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 et al.. Nature communications, 2025-11-27
Topic: Brain imaging, connectivity and assessment
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 < 0.05). Among non-CNS-treated survivors, results are similar for PCGrimAge, however, DunedinPACE is specifically associated with attention variability (p < 0.05). mLTL is not associated with neurocognition. EAA is associated with worse neurocognitive function and may identify survivors at risk for accelerated cognitive aging or serve as an efficacy biomarker for neurocognitive interventions.
Key findings
- 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 < 0.05).
- Among non-CNS-treated survivors, results are similar for PCGrimAge, however, DunedinPACE is specifically associated with attention variability (p < 0.05). mLTL is not associated with neurocognition.
- EAA is associated with worse neurocognitive function and may identify survivors at risk for accelerated cognitive aging or serve as an efficacy biomarker for neurocognitive interventions.
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Study details
- Study designcross-sectional
- Evidence strengthLow
How this study scored 54/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 30 of the 56 points we could judge it on, which is 54 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature communications) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41309628) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 30 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 30 of the 56 points we could judge it on is 54 out of 100. |
| Total | 54 / 100 | — |
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APA 7th
Williams, A. M., Phillips, N. S., Dong, Q., Ehrhardt, M. J., Gilmore, N., Loh, K. P., et al. (2025). Epigenetic age acceleration, telomere length, and neurocognitive function in long-term survivors of childhood cancer. Nature communications. https://doi.org/10.1038/s41467-025-65664-5
Vancouver
Williams AM, Phillips NS, Dong Q, Ehrhardt MJ, Gilmore N, Loh KP, et al. Epigenetic age acceleration, telomere length, and neurocognitive function in long-term survivors of childhood cancer. Nature communications. 2025. doi:10.1038/s41467-025-65664-5. PMID: 41309628.
BibTeX
@article{williams2025-41309628,
author = {Williams, AnnaLynn M and Phillips, Nicholas S and Dong, Qian and Ehrhardt, Matthew J and Gilmore, Nikesha and Loh, Kah Poh and Meng, Xiaoxi and Ness, Kirsten K and others},
title = {{Epigenetic age acceleration, telomere length, and neurocognitive function in long-term survivors of childhood cancer}},
journal = {Nature communications},
year = {2025},
doi = {10.1038/s41467-025-65664-5},
pmid = {41309628},
url = {https://doi.org/10.1038/s41467-025-65664-5}
}