Researchers found similarities between the “chemical brain” (cognitive problems encountered by chemotherapy patients after chemotherapy) and normal brain aging.
Research from the University of Oklahoma shows that both conditions involve the same harmful cell changes, including reduced blood flow, inflammation and accumulation of “zombie cells” that may occupy the key to cognitive decline in cancer survivors and older people.
These findings, published in three recent papers on Geroscience and aging cells, suggest that understanding one condition can unlock treatments for both. Lead researcher Anna Csiszar believes that this overlap provides unprecedented opportunities for developing therapies to address cognitive problems in different populations.
Parallel pathways of decline
“There are several similarities in both cases,” explains Csiszar, a professor of neurosurgery at the University of Oklahoma School of Medicine. “In both, blood flow decreases when the brain is in a quiescent state, and the increase in blood flow is smaller when the brain is active.”
Two conditions also destroy the blood-brain barrier – a protective layer that prevents harmful substances from entering the brain. This destruction triggers inflammation and leads to the accumulation of senescent cells, commonly known as “zombie cells”, which neither die nor perform their normal functions.
Chemotherapy link
The team studied several chemotherapy drugs in mice, including the commonly used paclitaxel and cisplatin. Although DNA damage is caused through different mechanisms, all drugs have the same effect on cognition and brain function.
The main findings of chemotherapy research include:
- Chemotherapy drugs do not enter the brain directly due to the blood-brain barrier
- Instead, they damage endothelial cells lined with blood vessels, making them aging
- These zombie cells produce inflammatory substances that damage brain protection
- Inflammation and reduced blood flow reflex mirror changes in natural aging
It is worth noting that even though different chemotherapy drugs work through different pathways, they all trigger the same pattern of brain change, suggesting a common underlying mechanism.
Targeting zombie cells show hope
The researchers tested promising interventions using a drug called nasal solvent that specifically eliminates senescent cells. In aging mice, these treatments improve cerebral blood flow, restore health of the blood-brain barrier, and improve cognitive abilities.
“Our research shows that if we remove these senescent cells, we can improve cerebral blood flow and blood-brain barrier health and ultimately improve cognition,” Csiszar noted.
The timing of treatment is crucial. The team found that Senolotics were best effective when administered to 16-month-old mice—equivalent to humans 50-55 years. This represents a critical window before cognitive changes become irreversible.
Key treatment window
Research shows an important limitation: While nasal soluble drugs can eliminate zombie cells and protect cerebrovascular, cognitive improvement will only occur later in life when treatment begins in middle age.
“We found this to be the best time frame to eliminate senescent cells and protect cognitive health,” Csiszar explained. “You can provide nasal solvents later, but you can still eliminate cells and protect the vasculature of the brain, but by then, cognitive changes are irreversible.”
This discovery has a significant impact on cancer treatment and aging research. It shows that preventive interventions during middle age can prevent cognitive decline, whether caused by chemotherapy or normal aging processes.
Future treatment possibilities
The fusion of aging and cancer research represents a paradigm shift close to cognitive decline. Research shows that rather than treating these problems as separate issues, common therapeutic targets can benefit multiple patient populations.
Whether caused by chemotherapy or normal aging, cognitive impairment can significantly affect the quality of life. Identification of senescent cells as a common mechanism opens up new avenues for drug development and therapeutic strategies.
“There is indeed an intersection between aging research and cancer research,” Csiszar concluded. “These teams represent the future of research and we have a great motivation on campus.”
These findings may ultimately lead to preventive treatment of middle-aged individuals at risk of cognitive decline, as well as protective therapies for cancer patients who are starting chemotherapy.
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