Faster biological aging in younger generations tied to early-onset cancer

Cancer has long been considered a disease that mostly strikes with age, since more years generally means more time for cellular damage to build up. But cancer diagnoses in adults under 55 have been rising, and researchers at Washington University School of Medicine in St. Louis wanted to know whether something else was accelerating that damage in younger people. Their new study, published in Nature Medicine, provides evidence that recent generations are aging faster biologically than earlier ones, and that this faster aging tracks with higher rates of early-onset cancer.

The study distinguishes between chronological age, meaning how many years a person has lived, and biological age, meaning how old the body's tissues and systems appear based on measurable markers. The difference between the two is called the age gap. Researchers found that people born more recently tend to have a larger gap, with their bodies appearing older than their birth year would predict, and that a larger gap was associated with higher cancer risk.

The team, led by molecular epidemiologist Yin Cao, analyzed data from more than 154,000 young adults in the UK Biobank and more than 10,000 people in the United States enrolled in the National Institutes of Health's All of Us Research Program. People in the UK born between 1965 and 1974 showed systemic aging levels that were 23% of one standard deviation higher than those born between 1950 and 1954, after accounting for chronological age. In the US cohort, people born between 1990 and 1999 showed a larger shift, 92% of one standard deviation higher, compared with those born between 1965 and 1969.

To estimate biological age, the researchers used two levels of measurement: aging across the whole body, called systemic aging, and aging within specific organs. For systemic aging, they applied established tools including PhenoAge and the Klemera-Doubal Method. PhenoAge relies on blood biochemistry markers such as albumin, made by the liver, and creatinine, a waste product filtered by the kidneys. They also used a metabolomic age score, a measure built from data on the body's metabolism.

For organ-specific aging, the researchers turned to blood proteomic data, which track levels of proteins linked to particular organ systems, to estimate how old each organ appeared to be relative to the person's actual age. This let them ask not just whether a person's body overall seemed older than expected, but whether specific organs, such as the immune system or fat tissue, were aging faster than the rest of the body. The researchers calculated an average age gap for each birth cohort and used a standard statistical measure of spread, called standard deviation, to compare how far each generation's aging levels departed from the study average.

Across the full study population, increased systemic aging was associated with an 8% higher risk of early-onset solid cancers overall, driven mainly by lung, gastrointestinal and uterine cancers, according to the Nature Medicine paper. People with the most advanced systemic aging had a 15% higher risk of early-onset solid cancer compared with those showing the least advanced aging. This increased risk held up even after the researchers accounted for inherited genetic risk of cancer and genetic tendency toward faster aging.

Zooming into individual organs revealed more specific patterns. An immune system that appeared older than a person's actual age was linked to increased risk of early-onset lung cancer. Fat tissue that appeared biologically older was linked to increased risk of early-onset colorectal cancer. The Nature Medicine paper reports that the association between systemic aging and early-onset lung cancer, measured with PhenoAge, showed a hazard ratio of 1.57 per standard deviation increase, meaning each additional unit of accelerated aging corresponded to a substantially higher relative risk of that cancer.

The researchers also tested an alternative aging measure, the Klemera-Doubal Method, and a metabolomic-based score, and found directionally similar but sometimes weaker results. The Klemera-Doubal measure showed a weaker overall association with early-onset solid cancers than PhenoAge did, but still showed increased risk for early-onset lung and gastrointestinal cancers. The metabolomic score showed a modest association with cancers overall, driven by lung and uterine cancer, while its link to gastrointestinal and colorectal cancer was not statistically significant. The researchers describe this as validation showing consistent direction across different aging measures, even where the strength of the association varied.

The study's authors and outside cancer researchers are careful to note what remains unresolved. David Scott, director of Cancer Grand Challenges, the initiative that helped fund the work, said there is no definitive answer yet for what is driving the global rise in early-onset cancers, and that studies like this one are helping researchers piece together a broader picture in which cancer may be shaped by changes across the whole body, not only inside individual cells. Cao's team has previously identified individual risk factors such as obesity, alcohol consumption, sedentary behavior, poor diet and cesarean delivery, but noted that the contribution of any single factor is modest, which is part of why they turned to a combined aging measure instead.

Separate research using a different method, called Mendelian randomization, complicates the picture further. A study covered in eLife examined genetic variants linked to several DNA-methylation-based aging clocks and tested whether those variants were also associated with cancer risk. It did not find many clear relationships between epigenetic aging clocks and the cancer types studied, with the strongest signal being a link between one clock, GrimAge, and colorectal cancer, an association the author called not straightforward to interpret because that clock also reflects smoking and other lifestyle-related effects on the epigenome. Other review work has similarly emphasized that while DNA methylation-based epigenetic clocks show promise as biological age predictors, the specific mechanisms connecting age-related molecular changes to cancer risk remain incompletely understood.

Cao's team frames the current findings as a step toward earlier identification of people at high cancer risk, rather than a finished explanation. Their stated next goal is to determine how environmental, lifestyle and societal changes become biologically embedded, leaving lasting marks such as accelerated aging that could be tracked and eventually acted on. Whether such measures can be translated into practical, personalized prevention or early-detection strategies is, per Cao, the aim of ongoing work rather than something this study alone demonstrates.