Brain Stem Cells May Control How We Age

Scientists at Albert Einstein College of Medicine have discovered specific stem cells in the brain’s hypothalamus which govern the pace of aging that occurs in the body; this research was published in the August edition of the journal Nature.

The hypothalamus is the part of the brain that regulates growth, development, reproduction and metabolism. In a 2013 Nature paper, Einstein researchers found that the hypothalamus also regulates aging throughout the body. Building upon that study, the scientists have identified the cells (in mice) in the hypothalamus that control aging: a group of adult neural stem cells, which have been 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,” says senior author Dongsheng Cai, MD, PhD, (professor of molecular pharmacology at Einstein). “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.”

In studying whether the hypothalamic stem cells are responsible for accelerated aging, the researchers first looked at the fate of those cells during aging of healthy mice. The team noted that 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. Old age in mice is about two years, and most of those specialized cells were gone in those mice considered elderly.

The next question was to differentiate if the progressive loss of the stem cells were a cause or consequence of aging. The researchers then selectively disrupted the hypothalamic stem cells in mice considered to be in their middle age, and found that the disruption significantly accelerated signs associated with aging compared to the control mice; further, the mice with the disruption in hypothalamic stem cells expired earlier in the typical life cycle than the control mice.

Often, it is very desirable to understand how something works – the mechanism of action (MOA), and in this study, Dr. Cai and his colleagues discovered that the hypothalamic stem cells release molecules known as microRNAs (miRNAs) that are involved in protein synthesis and assist in regulating gene expression. miRNAs are embedded in micro-particles called exosomes, which are released by hypothalamic stem cells into the cerebrospinal fluid.

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. The researchers found that the results of these injections significantly slowed aging in both groups.

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Reference:

  1. Yalin Zhang, et al “Hypothalamic stem cells control ageing speed partly through exosomal miRNAs.” Nature, 2017; DOI: 1038/nature23282

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