并支持有针对性的干预措施的发展，以延长健康寿命和对抗年龄相关的病理。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Ageing Research Reviews 医学-老年医学

CiteScore

19.80

自引率

2.30%

发文量

216

审稿时长

55 days

期刊介绍： With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.