06/03/2020
Getting rid of old brain cells may help prevent
Alzheimer's and dementia.
Cellular senescence, which is characterized by an irreversible cell cycle arrest is
accompanied by a distinctive secretory phenotype and
,can be induced through various intra-cellular and extra-cellular factors. Senescent cells that express the cell cycle inhibitory protein
p16INK4A have been found to actively drive naturally occurring
age-related tissue deterioration and contribute to several
diseases associated with ageing, including atherosclerosis
and
osteoarthritis.
Various markers of senescence have been observed
in patients with neurodegenerative diseases, however, a role for senescent cells in the etiology of these pathologies is unknown.
Here we show a causal link between the accumulation of senescent cells and cognition-associated neuronal loss. We found that a
mouse model of tau-dependent neurodegenerative
disease accumulates senescent astrocytes
and microglia. Clearance of these cells as they arise using transgenic mice prevents gliosis, hyperphosphorylation
of both soluble and insoluble tau leading to neurofibrillary tangle
deposition, and degeneration of cortical and hippocampal neurons,
thus preserving cognitive function. Pharmacological intervention
with a first-generation senolytic modulates tau aggregation.
Collectively, these results show that senescent cells have a role in
the initiation and progression of tau-mediated disease, and suggest
that targeting senescent cells may provide a therapeutic avenue for
the treatment of these pathologies.
https://doi.org/10.1038/s41586-018-0543-y
Clearance of senescent glial cells prevents
tau-dependent pathology and cognitive decline
Tyler J. Bussian1,3, Asef Aziz2,3, Charlton F. Meyer2
, Barbara L. Swenson2
, Jan M. van Deursen1,2 & Darren J. Baker1,2*
In a mouse model of tau-dependent neurodegenerative disease, the clearance of senescent glial cells prevents the degeneration of cortical and hippocampal neurons and preserves cognitive function.
