Abavisani Mohammad, Faraji Saba, Ebadpour Negar, Karav Sercan, Sahebkar Amirhossein
Student research committee, Mashhad University of Medical Sciences, Mashhad, Iran.
Student research committee, Mashhad University of Medical Sciences, Mashhad, Iran; Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Ageing Res Rev. 2025 Feb;104:102657. doi: 10.1016/j.arr.2025.102657. Epub 2025 Jan 7.
Cellular senescence, a complex biological process resulting in permanent cell-cycle arrest, is central to aging and age-related diseases. A key concept in understanding cellular senescence is the Hayflick Limit, which refers to the limited capacity of normal human cells to divide, after which they become senescent. Senescent cells (SC) accumulate with age, releasing pro-inflammatory and tissue-remodeling factors collectively known as the senescence-associated secretory phenotype (SASP). The causes of senescence are multifaceted, including telomere attrition, oxidative stress, and genotoxic damage, and they extend to influences from microbial sources. Research increasingly emphasizes the role of the microbiome, especially gut microbiota (GM), in modulating host senescence processes. Beneficial microbial metabolites, such as short-chain fatty acids (SCFAs), support host health by maintaining antioxidant defenses and reducing inflammation, potentially mitigating senescence onset. Conversely, pathogenic bacteria like Pseudomonas aeruginosa and Helicobacter pylori introduce factors that damage host DNA or increase ROS, accelerating senescence via pathways such as NF-κB and p53-p21. This review explores the impact of bacterial factors on cellular senescence, highlighting the role of specific bacterial toxins in promoting senescence. Additionally, it discusses how dysbiosis and the loss of beneficial microbial species further contribute to age-related cellular deterioration. Modulating the gut microbiome to delay cellular senescence opens a path toward targeted anti-aging strategies. This work underscores the need for deeper investigation into microbial influence on aging, supporting innovative interventions to manage and potentially reverse cellular senescence.
细胞衰老，是一个导致细胞永久停滞于细胞周期的复杂生物学过程，是衰老及与年龄相关疾病的核心。理解细胞衰老的一个关键概念是海弗利克极限，它指的是正常人类细胞的有限分裂能力，在此之后细胞就会衰老。衰老细胞会随着年龄的增长而积累，并释放出促炎和组织重塑因子，这些因子统称为衰老相关分泌表型（SASP）。衰老的原因是多方面的，包括端粒磨损、氧化应激和基因毒性损伤，还包括微生物来源的影响。研究越来越强调微生物群，尤其是肠道微生物群（GM）在调节宿主衰老过程中的作用。有益的微生物代谢产物，如短链脂肪酸（SCFAs），通过维持抗氧化防御和减轻炎症来支持宿主健康，可能会减缓衰老的发生。相反，像铜绿假单胞菌和幽门螺杆菌这样的病原菌会引入损害宿主DNA或增加活性氧的因子，通过NF-κB和p53-p21等途径加速衰老。这篇综述探讨了细菌因素对细胞衰老的影响，强调了特定细菌毒素在促进衰老中的作用。此外，还讨论了生态失调和有益微生物物种的丧失如何进一步导致与年龄相关的细胞退化。调节肠道微生物群以延缓细胞衰老为靶向抗衰老策略开辟了一条道路。这项工作强调了深入研究微生物对衰老的影响的必要性，为管理并可能逆转细胞衰老的创新干预措施提供支持。
