Metabolic reprogramming: a bridge between aging and tumorigenesis

• Published in: Molecular oncology Vol. 16; no. 18; pp. 3295 - 3318
• Main Authors: Drapela, Stanislav, Ilter, Didem, Gomes, Ana P.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.09.2022; Wiley
• Subjects: Adenosine; Aging; Antigens; Blood flow; Cancer; cellular energetics; Centenarians; Connective tissues; Cytotoxicity; Enzymes; Genomes; Glucose; Hypotheses; Hypoxia; immune response; Immune system; Immunosurveillance; Immunotherapy; Kinases; Lymphocytes; Medical prognosis; Medical screening; metabolic reprogramming; Metabolism; Metabolites; Mitochondrial DNA; Mutation; Oldest old people; Oxidation; Oxygenation; Phenotypes; Physiology; Proteins; Risk factors; Tumorigenesis; Aging; cellular energetics; tumorigenesis; immune response; metabolic reprogramming
• ISSN: 1574-7891; 1878-0261
• DOI: 10.1002/1878-0261.13261

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. Tumorigenicity and immune function are linked to the metabolic status of the host. As an organism ages, changes in metabolism, including changes in nutrient sensing, cellular energetics, and redox balance, produce an environment conducive to tumor initiation. Thus, strategies that promote metabolic rejuvenation might prevent age‐related tumor initiation and enhance the effectiveness of anticancer therapies.