Zombie cells are cells that can't die but that are equally unable to perform the functions of a normal cell. These zombie, or senescent, cells are implicated in a number of age-related diseases. And with a new letter in Nature, Mayo Clinic researchers have expanded that list.
In a mouse model of brain disease, scientists report that senescent cells accumulate in certain brain cells prior to cognitive loss. By preventing the accumulation of these cells, they were able to diminish tau protein aggregation, neuronal death, and memory loss.
"Senescent cells are known to accumulate with advancing natural age and at sites related to diseases of aging, including osteoarthritis; atherosclerosis; and neurodegenerative diseases, such as Alzheimer's and Parkinson's," says Darren Baker, Ph.D., a Mayo Clinic molecular biologist and senior author. "In prior studies, we have found that elimination of senescent cells from naturally aged mice extends their healthy life span."
In the current study, the team used a model that imitates aspects of Alzheimer's disease.
"We used a mouse model that produces sticky, cobweb-like tangles of tau protein in neurons and has genetic modifications to allow for senescent cell elimination," explains first author Tyler Bussian, a Mayo Clinic graduate student. "When senescent cells were removed, we found that the diseased animals retained the ability to form memories, eliminated signs of inflammation, did not develop neurofibrillary tangles, and had maintained normal brain mass." They also report that pharmacological intervention to remove senescent cells modulated the clumping of tau proteins.
Also, the team was able to identify the two different cell types that became senescent: microglia and astrocytes.
“These cells are important supporters of neuronal health and signaling,” says Bussian, “so it makes sense that senescence in either would negatively impact neuron health."
In terms of future work, Dr. Baker explains that this research lays out the best-case scenario, where prevention of damage to the brain avoided the disease state. "Clearly, this same approach cannot be applied clinically, so we are starting to treat animals after disease establishment and working on new models to examine the specific molecular alterations that occur in the affected cells.”