Cancer Treatment-Induced Accelerated Aging in Cancer Survivors: Biology and Assessment

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2021 Jan 27

PMID 33498754

Citations 37

Authors

Shuo Wang

Anna Prizment

Bharat Thyagarajan

Anne Blaes

Affiliations

Soon will be listed here.

Abstract

Rapid improvements in cancer survival led to the realization that many modalities used to treat or control cancer may cause accelerated aging in cancer survivors. Clinically, "accelerated aging" phenotypes in cancer survivors include secondary cancers, frailty, chronic organ dysfunction, and cognitive impairment, all of which can impact long-term health and quality of life in cancer survivors. The treatment-induced accelerated aging in cancer survivors could be explained by telomere attrition, cellular senescence, stem cell exhaustion, DNA damage, and epigenetic alterations. Several aging clocks and biomarkers of aging have been proposed to be potentially useful in estimating biological age, which can provide specific information about how old an individual is biologically independent of chronological age. Measuring biological age in cancer survivors may be important for two reasons. First, it can better predict the risk of cancer treatment-related comorbidities than chronological age. Second, biological age may provide additional value in evaluating the effects of treatments and personalizing cancer therapies to maximize efficacy of treatment. A deeper understanding of treatment-induced accelerated aging in individuals with cancer may lead to novel strategies that reduce the accelerated aging and improve the quality of life in cancer survivors.

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References

Levine M, Hosgood H, Chen B, Absher D, Assimes T, Horvath S . DNA methylation age of blood predicts future onset of lung cancer in the women's health initiative. Aging (Albany NY). 2015; 7(9):690-700. PMC: 4600626. DOI: 10.18632/aging.100809. View

Siddiqui M, Francois M, Fenech M, Leifert W . Persistent γH2AX: A promising molecular marker of DNA damage and aging. Mutat Res Rev Mutat Res. 2015; 766:1-19. DOI: 10.1016/j.mrrev.2015.07.001. View

Zaghlool S, Kuhnel B, Elhadad M, Kader S, Halama A, Thareja G . Epigenetics meets proteomics in an epigenome-wide association study with circulating blood plasma protein traits. Nat Commun. 2020; 11(1):15. PMC: 6941977. DOI: 10.1038/s41467-019-13831-w. View

Heylmann D, Kaina B . The γH2AX DNA damage assay from a drop of blood. Sci Rep. 2016; 6:22682. PMC: 4778029. DOI: 10.1038/srep22682. View

Soto-Perez-de-Celis E, Li D, Yuan Y, Lau Y, Hurria A . Functional versus chronological age: geriatric assessments to guide decision making in older patients with cancer. Lancet Oncol. 2018; 19(6):e305-e316. DOI: 10.1016/S1470-2045(18)30348-6. View

Sebastiani P, Thyagarajan B, Sun F, Schupf N, Newman A, Montano M . Biomarker signatures of aging. Aging Cell. 2017; 16(2):329-338. PMC: 5334528. DOI: 10.1111/acel.12557. View

Flach J, Bakker S, Mohrin M, Conroy P, Pietras E, Reynaud D . Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells. Nature. 2014; 512(7513):198-202. PMC: 4456040. DOI: 10.1038/nature13619. View

Alcorta D, Xiong Y, Phelps D, Hannon G, Beach D, Barrett J . Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. Proc Natl Acad Sci U S A. 1996; 93(24):13742-7. PMC: 19411. DOI: 10.1073/pnas.93.24.13742. View

Johnson A, Akman K, Calimport S, Wuttke D, Stolzing A, de Magalhaes J . The role of DNA methylation in aging, rejuvenation, and age-related disease. Rejuvenation Res. 2012; 15(5):483-94. PMC: 3482848. DOI: 10.1089/rej.2012.1324. View

10.

Kirkland J, Tchkonia T . Clinical strategies and animal models for developing senolytic agents. Exp Gerontol. 2014; 68:19-25. PMC: 4412760. DOI: 10.1016/j.exger.2014.10.012. View

11.

Halvorsen T, Beattie G, Lopez A, Hayek A, Levine F . Accelerated telomere shortening and senescence in human pancreatic islet cells stimulated to divide in vitro. J Endocrinol. 2000; 166(1):103-9. DOI: 10.1677/joe.0.1660103. View

12.

Garagnani P, Bacalini M, Pirazzini C, Gori D, Giuliani C, Mari D . Methylation of ELOVL2 gene as a new epigenetic marker of age. Aging Cell. 2012; 11(6):1132-4. DOI: 10.1111/acel.12005. View

13.

Ribatti D, Tamma R, Annese T . Epithelial-Mesenchymal Transition in Cancer: A Historical Overview. Transl Oncol. 2020; 13(6):100773. PMC: 7182759. DOI: 10.1016/j.tranon.2020.100773. View

14.

Coppe J, Desprez P, Krtolica A, Campisi J . The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol. 2010; 5:99-118. PMC: 4166495. DOI: 10.1146/annurev-pathol-121808-102144. View

15.

Maccormick R . Possible acceleration of aging by adjuvant chemotherapy: a cause of early onset frailty?. Med Hypotheses. 2006; 67(2):212-5. DOI: 10.1016/j.mehy.2006.01.045. View

16.

Liu Y, Sanoff H, Cho H, Burd C, Torrice C, Ibrahim J . Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging. Aging Cell. 2009; 8(4):439-48. PMC: 2752333. DOI: 10.1111/j.1474-9726.2009.00489.x. View

17.

Armenian S, Xu L, Ky B, Sun C, Farol L, Pal S . Cardiovascular Disease Among Survivors of Adult-Onset Cancer: A Community-Based Retrospective Cohort Study. J Clin Oncol. 2016; 34(10):1122-30. PMC: 7357493. DOI: 10.1200/JCO.2015.64.0409. View

18.

Lopez-Otin C, Blasco M, Partridge L, Serrano M, Kroemer G . The hallmarks of aging. Cell. 2013; 153(6):1194-217. PMC: 3836174. DOI: 10.1016/j.cell.2013.05.039. View

19.

Hirano T, Ishihara K, Hibi M . Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene. 2000; 19(21):2548-56. DOI: 10.1038/sj.onc.1203551. View

20.

Sandoval C, Pui C, Bowman L, Heaton D, Hurwitz C, Raimondi S . Secondary acute myeloid leukemia in children previously treated with alkylating agents, intercalating topoisomerase II inhibitors, and irradiation. J Clin Oncol. 1993; 11(6):1039-45. DOI: 10.1200/JCO.1993.11.6.1039. View