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

Anti-aging researchers have recently unveiled groundbreaking new findings that, if applicable to humans, could offer a safe and efficient means to enhance longevity. The research demonstrates how activating a specific group of cells in the brain's hypothalamus triggers a series of events that may extend lifespan.

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

The hypothalamus – the central hub for aging

Traditionally known for regulating hormone production through the pituitary gland and overseeing the autonomic nervous system, which transmits signals to peripheral organs like the liver, fat or adipose tissue, and skeletal muscle, the hypothalamus also serves as the command center for aging. It transmits signals to skeletal muscle via the sympathetic nervous system, which controls the fight-or-flight response. Subsequently, fat tissue modulates this process and regulates hypothalamic function from a distance through an inter-tissue feedback loop.

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

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

This is the mechanism at play.

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 cluster of neurons in the hypothalamus that, when activated, initiate the communication process.

These neurons, located 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 governing white adipose tissue. This tissue, in turn, releases fatty acids into the bloodstream to support physical activity and secretes an enzyme called eNAMPT, which returns to the hypothalamus, enabling the brain to generate fuel for its functions.

This feedback loop is crucial for sustaining the body and brain but diminishes with age.

As individuals age, Ppp1r17 relocates from the nucleus of neurons, leading to weakened signals. Reduced usage causes the nervous system connections throughout white adipose tissue to gradually retract, resulting in a sparse network of nerves where signals to release fatty acids and eNAMPT decline. This sequence leads to fat accumulation, weight gain, and decreased energy supply to the brain and other tissues.

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

Mice exhibit a seven percent increase in lifespan

Dr. Imai's team employed two techniques to maintain the activity of these specific hypothalamic neurons. They genetically manipulated brain cells in one approach and directly activated them in another, yielding identical results.

Aged mice displayed 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 approximately seven percent more extended lifespan, equivalent to about five additional years in humans.

The researchers are currently exploring practical methods to sustain the feedback loop, with one proposal 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 critical in the biosynthesis of nicotinamide adenine dinucleotide (NAD+), a pivotal molecule in cellular metabolism and energy production. Prior discussions have highlighted the significance of nicotinamide (a form of vitamin B3) and NAD+ in combatting age-related cellular changes.

As individuals age, NAD+ levels decrease, correlating with reduced cellular function and heightened susceptibility to age-related illnesses. 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 crucial role in the NAD+ salvage pathway by converting nicotinamide to nicotinamide mononucleotide (NMN), which is further transformed into NAD+. NAD+ is indispensable for various cellular processes, including DNA repair, gene expression, and energy metabolism.

The objective of eNAMPT supplements is to enhance NAMPT activity or levels, thereby boosting the NAD+ biosynthesis pathway. By increasing NAMPT activity, these supplements elevate NAD+ levels, supporting cellular health and function.

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

Dr. Imai remains hopeful about the prospects.

“We can envision a potential anti-aging therapy involving the delivery of eNAMPT through various methods,” he remarked. “We have already demonstrated that administering eNAMPT via extracellular vesicles [akin to capsules] enhances 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, aiming to promote longevity and health.”

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

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