More Animal Study Evidence for Senolytics to Improve Cognitive Function in Old Age

A growing number of rodent studies have demonstrated the ability of senolytics to improve cognitive function in old animals by clearing a sizable fraction of lingering senescent cells from aged tissues throughout the body. Specifically this means the dasatinib and quercetin combination, as both can cross the blood-brain barrier after oral administration. Researchers have undertaken a study in Alzheimer's patients, but it will be quite some time before results are published. Senescent cells generate inflammatory signaling, and inflammation in brain tissue is strongly implicated in the progression of neurodegenerative conditions. The degree to which this is the result of the activity of senescent cells in the brain versus the signaling of the many more senescent cells outside the brain is up for debate. Clearing such cells globally is in any case clearly beneficial in rodents.

Aging is associated with cognitive decline and accumulation of senescent cells in various tissues and organs. Senolytic agents such as dasatinib and quercetin (D+Q) in combination have been shown to target senescent cells and ameliorate symptoms of aging-related disorders in mouse models. However, the mechanisms by which senolytics improve cognitive impairments have not been fully elucidated particularly in species other than mice.

To study the effect of senolytics on aging-related multifactorial cognitive dysfunctions we tested the spatial memory of male Wistar rats in an active allothetic place avoidance task. Here we report that 8 weeks treatment with D+Q alleviated learning deficits and memory impairment observed in aged animals. Furthermore, treatment with D+Q resulted in a reduction of the peripheral inflammation measured by the levels of serum inflammatory mediators (including members of senescent cell secretome) in aged rats.

Significant improvements in cognitive abilities observed in aged rats upon treatment with D+Q were associated with changes in the dendritic spine morphology of the apical dendritic tree from the hippocampal CA1 neurons and changes in the level of histone H3 trimethylation at lysine 9 and 27 in the hippocampus. The beneficial effects of D+Q on learning and memory in aged rats were long-lasting and persisted at least 5 weeks after the cessation of the drugs administration.


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