4.7 Review

Metabolic reprogramming: a bridge between aging and tumorigenesis

Journal

MOLECULAR ONCOLOGY
Volume 16, Issue 18, Pages 3295-3318

Publisher

WILEY
DOI: 10.1002/1878-0261.13261

Keywords

aging; cellular energetics; immune response; metabolic reprogramming; tumorigenesis

Categories

Funding

  1. NCI [R00CA218686, R00CA218686-04S1, DP2AG0776980]
  2. OD/NIH [DP2AG0776980]
  3. American Lung Association
  4. Florida Health Department BankheadColey Research Program
  5. Florida Breast Cancer Foundation
  6. George Edgecomb Society of Moffitt Cancer Center
  7. Evolutionary Therapy Center of Excellence of Moffitt Cancer Center

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Aging is a significant risk factor for cancer, and the metabolic changes that occur during aging create a favorable environment for tumorigenesis while suppressing immune surveillance. Targeting the metabolic reprogramming that happens during aging may provide new opportunities for cancer prevention and improving the efficacy of cancer treatments.
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.

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