Protein Boosts Brain Stem Cell Activity, Reverses Aging

Researchers at the National University of Singapore's Yong Loo Lin School of Medicine have identified a key protein, DMTF1, that could potentially reverse age-related decline in the brain's ability to create new cells. Their study, published in Science Advances, highlights DMTF1, a transcription factor, as crucial for controlling neural stem cell activity in older brains. These stem cells are vital for generating new neurons involved in memory and learning, but their regenerative capacity diminishes with age, contributing to cognitive impairment.

Led by Assistant Professor Ong Sek Tong Derrick and with Dr. Liang Yajing as the first author, the research team aimed to pinpoint why neural stem cells weaken over time, seeking targets for therapies to combat neurological aging. They investigated DMTF1 in human and lab-model neural stem cells, including those experiencing premature aging. Using advanced genetic analysis, they mapped DMTF1's influence on gene expression, with a particular focus on its role in stem cells affected by telomere shortening, a known aging marker.

The study revealed significantly lower DMTF1 levels in aged neural stem cells. Crucially, reintroducing DMTF1 restored their regenerative capabilities, suggesting it could be a promising therapeutic target. Further investigation showed DMTF1 orchestrates the function of helper genes (Arid2 and Ss18) that modify DNA structure, thereby activating genes necessary for cell growth and renewal. Without sufficient DMTF1, neural stem cells fail to effectively multiply.

"The link between poor neural stem cell regeneration and neurological aging is well-established," stated Asst Prof Ong. "This deficiency hinders the creation of new cells essential for learning and memory. While partial restoration of this regeneration has been observed, the underlying mechanisms are still unclear. Understanding these mechanisms is foundational for addressing age-related cognitive decline."

These findings suggest that interventions aimed at boosting DMTF1 levels or its activity could potentially mitigate or reverse the age-induced loss of neural stem cell function. While current research is primarily in vitro, the team plans to explore whether increasing DMTF1 can enhance stem cell numbers and improve cognitive function in models of natural aging and telomere shortening, while ensuring no increased risk of brain tumors. The long-term goal is to develop safe small molecules that can stimulate DMTF1 to rejuvenate aging neural stem cells.

"Our results indicate DMTF1 plays a role in multiplying neural stem cells within the aging brain," commented Dr. Liang. "Although this research is in its early stages, it provides a vital framework for understanding how age-related molecular changes impact neural stem cell behavior and could pave the way for effective treatments."