A new study links accelerated aging to early-onset solid cancers, while showing that this gap is becoming wider with each new generation [1].
Why do more young people get cancer?
While life expectancy has been on the rise for decades (though it has slowed in recent years), counterintuitively, early-onset cancer is becoming more common. Cancers diagnosed before age 50 rose significantly worldwide between 1990 and 2019, and the trend is getting steeper [2].
Scientists have been struggling to understand the causes behind this phenomenon. Various environmental exposures, from ultra-processed food to air pollution to microplastic contamination, have been proposed. This is even more baffling considering that the prevalence of some of the most carcinogenic habits, such as smoking and alcohol consumption, has been falling.
A new study from Washington University in St. Louis, published in Nature Medicine, does not claim to provide a clear solution to this puzzle. Instead, the authors turned to the concept of the “age gap” – the difference between a person’s biological and chronological age – and asked whether this gap is wider for younger generations and whether it correlates with cancer statistics.
“Our ultimate goal is to decode how modern environments become biologically embedded to drive cancer risk, transforming prevention from broad recommendations to personalized interventions,” said Yin Cao, ScD, a molecular epidemiologist and an associate professor of surgery and of medicine at WashU Medicine. “This brings us closer to identifying risk earlier and developing prevention strategies that are tailored to an individual’s biology.”
Measuring how old you really are
The main tool that the researchers used to estimate biological age was PhenoAge, a popular clock based on a set of nine blood biochemistry markers and originally trained to predict mortality and morbidity. Turning to the UK Biobank, a repository of health data on half a million Britons, they asked if this age gap has shifted across generations.
Apparently, it has. Among more than 154 thousand participants under 55, those born in 1965 to 1974 carried a noticeably wider gap than their parents’ generation born in 1950 to 1954 (technically, a 0.23-standard-deviation increase). In other words, younger generations may be biologically older than their parents were at the same age, though the authors’ measurement is relative rather than absolute, so it does not establish that quite so cleanly.
An older body, a higher cancer risk
Tracking the participants over time, the researchers found that a larger age gap predicted more early-onset solid cancer. Each standard deviation increase raised the overall risk by 8%. The effect was concentrated at specific sites: lung (a massive 57% increase per standard deviation), gastrointestinal cancers, and uterine cancer.
Crucially, the association was much weaker for the same cancers diagnosed after 55, which suggests that this gap matters most early in life. It also survived adjustment for inherited risk factors, such as telomere length (a classic marker of cellular aging) and polygenic risk scores for both aging and cancer. Essentially, whatever the age gap is capturing, it is probably more than genetics.
The authors repeated the analysis with a blood-based clock that is trained to track chronological age (KDM) along with a metabolomic clock based on blood metabolites. While neither reproduced the overall association cleanly, both flagged the same outlier – lung cancer – and the metabolomic clock also picked up uterine cancer.
To connect the damage to specific organs, the team built organ-specific aging clocks using proteomics. In this analysis, an aged immune system tracked with early-onset lung cancer, and aged adipose tissue tracked with early-onset colorectal cancer. Both associations held up even after accounting for whole-body aging, hinting that individual organs age on their own schedules and carry their own risks – an idea supported by recent research on organ-specific aging [3].
Does it hold outside Britain?
Finally, the authors analyzed the pattern in a different population: the US All of Us Research Program, which skews younger and more diverse. The generational difference was even sharper: those born in the 1990s carried a much wider gap than people born in the late 1960s (a 0.92-standard-deviation increase). Here too, a bigger gap predicted early-onset cancer, with each standard deviation increase raising risk by 22%.
This observational study cannot prove causation, but it offers a testable idea: that whatever is aging us faster may also be contributing to the risk of early cancer. “If we can identify younger people with the highest cancer risk when they are still healthy, we can focus on prevention and early-detection strategies for the individuals who will benefit most from early interventions,” Cao said.
Literature
[1] Tian, R., Zong, X., Ren, D. et al. (2026). Biological aging and generational shifts in early-onset cancer risk. Nat Med.
[2] Zhao, J., Xu, L., Sun, J., Song, M., Wang, L., Yuan, S., … & Li, X. (2023). Global trends in incidence, death, burden and risk factors of early-onset cancer from 1990 to 2019. BMJ oncology, 2(1), e000049.
[3] Oh, H. S. H., Rutledge, J., Nachun, D., Pálovics, R., Abiose, O., Moran-Losada, P., … & Wyss-Coray, T. (2023). Organ aging signatures in the plasma proteome track health and disease. Nature, 624(7990), 164-172.
View the article at lifespan.io
