Metabolic reprogramming: a bridge between aging and tumorigenesis

Abstract

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.

The role of aging in cancer

“…At least some of these changes are likely causative of cancer. Ana Gomes and colleagues review how age-induced metabolic programming alters tissues to promote an environment that is conducive to transformation, and also to suppress immune surveillance and anti-tumor host defenses [50].…”

Finding regulatory modules of chemical reaction systems

“…Various physiological functions can arise even from a single CRN. For instance, a metabolic network is composed of many pathways, such as carbon metabolism and the amino acid synthesis pathway [10, 11]. Since different pathways can share the same chemicals, these pathways are interconnected with each other, forming a single connected metabolic network [12, 13, 14].…”