Markers indicating cellular aging, including DNA damage response, cellular senescence, and pathways related to inflammation, have been found to significantly rise in all breast cancer survivors, irrespective of the treatment they underwent.
A recent study conducted by researchers at the UCLA Health Jonsson Comprehensive Cancer Center has shown that standard breast cancer treatments, such as chemotherapy, radiation, and surgery, may speed up the process of biological aging in survivors.
According to the findings published in the Journal of the National Cancer Institute, there is a notable increase in markers of cellular aging among breast cancer survivors across the board, regardless of the treatment type. This indicates that the repercussions of breast cancer treatments on the body extend beyond what was previously understood.
“This is the first time we are demonstrating that the aging signals typically associated with chemotherapy are also evident in women receiving radiation and surgical treatments,” explained Judith Carroll, the lead author of the study and an associate professor of psychiatry and biobehavioral sciences at UCLA, who holds the George F. Solomon Professorship in Psychobiology and is part of the UCLA Health Jonsson Comprehensive Cancer Center. “We anticipated observing heightened gene expression associated with biological aging in women treated with chemotherapy, but we were taken aback to find comparable changes in those who solely underwent radiation or surgery.”
Innovations in cancer treatment have significantly increased survival rates, with approximately 4 million breast cancer survivors currently in the U.S. and predictions of over 6 million by 2040. Nonetheless, breast cancer is associated with accelerated aging, affecting physical capabilities, independence, and longevity. The biological aging processes, which contribute to issues such as fatigue, cognitive decline, frailty, and cardiovascular diseases, play a crucial role. Research indicates that treatments like chemotherapy may elevate the risk of earlier onset of these age-related conditions, highlighting the necessity to understand the specific pathways at play to effectively manage them.
To study how aging-related gene expression changes over time in women diagnosed with breast cancer, the research team performed a two-year longitudinal study, monitoring women before and after their breast cancer treatment to observe the evolution of their biological aging markers.
The team analyzed gene expression in blood cells through RNA sequencing, concentrating on markers that indicate biological aging. One notable focus was on cellular senescence, a condition where cells stop dividing yet remain alive. These “zombie cells” accumulate with time, releasing harmful substances that can harm neighboring healthy cells, contributing to the aging process and inflammation.
The gathered data was analyzed using statistical models to pinpoint aging-related transformations.
The researchers discovered that, regardless of the treatment type, there was an uptick in the expression of genes related to biological aging. Specifically, there was an increase in genes indicative of cellular senescence and the inflammatory signals from these cells, signifying that the immune cells were aging more rapidly than usual.
Additionally, they observed spikes in genes associated with DNA damage response, which activate upon DNA injury. While chemotherapy exhibited a somewhat distinctive pattern, similar to prior research, changes were also noted in women who did not undergo chemotherapy.
“The findings imply that women receiving breast cancer treatments exhibit a gene expression pattern that points to elevated DNA damage and inflammation, which could serve as vital targets for cancer recovery and enhancing the quality of life for survivors,” mentioned Julienne Bower, the study’s senior author and a professor of psychology in the UCLA College as well as in psychiatry and biobehavioral sciences, and a member of the UCLA Health Jonsson Comprehensive Cancer Center.
“We are just beginning to grasp the long-term implications of cancer treatments, and these results represent an important step toward understanding the biological pathways responsible for numerous post-treatment symptoms experienced by breast cancer survivors,” added Carroll. “Our objective is to discover methods to enhance survivorship, focusing not just on the duration of life but also on life quality and overall health.”
The team is now investigating a new biomarker designed to assess a woman’s biological age and her aging rate. This could help ascertain whether the aging indicators observed during cancer treatment have a lasting impact on biological age. They plan to explore potential influencing elements, particularly protective behaviors such as exercise, stress management, and healthy sleep patterns.
Carroll and Bower are also associated with the Cousins Center for Psychoneuroimmunology and the Semel Institute for Neuroscience and Human Behavior at UCLA. Additional authors from UCLA include Catherine Crespi, Steve Cole, Patricia Ganz, and Laura Petersen.
The study received funding from grants provided by the National Cancer Institute.
