In a study in mice, a research team at Albert Einstein College of Medicine has found that stem cells in the hypothalamus, a region of the brain that controls an immense number of bodily functions, govern how fast aging occurs in the body.

Electron microscopic images (false color) of hypothalamic neural stem/progenitor cells. Right high magnification of the outlined area on the left; arrows indicate the presence of multivescular bodies. Image credit: Zhang et al, doi: 10.1038/nature23282.

The hypothalamus, a deep brain region just in front of the brainstem, regulates arousal, sleep, hunger, body temperature, and other fundamental behaviors. It strictly controls the pituitary gland that in turn is responsible for the secretion of different hormones.

In a recent study, Professor Dongsheng Cai and his colleagues made the surprising finding that the hypothalamus also regulates aging throughout the body.

Now, the team has pinpointed 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.

Our research shows that the number of hypothalamic neural stem cells naturally declines over the life of the animal, and this decline accelerates aging, Professor Cai said.

But we also found that the effects of this loss are not irreversible. By replenishing these stem cells or the molecules they produce, its possible to slow and even reverse various aspects of aging throughout the body.

In studying whether stem cells in the hypothalamus held the key to aging, Professor Cai and co-authors first looked at the fate of those cells as healthy mice got older.

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, Professor Cai noted.

The team next wanted to learn whether this progressive loss of stem cells was actually causing aging and was not just associated with it.

So the authors observed what happened when they selectively disrupted the hypothalamic stem cells in middle-aged mice.

This disruption greatly accelerated aging compared with control mice, and those animals with disrupted stem cells died earlier than normal, Professor Cai said.

Could adding stem cells to the hypothalamus counteract aging?

To answer that question, the scientists 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.

The team found that the hypothalamic stem cells appear to exert their anti-aging effects by releasing molecules called microRNAs.

They are not involved in protein synthesis but instead play key roles in regulating gene expression.

microRNAs are packaged inside tiny particles called exosomes, which hypothalamic stem cells release into the cerebrospinal fluid of mice.

Professor Cai and colleagues extracted microRNA-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.

Details of the research were published online July 26 in the journal Nature.

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Yalin Zhang et al. Hypothalamic stem cells control ageing speed partly through exosomal miRNAs. Nature, published online July 26, 2017; doi: 10.1038/nature23282

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