The Complex Interplay Between Aging and Cancer

Overview

Journal Nat Aging

Specialty Geriatrics

Date 2025 Mar 4

PMID 40038418

Authors

Lucrezia A Trastus

Fabrizio dAdda di Fagagna

Affiliations

Soon will be listed here.

Abstract

Cancer is an age-related disease, but the interplay between cancer and aging is complex and their shared molecular drivers are deeply intertwined. This Review provides an overview of how different biological pathways affect cancer and aging, leveraging evidence mainly derived from animal studies. We discuss how genome maintenance and accumulation of DNA mutations affect tumorigenesis and tissue homeostasis during aging. We describe how age-related telomere dysfunction and cellular senescence intricately modulate tumor development through mechanisms involving genomic instability and inflammation. We examine how an aged immune system and chronic inflammation shape tumor immunosurveillance, fueling DNA damage and cellular senescence. Finally, as animal models are important to untangling the relative contributions of these aging-modulated pathways to cancer progression and to test interventions, we discuss some of the limitations of physiological and accelerated aging models, aiming to improve experimental designs and enhance translation.

References

Bray F, Laversanne M, Sung H, Ferlay J, Siegel R, Soerjomataram I . Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024; 74(3):229-263. DOI: 10.3322/caac.21834. View

DeSantis C, Miller K, Dale W, Mohile S, Cohen H, Leach C . Cancer statistics for adults aged 85 years and older, 2019. CA Cancer J Clin. 2019; 69(6):452-467. DOI: 10.3322/caac.21577. View

Mattiuzzi C, Lippi G . Current Cancer Epidemiology. J Epidemiol Glob Health. 2019; 9(4):217-222. PMC: 7310786. DOI: 10.2991/jegh.k.191008.001. View

Radkiewicz C, Jarkvik Kronmark J, Adami H, Edgren G . Declining Cancer Incidence in the Elderly: Decreasing Diagnostic Intensity or Biology?. Cancer Epidemiol Biomarkers Prev. 2021; 31(1):280-286. DOI: 10.1158/1055-9965.EPI-21-0797. View

Lopez-Otin C, Blasco M, Partridge L, Serrano M, Kroemer G . Hallmarks of aging: An expanding universe. Cell. 2023; 186(2):243-278. DOI: 10.1016/j.cell.2022.11.001. View

Zhao Y, Simon M, Seluanov A, Gorbunova V . DNA damage and repair in age-related inflammation. Nat Rev Immunol. 2022; 23(2):75-89. PMC: 10106081. DOI: 10.1038/s41577-022-00751-y. View

Niedernhofer L, Gurkar A, Wang Y, Vijg J, Hoeijmakers J, Robbins P . Nuclear Genomic Instability and Aging. Annu Rev Biochem. 2018; 87:295-322. DOI: 10.1146/annurev-biochem-062917-012239. View

Folgueras A, Freitas-Rodriguez S, Velasco G, Lopez-Otin C . Mouse Models to Disentangle the Hallmarks of Human Aging. Circ Res. 2018; 123(7):905-924. DOI: 10.1161/CIRCRESAHA.118.312204. View

Laconi E, Marongiu F, DeGregori J . Cancer as a disease of old age: changing mutational and microenvironmental landscapes. Br J Cancer. 2020; 122(7):943-952. PMC: 7109142. DOI: 10.1038/s41416-019-0721-1. View

10.

Guarente L, Sinclair D, Kroemer G . Human trials exploring anti-aging medicines. Cell Metab. 2024; 36(2):354-376. DOI: 10.1016/j.cmet.2023.12.007. View

11.

Foley N, Hughes G, Huang Z, Clarke M, Jebb D, Whelan C . Growing old, yet staying young: The role of telomeres in bats' exceptional longevity. Sci Adv. 2018; 4(2):eaao0926. PMC: 5810611. DOI: 10.1126/sciadv.aao0926. View

12.

Cagan A, Baez-Ortega A, Brzozowska N, Abascal F, Coorens T, Sanders M . Somatic mutation rates scale with lifespan across mammals. Nature. 2022; 604(7906):517-524. PMC: 9021023. DOI: 10.1038/s41586-022-04618-z. View

13.

Tian X, Azpurua J, Hine C, Vaidya A, Myakishev-Rempel M, Ablaeva J . High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature. 2013; 499(7458):346-9. PMC: 3720720. DOI: 10.1038/nature12234. View

14.

Seluanov A, Gladyshev V, Vijg J, Gorbunova V . Mechanisms of cancer resistance in long-lived mammals. Nat Rev Cancer. 2018; 18(7):433-441. PMC: 6015544. DOI: 10.1038/s41568-018-0004-9. View

15.

Hanahan D . Hallmarks of Cancer: New Dimensions. Cancer Discov. 2022; 12(1):31-46. DOI: 10.1158/2159-8290.CD-21-1059. View

16.

Lopez-Otin C, Pietrocola F, Roiz-Valle D, Galluzzi L, Kroemer G . Meta-hallmarks of aging and cancer. Cell Metab. 2023; 35(1):12-35. DOI: 10.1016/j.cmet.2022.11.001. View

17.

Boveri T . Concerning the origin of malignant tumours by Theodor Boveri. Translated and annotated by Henry Harris. J Cell Sci. 2008; 121 Suppl 1:1-84. DOI: 10.1242/jcs.025742. View

18.

Martincorena I, Campbell P . Somatic mutation in cancer and normal cells. Science. 2015; 349(6255):1483-9. DOI: 10.1126/science.aab4082. View

19.

Maciejowski J, Li Y, Bosco N, Campbell P, de Lange T . Chromothripsis and Kataegis Induced by Telomere Crisis. Cell. 2015; 163(7):1641-54. PMC: 4687025. DOI: 10.1016/j.cell.2015.11.054. View

20.

Lee-Six H, Olafsson S, Ellis P, Osborne R, Sanders M, Moore L . The landscape of somatic mutation in normal colorectal epithelial cells. Nature. 2019; 574(7779):532-537. DOI: 10.1038/s41586-019-1672-7. View