Does Childhood Cancer Accelerate Brain Aging Later in Life?

More than half a million people in the United States are survivors of childhood cancer. Many go on to live long, full lives — but for some, the effects of cancer treatment don’t fully fade with time.

About 40 percent of childhood cancer survivors experience lasting problems with memory, attention, or learning years after treatment ends. Radiation and chemotherapy, even when used to treat cancers outside the brain or nervous system, can still leave lasting neurological damage. 

A new study published in Nature Communications found that these cognitive challenges may be tied to something deeper: accelerated biological aging of the brain that can persist for decades after treatment. 

“Survivors of childhood cancer are experiencing accelerated biologic aging, and that is highly correlated with their cognitive function,” AnnaLynn Williams, a researcher at University of Rochester Wilmot Cancer Institute, who led the study, told Being Patient. 

Previous research has shown that young cancer survivors are less likely to attend college and more likely to be unemployed. “The earlier we intervene, the better chance we have of changing that trajectory,” Williams said.

How researchers measured biological aging

Researchers from St. Jude’s Children’s Research Hospital compared 1,413 childhood cancer survivors to 282 control participants, on average 26 years after diagnosis. More than three-quarters of the survivors had received treatments that targeted the brain or nervous system.  

They analyzed DNA from white blood cells, searching for chemical tags that influence gene activity. By inputting this information into five different “epigenetic clock” algorithms, they could estimate the levels of biological aging. Many of these epigenetic clocks have also been linked to brain aging and dementia.

“You’re looking at wear and tear on the DNA,” Dr. Suriya Jeyapalan, a neuro-oncologist at Tufts Medical Center, who wasn’t involved in the study, told Being Patient. “If the epigenetic aging clock says you’re older than your real age, that’s what they call accelerated aging.”

The team found that the cancer survivors aged faster on a cellular level than those in the control group.

They also measured telomere length — the protective caps at the ends of chromosomes that safeguard DNA — and found they were shorter among the cancer survivors, another indicator of biological aging.    

The epigenetic clocks, but not shorter telomeres, were linked to worse attention, processing speed, memory and executive functions. The effects were most pronounced among survivors who received a cancer treatment targeted at the brain and nervous system. 

However, Jeyapalan said there were some caveats. The epigenetic aging clocks aren’t direct measures of brain aging and the researchers only had data from one time point, about 26 years after diagnosis. As a result, researchers don’t know whether childhood cancer survivors are slowly improving over those years. 

Are young cancer survivors predisposed to dementia?

These findings have raised the possibility that neurocognitive dysfunction in childhood cancer survivors may make the brain less resilient and more vulnerable to later-life neurological disease. 

“We have to wonder if this means that they’ll be predisposed to Alzheimer’s and other related dementias, or at least mild cognitive impairment at a much higher rate,” Williams said. 

The idea appears at odds with prior research findings that a cancer diagnosis lowered the risk of Alzheimer’s and other dementias. 

“Aging adults who develop cancer in their 6th or 7th decade of life are at lower risk for dementia, perhaps because they develop a more healthy lifestyle to limit cancer relapse,” Kevin Krull, a researcher at St. Jude Children’s Research Hospital who also authored the study, told Being Patient. 

However, the cumulative neurocognitive burden for childhood cancer survivors might predispose them to an elevated risk earlier in life.  

“We have to remember they were treated during a very vulnerable developmental stage in their life where the brain and the central nervous system were not fully mature yet,” Williams said, adding we don’t yet have enough long-term data to know for sure. 

Reversing cellular and cognitive aging

Researchers are now exploring ways to mitigate or even reverse biological and cognitive aging in childhood cancer survivors. 

Some teams are testing dietary strategies and exercise programs that could alter the epigenetic markers on the DNA, thereby reducing the biological age. However, Williams cautioned that it remains unclear whether these epigenetic changes are involved in the mechanism that’s responsible for the cognitive deficits or whether they simply occur alongside them. 

Other groups are developing cognitive training programs and behavioral interventions to improve memory, attention, and overall brain function. Healthy sleep, good nutrition, and adaptive habits — like using reminders or organizational tools — can also help survivors manage daily challenges.

“Can we do one intervention that could improve biological and cognitive aging?” Williams asked. 

Ultimately, the goal is to allow young cancer survivors to lead the same independent lives as their peers. 

“If the treatment was a success, but the patient really wasn’t able to go out and have the life that they wanted to live, then we’re failing in that regard,” Jeyapalan said.