Department of Molecular Oncology, H. Lee Moffit Cancer Center & Research Institute, Tampa, FL, USA.
Mol Oncol. 2022 Sep;16(18):3295-3318. doi: 10.1002/1878-0261.13261. Epub 2022 Jun 19.
Aging is the most robust risk factor for cancer development, with more than 60% of cancers occurring in those aged 60 and above. However, how aging and tumorigenesis are intertwined is poorly understood and a matter of significant debate. Metabolic changes are hallmarks of both aging and tumorigenesis. The deleterious consequences of aging include dysfunctional cellular processes, the build-up of metabolic byproducts and waste molecules in circulation and within tissues, and stiffer connective tissues that impede blood flow and oxygenation. Collectively, these age-driven changes lead to metabolic reprogramming in different cell types of a given tissue that significantly affects their cellular functions. Here, we put forward the idea that metabolic changes that happen during aging help create a favorable environment for tumorigenesis. We review parallels in metabolic changes that happen during aging and how these changes function both as adaptive mechanisms that enable the development of malignant phenotypes in a cell-autonomous manner and as mechanisms that suppress immune surveillance, collectively creating the perfect environment for cancers to thrive. Hence, antiaging therapeutic strategies that target the metabolic reprogramming that occurs as we age might provide new opportunities to prevent cancer initiation and/or improve responses to standard-of-care anticancer therapies.
衰老是癌症发展最强大的风险因素，超过 60%的癌症发生在 60 岁及以上的人群中。然而，衰老和肿瘤发生是如何相互交织的还知之甚少，这是一个非常有争议的问题。代谢变化是衰老和肿瘤发生的共同特征。衰老的有害后果包括细胞功能失调、代谢副产物和循环及组织内废物分子的积累，以及更僵硬的结缔组织阻碍血液流动和氧气供应。这些由年龄驱动的变化共同导致特定组织中不同细胞类型的代谢重编程，从而显著影响其细胞功能。在这里，我们提出这样一种观点，即衰老过程中发生的代谢变化有助于为肿瘤发生创造有利的环境。我们回顾了衰老过程中发生的代谢变化的相似之处，以及这些变化如何既能作为使恶性表型在细胞自主方式中发展的适应性机制，又能作为抑制免疫监视的机制，共同为癌症的蓬勃发展创造完美的环境。因此，针对我们衰老时发生的代谢重编程的抗衰老治疗策略可能为预防癌症的发生和/或改善对标准抗癌治疗的反应提供新的机会。
