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How Do Childhood Cancer Treatments Accelerate Biological Aging?

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Key Takeaways

  • Childhood cancer treatments can accelerate biological aging, increasing risks for long-term health issues like heart disease and hypertension.
  • Epigenetic age acceleration measures the difference between biological and chronological age, indicating accelerated aging in cancer survivors.
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Childhood cancer treatments can accelerate biological aging which increases survivors’ risk for long-term health issues like heart disease and obesity.

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Childhood cancer treatments can accelerate biological aging which increases survivors’ risk for long-term health issues like heart disease and obesity.

Childhood cancer treatments can accelerate biological aging which increases survivors’ risk for long-term health issues like heart disease and high blood pressure, according to Dr. Zhaoming Wang and Meng Zhang. The pair go on to emphasize that understanding this connection could enable interventions to better manage and prevent these complications as survivors age.

“Epigenetic age acceleration measures the difference between your biological age and your chronological age,” Wang explained.

“Accelerated epigenetic aging, is modifiable. If we can confirm that it links a past treatment to a future health outcome, then we can potentially [stop] this process to reduce the negative effects of the treatment,” Zhang added.

To further break down the connection between childhood cancer treatments and accelerated biological aging in survivors, Wang and Zhang sat down for an interview with CURE. In the interview, they explained what epigenetic age acceleration means and how it may lead to long-term conditions like heart disease or high blood pressure.

Wang is a full member of the Department of Epidemiology and Cancer Control and the Department of Computational Biology at St. Jude Children’s Research Hospital, where he also serves on the faculty of the St. Jude Graduate School of Biomedical Sciences and the institution’s Comprehensive Cancer Center.

Zhang is a senior scientist at St. Jude Children’s Research Hospital.

In the interview, they also discussed what role clinicians have in helping survivors of cancer reduce long-term risks after treatment.

CURE: Your study found that childhood cancer treatments can speed up biological aging in survivors. Can you explain what “epigenetic age acceleration” means in simple terms, and how it affects a person’s health long after treatment ends?

Wang: To explain it in simple terms, epigenetic age acceleration is the difference between your biological age and your chronological age, specifically using a type of biological age measurement called epigenetic age. There are various ways to measure biological age, and epigenetic age is one of them.

Epigenetic age acceleration essentially tells you if you are biologically older or younger than your actual chronological age. For example, if someone is chronologically 40 years old but their biological age is 45, they have a positive epigenetic age acceleration value. This means they are biologically older than they should be when compared to the average for their chronological age. A high epigenetic age acceleration value indicates that a person is biologically older.

Many diseases are age-related; for instance, older individuals tend to develop heart attacks, cardiovascular conditions, hypertension, or high blood sugar more frequently. What we observe in cancer survivors is that their cancer treatment actually accelerates this aging process, putting them on a fast track in terms of advancing aging. Chronologically, a 10-year-old survivor might be only five years out from treatment, but biologically, they could be closer to a 15-year-old in the non-cancer population. Similarly, a 20-year-old cancer survivor might biologically appear to be 30.

I hope this helps you understand that epigenetic age acceleration measures the difference between your biological age and your chronological age.

What made you and your team decide to explore the role of epigenetic age acceleration as a ‘bridge’ between cancer treatment and long-term conditions like heart disease or high blood pressure?

My lab's research isn't a one-stop shop; it's a continuous process. Our mission is to understand the biological mechanisms behind treatment toxicity. While cancer treatment happens in the past, over 85% of children with cancer survive long-term. We're trying to bridge the gap between past treatment and present health.

Our previous research has already shown that certain cancer treatments in childhood are linked to accelerated aging. For instance, many children with Hodgkin lymphoma receive radiation to the chest. We found that Hodgkin lymphoma survivors age much faster, which is reflected in greater epigenetic age acceleration.

Following up on that, we conducted several studies and discovered that epigenetic age acceleration is also predictive of the development and worsening of long-term health conditions. In our recently published study, we describe how these conditions include cardiometabolic and cardiovascular issues like heart disease, high blood pressure, high blood sugar, and obesity, among others. These are just a few of the adverse long-term health outcomes we've been investigating.

Building on our prior research, the new question we're exploring is whether epigenetic age acceleration acts as an intermediary between past treatment and current health. Our hypothesis is that aging is the underlying mechanism. In other words, exposure to cancer treatment triggers accelerated aging, which in turn leads to the early onset of age-related diseases.

Zhang: Besides what Dr. Wang mentioned, we also know that aging, or more specifically, accelerated epigenetic aging, is modifiable. If we can confirm that it links a past treatment to a future health outcome, then we can potentially target and block this process to reduce the negative effects of the treatment.

Many survivors worry about their future health. How might understanding a survivor’s epigenetic age one day help doctors predict or prevent complications like obesity, hypertension, or heart problems?

Our findings suggest that survivors with greater epigenetic age acceleration have an increased risk of developing complications such as obesity, hypertension, and heart problems. These are often related to both their past treatments and the natural aging process, as advanced age is one of the strongest risk factors for these conditions.

This information could allow doctors to recommend heightened screening for these survivors. For example, they could increase the frequency of screenings, including imaging and other diagnostic tests, to catch these diseases early. The goal is to intercept these conditions before they progress to an incurable state.

In addition to using this information for screening, there are potential interventions. We know that certain lifestyle modifications can help. Two key examples are diet, specifically caloric restriction, which involves eating less to boost the immune system and promote health, and exercise, such as walking, running, or other sports.

There is also a lot of research into pharmacological interventions, or “exercise pills,” as I like to joke with my colleagues. This involves drug repurposing, where we use existing drugs to treat new conditions. For example, drugs like metformin (traditionally for diabetes), rapamycin, or GLP-1 (often used for obesity and now diabetes) are being researched for their potential to slow down the aging process.

Essentially, epigenetic age acceleration provides a metric that helps us classify people into high, intermediate, and low-risk groups. This allows us to adjust screening frequency and preventive strategies, ultimately offering a more personalized approach to care.

Reference

  1. “Epigenetic Age Acceleration Mediates Treatment Effects on Cardiometabolic and Cardiovascular Risk in Childhood Cancer Survivors,” by Dr. Xiaoxi Meng, et al. JACC: CardioOncology.

Transcript has been edited for clarity and conciseness

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