Here\u2019s what you\u2019ll learn when you read this story:<\/p>\n
As the human brain ages, the regeneration of neuronal stem cells declines.<\/p>\n
A new study analyzed DMTF1\u2014a specialized protein that regulates gene expression\u2014and found that it was repressed in \u201caged\u201d neural stem cells.<\/p>\n
This could be the key to promoting regeneration in an aging brain, and to avoid the worst cognitive outcomes in the future.<\/p>\n
Aging<\/a> has always been an inevitable part of life, but now scientists hope that one of its cellular mechanisms could help reverse its effects. The mechanism in question is the seemingly unavoidable decline of neural stem cells. That decline is a pretty big piece of biological bad news, as a dip in neuronal regeneration can have profound impacts on learning and memory. Recently, a team of scientists from the National University of Singapore (NUS) wondered if investigating the underlying mechanism of decline could help them find the key to halting the process.<\/p>\n This search led them to a transcription factor (a specialized protein that regulates gene expression) whose name is a bit of a mouthful\u2014cyclin D-binding myb-like transcription factor 1, or DMTF1. In their experiments, they found that DMTF1 appears repressed in \u201caged\u201d neural stem cells<\/a>, and conversely, that restoring DMTF1\u2019s expression helped stem cells get their mojo back. The results of the study were published in the journal Science Advances<\/a>.<\/p>\n \u201cWhile [previous] studies have found that defective neural stem cell regeneration can be partially restored, its underlying mechanisms remain poorly understood,\u201d Derrick Sek Tong Ong, the senior author of the study from NUS, said in a press statement<\/a>. \u201cUnderstanding the mechanisms for neural stem cell regeneration provides a stronger foundation for studying age-related cognitive decline<\/a>.\u201d<\/p>\n The NUS research team used human stem cell systems and mouse models to simulate aging, and then analyzed how DMTF1 influenced neural stem cell function through transcriptome analyses and genome<\/a> binding. Telomeres are repetitive DNA sequences capping the ends of chromosomes to prevent them from fraying or tangling, and they naturally get shorter over time as cells divide inside an aging organism. Thus, reduced telomere length is a telltale sign of aging. Indeed, short telomeres can trigger cellular senescence, which in turn leads to decreased cell division and a rise in inflammation.<\/p>\n What the researchers discovered is that DMTF1 can control the expression of helper genes that activate other, growth-related genes through chromatin remodeling. Crucially, this mechanism rescued the proliferation of neural stem cells impaired by telomere shortening, even without restoring telomere length itself. This discovery suggests that in the future, therapies targeting DMTF1 can reverse age-related decline in brain stem cells by reactivating the molecular machinery that drives cell division.<\/p>\n \u201cOur findings suggest that DMTF1 can contribute to neural stem cell multiplication in neurological aging,\u201d Liang Yajing, a co-author of the study from NUS, said in a press statement. \u201cWhile our study is in its infancy, the findings provide a framework for understanding how aging-associated molecular changes affect neural stem cell behavior<\/a>, and may ultimately guide the development of successful therapeutics.\u201d<\/p>\n