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

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.

Fig. 1:

Scatterplots and linear regression lines of biological age by chronological age (i.e., age at DNA sampling) for childhood cancer survivors (N = 4117) and community controls (N = 606) in the St. Jude Lifetime Cohort Study.

Fig. 2:

Kaplan-Meier survival curves of biological age acceleration and all-cause mortality among St. Jude Lifetime Cohort Study childhood cancer survivors (N = 4117). Note: all models are unadjusted and the sample sizes analyzed (n = (2,044, 3,658)) differ by biological age measure.

Fig. 3:

Consort diagram of the St. Jude Lifetime (SJLIFE) Cohort Study childhood cancer survivors (N = 8,777) and community controls (N = 836), and the National Health and Nutrition Examination Survey (NHANES) III (N = 39,695) study samples.