A large cohort study in the United Kingdom and United States found that accelerated biological aging is associated with an increased risk of early-onset solid cancers, according to a June 29 publication in Nature Medicine. The research analyzed data from more than 150,000 participants in the United Kingdom Biobank and identified a link between faster systemic biological aging and a higher likelihood of developing cancers before age 55.
The study showed that individuals born between 1965 and 1974 had a 23% higher standardized PhenoAge-defined age gap compared to those born between 1950 and 1954. This suggests that people from later birth cohorts may experience more advanced biological aging profiles, which are linked to an increased risk of early-onset cancer. Researchers said, "People with greater systemic aging, reflected by a higher PhenoAge-determined age gap, showed an increased likelihood of developing early-onset cancers (HR, 1.08 per standard-deviation increase)." Higher age gaps were also connected to elevated risks for lung, gastrointestinal tract, and uterine cancers.
Participants provided demographic information and lifestyle details such as smoking habits, alcohol consumption, educational attainment, family history of cancer, reproductive health factors for women, comorbidities, socioeconomic status using the Townsend Deprivation Index, physical activity levels via the International Physical Activity Questionnaire (IPAQ), genetic ancestry data for polygenic risk scores (PRS), as well as food frequency questionnaires. The researchers excluded individuals with prior or recent cancer diagnoses (except nonmelanoma skin cancer), those with body mass index below 18.5 kg/m², or missing genetic ancestry information.
The team used several methods—including generalized additive models (GAMs) for visualizing trends by birth year; Cox proportional hazards regression models for estimating hazard ratios; alternative systemic aging measures such as Klemera-Doubal method (KDM) and nuclear magnetic resonance metabolomics; proteomic-based organ-specific clocks; and comparison data from over ten thousand participants in the US All of Us Research Program—to validate their findings. They reported directionally consistent associations across different measures but noted some variation depending on the specific clock used.
Researchers found immune tissue aging was associated with early-onset lung cancer while adipose tissue aging was linked to early colorectal cancers. These associations remained after adjusting for systemic aging effects. The findings persisted after excluding participants followed less than two years or adjusting for leukocyte telomere length.
The authors cautioned that because this was an observational study, residual confounding cannot be excluded and organ-specific analyses should be considered exploratory at this stage: "If validated in subsequent studies," they said, "biological aging clocks could help refine future research on early-onset cancer risk and prevention strategies rather than being used immediately in clinical decision-making." They suggested further exploration into underlying mechanisms using longitudinal measurements across diverse populations.
