At age 6, Alique Topalian developed an immunoglobulin deficiency that made it harder to fight infections. At age 7, she was diagnosed with learning disabilities. By age 12, she had developed high blood pressure.
Topalian’s physicians suspected the conditions all stemmed from her acute myeloid leukemia (AML) diagnosis and treatment at age 4. Research shows that children who receive intensive chemotherapy often face complications — including heart damage, weakened bones, cognitive difficulties, and high blood pressure— that may emerge months, or even years, after treatment and remission.
But Topalian’s health issues didn’t stop after a few years. In her teens to mid-twenties, she faced an unending stream of new challenges: irritable bowel syndrome, metabolic syndrome, fainting spells, and muscle wasting.
These latest chronic problems often stumped her clinicians.
Topalian relapsed in her late twenties, and although now in remission, the 31-year-old has a constant fever of 100.4 “that my care team and I have no explanation for. We think it is something wrong with my autonomic nervous system but don’t actually know,” said Topalian, a research scientist and public health educator at the University of Cincinnati, Cincinnati.
Topalian is not alone. While the survival rates for those with pediatric cancers have improved substantially over the past few decades, clinicians are now seeing more and more survivors suffering from a host of late and long-term side effects from their cancer. Some conditions can more easily be tied to the cancer or treatment, but as time passes, the link may become more tenuous. However, experts are starting to recognize that the chronic health issues emerging in long-term survivors may represent an unintended consequence of living decades after cancer: accelerated aging.
“Individuals who are treated for their cancer, when we compare them to their siblings or to healthy control, we see that they develop a faster trajectory of aging,” said Mina S. Sedrak, MD, associate professor of hematology and oncology at UCLA.
Many oncologists also hear directly from long-term cancer survivors about challenges that indicate faster aging. “Our patients tell us that even though they have finished their treatment and the side effects have somewhat improved, they still don’t feel like they’ve bounced back to their baseline in terms of their physical function, their cognitive function, their health, and well-being,” Sedrak said.
A growing body of evidence indicates this issue is real: Cancer survivors appear to be aging more rapidly. And increasingly, research is starting to explain why: Cancer and cancer treatments can speed up survivors’ basic aging processes, pushing the body’s biological clock past its chronological age. These subtle but persistent changes could explain why young survivors, like Topalian, are often more susceptible to developing age-related chronic conditions as well as frailty decades after their diagnosis and much sooner than expected in the general population.
The Evidence Mounts
The evidence of accelerated aging among cancer survivors, and its impact on their long-term health, continues to pile up.
One analysis, published in Nature Communications earlier this year, reported that cancer survivors appear to have a higher biological age compared with those without cancer. The study assessed the association of biological age with cancer prevalence and all-cause mortality over 4 years in cancer survivors who had received radiation, surgery, or chemotherapy and cancer-free individuals, looking at nine aging metrics, including different epigenetic clocks and age-related clinical markers, such as blood chemistry levels and blood pressure.
The analysis revealed that compared with cancer-free individuals, cancer survivors were more likely to have a host of comorbidities, including hypertension, cardiac disorders, stroke, arthritis, and diabetes. Overall, after multivariable adjustments, cancer survivors demonstrated significantly greater age acceleration in four of the nine aging constructs.
When looking at mortality in survivors by treatment type, higher levels of several aging metrics were associated with higher all-cause mortality over 4 years. The associations between certain aging measures and mortality appeared to be most notable among those who had received chemotherapy compared with those who hadn’t.
This and other research suggest it may be the very cancer treatments aimed at prolonging life that accelerate the aging process in survivors and increase patients’ risk of developing a range of other conditions.
A large 2021 study found that among more than 10,000 adult survivors of childhood cancer diagnosed between 1970 and 1986 who received a range of treatments, including chemotherapy, radiation, and surgery, survivors were about three times more likely to develop a chronic condition compared with their siblings without a history of cancer. The risk of developing two chronic conditions was almost fivefold higher. The risk for a severe or life-threatening condition, such as congestive heart failure or a second cancer, was even greater — about eight times more likely.
When looking at cancer types, those diagnosed with bone, brain, or spinal tumors, or Hodgkin’s lymphoma as children faced the highest risks of developing a severe chronic conditions — almost 40 times for survivors of bone tumors, 12.6 times for central nervous system tumors, and about 10 times for Hodgkin’s disease.
And notably, as survivors aged, they appeared to continue to accumulate more chronic conditions — a trend that “does not appear to plateau,” the authors wrote.
Another 2025 analysis focused on the impact of radiation therapy and projected childhood cancer survivors’ risk of developing eight conditions following treatment. These included six aging-related conditions — breast cancer, colon cancer, heart failure, myocardial infarction or coronary artery disease, valvular disease, and stroke — and two life-threatening secondary cancers — glial tumors and sarcomas. After grouping survivors diagnosed between 1970 and 1999 by radiation therapy exposures and age-related factors, the team projected the long-term outcomes for patients who survived 5 years.
By about age 47, 20% of the 5-year cancer survivors had developed at least one of the eight conditions. It took almost 18 more years for the general population to reach that threshold — by age 65, 20% of people in the general population had developed at least one condition. By the time cancer survivors reached age 65, 55% were projected to develop at least one condition — a 2.7-fold greater risk compared with the general population.
While radiation therapy posed greater risks and led to earlier onset of aging-related conditions, survivors not exposed to radiation still developed an age-related condition 13.5 years earlier than the general population.
Taken together, the findings “did make me wonder if there’s something about the cancer diagnosis or the treatment exposures that might initiate that first accelerated aging burst,” which research suggests may occur naturally at about age 44, and then again at age 60, said first author Jennifer M. Yeh, PhD, an epidemiologist and associate professor of pediatrics at Harvard Medical School, Boston.
Research also now points to molecular-level processes that may accelerate aging in cancer survivors and helps explain the faster aging trajectories observed among many long-term survivors.
A key hallmark of aging is the natural accumulation of senescent or zombie cells in the body. These damaged cells have stopped dividing and wield a host of influences: they secrete inflammatory molecules that increase inflammation, prevent muscles and tissues from regenerating, intercept cell processes involved in nutrient uptake, and alter DNA in ways that can trigger mutations.
Researchers have begun digging into whether, and why, cancer survivors appear to encounter these hallmarks of aging earlier. In a review of the evidence, published last year, experts highlighted how chemotherapy and radiation suppress tumors by triggering senescence in tumor cells but may also do the same in nearby healthy cells. The effect is an overall increase in senescent cells that linger in the body, hastening aging.
“With treatments like chemotherapy, we have drugs that kill the cancer but also disrupt some of these key repair mechanisms, or the mechanisms that can induce faster damage, which then leads to more damage, less repair, and more altered rate of biological aging,” Sedrak said.
The Frailty Factor
Early in her career, as a physical therapist working with survivors of childhood leukemia and brain tumors, Kirsten Ness, PT, PhD, recognized signs of early aging in her patients.
“They looked like old people. They had gray hair. They had wrinkles. They had low lean muscle mass. They had reduced strength,” said Ness, a faculty member at St. Jude Children’s Research Hospital in Memphis, Tennessee.
Ness became an epidemiologist and built the St. Jude Human Performance Lab, where researchers measure physical capabilities and movement in childhood cancer survivors. Ness led a team of researchers that assessed frailty — an increased vulnerability to illness and injury common among people older than 80 years — in adult survivors of childhood cancer who spanned 18-45 years at study entry or a mean age of 30 years. She relied on the Fried Frailty Index, developed by Linda Fried, which evaluates self-reported exhaustion, unintended weight loss, weakness, slow walking speed, and low physical activity.
When survivors returned to the Human Performance Lab for an assessment after 5 years, their frailty prevalence had nearly doubled from 6.2% to 13.6% of the cohort, which Ness called “astounding in that age range.” A 2013 study had found that 7.9% of childhood cancer survivors exhibit frailty in their thirties.
This 13.6% frailty prevalence in young survivors seemed notable against a frailty prevalence estimate of almost 10% in adults aged 65 years or older in the general population (though this estimate can vary depending on the study).
“Our 30-year-old survivors had a higher prevalence of frailty using her phenotype than the aging cohort did,” said Ness.
Importantly, Ness and colleagues also found that survivors who were already frail at study entry were more likely to die compared with those who were not yet frail (hazard ratio, 3.53), and that frailty leaves survivors of childhood cancers more vulnerable to early cognitive decline — an issue Topalian knows all too well.
In her late twenties, Topalian had just finished her PhD in health promotion education and was working 80-hour weeks when her AML came roaring back. Although the treatment worked, her regimen of chemotherapy and immunotherapy affected her ability to recall words and form sentences.
Although much better these days, “I cannot say that I am fully back to how I was before,” Topalian said.
Care for Long-Term Survivors
While life expectancy for cancer survivors has improved decade by decade, 2020 research from Yeh shows that childhood cancer survivors still tend to have a lower life expectancy compared with people without a history of cancer. For those diagnosed and treated as children in the 1990s, for instance, Yeh and colleagues projected a life expectancy of 57.1 years among those who survived 5 years following their diagnosis vs 66.3 years in the general population.
Accelerated aging processes, and subsequently early onset of chronic conditions and frailty, are at least partly to blame for this survival gap.
Drugs that could slow the progression of aging, like senolytics that clear away senescent cells, may help slow this process in cancer survivors. A clinical trial underway in patients with postmenopausal breast cancer is investigating if a combination of exercise and a nutritional supplement called fisetin can eliminate senescent cells and prevent frailty. But until more human data becomes available, Ness said, “I don’t know if I’m convinced.”
Outside of therapeutics, patients and physicians can work closely to address age-related symptoms and chronic conditions that interfere with daily life.
“We know that exercise works,” said Sedrak, who also found that risk factors for frailty included lack of strength training and a sedentary lifestyle. “Exercise has been shown in the lab to have anti-aging effects on some of the pathways that we believe are also altered or disrupted by chemotherapy and radiation.”
But it may be a challenge for survivors to find a primary care doctor with awareness of their specific challenges and needs, given their elevated risks for secondary cancers and other chronic conditions. Survivors exposed to chest radiation for lymphoma should, for instance, get earlier and more aggressive breast cancer screening and those exposed to abdominal radiation should get earlier colon cancer screenings.
“Screening for secondary cancers is different for survivors compared to what primary care doctors are trained to do for a routine patient population,” said Ilana Rachel Yurkiewicz, MD, a clinical assistant professor of primary care and population health at Stanford Medicine, Palo Alto, California. But “most primary care doctors are not going to know the nuances of that early screening, and so it often doesn’t happen according to guidelines.”
Topalian can vouch for that. She was treated for her first AML diagnosis in Cleveland and later became a patient in the oncology primary care clinic at the University of Cincinnati, before becoming employed there. But after her AML relapse, while on maintenance chemotherapy, Topalian was living in a different city with a primary care doctor who lacked experience treating survivors.
“As I was getting more sick, I couldn’t get in for an MRI. I couldn’t get in for an x-ray,” Topalian said. Being an AML survivor puts her at greater risk for things like pneumonia and neutropenia, so her diagnostic needs exceed those of typical patients. Her primary care doctor told her to go to the emergency room.
As a researcher focused on the long-term well-being of cancer survivors, Topalian often meets with survivors who are unaware of their specific vulnerabilities. Many are shuttled between oncology and primary care without coordination or sensitivity — something that needs to change, she said.
Topalian is doing her part to propel research on the benefits of oncology primary care for young survivors, presenting her findings at this year’s American Society of Clinical Oncology annual meeting. Her efforts come as the National Cancer Institute’s working group, focused on survivorship-informed primary care, concludes its first year.
“When we’re living decades posttreatment, we need providers who know how to handle [what] might happen. A lot of us don’t even know what might happen,” Topalian said. “How can we take care of people for their entire lifetime after treatment because cancer doesn’t just stop when treatment ends?”
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