David Sinclair bestseller:
"How to live long.
Why we age and do we really need to." NMN and resveratrol in diseases ranging from diabetes to Alzheimer's disease and ischemia.
The science behind NMN - a stable, reliable NAD+ activator and anti-aging molecule
In June 2018, the World Health Organization (WHO) published the 11th edition of its International Classification of Diseases and added aging as a disease for the first time.
The classification of aging as a disease paves the way for new research into new drugs to delay or reverse age-related diseases such as cancer, cardiovascular and metabolic diseases, and neurodegeneration.
Nutrient sensing systems including mTOR (mammalian target of rapamycin) for regulating protein synthesis and cell growth have been extensively studied; AMPK (activated protein kinase) for detecting low-energy states; and sirtuins, a family of seven proteins critical to DNA expression and aging that can only function in conjunction with NAD+ (nicotinamide adenine dinucleotide), a coenzyme found in all living cells.
Throughout the realm of life, increases in intracellular NAD+ levels trigger changes that enhance survival, including increased energy production and upregulation of cellular repair.
In fact, the slow, inevitable process of aging has been described as "a cascade of immune breakdown triggered by a decrease in systemic NAD+ biosynthesis and consequent functional defects in susceptible organs and tissues."
Aging is characterized by epigenetic shifts, genomic instability, altered nutrient sensing capacity, telomere abrasion, mitochondrial dysfunction, cell aging, stem cell depletion, and dysregulation of intercellular communication.
In middle age, our NAD+ levels have halved compared to our youth.
Numerous studies have shown that increasing NAD+ levels increases insulin sensitivity, reverses mitochondrial dysfunction, and extends life.
NAD+ levels can be increased by activating enzymes that stimulate NAD+ synthesis, by inhibiting the enzyme (CD38) that breaks down NAD+, and by supplementing with NAD precursors, including nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN).
A conceptual framework called NAD World, developed over the past decade by developmental biologist Shin-ichiro Imai, MD, PhD, of the Washington University School of Medicine, posits NMN as a critical, systemic signaling molecule that maintains the biological resilience of the communication network supporting NAD+.6
When taken orally, NMN is rapidly absorbed and converted to NAD+
In numerous studies, NMN supplementation increased NAD+ biosynthesis, suppressed age-related adipose tissue inflammation, increased insulin secretion and action, improved mitochondrial function, improved neuronal function in the brain, and more. Here we take a look at the science behind NMN, its stability, possible pharmacokinetics, transport, function and ability to induce NAD+ biosynthesis
NMN supplementation may be an effective anti-aging nutraceutical intervention, with beneficial effects on a wide range of physiological functions.
Paths to NMN in the human body
A real symphony of interlocking transformations allows the synthesis and regulation of NAD+ in the body. It is well known that vitamin B3 is a building block of nicotinamide adenine dinucleotide (NAD+). It is also widely recognized that NMN is a potent NAD+ precursor. Although NMN is naturally found in small amounts in fruits and vegetables such as avocados, broccoli, cabbage, edamame, and cucumbers, in mammals most NMN is synthesized from vitamin B3 in the form of nicotinamide. At the center is nicotinamide phosphoribosyl transferase (NAMPT), an essential rate-limiting enzyme that catalyzes the conversion from nicotinamide to NMN, which exists in both intracellular (iNAMPT) and extracellular (eNAMPT) forms. The extracellular form has higher enzyme activity than the intracellular form and has been found in blood plasma, seminal plasma and cerebrospinal fluid in humans. In addition, eNAMPT appears to be produced by a wide range of cell types - including fat (adipocytes), liver (hepatocytes), leukemia blood cells (leukocytes and monocytes), and heart and brain cells (cardiomyocytes and glial cells). Like NAD+ and NMN, eNAMPT decreases with age. Both white and brown adipocytes actively secrete eNAMPT, suggesting that adipose tissue may be a modulator of NAD+ biosynthesis. Electric vehicles are membrane-derived molecules surrounded by a phospholipid bilayer that are released by cells in the human body. These electric vehicles not only protect their cargo, but can also deposit their cargo when needed.23
NMN and NR dance together. NMN can be converted by the body into NR, which then enters cells and is converted back to NMN by an enzyme called nicotinamide riboside kinase (NRK). Recently, an "elusive" transporter has been discovered that can directly carry NMN
