Aging is an accumulation of forms of cell and tissue damage, and a complex network of downstream consequences of that damage that interact with one another to accelerate further dysfunction. It should not be too surprising to find that other approaches to producing damage in a living individual resemble aging, at least superficially. This is the case in DNA repair deficiency conditions, and, as researchers note here, it is the case in the aggressive use of chemotherapy to treat cancer.
While chemotherapy can be lifesaving, it also damages DNA and leads to cognitive issues known as "chemo brain." These effects resemble the memory and learning problems seen in older adults. 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. In addition, the blood-brain barrier, a protective layer that prevents harmful substances from entering the brain, is disrupted, which triggers inflammation in the brain. Finally, there is an accumulation of senescent cells in both brains. Senescent cells are in a suspended state of not being dead nor being able to fulfill their normal function, which also causes inflammation.
The research team studied several chemotherapy drugs in mice for their effects on the brain, including the commonly used paclitaxel and cisplatin. They found that even though the chemo drugs caused DNA damage in different ways, their characteristics were the same in how they affected cognition. Because of the blood-brain barrier, chemotherapy drugs do not directly enter and damage the brain. Instead, chemotherapy harms endothelial cells, the type of vascular cell most susceptible to damage. When the endothelial cells are impaired, they become senescent and produce inflammatory substances that compromise the blood-brain barrier.
The researchers also studied ways to improve cognition. They tested senolytics in aging mice. Senolytics are drugs that can induce senescent cells to die through apoptosis, the typical process by which cells are removed. By selectively removing senescent cells, cognition improved. Researchers took the study a step further to determine the ideal time window for administering senolytics to have the most positive effect on the brain's vasculature and cognition. They tested senolytics in mice of all ages and ultimately discovered the drug was most effective when the mice were about 16 months old, which researchers believe equates to 50 to 55 years old in humans.
Link: https://www.ou.edu/n...roved-cognition
View the full article at FightAging
