A newly identified protein called DMTF1 can restore the regenerative capacity of aging neural stem cells — even after significant age-related decline has already set in — researchers at the Salk Institute for Biological Studies report in Nature Aging. When introduced into the hippocampal region of 18-month-old mice (roughly equivalent to a 60-year-old human), DMTF1 restored neurogenesis rates to levels comparable to those seen in young adults, accompanied by measurable improvements in memory performance on maze and object recognition tests.
The hippocampus is the brain region most central to the formation of new memories and one of the most dramatically affected by aging. The progressive decline in its ability to generate new neurons — a process called neurogenesis — is thought to be a major driver of age-related memory loss and cognitive slowing, and is implicated in Alzheimer's disease pathology.
How the Discovery Was Made
Researchers screened hundreds of transcription factors — proteins that switch genes on and off — for their ability to reactivate dormant neural stem cells taken from aged mouse brains. DMTF1 emerged as the most effective candidate. When introduced into aged cells, it reprogrammed their gene expression patterns to resemble those of young stem cells, reversing the silencing of genes needed for active cell division and new neuron production.
Animals treated with DMTF1 showed improved performance on memory tasks within three weeks of treatment, with benefits persisting for the full three-month observation period and no adverse effects observed. Clinical translation will require significant additional work, but researchers describe the findings as a "proof of concept" for the reversibility of brain aging.