A causal link between senescent cells and neurodegeneration in mice is reported in a paper published online this week in Nature. The findings could open up a potential new therapeutic avenue for the treatment of neurodegenerative diseases.
Previous research has shown that senescent cells (dysfunctional cells that have lost their capacity to divide) accumulate with age throughout the body and actively promote tissue degeneration. Removal of these cells can counteract many effects of ageing. Senescent cells have also been detected in the context of brain ageing and neurodegenerative disease, although their role here is not yet known.
Using transgenic mice modelling neurodegenerative disease, Darren Baker and colleagues report the accumulation of senescent cells in regions of the brain such as the hippocampus. Removing these cells via genetic modification throughout the life of the mouse reduces neuronal tau protein phosphorylation (and subsequent neurofibrillary tangle accumulation), and prevents degeneration of neurons in the cortices and hippocampus - regions of the brain involved in cognitive processes. The mice display reduced memory loss compared to unmodified mice, suggesting that senescent cells promote neurodegeneration and the loss of cognition function.
These findings demonstrate that the continuous clearance of senescent cells prior to the onset of neurodegenerative disease in a mouse model may have a significant effect on disease progression. Further research will be required to determine whether these findings translate to humans and could therefore be utilized in a clinical setting.