DMTF1 Protein: Restoring Brain Cell Regeneration & Slowing Aging
Scientists at the National University of Singapore’s Yong Loo Lin School of Medicine have identified a protein, cyclin D-binding myb-like transcription factor 1 (DMTF1), that appears to restore the brain’s capacity for cellular regeneration as it ages. The discovery, published in the journal Science Advances on February 12, 2026, offers a potential pathway for therapies aimed at slowing or reversing cognitive decline associated with aging.
The research, led by Assistant Professor Ong Sek Tong Derrick and spearheaded by Dr. Liang Yajing, both from the Department of Physiology and the Healthy Longevity Translational Research Programme at NUS Medicine, focused on understanding the mechanisms behind the weakening of neural stem cells over time. These cells are crucial for generating new neurons, a process vital for learning and memory. As individuals age, the regenerative capacity of these stem cells diminishes, contributing to cognitive impairment.
The team investigated DMTF1’s function by examining neural stem cells derived from both human sources and laboratory models designed to replicate premature aging. Through genome binding and transcriptome analyses, they mapped how DMTF1 influences gene activity, with a particular focus on its interaction with stem cells affected by telomere dysfunction. Telomeres, the protective caps on the ends of chromosomes, shorten with each cell division, a well-established marker of aging.
Researchers found that levels of DMTF1 were significantly reduced in aged neural stem cells. Restoring DMTF1 expression, but, enabled the cells to regain their ability to regenerate. This suggests that DMTF1 plays a critical role in maintaining neural stem cell function and could be a viable therapeutic target.
Further analysis revealed that DMTF1 operates by regulating “helper genes” – Arid2 and Ss18 – which loosen the tightly packed structure of DNA. This loosening allows growth-related genes to become active. Without the presence of these helper genes, neural stem cells struggle to renew themselves effectively.
“Impaired neural stem cell regeneration has long been associated with neurological aging. Inadequate neural stem cell regeneration inhibits the formation of new cells needed to support learning and memory functions,” said Assistant Professor Ong. “Understanding the mechanisms for neural stem cell regeneration provides a stronger foundation for studying age-related cognitive decline.”
The findings suggest that strategies to increase DMTF1 levels or enhance its activity could potentially mitigate the decline in neural stem cell function linked to aging. Even as the current research is primarily based on in vitro experiments, the team plans to investigate whether boosting DMTF1 can increase neural stem cell numbers and improve learning and memory in conditions involving telomere shortening and natural aging. A key consideration in these future studies will be to ensure that increasing DMTF1 activity does not raise the risk of brain tumors.
“Our findings suggest that DMTF1 can contribute to neural stem cell multiplication in neurological aging,” Dr. Liang stated. “While our study is in its infancy, the findings provide a framework for understanding how aging-associated molecular changes affect neural stem cell behavior, and may ultimately guide the development of successful therapeutics.”
The NUS Yong Loo Lin School of Medicine, Singapore’s first and largest medical school, has been at the forefront of medical education and research since its establishment in 1905. The school has produced over 12,000 graduates and continues to drive innovation in healthcare, according to information published on the school’s official website.