Associations of Seven Measures of Biological Age Acceleration with Frailty and All-cause Mortality Among Adult Survivors of Childhood Cancer in the St. Jude Lifetime Cohort

Overview

Journal Nat Cancer

Specialty Oncology

Date 2024 Mar 30

PMID 38553617

Authors

Jennifer L Guida

Geehong Hyun

Daniel W Belsky

Gregory T Armstrong

Matthew J Ehrhardt

Melissa M Hudson

Paige A Green

Leslie L Robison

Brennan P Streck

Emily S Tonorezos

Yutaka Yasui

Carmen L Wilson

Zhaoming Wang

Kirsten K Ness

Affiliations

Soon will be listed here.

Abstract

Survivors of childhood cancer may experience accelerated biological aging, resulting in premature frailty and death. We used seven measures of biological age in the St. Jude Lifetime (SJLIFE) Cohort to compare biological age acceleration between the SJLIFE Cohort and the third United States National Health and Nutrition Examination Survey controls, explore trajectories of biological age according to cancer treatment and type, and test associations of biological age acceleration with frailty and death (mean follow-up of 26.5 years) among survivors. Survivors of cancer aged 5% faster per year and measured, on average, 0.6-6.44 years biologically older compared to controls and 5-16 years biologically older compared to age-matched individuals at the population level. Survivors treated with hematopoietic cell transplant and vinca alkaloid chemotherapy evidenced the fastest trajectories of biological aging. Biologically, older and faster-aging survivors consistently and robustly had a higher risk of frailty and died earlier than those with slower biological aging, suggesting a potential opportunity to intervene on excess aging.

Citing Articles

Epidemiology of multimorbidity in childhood cancer survivors: a matched cohort study of inpatient hospitalisations in Western Australia.

Abdalla T, Ohan J, Ives A, White D, Choong C, Bulsara M BJC Rep. 2025; 3(1):15.

PMID: 40082620 PMC: 11906868. DOI: 10.1038/s44276-024-00114-1.

Effects of Systemic Anticancer Treatment on Cardiorespiratory Fitness: A Systematic Review and Meta-Analysis.

Johansen S, Wisloff T, Edvardsen E, Kollerud S, Jensen J, Agwu G JACC CardioOncol. 2025; 7(2):96-106.

PMID: 39967210 PMC: 11866419. DOI: 10.1016/j.jaccao.2024.11.004.

Digital humanistic program to manage premature frailty in young breast cancer survivors with gender perspective.

Hu Y, Wiley J, Jiang L, Wang X, Yi R, Xu J NPJ Digit Med. 2025; 8(1):35.

PMID: 39820349 PMC: 11739469. DOI: 10.1038/s41746-025-01439-y.

Rethinking the rise of early-onset gastrointestinal cancers: a call to action.

Weinberg B, Murphy C, Freyer D, Greathouse K, Blancato J, Stoffel E JNCI Cancer Spectr. 2025; 9(1).

PMID: 39814070 PMC: 11804804. DOI: 10.1093/jncics/pkaf002.

Frailty and neurocognitive impairments in Chinese survivors of childhood cancer.

Wei Y, Deng W, To K, Lam T, Tso W, Chan A J Cancer Surviv. 2025; .

PMID: 39753896 DOI: 10.1007/s11764-024-01739-4.

References

Belsky D, Caspi A, Houts R, Cohen H, Corcoran D, Danese A . Quantification of biological aging in young adults. Proc Natl Acad Sci U S A. 2015; 112(30):E4104-10. PMC: 4522793. DOI: 10.1073/pnas.1506264112. View

Daniel S, Nylander V, Ingerslev L, Zhong L, Fabre O, Clifford B . T cell epigenetic remodeling and accelerated epigenetic aging are linked to long-term immune alterations in childhood cancer survivors. Clin Epigenetics. 2018; 10(1):138. PMC: 6219017. DOI: 10.1186/s13148-018-0561-5. View

Ness K, Krull K, Jones K, Mulrooney D, Armstrong G, Green D . Physiologic frailty as a sign of accelerated aging among adult survivors of childhood cancer: a report from the St Jude Lifetime cohort study. J Clin Oncol. 2013; 31(36):4496-503. PMC: 3871511. DOI: 10.1200/JCO.2013.52.2268. View

Elliott M, Caspi A, Houts R, Ambler A, Broadbent J, Hancox R . Disparities in the pace of biological aging among midlife adults of the same chronological age have implications for future frailty risk and policy. Nat Aging. 2021; 1(3):295-308. PMC: 8009092. DOI: 10.1038/s43587-021-00044-4. View

Margolick J, Ferrucci L . Accelerating aging research: how can we measure the rate of biologic aging?. Exp Gerontol. 2015; 64:78-80. PMC: 4612579. DOI: 10.1016/j.exger.2015.02.009. View

Song N, Li Z, Qin N, Howell C, Wilson C, Easton J . Shortened Leukocyte Telomere Length Associates with an Increased Prevalence of Chronic Health Conditions among Survivors of Childhood Cancer: A Report from the St. Jude Lifetime Cohort. Clin Cancer Res. 2020; 26(10):2362-2371. PMC: 7231652. DOI: 10.1158/1078-0432.CCR-19-2503. View

Guida J, Ahles T, Belsky D, Campisi J, Cohen H, DeGregori J . Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors. J Natl Cancer Inst. 2019; 111(12):1245-1254. PMC: 7962788. DOI: 10.1093/jnci/djz136. View

Arora M, Sun C, Ness K, Teh J, Wu J, Francisco L . Physiologic Frailty in Nonelderly Hematopoietic Cell Transplantation Patients: Results From the Bone Marrow Transplant Survivor Study. JAMA Oncol. 2016; 2(10):1277-1286. PMC: 5078990. DOI: 10.1001/jamaoncol.2016.0855. View

Walsh K . Telomere Attrition in Childhood Cancer Survivors. Clin Cancer Res. 2020; 26(10):2281-2283. DOI: 10.1158/1078-0432.CCR-20-0380. View

10.

Piercy K, Troiano R, Ballard R, Carlson S, Fulton J, Galuska D . The Physical Activity Guidelines for Americans. JAMA. 2018; 320(19):2020-2028. PMC: 9582631. DOI: 10.1001/jama.2018.14854. View

11.

Fried L, Tangen C, Walston J, Newman A, Hirsch C, Gottdiener J . Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001; 56(3):M146-56. DOI: 10.1093/gerona/56.3.m146. View

12.

Levine M . Modeling the rate of senescence: can estimated biological age predict mortality more accurately than chronological age?. J Gerontol A Biol Sci Med Sci. 2012; 68(6):667-74. PMC: 3660119. DOI: 10.1093/gerona/gls233. View

13.

Smitherman A, Wood W, Mitin N, Miller V, Deal A, Davis I . Accelerated aging among childhood, adolescent, and young adult cancer survivors is evidenced by increased expression of p16 and frailty. Cancer. 2020; 126(22):4975-4983. PMC: 7607511. DOI: 10.1002/cncr.33112. View

14.

Arnold N, Merzenich H, Wingerter A, Schulz A, Schneider A, Prochaska J . Promotion of Arterial Stiffness by Childhood Cancer and Its Characteristics in Adult Long-Term Survivors. J Am Heart Assoc. 2021; 10(5):e015609. PMC: 8174251. DOI: 10.1161/JAHA.119.015609. View

15.

Ariffin H, Azanan M, Abd Ghafar S, Oh L, Lau K, Thirunavakarasu T . Young adult survivors of childhood acute lymphoblastic leukemia show evidence of chronic inflammation and cellular aging. Cancer. 2017; 123(21):4207-4214. DOI: 10.1002/cncr.30857. View

16.

Armenian S, Sun C, Kawashima T, Arora M, Leisenring W, Sklar C . Long-term health-related outcomes in survivors of childhood cancer treated with HSCT versus conventional therapy: a report from the Bone Marrow Transplant Survivor Study (BMTSS) and Childhood Cancer Survivor Study (CCSS). Blood. 2011; 118(5):1413-20. PMC: 3152502. DOI: 10.1182/blood-2011-01-331835. View

17.

Klemera P, Doubal S . A new approach to the concept and computation of biological age. Mech Ageing Dev. 2005; 127(3):240-8. DOI: 10.1016/j.mad.2005.10.004. View

18.

Horvath S, Raj K . DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet. 2018; 19(6):371-384. DOI: 10.1038/s41576-018-0004-3. View

19.

Hudson M, Ness K, Nolan V, Armstrong G, Green D, Morris E . Prospective medical assessment of adults surviving childhood cancer: study design, cohort characteristics, and feasibility of the St. Jude Lifetime Cohort study. Pediatr Blood Cancer. 2011; 56(5):825-36. PMC: 3088729. DOI: 10.1002/pbc.22875. View

20.

Liu Z, Kuo P, Horvath S, Crimmins E, Ferrucci L, Levine M . A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study. PLoS Med. 2019; 15(12):e1002718. PMC: 6312200. DOI: 10.1371/journal.pmed.1002718. View