Enhance communication between your organs to enjoy a longer and healthier life.

Anti-aging researchers have recently shared groundbreaking new discoveries that, if relevant to humans, could provide a safe and effective way to improve longevity. The research reveals how activating a specific set of cells in the brain's hypothalamus can trigger a series of events that might extend lifespan.

The initial confirmation was made in insects and worms, and a recent study has confirmed these findings in mice.

The hypothalamus – the central hub for aging

Traditionally known for controlling hormone production through the pituitary gland and overseeing the autonomic nervous system, which sends signals to peripheral organs such as the liver, fat or adipose tissue, and skeletal muscle, the hypothalamus also acts as the control center for aging. It sends signals to skeletal muscle via the sympathetic nervous system, which manages the fight-or-flight response. Subsequently, fat tissue influences this process and regulates hypothalamic function from a distance through an inter-tissue feedback loop.

Researchers propose that a breakdown in communication between the hypothalamus, skeletal muscle, and adipose tissue contributes to the physiological decline associated with aging. This breakdown prevents organs from receiving the necessary molecular and electrical signals for proper functioning.

Described as "Interorgan Communication in Aging," this concept was introduced at the September 2022 National Advisory Council on Aging meeting.

This is the mechanism in action.

Interorgan feedback loop deterioration with age

Shin-ichiro Imai, M.D., Ph.D., from Washington University School of Medicine in St. Louis, has dedicated years to this field. He and his team identified a specific group of neurons in the hypothalamus that, when activated, initiate the communication process.

These neurons, found in the dorsomedial hypothalamus, produce a protein called Ppp1r17. Its presence in the nucleus indicates active neurons that stimulate the sympathetic nervous system, triggering subsequent events that activate neurons controlling white adipose tissue. This tissue then releases fatty acids into the bloodstream to support physical activity and secretes an enzyme called eNAMPT, which returns to the hypothalamus, allowing the brain to produce fuel for its functions.

This feedback loop is essential for maintaining the body and brain but weakens with age.

As individuals age, Ppp1r17 moves from the nucleus of neurons, leading to weakened signals. Reduced activity causes the nervous system connections in white adipose tissue to gradually diminish, resulting in a sparse network of nerves where signals to release fatty acids and eNAMPT decrease. This sequence results in fat accumulation, weight gain, and reduced energy supply to the brain and other tissues.

Reactivating this communication system has been found to extend the lifespan of fruit flies and worms, raising the question of whether it could have a similar impact on mammals.

Mice exhibit a seven percent increase in lifespan

Dr. Imai's team utilized two methods to maintain the activity of these specific hypothalamic neurons. They genetically manipulated brain cells in one approach and directly activated them in another, producing similar outcomes.

Aged mice showed increased physical activity, a more youthful appearance, thicker and glossier coats in later stages—indicating extended periods of improved health—and a longer lifespan. While control mice typically lived around a thousand days, mice with the open brain-fat tissue feedback loop lived 60 to 70 days longer, translating to roughly seven percent longer lifespan, equivalent to about five additional years in humans.

The researchers are currently investigating practical ways to sustain the feedback loop, with one suggestion involving eNAMPT supplements.

Understanding eNAMPT supplements

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

NAMPT is an enzyme crucial in the biosynthesis of nicotinamide adenine dinucleotide (NAD+), a vital molecule in cellular metabolism and energy production. Previous discussions have emphasized the importance of nicotinamide (a form of vitamin B3) and NAD+ in counteracting age-related cellular changes.

As individuals age, NAD+ levels decrease, leading to reduced cellular function and increased susceptibility to age-related diseases. Enhancing NAD+ levels through supplements has become a focal point in aging and longevity research.

Here is a deeper look into eNAMPT supplements:

NAMPT plays a critical role in the NAD+ salvage pathway by converting nicotinamide to nicotinamide mononucleotide (NMN), which is further converted into NAD+. NAD+ is essential for various cellular processes, including DNA repair, gene expression, and energy metabolism.

The goal of eNAMPT supplements is to increase NAMPT activity or levels, thereby enhancing the NAD+ biosynthesis pathway. By boosting NAMPT activity, these supplements raise NAD+ levels, supporting cellular health and function.

Some researchers believe that eNAMPT supplements may improve cellular energy production, stimulate DNA repair mechanisms, enhance metabolic health, and potentially extend lifespan.

Dr. Imai is optimistic about the possibilities.

“We can envision a potential anti-aging therapy involving the delivery of eNAMPT through various methods,” he stated. “We have already shown that administering eNAMPT via extracellular vesicles [similar to capsules] boosts cellular energy levels in the hypothalamus and extends lifespan in mice. We are eager to continue exploring ways to maintain this essential feedback loop between the brain and the body's fat tissues, with the goal of promoting longevity and health.”

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

While promising research exists, particularly in animal models, further investigation is needed to determine the effectiveness and safety of eNAMPT supplements in humans. Additional clinical trials are required to establish their benefits and potential side effects.