Accelerated epigenetic aging of cancer survivors: insights from NHANES 1999–2002 data

Background

Cancer survivors experience more aging-related health conditions than non-cancer controls. However, evidence directly linking biological aging to cancer survivorship remains limited. This study investigated the associations between epigenetic age acceleration, the pace of aging, and cancer survivorship, focusing on variations in biological aging across different cancer types and years since diagnosis.

Methods

A cross-sectional analysis of NHANES 1999–2002 data examined 2,198 participants with a reported cancer history, detailing cancer type and years since diagnosis. Cancer types were categorized into eight groups: digestive system, gynecologic, skin, hematologic, respiratory system, bladder and kidney, prostate and testis, and other cancers. Time since diagnosis was categorized into four intervals: <7, 7–13, 14–20, and >20 years. The study assessed DNAm-based epigenetic age using various clocks, including HannumAge, HorvathAge, SkinBloodAge, PhenoAge, GrimAge, GrimAge version 2, and DunedinPACE as an indicator of aging pace.

Results

Cancer survivors showed significantly higher chronologic age and epigenetic clocks compared to non-cancer controls. Multivariable regression analysis revealed significant associations between cancer survivorship and second-generation epigenetic clocks, including PhenoAge, GrimAge, and GrimAge2. These associations varied by cancer type. The DunedinPACE indicated a significantly faster pace of aging in survivors, particularly in those with gynecologic, hematologic, and respiratory system cancers. Accelerated epigenetic aging was most evident 7–14 years after cancer diagnosis.

Interpretation

We found a significant association between epigenetic age, the pace of aging, and cancer survivorship. Our findings suggest early interventions targeting age-related conditions in cancer survivors, which could help alleviate disease burden and enhance long-term outcomes.

Key messages

• Cancer survivors exhibit accelerated epigenetic aging compared to controls, particularly across certain cancer types and 7–14 years post-diagnosis.

• Cancer survivorship is significantly associated with biological aging, highlighting the importance of early interventions to improve long-term health outcomes.