Epigenetic age acceleration, telomere length, and neurocognitive function in long-term survivors of childhood cancer

AnnaLynn M. Williams (), Nicholas S. Phillips, Qian Dong, Matthew J. Ehrhardt, Nikesha Gilmore, Kah Poh Loh, Xiaoxi Meng, Kirsten K. Ness, Melissa M. Hudson, Leslie L. Robison, Zhaoming Wang and Kevin R. Krull ()
Additional contact information
AnnaLynn M. Williams: St. Jude Children’s Research Hospital, Department of Epidemiology and Cancer Control
Nicholas S. Phillips: St. Jude Children’s Research Hospital, Department of Psychology and Biobehavioral Sciences
Qian Dong: St. Jude Children’s Research Hospital, Department of Epidemiology and Cancer Control
Matthew J. Ehrhardt: St. Jude Children’s Research Hospital, Department of Epidemiology and Cancer Control
Nikesha Gilmore: University of Rochester School of Medicine and Dentistry, Department of Surgery
Kah Poh Loh: University of Rochester School of Medicine and Dentistry, Department of Medicine
Xiaoxi Meng: St. Jude Children’s Research Hospital, Department of Epidemiology and Cancer Control
Kirsten K. Ness: St. Jude Children’s Research Hospital, Department of Epidemiology and Cancer Control
Melissa M. Hudson: St. Jude Children’s Research Hospital, Department of Epidemiology and Cancer Control
Leslie L. Robison: St. Jude Children’s Research Hospital, Department of Epidemiology and Cancer Control
Zhaoming Wang: St. Jude Children’s Research Hospital, Department of Epidemiology and Cancer Control
Kevin R. Krull: St. Jude Children’s Research Hospital, Department of Psychology and Biobehavioral Sciences

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: Abstract Survivors of childhood cancer are prone to neurocognitive impairment and premature aging, raising concerns about early onset dementia. In this cross-sectional study, 1413 survivors of childhood cancer complete a neuropsychological battery. Mean leukocyte telomere length residual (mLTL) and epigenetic age acceleration (EAA) from five different epigenetic clocks, are derived from linear regression of mLTL or epigenetic age on chronological age. Among survivors treated with CNS-directed therapy, higher EAA, measured by PCGrimAge, or DunedinPACE is associated with worse performance on multiple measures of attention, processing speed, and executive functions (p’s

Date: 2025
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DOI: 10.1038/s41467-025-65664-5

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