Faster aging in younger generations linked to rise in early-onset cancer
Immune system aging linked to earlier lung cancer; fat tissue aging linked to earlier colorectal cancer
Sara Moser/WashU MedicineA new study led by researchers at WashU Medicine suggests that younger generations are aging biologically faster than their older counterparts. This faster biological aging (represented by the right red clock) was also linked to early-onset cancers.
Cancer is often considered a disease of aging. Older adults are at higher risk because they have had more time to accumulate cellular damage that can trigger tumor formation. But as cancer rates in younger adults rise, with each successive generation facing higher risks than the one before it, researchers are asking whether cellular damage is accumulating faster in recent generations, accelerating their body’s biological aging.
A new study led by researchers at Washington University School of Medicine in St. Louis provides evidence that younger generations are indeed aging faster biologically than their older counterparts. The causes remain under investigation around the world, including global efforts led by research members of Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, and Cancer Grand Challenges, a global initiative co-founded by the National Cancer Institute and Cancer Research U.K.; but importantly, the new research links this accelerated aging to an increased risk of early-onset cancers in younger generations. In general, early-onset cancers are those diagnosed at age 55 or younger.
The larger the gap between biological age — that is, how old our bodies appear to be — and chronological age — which is how many years we have actually lived — the higher the cancer risk, according to the researchers. They found that people in more recent birth cohorts had larger age gaps than those in older birth cohorts, which may help explain the rise in early-onset cancer in recent generations.
Their study also identified links between faster aging in particular organ systems and increased risks for certain cancers. For instance, an immune system that appears older than its actual age was associated with early-onset lung cancer. Similarly, fat tissue that appears older than its chronological age was associated with early-onset colorectal cancer.
The study, published June 22 in the journal Nature Medicine, suggests that measures of accelerated aging could help identify individuals at higher risk of early-onset cancer and guide new strategies for cancer prevention and early detection.
“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.”
Exploring biological aging
Cao’s team has been at the forefront of identifying individual factors that influence cancer risk across the life course, such as obesity, metabolic dysregulation, alcohol consumption, sedentary behavior, poor diet quality and cesarean delivery. Although these discoveries have revealed important clues to the origins of cancer at younger ages, the contribution of any single factor is modest.
With that in mind, Cao, also a research member of Siteman, and her colleagues have sought ways to capture the influence of multiple risk factors operating together to spur cancer development. With support from Cancer Grand Challenges, Cao, as co-lead of Team PROSPECT, has been able to go after this problem.
For the current study, Cao’s team analyzed data from more than 154,000 young adults in the UK Biobank, a large biomedical dataset containing biological, health and lifestyle data, and from more than 10,000 individuals in the U.S. participating in the National Institutes of Health’s (NIH) All of Us Research Program, an effort to build a comprehensive health dataset on more than 1 million people living in the U.S.
To estimate the level of biological aging — or age gap — the researchers, including first author Ruiyi Tian, a doctoral student in the Cao lab, examined aging at two levels: across the body as a whole, known as systemic aging, and within individual organs, known as organ-specific aging. For systemic aging, the researchers used established measures, including clinical biomarker-based measures such as PhenoAge and the Klemera-Doubal Method, as well as a metabolomic age score, which provides a measure of individual metabolism.
PhenoAge, for example, measures nine blood biochemistry markers such as albumin, made by the liver, and creatinine, a waste product removed by the kidneys. For organ-specific aging, the researchers used blood proteomic data, which measure levels of multiple proteins linked to specific organ systems, to estimate biological aging in individual organs.
The researchers calculated the average age gap for each birth cohort and used standard deviation to describe how much each group differed from the study average. Standard deviation is a measure of how spread out data points are around the average.
The researchers found that individuals in the UK born between 1965 and 1974 had systemic aging that was 23% of one standard deviation higher compared with those born between 1950 and 1954, after accounting for chronological age. In other words, people in the younger birth cohort showed a modest shift toward older biological profiles than people in the older birth cohort when at the same chronological age.
The researchers observed a similar pattern in the U.S cohort. Participants born between 1990 and 1999 had systemic aging that was 92% of one standard deviation higher compared with those born between 1965 and 1969.
This increased systemic aging in the younger group was associated with an 8% increased risk of early-onset solid cancers, especially lung, gastrointestinal and uterine cancers. When participants were divided into three groups based on their level of systemic aging, those with the most advanced systemic aging had a 15% increased risk of early-onset solid cancer compared with those with the least advanced systemic aging. According to the analysis, the increased risk persisted even after controlling for inherited genetic risks of cancer and genetic susceptibility to accelerated aging.
By zooming into organ-specific aging, the researchers found that advanced immune system aging was associated with increased risk of early-onset lung cancer, and advanced adipose (fat) tissue aging was associated with increased 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.
This research is part of Team PROSPECT, a Cancer Grand Challenges team co-led by Cao. Cancer Grand Challenges is a global research funding initiative co-founded by Cancer Research UK and the National Cancer Institute (NCI) that brings together world-leading researchers to take on cancer’s toughest challenges.
“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. “Research on this scale is possible through Cancer Grand Challenges, which brings together scientists from different fields around the world to tackle these complex questions together.”
Cao and her colleagues are leading efforts to transform the understanding of why cancers are increasingly striking younger generations. Their next frontier is to decipher how environmental, lifestyle and societal changes leave lasting biological imprints, including accelerated aging and other markers of heightened susceptibility. By illuminating the pathways through which risk accumulates across the life course, they seek to uncover the origins of early-onset cancers and redefine opportunities for prevention. In parallel, their work will enable more precise approaches to identify those at greatest risk and intervene earlier, shifting the paradigm from reacting to disease to preventing it before it begins.
