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Scientists searching for answers about why some forms of cancer are on the rise for young people may have made a breakthrough. Accelerated biological aging could be the cause.
Getting older is a major risk factor for many types of cancer, meaning that the longer you live, the more likely you are to get diagnosed with it. But many experts now argue that age isn’t simply a number. It’s also a measure of wear and tear on the body caused by lifestyle choices, stress levels and genetic factors, all referred to as biological age.
“It is clear that cancer is an aging disease,” said Dr Yin Cao, senior author of new research presented Sunday at the American Association of Cancer Research’s annual conference in San Diego and associate professor of surgery at Washington University School of Medicine in St. Louis. “However, it is coming into a younger population. So whether we can apply this well-established concept (of) biological aging into those young populations is very unknown.”
Biological Aging Factors
Cao and her team reviewed health records from 148,724 participants between ages 37 and 54 in UK Biobank — a large data registry.
The scientists then focused on nine blood markers previously tied to biological aging:
Albumin: Produced by liver cells as we grow older
Creatinine: Produced when protein is digested and muscle tissue breaks down; poor kidney function results in lower creatinine levels
Glucose: Stays high for longer after meals as we age
C-reactive protein: Produced by liver cells during times of inflammation; higher levels mean faster aging
Lymphocyte percent: Concentration goes down as we grow older
Mean cell volume: Size generally increases with age
Red cell distribution width: Measures difference between smallest and largest red blood cells; tends to grow with age
Alkaline phosphatase: Enzyme largely made by liver and bones; increases with age
White blood cell counts: A higher count in the upper range of what’s considered normal may mean more rapid aging.
The team then used an algorithm called PhenoAge to calculate biological ages from these nine values. Accelerated aging was determined by comparing how old a participant was biologically versus their actual chronological age.
Next, the researchers checked cancer registries to see who among this group had been diagnosed with early-stage cancers — those appearing before age 55. In total, roughly 3,200 such cancers were detected.
People born in or after 1965 had a 17% greater chance than those born between 1950 and 1954 of exhibiting accelerated aging, according to the data.
The connection between faster aging and higher cancer risk
After accounting for potential bias related to different factors, the team discovered that accelerated aging corresponded with increased likelihood of being diagnosed with cancer. The most robust connections appeared for lung, stomach and intestinal tumors that could be malignant, as well as uterine cancers.
Individuals who were fastest to age biologically had double the risk of early-onset lung cancer, over 60% higher risk of gastrointestinal tumors and more than 80% higher risk of uterine cancer compared with those who had the lowest scores.
The study didn’t try to figure out why these cancer types seemed most strongly related to faster aging. But Ruiyi Tian, the graduate student who led the research, has some theories. She said that lungs may be more vulnerable to aging than other tissues because they have a limited ability to regenerate. Stomach and intestinal cancers have been linked to inflammation, which increases with age.
The strength of the research is that it uncovered these signals in so many people at once, Cao said. But she acknowledged that the study also has limitations.
People weren’t followed over time in this study, so researchers don’t know whether their results hold up years later. And although finding and following many people in a health database cuts down on costs compared with enrolling participants from scratch, those efforts still come at a price.
‘Ideal scenario’. The blood test results were from one test only — it would be better if each person’s risk could be measured repeatedly as they aged. “The ideal scenario is that we would have multiple blood collections throughout the life course,” Cao said — something impossible even for such massive studies as UK Biobank.
Cao’s lab is working on follow-up research focused on this issue: how often testing needs to happen and what might drive rapid biological aging.
Ideally, Cao said, her team would like to see these associations tested further in other populations. The current group was primarily made up of older white individuals living in Britain — not exactly an accurate representation of everyone worldwide.
But beyond simple demographics are complex social factors tied to systemic racism and discrimination that we know can impact health outcomes. Those need to be better illuminated too, she said.
Dr. Anne Blaes, a professor and director of the Division of Hematology and Oncology at UM medical school, who studies the impact of biological aging in cancer survivors, was excited by these study results because they offer a pathway to identify people who are at higher risk of getting cancer when they’re young. Right now, young adults who don’t have any family history or other risk factor aren’t regularly screened for most types of cancer.