Researchers Are Looking for New Ways to Extend Lifespan

People want to stay young and fit as long as possible, but the aging process seems inevitable. In recent years, research has begun to reveal that the communication pathways between the body’s organs are important regulators of aging. When these pathways are open, the body’s organs and systems work well together. But as we age, communication pathways deteriorate and organs no longer receive the molecular and electrical messages they need to function properly.

A new study from Washington University School of Medicine in St. Louis identified a critical communication pathway in mice that connects the brain and the body’s fatty tissue in a feedback loop and appears to be central to energy production throughout the body. This research suggests that the gradual deterioration of this feedback loop contributes to the increasing health problems typical of natural aging.

Brain Cells Communicate With Fatty Tissue to Produce Cellular Fuel and Counteract the Effects of Aging

The study, published in the journal Cell Metabolism, has implications for developing future interventions that could maintain the feedback loop for longer and slow the effects of increasing age. The researchers identified a specific group of neurons in the brain’s hypothalamus that, when active, send signals to the body’s fatty tissue to release energy. Using genetic and molecular methods, they examined mice that were programmed to have this communication path constantly open after a certain age. The scientists found that these mice were more physically active, showed signs of delayed aging, and lived longer than mice in which this communication pathway gradually slowed as part of the normal aging process. By manipulating an important part of the brain, researchers were able to extend lifespan in mice.

Specific neurons in a part of the brain called the dorsomedial hypothalamus produce an important protein – Ppp1r17. When this protein is present in the cell nucleus, the neurons are active and stimulate the sympathetic nervous system, which controls the body’s fight or flight response. The fight-or-flight response is known to have widespread effects throughout the body, including increased heart rate and slowed digestion. As part of this response, the researchers found that the neurons in the hypothalamus cause a chain of events that trigger neurons that control white adipose tissue – a type of fatty tissue – stored under the skin and in the abdominal area. The activated fatty tissue releases fatty acids into the bloodstream that can be used to promote physical activity. 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 to fueling the body and brain, but it slows down over time. The researchers found that the protein Ppp1r17 tends to leave the nucleus of neurons as we age, and when that happens, these 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 interconnected nerves becomes sparser. Adipose tissue no longer receives as many signals to release fatty acids and eNAMPT, resulting in fat accumulation, weight gain, and less energy to fuel the brain and other tissues. The researchers also used a technique to directly activate these specific neurons in the hypothalamus of old mice and observed similar anti-aging effects.

Possible Anti-Aging Therapy

On average, the upper lifespan of a typical laboratory mouse is about 900 to 1,000 days, or about 2.5 years. In this study, all normally aged control mice died at 1,000 days of age. Those who received interventions to maintain the feedback loop between the brain and fat tissue lived 60 to 70 days longer than control mice. This corresponds to an extension of the service life of around 7%. In humans, a 7% increase in life expectancy means about five more years. The mice that received the interventions were also more active at later ages and looked younger, with thicker and shinier fur.

The research team continues to look for ways to maintain the feedback loop between the hypothalamus and adipose tissue. One avenue they are exploring is supplementing mice with eNAMPT, the enzyme produced by fatty tissue that returns to the brain and supplies energy to the hypothalamus, among other functions. When the enzyme is released from fatty tissue into the bloodstream, it is packaged in so-called extracellular vesicles, which can be collected and isolated from the blood.

Researchers can envision a possible anti-aging therapy that involves administering eNAMPT in several ways. They continue to look for ways to maintain this central feedback loop between the brain and the body’s fatty tissue in a way that is expected to extend health and lifespan.