New Research Unveils Links Between Chemotherapy Effects and Aging Brain

A recent study conducted by researchers at the University of Oklahoma has uncovered significant parallels between the cognitive impairments caused by chemotherapy and those typically associated with aging. The research, led by Dr. Anna Csiszar, M.D., Ph.D., a professor of neurosurgery at the University of Oklahoma College of Medicine, aims to illuminate how the side effects of chemotherapy, commonly referred to as 'chemo brain,' overlap with the cognitive decline that occurs in older adults.

The findings, published in the journals *GeroScience* and *Aging Cell*, highlight that both conditions exhibit decreased cerebral blood flow and an increase in inflammation, which is exacerbated by the presence of senescent cells—cells that have lost their ability to divide and function properly. This study raises critical questions about the long-term impacts of chemotherapy on cognitive health, particularly as the population ages and more individuals survive cancer treatments.

Dr. Csiszar noted, 'There are several parallels in these two situations. In both, there is decreased blood flow in the brain when it is at rest and a smaller increase in blood flow when the brain is active. Additionally, the blood-brain barrier, which protects the brain from harmful substances, becomes disrupted, leading to inflammation.' This disruption is particularly concerning given that it may affect not only cancer survivors but also the aging population at large.

Chemotherapy, while a lifesaving treatment for cancer, is known to damage DNA and healthy cells, particularly those that divide rapidly. The study specifically examined the effects of chemotherapy drugs such as paclitaxel and cisplatin on mice, revealing that these drugs induce similar patterns of cognitive impairment as those seen in aging. According to Dr. Csiszar, 'Even though the chemo drugs caused DNA damage in different ways, their effects on cognition were remarkably similar.'

In their exploration of potential interventions, the research team investigated the use of senolytics—drugs designed to eliminate senescent cells. In a study published in *Aging Cell*, they found that administering senolytics to aging mice improved cerebral blood flow and cognitive function. 'We found that removing these senescent cells can enhance the health of the blood-brain barrier, ultimately improving cognition,' Dr. Csiszar explained.

The timing of treatment with senolytics appears critical; the researchers discovered that administering these drugs around the age of 16 months in mice—equivalent to approximately 50 to 55 years in humans—yielded the most significant cognitive benefits. Delaying treatment, while still effective in removing senescent cells, resulted in irreversible cognitive changes.

These findings not only add a new dimension to our understanding of chemotherapy-related cognitive decline but also suggest potential pathways for enhancing cognitive health in aging individuals. Dr. Csiszar expressed hope that this intersection of aging and cancer research could bridge gaps in our knowledge and lead to improved therapeutic strategies. 'There is truly an intersection between aging research and cancer research. These teams represent the future of research, and we have wonderful momentum on our campus,' she concluded.

As the incidence of cancer continues to rise and more individuals survive treatments, understanding the long-term cognitive effects and developing interventions will be vital for enhancing the quality of life among cancer survivors and older adults alike. This research underscores the urgent need for continued exploration at the nexus of cancer treatment and aging, which could have profound implications for public health and patient care.