Accelerated Biological Aging May Explain Rising Early-Onset Cancer Rates, Study Suggests
核心洞察
A new study in Nature Medicine links faster biological aging in younger generations to increased risk of early-onset solid cancers (搜索), including lung, gastrointestinal, and uterine cancers.
UK Biobank data shows participants born between 1965 and 1974 had larger age gaps than those born between 1950 and 1954 at the same chronological ages.
Those in the highest biological aging group had a roughly 15% higher risk of early-onset solid cancer compared to the lowest group, though causality remains unproven.
Researchers have uncovered a potential new clue in the puzzling rise of early-onset cancers: younger generations may be aging faster at a biological level than their predecessors, and this accelerated aging appears linked to a higher risk of developing certain cancers before age 50.
The study, published June 22 in Nature Medicine, analyzed data from more than 150,000 adults in the UK Biobank, a long-running project tracking the health of approximately half a million U.K. adults since the mid-2000s. Researchers found that participants born between 1965 and 1974 had a larger "age gap" — the difference between chronological age and biological age — than those born between 1950 and 1954 at the same chronological ages.
"This is really proof-of-concept," said study co-author Yin Cao, a molecular and clinical epidemiologist at the Washington University School of Medicine and Siteman Cancer Center.
Biological age versus chronological age
Chronological age is straightforward: the number of years since birth. Biological age, however, can vary significantly from person to person. This measure encompasses a range of metrics, including markers on DNA and in the bloodstream, often assessed using "aging clocks" that aim to determine whether the body is functioning as older than its chronological age would suggest.
The study authors used PhenoAge, a statistical model that estimates a person's age gap at a given chronological age. Based on PhenoAge's metrics, the younger UK Biobank cohort had systemic aging levels about 0.23 standard deviations higher than the older cohort — a modest but measurable shift toward older-looking biology.
The researchers applied the same approach to approximately 10,000 participants in the U.S. National Institutes of Health's All of Us Research Program. There, the pattern was more pronounced: people born between 1990 and 1999 had age gaps about 0.92 standard deviations higher than those born between 1965 and 1969. Another blood-based aging clock, the Klemera-Doubal method, showed broadly similar patterns, albeit slightly weaker.
Cancer risk and biological aging
In the UK Biobank cohort, participants with higher age gaps were more likely to develop early-onset solid cancers (搜索) — tumors appearing in tissues, rather than "liquid" cancers present in bodily fluids. The link was strongest for lung, gastrointestinal, and uterine cancers.
When participants were divided into three groups based on biological age, those in the highest group had a roughly 15% higher risk of early-onset solid cancer than those in the lowest group.
To probe deeper, the authors used a different model estimating biological aging at the level of specific organs and systems through patterns of proteins in the blood. In nearly 20,000 UK Biobank participants, markers suggesting an "older-than-expected" immune system were linked with a higher risk of early-onset lung cancer (搜索). Similarly, markers indicating older-than-expected fat tissue were associated with a higher risk of early-onset colorectal cancer (搜索).
Causality remains elusive
Despite the intriguing correlations, researchers caution that the study cannot prove faster biological aging causes early-onset cancer. "The main issue for this paper is one of correlation versus causality," said Dr. Jyoti Nangalia, a hematologist and cancer researcher at the Wellcome Sanger Institute (搜索) in the U.K., who was not involved in the study. "Either way, it is useful — with the first, as a potential way of tracking population health and cancer risk, and with the second, as insights into cancer-causing mechanisms."
Stephen Burgess, a professor of biostatistics at the University of Cambridge who was also not involved, noted that the differences PhenoAge uncovered between younger and older people may relate to how the test was originally calibrated. Cao acknowledged that while PhenoAge scores have been tied to mortality risk across a range of adults, the test "requires further validations" when it comes to assessing cancer risk.
A growing global concern
The study arrives amid mounting concern over early-onset cancers. One 2023 paper suggests that early-onset cancer diagnoses rose by 25% globally between 1990 and 2019. In the United States, the incidence of advanced colorectal cancer (搜索) has increased by about 3% each year since around 2010 in people between the ages of 20 and 49, and in 2023, colorectal cancer became the leading cause of cancer death in this age group.
"The trend of increased cancers at younger ages is very real, and it is not simply because of more efficient diagnosis, or diagnosis at earlier stages," Nangalia said. "It is possible that we are being exposed to new cancer-causing risks or that [our] defences to them are somehow altered."
Cao hopes the team's approach will serve as another useful tool to investigate why more young people are developing cancer. "Hopefully this is just a starting point," she said.