Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110136, China; Liaoning Clinical Research Center for Laboratory Medicine, Shenyang, Liaoning 110136, China.
Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China.
Semin Cancer Biol. 2024 Sep;104-105:32-45. doi: 10.1016/j.semcancer.2024.07.004. Epub 2024 Aug 8.
Cancer is generally defined as a disease of aging. With aging, the composition, diversity and functional characteristics of the gut microbiota occur changes, with a decline of beneficial commensal microbes triggered by intrinsic and extrinsic factors (e.g., diet, drugs and chronic health conditions). Nowadays, dysbiosis of the gut microbiota is recognized as a hallmark of cancer. At the same time, aging is accompanied by changes in innate and adaptive immunity, known as immunosenescence, as well as chronic low-grade inflammation, known as inflammaging. The elevated cancer incidence and mortality in the elderly are linked with aging-associated alterations in the gut microbiota that elicit systemic metabolic alterations, leading to immune dysregulation with potentially tumorigenic effects. The gut microbiota and immunosenescence might both affect the response to treatment in cancer patients. In-depth understanding of age-associated alterations in the gut microbiota and immunity will shed light on the risk of cancer development and progression in the elderly. Here, we describe the aging-associated changes of the gut microbiota in cancer, and review the evolving understanding of the gut microbiota-targeted intervention strategies. Furthermore, we summarize the knowledge on the cellular and molecular mechanisms of immunosenescence and its impact on cancer. Finally, we discuss the latest knowledge about the relationships between gut microbiota and immunosenescence, with implications for cancer therapy. Intervention strategies targeting the gut microbiota may attenuate inflammaging and rejuvenate immune function to provide antitumor benefits in elderly patients.
癌症通常被定义为一种衰老疾病。随着年龄的增长，肠道微生物群落的组成、多样性和功能特性发生变化，内在和外在因素（如饮食、药物和慢性健康状况）引发有益共生微生物的减少。如今，肠道微生物群落失调被认为是癌症的一个标志。同时，衰老伴随着固有和适应性免疫的变化，称为免疫衰老，以及慢性低度炎症，称为炎症衰老。老年人癌症发病率和死亡率的升高与与年龄相关的肠道微生物群落改变有关，这些改变会引起全身代谢改变，导致免疫失调，可能具有致癌作用。肠道微生物群落和免疫衰老都可能影响癌症患者的治疗反应。深入了解与年龄相关的肠道微生物群落和免疫改变将揭示老年人癌症发展和进展的风险。在这里，我们描述了癌症中与年龄相关的肠道微生物群落变化，并综述了对肠道微生物群落靶向干预策略的不断发展的认识。此外，我们总结了关于免疫衰老的细胞和分子机制及其对癌症影响的知识。最后，我们讨论了关于肠道微生物群落和免疫衰老之间关系的最新知识，这对癌症治疗具有重要意义。靶向肠道微生物群落的干预策略可能会减轻炎症衰老，恢复免疫功能，为老年患者提供抗肿瘤益处。
