Longitudinal change in epigenetic aging and telomere length in breast cancer survivors

PURPOSE: Cancer treatments may accelerate biological aging, but longitudinal studies of biological markers of aging are needed to better characterize patterns of biological aging over time. METHODS: We followed 184 women with breast cancer (stage 0-III) from diagnosis to 18 months post treatment. We evaluated biological aging in three treatment groups: chemotherapy (with or without radiotherapy), radiotherapy (without chemotherapy), and neither chemotherapy or radiotherapy. Measures of epigenetic age (PCPhenoAge, GrimAge, DunedinPACE) and telomere length were obtained. Linear mixed models estimated within-group change from pre-treatment to immediate post, 6, 12, and 18 months post-treatment. RESULTS: Women who received chemotherapy exhibited increased epigenetic age in PCPhenoAge, GrimAge, and DunedinPACE and shortening of telomere length acutely following treatment (Ps<0.001). The change attenuated but remained significantly different than baseline for GrimAge, DunedinPACE, and telomere length out to 18 months. Women treated with radiotherapy exhibited a trend for increases in PCPhenoAge and significant telomere length shortening 6 months following treatment that remained modified at 18 months (Ps<0.05). There were no significant changes in epigenetic age or telomere length among women who did not receive either chemotherapy or radiation. CONCLUSION: We observed an acceleration of epigenetic age, an increase in the pace of aging, and telomere shortening among women receiving treatment for breast cancer. The effect was predominantly amongst women who received chemotherapy with or without radiation, pointing to this treatment regimen having the most damaging effects. These results support the premise that cancer treatment may accelerate aging and support further research to identify key clinical and biological targets to remediate these effects.