The promise of reclaiming youthful cognitive function has long been a holy grail for neuroscientists, but researchers may have just uncovered a critical microscopic switch that dictates how well our brains can repair themselves over time.
A team at the National University of Singapore says a single regulator protein may be one of the reasons older brains stop replacing neurons as easily, and that dialing it back up can make aging stem cells behave younger again in lab tests.
The protein in question is called DMTF1, and it sits upstream of the gene activity that helps neural stem cells keep renewing themselves. These stem cells matter because they generate new neurons, and the process is closely linked to learning and memory. With age, the renewal slows down, and the pool becomes less active, which is when cognitive decline starts getting a foothold.
Pinpointing the Mechanism
In the new study, published recently in the peer-reviewed journal Science Advances, the researchers looked at neural stem cells taken from humans and also used lab models meant to mimic accelerated aging. A big part of the work focused on telomere dysfunction, i.e., damage at the ends of chromosomes, widely treated as a marker of biological aging.
What the team saw was blunt: “aged” stem cells had much lower DMTF1. When the team increased DMTF1 again, those same cells regained regeneration capacity.
They then traced a possible chain of control. DMTF1 appears to act through helper genes called Arid2 and Ss18, which affect how tightly DNA is packed inside the cell. When the DNA is less locked down, genes involved in growth and renewal can switch back on. When that pathway is weak, stem cells struggle to reset and multiply.
Context, Caution, and The Road Ahead
The project, led by Assistant Professor Ong Sek Tong Derrick with Dr. Liang Yajing as first author, was conducted in NUS Medicine’s Department of Physiology and the Healthy Longevity Translational Research Programme, where scientists work to translate discoveries in aging biology into strategies for healthier lifespans.
Even as the program pursues such translational insights, this discovery isn’t a “brain aging reversed” headline yet, and the team doesn’t present it that way. The current results are mostly from cell-based experiments.
Next, the researchers plan to test whether boosting DMTF1 can increase neural stem cell numbers and improve learning and memory in settings that involve telomere shortening and natural aging. They also flag a safety question they want to watch closely: avoiding an increased risk of brain tumors.
Long-term, the team’s stated goal is to find small molecules that can stimulate DMTF1 activity in a controlled way. Essentially, something that could be developed into a treatment rather than a genetic tweak in a lab dish.
Sources: Science Advances, Science Daily