By Kathleen Berger, Executive Producer for Science and Technology

The multibillion-dollar anti-aging market includes products, services, and technologies, much of which involves skin care. But beneath the surface, related to the dorsomedial hypothalamus, a structure deep in the brain, there’s been a significant breakthrough at Washington University School of Medicine in St. Louis.

“This is actually the first demonstration that manipulating specific neurons delays aging and extends lifespan in mice,” said Shin-ichiro Imai, MD, PhD, the Theodore and Bertha Bryan Distinguished Professor in Environmental Medicine and a professor in the Department of Developmental Biology at Washington University School of Medicine in St. Louis. “What we found is a feedback loop between the hypothalamus and adipose tissue, our fat. This circuit, or feedback loop, regulates the pace of aging, the process of aging, and lifespan.”

The research began when Imai helped identify the hypothalamus of the brain as a control center for aging and longevity. This led to the discovery of key neurons and the identification of a subpopulation of neurons that could be targets for anti-aging therapies.

The critical communication pathway, connecting the brain and the body’s fat tissue in a feedback loop, appears to be central to energy production throughout the body. The research suggests that the gradual deterioration of this feedback loop contributes to the increasing health problems typical of natural aging.

In mice, lifespan increased when specific brain cells were activated. These cells would then communicate with fat tissue to produce cellular fuel, counteracting the effects of aging.

These specific neurons produce an important protein — Ppp1r17. When this protein is present in the nucleus, the neurons are active and stimulate the sympathetic nervous system, activating a type of fat tissue to produce cellular fuel. This tissue is stored under the skin and in the abdominal area. The activated fat tissue also releases another important protein — an enzyme called eNAMPT — which returns to the hypothalamus and allows the brain to produce fuel for its functions.

This feedback loop is critical for fueling the body and brain, but it slows down over time. With age, the researchers found that the protein Ppp1r17 tends to leave the nucleus of the neurons. When that happens, the neurons in the hypothalamus send weaker signals. With less use, the nervous system wiring throughout the white adipose tissue gradually retracts, and what was once a dense network of interconnecting nerves becomes sparse. The fat tissues no longer receive as many signals to release fatty acids and eNAMPT, leading to fat accumulation, weight gain, and less energy to fuel the brain and other tissues.

The study shows what happens in mice when key neurons in the brain are activated in older mice, continuing the loop. The activated mice live longer than the control mice, whose feedback loops lose the important proteins. In the study, the signs of aging are undeniable when comparing the mice.

“You can clearly see the difference. One has a shinier, richer fur coat, and the other has a shabby fur coat,” said Imai.

The goal now is the development of anti-aging therapies. Imai said that one day, the average lifespan for humans may be 100 to 120 years, and possible therapies could improve the look and feel of aging.

“It’s still in a preclinical study stage,” said Imai. “By understanding all of the feedback mechanisms, we could come up with very effective preventive methods, which could allow us to avoid various diseases and maintain proper body functions. That’s actually the goal of aging research.”