Cell Rest and Teen Exercise Are Keys To Later Brain Health
July 1, 2010
It can’t be said too often: to protect your brain, exercise! Now, two new studies are adding more emphasis to physical activity— and greater understanding to the interplay between exercise, aging and the exquisite balance that preserves the brain’s reservoir of stem cells for later life.
One study focused on the cellular mechanism that keeps neural stem cell division in check. The other correlated the lack of teenage exercise with cognitive impairment in later life.
In the first, scientists at the Salk Institute of Biological Research in La Jolla, California, underscored how physical activity balances neural stem cell quiescence— stem cells are at rest— and keep them from their dormancy from becoming dominant in later life while it helps stimulate the growth of new neurons in the hippocampus, the brain’s hub of memory.
Image: Courtesy of Dr. Helena Mira, Carlos III Health Institute, Madrid
The other study, of 9,344 women from Maryland, Minnesota, Oregon, and Pennsylvania, compared at activity levels at teenage, age 30, age 50, and late life with cognitive decline. Reported June 30 in the Journal of the American Geriatrics Society, it held alarming implications in an era of declining physical activity for youths.
“Our study shows that women who are regularly physically active at any age have lower risk of cognitive impairment than those who are inactive,” said lead researcher Laura Middletton, Ph. D., of Sunnybrook Health Sciences Center in Toronto. “But … being physically active at teenage is most important in preventing cognitive impairment.”
Researchers, led by Laura Middleton, Ph. D., of Sunnybrook Health Sciences Centre, found that being physically active at any stage of life lowers the risk of cognitive impairment in old age. But “being physically active at teenage is most important in preventing cognitive impairment,” said lead researcher Laura Middleton, Ph. D., of Sunnybrook Health Sciences Centre, Canada.
The researchers also determined that women who were physically inactive at teenage but became physically active at age 30 and age 50 had significantly reduced odds of cognitive impairment relative to those who remained physically inactive. In contrast, being physically active at age 30 and age 50 was not significantly associated with rates of cognitive impairment in those women who were already physically active at teenage.
“To minimize the risk of dementia, physical activity should be encouraged from early life,” Middleton said, adding, “Not to be without hope, people who were inactive at teenage can reduce their risk of cognitive impairment by becoming active in later life.”
The mechanisms by which cognition benefits from physical activity across the life course are believed multi-factorial. Much evidence already suggests that physical activity positively effects brain plasticity and cognition and that physical activity reduces the rates and severity of vascular risk factors, such as hypertension, obesity, and type II diabetes associated with increased risk of cognitive impairment.
“Low physical activity levels in today’s youth may mean increased dementia rates in the future. Dementia prevention programs and other health promotion programs encouraging physical activity should target people starting at very young ages, not just in mid- and late life,” said Middleton.
Some of the cognitive issues of aging may be the result of an unchallenged process by which stem cells in the brain remain dormant until called upon to produce more neurons, ensuring a pool of neurons that lasts a lifetime.
In research published in the July 1 issue of Cell Stem Cell, researchers identified the importance of bone morphogenetic factor protein (BMP) in preventing the rampant proliferation and depletion of neural stem cells.
Using prior observation that quiescent neural stem cells express the BMP receptor 1A as a starting point, co-first author Helena Mira, formerly a post-doc in senior author Fred H. Gage’s Laboratory for Genetics at the Salk Institute and now an assistant professor in the Department of Cell Biology and Development at the Carlos III Health Institute in Madrid, and her collaborators investigated the role of BMP signaling in regulating the proliferation of stem cells located in the hippocampus, one of two brain regions harboring neural stem cells.
They found that BMP signaling, which is triggered by the interaction of BMPs with their receptors, is inactive in most proliferating cells, whereas it is active in non-dividing cells, including quiescent stem cells and differentiated neurons. Unlike stem cells, mature neurons express BMP receptor 1B, which will be the focus of future studies.
Experiments with cultured neural stem cells confirmed that it was indeed BMP that kept them quiet. BMP’s anti-proliferative effect was blocked when BMP was replaced with a protein known as Noggin, which binds and inactivates members of the BMP family.
The researchers observed the same effect when they delivered Noggin directly into the brains of adult mice. Here, too, Noggin successfully interfered with BMP signaling and raised quiescent stem cells out of their slumber. After one week, those neural stem cells had started dividing and their offspring were well on their way to becoming neurons.
When neural stem cells were forced to proliferate over prolonged periods of time, however, the pool of active neural stem cells was depleted, suggesting to Gage and his team that quiescence functions as a protective mechanism that counteracts stem cell exhaustion.
“It tells you how finely this process is regulated,” says Mira. “BMP ensures a sufficiently big population of quiescent stem cells that can feed into the system when called upon.”
Gage, the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Diseases, will next investigate whether BMP is the linchpin that links exercise, aging and neurogenesis. “As we age, the number of new neurons declines but physical exercise brings that number back up,” he said. “Our findings raise the possibility that the BMP signal becomes dominant over time, forcing neural stem cells deeper into quiescence and thus making it harder to generate new brain cells.”
This post was based on reports at the Salk Insitute website, at http://www.salk.edu/news/pressrelease_details.php?press_id=428