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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

Nature Cancer volume 5, pages 731–741 (2024)Cite this article

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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.

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Fig. 1: CONSORT diagram.
Fig. 2: Biological age according to chronological age.
Fig. 3: Kaplan–Meier survival curves of BAA and all-cause mortality.

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Data availability

The dataset supporting the findings of this study has been deposited in Zenodo and is publicly available online at https://doi.org/10.5281/zenodo.1003525 and https://stjude.cloud. The DNA methylation data used in this study are accessible at the NCBI Gene Expression Omnibus website under accession no. GSE197674 for survivors and accession no. GSE197676 for controls. Source data are provided with this paper (Supplementary Data 2). All other data supporting the findings of this study are available from the co-corresponding authors upon reasonable request.

Code availability

The code supporting this study’s findings is publicly available at https://doi.org/10.5281/zenodo.10035257 (ref. 45) and are provided in Supplementary Data 1.

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Acknowledgements

Research reported in this publication was supported by the National Cancer Institute (NCI) of the National Institutes of Health (NIH) under award nos. U01CA195547 and P30CA021765, the American Lebanese Syrian Associated Charities and an NCI postdoctoral Cancer Research Training Award fellowship awarded to J.L.G. This work is solely the authors’ responsibility and does not necessarily represent the official views of the NCI or the NIH.

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Authors and Affiliations

  1. Division of Cancer Control and Populations Sciences, National Cancer Institute, Rockville, MD, USA

    Jennifer L. Guida, Paige A. Green & Brennan P. Streck

  2. Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Geehong Hyun, Gregory T. Armstrong, Matthew J. Ehrhardt, Melissa M. Hudson, Leslie L. Robison, Yutaka Yasui, Carmen L. Wilson, Zhaoming Wang & Kirsten K. Ness

  3. Department of Epidemiology and Butler Columbia Aging Center, Columbia University Mailman School of Public Health, New York, NY, USA

    Daniel W. Belsky

  4. Office of Cancer Survivorship, National Cancer Institute, Rockville, MD, USA

    Emily S. Tonorezos

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Contributions

J.L.G., G.H., D.W.B., G.T.A., M.J.E., M.M.H., P.A.G., L.L.R., B.P.S., E.S.T., Y.Y., C.L.W., Z.W. and K.K.N. contributed to study design, and manuscript writing, reviewing and editing. M.M.H., G.T.A., L.L.R., K.K.N., Z.W., G.H., C.L.W. and Y.Y. prepared the materials and collected the data. Z.W. and G.H. curated the data. G.H. conducted the statistical analysis. J.L.G. provided project administration and wrote the original draft. K.K.N. and P.A.G. supervised the project. All authors read and approved the final manuscript.

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Correspondence to Zhaoming Wang or Kirsten K. Ness.

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Guida, J.L., Hyun, G., Belsky, D.W. et al. 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. Nat Cancer 5, 731–741 (2024). https://doi.org/10.1038/s43018-024-00745-w

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