Accelerated biological aging may help explain why cancer is increasingly being diagnosed in younger adults. Cancer has long been associated with age, yet newer generations appear to be at greater risk than their predecessors at the same chronological age, according to researchers.
The pattern has led scientists to examine whether younger generations are accumulating biological damage more quickly. A team at Washington University School of Medicine in St. Louis reports evidence that younger cohorts show faster aging on a biological level than older cohorts did at comparable ages.
Investigators are exploring what drives these changes through international collaborations that include members of Siteman Cancer Center at Barnes-Jewish Hospital and WashU Medicine, and Cancer Grand Challenges, a global initiative co-founded by the National Cancer Institute and Cancer Research UK.
Importantly, the study also links accelerated biological aging to a higher likelihood of early-onset cancers, typically defined as diagnoses at age 55 or younger.
A Gap Between Biological Age and Actual Age
Chronological age counts years lived. Biological age reflects how old the body appears based on measurable cellular, organ, metabolic, and other physiological changes.
Researchers found cancer risk rose as the gap between biological and chronological age widened. People from more recent generations tended to have larger gaps than those born earlier, indicating their bodies appeared biologically older at the same chronological age.
This generational shift could help account for part of the increase in cancer among younger adults.
Aging also did not affect all organ systems uniformly. Faster aging in targeted systems correlated with particular cancers. An immune system that appeared older was associated with early-onset lung cancer, and older-appearing adipose tissue was linked to early-onset colorectal cancer.
The findings were published in Nature Medicine.
Measurements of accelerated aging could eventually help clinicians identify younger people at unusually high risk, enabling earlier prevention or screening.
“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 associate professor of surgery and of medicine at WashU Medicine.
Looking Beyond Individual Cancer Risk Factors
Cao’s group has examined lifetime influences on cancer risk, including obesity, metabolic dysregulation, alcohol consumption, sedentary behavior, poor diet quality, and cesarean delivery.
While each factor offers clues, none alone explains the overall rise. This led the team to seek broader measures that capture how multiple influences interact over time to heighten susceptibility.
Backed by Cancer Grand Challenges, Cao, co-lead of Team PROSPECT, expanded the inquiry at scale.
For the study, researchers analyzed data from more than 154,000 young adults in the UK Biobank, which includes extensive biological, health, and lifestyle information.
They also assessed over 10,000 U.S. participants in the National Institutes of Health’s All of Us Research Program, an initiative building a comprehensive health database of more than 1 million people in the United States.
Measuring How Fast the Body Is Aging
To quantify accelerated biological aging, the team, including first author Ruiyi Tian, a doctoral student in the Cao lab, evaluated systemic and organ-specific aging.
Systemic aging captures overall aging across the body. Organ-specific aging estimates how rapidly individual organs or biological systems age.
For systemic aging, the researchers used established clinical biomarker approaches, including PhenoAge and the Klemera-Doubal Method, and a metabolomic age score that reflects age-related metabolic patterns.
PhenoAge, for instance, draws on nine blood biochemistry markers to estimate biological aging, including albumin and creatinine.
For organ-specific aging, the team analyzed blood proteomic data, measuring proteins tied to specific organ systems. Protein patterns informed estimates of biological age for individual organs.
They calculated the average difference between biological and chronological age for each birth cohort and used standard deviation to assess how far each group differed from the overall study average.
Younger Generations Show Older Biological Profiles
The UK and U.S. datasets showed similar generational differences.
In the UK, people born between 1965 and 1974 had systemic aging that was 23 percent of one standard deviation higher than those born between 1950 and 1954, after accounting for chronological age. In practical terms, the younger group tended to have slightly older biological profiles when compared at the same age.
The U.S. data showed a larger gap. Participants born between 1990 and 1999 had systemic aging that was 92 percent of one standard deviation higher than those born between 1965 and 1969.
The researchers then assessed whether these biological aging differences were linked to cancer outcomes.
Accelerated biological aging linked to early-onset cancer
Greater systemic aging in the younger group correlated with an 8 percent increased risk of early-onset solid cancers, with the strongest associations in lung, gastrointestinal, and uterine cancers.
When participants were grouped by systemic aging level, those with the most advanced aging had a 15 percent higher risk of early-onset solid cancer compared with those with the least advanced aging.
These associations persisted after accounting for inherited genetic cancer risk and genetic susceptibility to accelerated aging.
Organ-by-organ analyses revealed targeted links. Advanced immune system aging was associated with a higher risk of early-onset lung cancer. Advanced adipose tissue aging was tied to higher risk of early-onset colorectal 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.
Searching for the Causes of Cancer in Younger Adults
The research forms part of Team PROSPECT, a Cancer Grand Challenges team co-led by Cao.
Cancer Grand Challenges is an international funding initiative co-founded by Cancer Research UK and the National Cancer Institute that convenes scientists across specialties and countries to tackle difficult problems in cancer research.
One key challenge is understanding why early-onset cancers are becoming more common.
“Right now, we don’t have a definitive answer to what’s driving the rise of early-onset cancers around the world, but studies like this are helping us piece together the bigger picture, showing that cancer may be influenced not just by changes inside individual cells, but by wider changes happening across the body as a whole,” said David Scott, PhD, director of Cancer Grand Challenges.
Cao and colleagues are now working to clarify why younger generations are increasingly affected.
A major focus is how environmental, lifestyle, and societal changes may leave lasting biological marks, including accelerated aging and other vulnerabilities to disease.
By tracing how risks build up across the lifespan, the team aims to uncover biological origins of early-onset cancers.
The long-term goal is to pinpoint elevated risk while people are still healthy, enabling earlier prevention and screening and tailoring interventions to individual biology.
Funding support was provided through Cancer Grand Challenges, Cancer Research UK, the National Cancer Institute of the NIH, the French National Cancer Institute, the Bowelbabe Fund for Cancer Research UK, the Alvin J. Siteman Cancer Center, and multiple NIH grants, among others. The authors note the content is solely their responsibility and does not necessarily represent the official views of the NIH.