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Brain cells that influence aging

Stem cells in the hypothalamus may play a key role in aging.Margaret I. Davis, NIH

The brain controls many aspects of thinking—remembering, planning and organizing, making decisions, and much more. These cognitive abilities can decline with age. Exactly what controls aging in the brain, however, is not clear.

You naturally lose brain cells with age. Certain regions of the brain have cells called neural stem cells that can regenerate. These stem cells serve as a sort of internal repair system, dividing to replenish other cells. They have only been found in a few brain regions, including the hypothalamus. The hypothalamus is critical for regulating the endocrine system—the glands and hormones throughout the body. The region is known to play a role in development, reproduction, and metabolism. It has also recently been implicated in aging.

To investigate whether stem cells in the hypothalamus influence the aging process, a team of scientists led by Dr. Dongsheng Cai at Albert Einstein College of Medicine examined these cells in mice. The study was funded by NIH’s National Institute on Aging (NIA), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and National Heart, Lung, and Blood Institute (NHLBI). Results were published in the August 3, 2017, issue of Nature.

The researchers first observed what happens to stem cells in the hypothalamus as healthy mice age. They found that the number of stem cells gradually diminished in early to middle-aged mice and were almost completely absent in older mice. They then experimentally disrupted these stem cells in middle-aged mice and examined the effects on aging over 3–4 months. Mice with the disrupted stem cells showed signs of cognitive impairment and other signs of aging earlier than control mice. Mice with the disrupted stem cells also had a shortened lifespan.

The researchers were able to slow these signs of aging by implanting hypothalamic stem cells harvested from newborn mice into the brains of middle-aged mice. The mice also lived longer than control mice. These anti-aging effects could be replicated by injecting the tiny fluid-filled sacs, called exosomes, that are secreted by hypothalamic neural stem cells. Exosomes circulate in blood and carry genetic material called miRNA, which regulates genes in tissues throughout the body.

These results suggest that it’s the endocrine function of the hypothalamic stem cells that essentially controls the aging process. It remains to be seen what role the cells’ regenerative properties play in the long-term control of 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,” Cai says. “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.”

—Tianna Hicklin, Ph.D.