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Cellular Understanding of How the Brain Controls Aging

Researchers have discovered cellular mechanisms by which the brain regulates aging in mice, providing novel therapeutic targets to combat health consequences associated with aging. The research focused on cells, called adult neural stem/progenitor cells (NSCs), which through a complex signaling cascade called neurogenesis turn into mature nerve cells. NSCs are found in the hypothalamus, a part of the brain governing many physiologic functions, and in other brain regions, most notably, the hippocampus, involved in the formation of new memories and the site of early age-related degeneration in Alzheimer’s disease and related dementia (ADRD). The study examined whether NSCs in the hypothalamus were involved in regulating aging in male mice. First, the scientists observed that the number of NSCs declined with aging in mice. NSCs were abundant in the hypothalamus of young mice, diminished in middle-age mice, and were nearly entirely lost in aged animals. To determine if the loss of NSCs was causing the mice to age or was a consequence of aging, the scientists experimentally depleted most of the NSCs in the animals’ hypothalami. Compared to control animals, mice lacking NSCs showed accelerating signs of aging, such as a shortened lifespan. These findings suggest that NSCs control the speed of aging.

Confirming this role, aging was slowed when NSCs were implanted into middle-age mice, with the animals living longer than their control counterparts. Because NSC loss or implantation produced effects on aging in a relatively short timeframe, the scientists hypothesized that the outcomes might be mediated by factors produced by the NSCs rather than by their maturation. Indeed, additional experiments showed that NSCs exert some of their anti-aging effects by secreting small particles called exosomes that contain microRNAs (miRNAs) into the cerebrospinal fluid of mice. miRNAs are involved in regulating gene activity and can be taken up by other cells. Thus, it appears that it is a specialized function of NSCs related to secreting these particles, rather than their function of turning into new mature nerve cells, that plays a key role in how NSCs govern aging in mice.

If NSCs play a similar role in women and men, they represent novel therapeutic targets to combat the health consequences associated with aging, such as diabetes and ADRD. Further research that delves into the detailed mechanisms by which these cells exert their effects—such as identifying what miRNAs are released by NSCs—may illuminate other targets and potential therapies.

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