‘Retired’ cells in the brain could contribute to neurodegenerative diseases like Alzheimer’s

Cells in the human body have a limited capacity to divide and grow; once this capacity is used up, the cells retire and become senescent. Senescent cells no longer grow or divide and instead begin to release proteins that are associated with inflammation and numerous chronic diseases. Senescent cells have been associated with chronic diseases like atherosclerosis and osteoarthritis, and some reports have linked these retired cells to neurodegenerative disorders like Alzheimer’s and dementia. Up until now however, there was no experimental evidence that these senescent cells were important in the development of neurodegenerative diseases or that targeting them could prevent or reveres the disease. This is what a team of researchers from Minnesota set out to show, that targeting these senescent cells could be a viable treatment option in Alzheimer’s and other chronic brain disease.

The researchers used a mouse model that spontaneously develops neurodegenerative disease that is similar to Alzeheimer’s disease. In the brains of patients with Alzeheimer’s, tangled masses of a protein called tau build up eventually killing the neurons and leading to cognitive loss, this same build up of proteins is witnessed in these special mice and so makes them a valuable tool in neurodegenerative research. In the brains of these mice the researchers found significant accumulation of senescent cells in the cells that help protect and maintain the brain (the microglia and the astrocytes). When the team cleared out the senescent cells with a drug that specifically targets them, they noted an improvement in the cognitive function in the mice as well as a decrease in the amount of neurons that are being lost in the brain. There was also a reduction in the amount of tangle tau proteins in the brain of these mice which correlated with their improved outcomes.

These results suggest that these ‘retired’ or senescent cells have a role in the development of these tau protein tangles and that targeting these cells with drugs that specially kill them could be a way to halt the progression of age related brain diseases. This research adds to a growing field that suggests drugs that target senescent cells, called senolytics, could be treatment options in a variety of age related disease. There have been no clinical trials yet testing these drugs in age related diseases but the animal and cell work suggests that these types of studies may no be far away.

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