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An epigenetic clock reads chemical marks on DNA and estimates how old the body looks, which is not always the age on a birth certificate. In survivors of childhood cancer the clock runs ahead of chronological age, and the gap is larger after radiotherapy and after certain chemotherapy drugs. What the gap means for any one person is not yet known, and the clocks do not agree with each other.
Epigenetic clocks estimate biological age from DNA methylation at a few hundred sites. In the St Jude Lifetime Cohort, methylation was measured in blood from 2,139 adult survivors of childhood cancer and 282 matched controls. Epigenetic age acceleration, the residual of epigenetic age regressed on chronological age using Levine's clock, was higher in survivors than in controls: adjusted least-square mean 0.63 years (95% CI 0.26 to 1.01) in survivors against -3.61 in controls. Within survivors, acceleration was significantly higher after chest radiotherapy, abdominal or pelvic radiotherapy, alkylating agents, glucocorticoids or epipodophyllotoxins, and it tracked health behaviour: 0.26 years with favourable behaviours, 1.07 with intermediate, 1.45 with unfavourable.
The acute picture is less tidy, and this is where cohorts disagree. In 94 women with early breast cancer sampled before and after adjuvant treatment, extrinsic, phenotypic and GrimAge acceleration and the estimated proportion of senescent T lymphocytes all rose; but when the groups were separated, most of those rises were significant only in the women who had radiotherapy alone, not in those who had chemotherapy and radiotherapy. A clock can also move because the mix of blood cells changed rather than because tissue aged, which is why intrinsic and extrinsic measures diverge.
In 1,413 long-term survivors of childhood cancer, higher acceleration on the PCGrimAge and DunedinPACE clocks was associated with worse attention, processing speed and executive function; mean leukocyte telomere length was not associated with neurocognition in the same study. No clock is validated as a clinical test, none is used to make a treatment decision, and no trial has shown that moving a clock changes what happens to a person. Clocks sold direct to consumers are not these clocks and are not interpretable against this literature.
DNA methylation at CpG sites changes with age in a sufficiently regular way that a penalised regression can predict chronological age from it; the residual, how much older or younger the methylation looks than the calendar says, is called epigenetic age acceleration. Later clocks (PhenoAge, GrimAge, DunedinPACE) are trained on mortality, clinical biomarkers or rate of change rather than on calendar age, which is why they behave differently from the first-generation clocks in the same blood sample.
Query for this technology: (TITLE:"epigenetic age acceleration" OR ABSTRACT:"epigenetic age acceleration" OR TITLE:"epigenetic clock" OR ABSTRACT:"epigenetic clock" OR TITLE:"DNA methylation age" OR ABSTRACT:"DNA methylation age") AND ((cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma) OR survivor). Results are unfiltered search hits about Epigenetic age after cancer treatment, not a curated reading list.
Shares Senescent cells and p16 after chemotherapy, Cellular senescence, What actually works after treatment, Late effects and survivorship toxicity and the tags rejuvenation, survivorship.
Shares What actually works after treatment, Quality of life, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance and the tags rejuvenation, survivorship.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance and the tags rejuvenation, survivorship.
Shares What actually works after treatment, Quality of life, Survivorship care and late-effects surveillance and the tags rejuvenation, survivorship.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.