Shen Weiyi, He Jiamin, Hou Tongyao, Si Jianmin, Chen Shujie
1Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang, China.
2Institute of Gastroenterology, Zhejiang University, Hangzhou 310016, Zhejiang, China.
Aging Dis. 2022 Jul 11;13(4):1063-1091. doi: 10.14336/AD.2021.1208.
Recently, there has been an increase in the incidence of malignant tumors among the older population. Moreover, there is an association between aging and cancer. During the process of senescence, the human body suffers from a series of imbalances, which have been shown to further accelerate aging, trigger tumorigenesis, and facilitate cancer progression. Therefore, exploring the junctions of aging and cancer and searching for novel methods to restore the junctions is of great importance to intervene against aging-related cancers. In this review, we have identified the underlying pathogenetic mechanisms of aging-related cancers by comparing alterations in the human body caused by aging and the factors that trigger cancers. We found that the common mechanisms of aging and cancer include cellular senescence, alterations in proteostasis, microbiota disorders (decreased probiotics and increased pernicious bacteria), persistent chronic inflammation, extensive immunosenescence, inordinate energy metabolism, altered material metabolism, endocrine disorders, altered genetic expression, and epigenetic modification. Furthermore, we have proposed that aging and cancer have common means of intervention, including novel uses of common medicine (metformin, resveratrol, and rapamycin), dietary restriction, and artificial microbiota intervention or selectively replenishing scarce metabolites. In addition, we have summarized the research progress of each intervention and revealed their bidirectional effects on cancer progression to compare their reliability and feasibility. Therefore, the study findings provide vital information for advanced research studies on age-related cancers. However, there is a need for further optimization of the described methods and more suitable methods for complicated clinical practices. In conclusion, targeting aging may have potential therapeutic effects on aging-related cancers.
近年来,老年人群中恶性肿瘤的发病率呈上升趋势。此外,衰老与癌症之间存在关联。在衰老过程中,人体会出现一系列失衡,这些失衡已被证明会进一步加速衰老、引发肿瘤发生并促进癌症进展。因此,探索衰老与癌症的交汇点并寻找恢复这些交汇点的新方法对于干预与衰老相关的癌症至关重要。在这篇综述中,我们通过比较衰老引起的人体变化和引发癌症的因素,确定了与衰老相关癌症的潜在发病机制。我们发现衰老和癌症的共同机制包括细胞衰老、蛋白质稳态改变、微生物群紊乱(益生菌减少和有害细菌增加)、持续性慢性炎症、广泛的免疫衰老、过度的能量代谢、物质代谢改变、内分泌紊乱、基因表达改变和表观遗传修饰。此外,我们提出衰老和癌症有共同的干预手段,包括常用药物(二甲双胍、白藜芦醇和雷帕霉素)的新用途、饮食限制以及人工微生物群干预或选择性补充稀缺代谢物。此外,我们总结了每种干预措施的研究进展,并揭示了它们对癌症进展的双向影响,以比较其可靠性和可行性。因此,该研究结果为与年龄相关癌症的进一步研究提供了重要信息。然而,需要进一步优化所描述的方法,并为复杂的临床实践找到更合适的方法。总之,针对衰老可能对与衰老相关的癌症具有潜在治疗作用。