WHEN ANDREW CHAN, M.D., became a gastroenterologist two decades ago, he had to get used to the brutal reality that seemingly healthy young people would show up in his office with colorectal cancer. Even though he specialized in high-risk cancer genetics, they didn’t all have family histories of the disease: Most weren’t obese. Some were marathoners. Some were vegetarians. Some didn’t drink.
At the time, “early onset” patients made up less than 10 percent of his caseload. Then about a decade ago, he started getting more of them. Today it’s more than double—a trend he calls “truly stunning” because they’re his age or even 20 years younger. Dr. Chan, Professor of Medicine at Harvard Medical School, turned 50 this year.
So Dr. Chan decided to help solve one of the decade’s most disturbing medical mysteries: Why are more younger adults getting diagnosed with cancers that have historically been linked to old age? According to the latest report by the American Cancer Society, new cases among younger people rose 1 to 2 percent each year between 1995 and 2020—while rates decreased for other age groups. Twenty percent of new colorectal cases are under 55. And they tend to be more aggressive than those diagnosed at an older age.
What’s Going On?
THERE ARE A lot of trails to chase: Did we eat too many processed foods as kids and mess up our microbiomes? Ingest too many microplastics or absorb too many “forever chemicals”? Was it too many years of binge drinking or burning the midnight oil? Or something else entirely?
These questions are what prompted Dr. Chan to step up to be a leader of Team Prospect, a $25 million project funded by the National Cancer Institute along with research groups in the UK, France, Italy and India. The initiative will enlist epidemiologists, clinicians, chemists, computational scientists and microbiome experts to investigate all these factors.
Already, Chan’s co-leader, cancer epidemiologist Yin Cao, is creating buzz with work she presented at the annual meeting of the American Association of Cancer Research this year. Her team at Washington University School of Medicine in St. Louis found evidence that younger people with cancer were somehow aging faster than their peers. They crunched the so-called biological age of nearly 150,000 people’s blood samples in the U.K. Biobank database.
By looking at nine blood biomarkers, including creatinine, C-reactive protein, glucose and white blood cell count, they calculated that people who were born after 1965 had a 17 percent higher likelihood of accelerated aging than those born between 1950 and 1954.
The evidence that their bodies were getting old faster was linked with a dramatic increase in cancer risk: A 42 percent increase for lung cancer and 22 percent higher one for gastrointestinal cancer. Cao told Men’s Health that she won’t discuss the findings until the results are published in a peer-reviewed journal.
While we wait, her team’s research has teed up the urgent question: If we could hold back abnormal cellular aging, could we hold back cancer, too?
Cancer has traditionally been seen as a disease of aging. That’s because as we add years, our bodies experience more oxidative stress and DNA damage, which can alter cells and lead to the growth of tumors. Also with age, the body gets less efficient at clearing out old “senescent” cells that can be inflammatory and fuel those tumors. Ultimately, our immune system’s ability to fight those tumors weakens.
Can Aging Clocks Help Us?
THIS NEWS OF cancer in rapidly aging younger bodies comes at a time when aging science is exploding. That’s a good thing, since aging starts earlier than you think: Research by Vadim Gladyshev, Ph.D., professor of medicine at Harvard Medical School who studies aging clocks, lifespan control and age reversal, suggests that the aging process starts after our third week in the womb. From there, people will naturally age at different rates throughout their lifetimes. While we still don’t fully understand why, we’ve found ways to measure it.
In 2013, geneticist Steve Horvath, Ph.D., invented the breakthrough that made this conversation even possible: the epigenetic clock. While at UCLA, he published a landmark paper explaining that the so-called “Horvath clock” could estimate someone’s age by using DNA methylation from any tissue and cell type in the human body. (Methylation refers to chemical changes that happen to DNA and are influenced by genetics, lifestyle and environment; there are 28 million locations in the human body where this can happen, and a quarter change with age.) His clock looks at several hundred of them to come up with someone’s biological age estimate.
In a newer method, scientists measure someone’s age-related changes through 10,000 plasma proteins in a fraction of a drop of blood, adds geriatrician Luigi Ferrucci, M.D., Ph.D., scientific director of the National Institute on Aging. He envisions a future in which we’d get our biological age routinely measured—maybe as part of an annual physical—so doctors could identify people who are “accelerated agers” decades before they develop age-related diseases. Then, they could be closely monitored for cancer, heart disease or diabetes.
Yet while science is getting more precise about how it measures our biological clocks, a wrinkle is starting to emerge that these may not be able to tell the full story of how your body is handling aging. “It’s a new understanding that our biological age can fluctuate,” says Gladyshev. His team published a paper last year showing that someone’s biological age increases during times of several stress—like surgery, severe Covid, and pregnancy—but goes back down once they recover.
How much we can drive it down is also up for debate. There’s increasing evidence that we may not be able to push back that number very far. Scientists know that smokers and obese people will age faster, but all those healthy lifestyle changes we’ve been trusting to buy us more time might only pay off to a certain extent. “There are things you can do, but they reduce your epigenetic age by just a couple of years. They won’t reduce it by 40 years,” says Horvath, now principal investigator at Altos Labs, a biotech company focused on cell rejuvenation therapies.
In fact, Horvath’s team developed what he calls the GrimAge Clock (that’s geneticist dark humor for you) that looks at 1030 epigenetic locations. (It’s available through his nonprofit Epigenetic Clock Development Foundation.) Horvath’s chronological age is 56 and is a self-described “health nut,” and the lowest it dipped recently was 52.
During one year when his GrimAge was three years higher than usual, he buckled down and made every health change known to research: He cut out sugar and reduced his carb intake. He started a statin and added even more vegetables to his diet. After a year of sacrifices, he brought down his score by a couple years.
Promise from Other Places
EVEN IF TINKERING with our biological age isn’t as easy as we’d like it to be, that hasn’t stopped science from trying to find ways to stave off the damage of aging. “There’s a lot of work being done to find an intervention,” says Ferrucci. (The longevity research sector was projected to reach $600 billion by next year.)
Those include drugs that clear out old damaged senescent cells that can harm neighboring cells. (Several are in Phase 2 trials.) Other investigators are looking at repurposing idiopathic pulmonary fibrosis and diabetes treatments as anti-aging drugs. Another compound urolithin A, derived from gut microbiota, is being studied for its ability to fend off disease by increasing mitochondrial function to help age-related muscle atrophy. Finally, the molecule nicotinamide adenine dinucleotide (NAD+) is being investigated for combatting age-related vascular disorders.
All this is hopeful, and it softens the alarming possibility that some uncontrollable force may be hijacking our aging process with grim results. If the effects of aging can be forestalled, then perhaps disease can be, too.
And while cancers are striking earlier, detection systems like blood tests are increasingly used to hunt early signs of many cancers. Some people are even undergoing full-body MRIs with the same goal in mind, although neither is standard procedure in mainstream medicine.
Meanwhile, the rise in young onset cancer is a compelling reason to get screened on time, and push for an earlier screening if you have symptoms (check out the symptoms of lung cancer and colorectal cancer) or are at high risk. For colon cancer, that means people at average risk should start getting colonoscopies at age 45. If someone in your immediate family (sibling, child, parent) had colorectal cancer, you need to talk with your physician about getting screened before that. There are even at-home screening tests that you can do. “It would be ideal to treat someone in the early phases of disease when they have a healthy body,” says Ferrucci.
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