Friday, November 05, 2021

Study links MEF2 gene family to cognitive resilience in the elderly

Good news! This study confirms again that intellectually stimulating activities by elderly significantly decreases the chances of cognitive decline!

"... A new study by MIT researchers shows that this kind of enrichment appears to activate a gene family called MEF2, which controls a genetic program in the brain that promotes resistance to cognitive decline.

The researchers observed this link between MEF2 and cognitive resilience in both humans and mice. The findings suggest that enhancing the activity of MEF2 or its targets might protect against age-related dementia. ...
MEF2 is a transcription factor that was originally identified as a factor important for cardiac muscle development, but later was discovered to play a role in neuron function and neurodevelopment. In two human datasets comprising slightly more than 1,000 people all together, the MIT team found that cognitive resilience was highly correlated with expression of MEF2 and many of the genes that it regulates
Many of those genes encode ion channels, which control a neuron’s excitability, or how easily it fires an electrical impulse. The researchers also found, from a single-cell RNA-sequencing study of human brain cells, that MEF2 appears to be most active in a subpopulation of excitatory neurons in the prefrontal cortex of resilient individuals. ..."

"... Now, Barker et al., using human data and experimental models, report that the expression of the transcription factor MEF2 was a predictor of end-stage cognition in individuals with Alzheimer’s disease, and MEF2 expression was increased in resilient patients. In mice, enriched environment–associated cognitive improvement increased MEF2 activity, whereas Mef2 KO resulted in cognitive impairments and neuronal overexcitability. Overexpressing Mef2a/c in a mouse model of tauopathy improved cognition and reduced overexcitability. The results suggest that MEF2 might be a valuable target for limiting cognitive impairments in patients with neurodegenerative diseases. ..."

From the abstract:
"... we began by profiling the molecular changes that arise from environmental enrichment in mice, which led to the identification of MEF2 transcription factors (TFs). We next turned to repositories of human clinical and brain transcriptomic data, where we found that the MEF2 transcriptional network was overrepresented among genes that are most predictive of end-stage cognition. ..."

Study links gene to cognitive resilience in the elderly | MIT News | Massachusetts Institute of Technology The findings may help explain why some people who lead enriching lives are less prone to Alzheimer’s and age-related dementia.

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