When trying to visually represent the brain, the image of a series of question marks joining together is among the most exploited and perfectly illustrates the complexity of knowledge and the need to obtain as complete a puzzle as possible of the connections and functions of the central nervous system. In this mosaic logic that changes over time in the same person, it really seems like a feat to be able to precisely arrange all the pieces relating to brain decay and the progressive loss of thinking and memory capacity, in the “mare magnum” of knowledge, all of which must be carefully pigeonholed. However, now a scientific acquisition has been added which gives rise to hope.
This is demonstrated by Science Advances, which publishes research conducted by scholars from the Yong Loo Lin School of Medicine of the National University of Singapore. Experts have identified a protein that could help restore the brain’s ability to produce new cells as it ages. It is a transcription factor, hence the name, transcription factor 1 or DMTF1. And it’s a protein that works by controlling the activity of neural stem cells in older brains, turning genes on or off.
What happens in the elderly
Normally, neural stem cells are responsible for the generation of new neurons, resulting in learning and memory activity. With aging, the action of stem cells is also limited due to the loss of their ability to renew themselves. And this can promote cognitive decline.
The Singaporean scholars, coordinated by Ong Sek Tong Derrick (first name Liang Yajing) went to study and discover the biological changes that cause the weakening of neural stem cells over time, to find new possible therapeutic targets. To understand how DMTF1 works, researchers examined neural stem cells derived from humans and laboratory models designed to mimic premature aging. They used genomic linkage and transcriptome analyzes to map how DMTF1 influences gene activity, with a particular focus on the protein’s activity on stem cells affected by telomere dysfunction. Telomeres are the protective ends of chromosomes that gradually shorten each time a cell divides. This shortening is widely recognized as a marker of aging.
Towards new therapies?
The research clearly shows that the availability of DMTF1 has been reduced in “aged” nervous system stem cells. By restoring the expression of DMTF1, however, the cells regained their ability to regenerate. This suggests that DMTF1 may represent a promising therapeutic target for restoring stem cell function in the aging brain. The action of DMTF1 would pass through the regulation of helper genes (Arid2 and Ss18): without this activity neural stem cells cannot renew themselves effectively.
The ending of this research is simple and at the same time, although it should not be exaggerated, full of future prospects. Treatments designed to increase DMTF1 levels or improve its activity could potentially reverse or delay the age-related decline in neural stem cell function.
At the moment, it must be said, we are still in test tube studies. But in the future we need to understand whether increasing DMTF1 can increase the number of neural stem cells and improve learning and memory in conditions that involve telomere shortening and natural aging, without increasing the risk of brain tumors. Once data on the safety of the approach have been obtained, it will be possible to think about tailor-made therapy to safely stimulate the activity of DMTF1. And thus rejuvenate aged neural stem cells.
