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Healthy brain activity is achieved by maintaining a balance between neural excitation and inhibition. Impairment in this balance is related to many neurological and neurodegenerative disorders, including epilepsy, autism, Parkinson’s, Alzheimer’s, and schizophrenia. In Caenorhabditis elegans, a model organism for studying both the nervous system and aging, neural excitation increases with age and age-related cognitive decline, but lifespan increases with inhibition. A recent study demonstrates that extended longevity in humans is associated with lower levels of genes related to neural excitation.
The multi-arm study focused on three organisms: C. elegans, humans, and mice. The authors of the study found that global inhibition of neural excitation increased the lifespan of C. elegans. RNA sequencing and microarray analysis of human genes revealed that long-lived people (older than 85 years) have higher levels of REST, a gene-silencing transcription factor that downregulates neural excitation-related genes. In addition, they found that mice that are deficient in REST exhibit higher levels of neural excitation. REST and lower levels of neural excitation activate FOXO1, a longevity-associated transcription factor in mammals, suggesting that REST regulates a conserved mechanism of aging.
The authors of the study suggested that REST activation and subsequent reduction of excitatory neural activity may be a means to slow aging in humans.