Researchers have found that stem cells in the brain’s hypothalamus govern how fast aging occurs in the body. The finding, made in mice, could lead to new strategies for warding off age-related diseases and extending lifespan.
In the brain, the hypothalamus is known to regulate important processes including growth, development, reproduction and metabolism. In a 2013 Nature paper, scientists made the surprising finding that the hypothalamus also regulates aging throughout the body.
Now, the researchers at the Albert Einstein College of Medicine have precisely identified the cells in the hypothalamus that control aging: a tiny population of adult neural stem cells, which were known to be responsible for forming new brain neurons.
The team's work has been published in the journal Nature.
"Our research shows that the number of hypothalamic neural stem cells naturally declines over the life of the animal, and this decline accelerates aging."
"Our research shows that the number of hypothalamic neural stem cells naturally declines over the life of the animal, and this decline accelerates aging," says senior author Dongsheng Cai, M.D., Ph.D., professor of molecular pharmacology at the school. "But we also found that the effects of this loss are not irreversible. By replenishing these stem cells or the molecules they produce, it’s possible to slow and even reverse various aspects of aging throughout the body."The researchers first looked at the fate of those cells as healthy mice got older to see if stem cells in the hypothalamus held the key to aging. The number of hypothalamic stem cells began to diminish when the animals reached about 10 months, which is several months before the usual signs of aging start appearing. "By old age—about two years of age in mice—most of those cells were gone," says Dr. Cai.
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The team hypothesized that adding stem cells to the hypothalamus could counteract aging. To test that experiment, the researchers injected hypothalamic stem cells into the brains of middle-aged mice whose stem cells had been destroyed as well as into the brains of normal old mice. In both groups of animals, the treatment slowed or reversed various measures of aging.Dr. Cai and his colleagues found that the hypothalamic stem cells appear to exert their anti-aging effects by releasing molecules called microRNAs (miRNAs). They are not involved in protein synthesis but instead play key roles in regulating gene expression. miRNAs are packaged inside tiny particles called exosomes, which hypothalamic stem cells release into the cerebrospinal fluid of mice.
The researchers extracted miRNA-containing exosomes from hypothalamic stem cells and injected them into the cerebrospinal fluid of two groups of mice: middle-aged mice whose hypothalamic stem cells had been destroyed and normal middle-aged mice.
This treatment significantly slowed aging in both groups of animals as measured by tissue analysis and behavioral testing that involved assessing changes in the animals’ muscle endurance, coordination, social behavior and cognitive ability.
Dr. Cai and his team are now trying to identify the particular populations of microRNAs and perhaps other factors secreted by these stem cells that are responsible for these anti-aging effects—a first step toward possibly slowing the aging process and treating age-related diseases.
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