Increase Your Interorgan Communication And Live A Longer, Healthier Life

Anti-aging researchers just revealed some fascinating new science that, if it holds true for humans, may be a way to safely and effectively increase longevity. The research shows how activating a specific set of cells in the brain’s hypothalamus sets off a chain of events that can increase lifespan.

Scientists first proved this in insects and worms; in a new study, they did the same for mice.

The hypothalamus – the mission control center for aging

The hypothalamus has long been known to regulate the production of many hormones via the pituitary gland and control the autonomic nervous system, which directs signals to various peripheral organs such as the liver, fat or adipose tissue, and skeletal muscle.

But it also acts as mission control for aging, sending a signal to skeletal muscle via the sympathetic nervous system—which governs the fight-or-flight response. Fat tissue then modifies the process and remotely regulates the function of the hypothalamus in a kind of inter-tissue feedback loop.

Researchers believe that dysfunction within this communication system between the hypothalamus, skeletal muscle, and adipose tissue underlies the physiological decline that comes with aging. This blocks organs from getting the molecular and electrical messages they need to function correctly.

This concept, which scientists call “Interorgan Communication in Aging,” was introduced at the September 2022 National Advisory Council on Aging meeting.

This is how it works.

Interorgan feedback loop slows down with aging

Shin-ichiro Imai, M.D., Ph.D. at Washington University School of Medicine in St. Louis, has worked in this area for some years. He and his team identified a specific set of neurons in the hypothalamus that, when active, send signals to set off the communication process.

This set of neurons lies in the dorsomedial hypothalamus and produces a protein called Ppp1r17. When it’s present in the nucleus, the neurons are active and stimulate the sympathetic nervous system, setting off a chain of events that triggers neurons that govern white adipose tissue stored under the skin and in the abdominal area.

The activated fat tissue releases fatty acids into the bloodstream to fuel physical activity. It also releases an enzyme called eNAMPT, which returns to the hypothalamus, allowing the brain to produce fuel for its functions.

This feedback loop is critical for fueling the body and the brain, but it slows down over time.

With aging, Ppp1r17 leaves the nucleus of the neurons, causing signals to weaken. With less use, the nervous system wiring throughout the white adipose tissue gradually retracts, and the formerly dense network of interconnecting nerves becomes sparse. Fat tissues no longer receive as many signals to release fatty acids and eNAMPT. This leads to fat accumulation, weight gain, and less energy fueling the brain and other tissues.

Rebooting this communication system was shown to extend the lifespan of fruit flies and worms, but would it extend the life of mammals?

Mice live seven percent longer

Dr. Imai’s group used two methods to allow these specific neurons in the hypothalamus to remain open and constantly send signals. In one, they genetically manipulated the brain cells, and in another, they activated them directly. The results using both methods were the same.

Aging mice became physically more active, looked younger, and had thicker and shinier coats at later ages—suggesting more time with better health—and lived longer. While control mice lived around a thousand days as normal, mice who had the brain-fat tissue feedback loop kept open lived 60 to 70 days longer, or about seven percent longer. In humans, this translates to about an extra five years.

The researchers are now looking at more practical ways to maintain the feedback loop. One idea is to use eNAMPT supplements.

What are eNAMPT supplements?

eNAMPT supplements are nutritional or dietary supplements designed to increase the body's levels of nicotinamide phosphoribosyltransferase (NAMPT).

NAMPT is an enzyme that plays a crucial role in the biosynthesis of nicotinamide adenine dinucleotide (NAD+), a vital molecule in cellular metabolism and energy production. We’ve written about nicotinamide (a form of vitamin B3) and NAD+ before and shared the science of their value in fighting the signs and symptoms of aging on a cellular level.

As we age, NAD+ levels in the body tend to decline, which is associated with decreased cellular function and increased vulnerability to age-related diseases. Enhancing NAD+ levels through supplements has become a research focus in aging and longevity.

Now, here's a closer look at eNAMPT supplements:

NAMPT is essential in the NAD+ salvage pathway. It converts nicotinamide into nicotinamide mononucleotide (NMN), which is then converted into NAD+. NAD+ is crucial for various cellular processes, including DNA repair, gene expression, and energy metabolism.

eNAMPT supplements aim to boost NAMPT activity or levels, thereby enhancing the NAD+ biosynthesis pathway. By increasing NAMPT activity, these supplements can raise NAD+ levels, supporting cellular health and function.

Some researchers believe the science suggests that eNAMPT supplements can improve cellular energy production, enhance DNA repair mechanisms, promote better metabolic health, and extend lifespan.

Dr. Imai is optimistic.

“We can envision a possible anti-aging therapy that involves delivering eNAMPT in various ways,” he said. “We already have shown that administering eNAMPT in extracellular vesicles [similar to capsules] increases cellular energy levels in the hypothalamus and extends life span in mice. We look forward to continuing our work investigating ways to maintain this central feedback loop between the brain and the body’s fat tissues in ways that we hope will extend health and lifespan.”

eNAMPT supplements are available in various forms, such as capsules or powders.

While promising research exists, especially in animal models, the efficacy and safety of eNAMPT supplements in humans are still under investigation. We need more clinical trials to establish their benefits and potential side effects.