Accelerated aging linked to cancer risk in younger adults, research shows

Researchers looking for clues about why some types of cancer are on the rise in younger adults say they’ve found an interesting lead: a connection to accelerated biological aging.

Aging is the major risk for many types of cancer, meaning the older you get, the more likely you are to be diagnosed. And increasingly, experts recognize that age is more than just the number of candles on a birthday cake. It’s also the wear and tear on the body, caused by lifestyle, stress and genetics, which is sometimes referred to as a person’s biological age.

“We all know cancer is an aging disease. However, it is really coming to a younger population. So whether we can use the well-developed concept of biological aging to apply that to the younger generation is a really untouched area,” said Dr. Yin Cao, an associate professor of surgery at the Washington University School of Medicine in St. Louis and senior author of the new research, which was presented Sunday at the American Association of Cancer Research’s annual conference in San Diego.

Factors of biological aging

Cao and her team looked at the medical records of 148,724 people ages 37 to 54 who are participants in a large data registry called the UK Biobank.

They homed in on nine blood-based markers that have been shown to correlate with biological age:

  • albumin: a protein made by the liver that declines with age
  • creatinine: a waste product in blood produced by protein digestion and the breakdown of muscle tissue; a measure of kidney function. Lower levels correlate with better longevity.
  • glucose: With age, blood sugar stays higher for longer after meals.
  • c-reactive protein: made by the liver in response to inflammation; relatively higher levels correspond to faster aging
  • lymphocyte percent: The concentration of these white blood cells related to immune function tends to decrease with age.
  • mean cell volume: a measure of the average size of red blood cells, which increases with age
  • red cell distribution width: the difference between the size of a person’s smallest and largest red blood cells, which tends to increase with age
  • alkaline phosphatase: an enzyme produced mainly by the liver and bones that tends to increase with age
  • white blood cell counts: Numbers of white cells in the high end of the normal range in the blood may correspond with greater aging.

These nine values were then plugged into an algorithm called PhenoAge that was used to calculate each person’s biological age. The researchers determined accelerated aging by comparing people’s biological ages with their chronological ages.

They then checked cancer registries to see how many in the group had been diagnosed with early cancers, which the researchers defined as cancers appearing before age 55. There were nearly such 3,200 cancers diagnosed.

The researchers found that people born in 1965 or later were 17% more likely to show accelerated aging than those born from 1950 through 1954.

What faster aging could tell us about cancer risk

After adjusting the data for factors they thought might bias their results, the researchers found that accelerated aging was associated with increased risk for cancer. The strongest associations were seen with lung, stomach and intestinal, and uterine cancers.

Compared with people who had the smallest amount of faster aging in the biobank sample, those who scored highest had twice the risk of early-onset lung cancer, more than 60% higher risk of a gastrointestinal tumor and more than 80% higher risk of uterine cancer.

The study wasn’t designed to answer questions about why these cancer types seemed to have the strongest ties to accelerated aging, but Ruiyi Tian, the graduate student who led the research, has some theories.

Tian said it’s possible that lungs are more vulnerable to aging than other types of tissues because the lung has a limited ability to regenerate. Stomach and intestinal cancers, she says, have been linked to inflammation, which increases with aging.

Cao said the strength of the research is that the researchers saw these signals in such a large number of people, but she acknowledges that the study has limitations, too.

For example, people in the study weren’t followed over time. The blood test results were from a single test, so they gave only a snapshot of risk, which may change. Ideally, she said, researchers would be able to follow the same group for years, taking blood samples along the way to get a more accurate trajectory of their risk.

“The ideal scenario is that we would have multiple blood collections throughout the life course, which is not feasible even in biobanks like UK Biobank,” Cao said.

She said the association should also be tested in more diverse populations, since the effects of social factors tied to racial discrimination need to be better illuminated, as well.

Dr. Anne Blaes, who studies the impact of biological aging in cancer survivors at the University of Minnesota, said the study results are exciting because they could point to a better way to find people who are at higher risk of getting cancer when they’re young. Right now, young adults who don’t have a family history or other risk factor aren’t regularly screened for most kind of cancer.

“We’re seeing more and more cancers, especially GI cancers and breast cancers, in younger individuals. And if we had a way of identifying who’s at higher risk for those, then really, you can imagine we’d be recommending screening at a different time,” said Blaes, a professor and director of the Division of Hematology and Oncology at UM medical school. She was not involved in the new research.

Blaes said that if you can find people who are at higher risk because their cells are aging faster, you can target lifestyle interventions too: things like nutrition, exercise and sleep.

“There are medications that also look like they can slow down accelerated aging,” said Blaes, who is testing two of them in cancer survivors. Cancer survivors often show greater biological aging, perhaps because of the after effects of therapies like chemotherapy and radiation.

The medications belong to a class called senolytics, drugs thought to target and get rid of damaged and aging cells.

Right now, it’s not clear who might benefit from these drugs, but assessments of accelerated aging like PhenoAge could one day help point doctors to the people who most need them.

“It’s super interesting. It’s not quite prime time, where we would go out and prescribe those medications for people, but this is really, really important work,” Blaes said.


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