Is it curious that the “mysterious force” of this small anti-aging circle in the body – NAD+, how is it hooked with anti-aging and health?
NAD+ : The “Energy Engine” in cells
NAD+, the name is called nicotinamide adenine dinucleotide, although the name is difficult to pronounce, it is a super “busy person” in our cells!
As early as 1906, scientists discovered that it allows yeast to ferment alcohol faster, and its importance has been continuously unearthed ever since.
Imagine that the cell is like a small factory, and NAD+ is the most reliable “porter” in the factory.
In the process of energy production in cells, glycolysis, tricarboxylic acid cycle, oxidative phosphorylation, these links are inseparable from NAD+ to transfer electrons back and forth, maintaining the “energy relay” of NAD+ and NADH, ensuring that cells have a steady stream of power.
As we age, our levels of NAD+ in our bodies, like the ebb, get lower and lower.
This is not a small problem, cell metabolism is starting to mess up, chronic diseases are more easily found.
In order to pull the NAD+ level back, scientists have racked their brains and explored several ways to synthesize it.
It has three main synthetic “channels” in animals.
De novo synthesis is like “building a car” from the source, using tryptophan as the raw material, through a series of complex enzymatic reactions, in different places in the cell, such as the nucleus, neuron cytoplasm, mitochondria, etc., relying on different “craftsmen” – NMNAT enzyme, step by step to create NAD+.
The Preiss-Handler path is to take a “shortcut”, take niacin as a raw material, and quickly convert it into NAD+ in the cytoplasm through “tools” such as niacin phosphoribosyl transferase.
There is also the Salvage path, which will especially “pick up leaks” to recycle NMN and NAM in the cell, and niacinamide ribose (NR) and niacinamide (NAM) will pass through a special “entrance” – transporter protein, or directly “slip” into the cell, and with the help of enzymes, transform into NAD+.
Recently, we also discovered the NRH Salvage path, and also came to help supplement NAD+, which is really “strength in numbers”!
NAD+ : The ‘all-rounder’ for Health
NAD+ is not only the energy of cells, but also the “fuel” of many important protein families, which is closely related to our health.
The PARPs family is like a “repair team” in the cell, when the DNA is injured, PARP1 acts as the main, PARP2 assists, quickly cracking NAD+, starting the repair process, just like putting a strong patch on a broken bridge, so that the DNA can be restored as before.
The Sirtuins family is even more powerful, distributed in the nucleus, mitochondria and other corners, like a group of “wise elders”, by removing chemical markers for proteins, regulate cell metabolism, and even affect the length of life.
If they’re out of whack, the genome is like a ship without navigation, unstable and with a shortened lifespan.
The transmembrane protein CD38 is a bit special, both a “signal soldier” and a “disassembly worker”.
While receiving signals from the outside world, it breaks down NAD+ to produce signaling molecules that regulate calcium levels inside the cell.
Unfortunately, with age, its activity becomes stronger, a strong consumption of NAD+, cell function is greatly reduced.
In terms of premature aging and neurological diseases, NAD+ depletion is like a “trigger.”
In normal aging, it causes oxidative stress in the mitochondria, just like rust corrodes the machine, affecting sirtuins activity, cellular energy metabolism also follows “temper”, nucleo-mitochondrial communication is also disrupted, and a series of aging problems ensue.
In neurodegenerative diseases, the mitochondrial autophagy of neurons in the brain of Alzheimer’s disease (AD) patients has problems, just like the garbage collector has gone on strike, and the supplement of NAD+ precursors is like a “cleaner” for neurons, which can improve pathological characteristics, reduce neuroinflammation, and alleviate the cognitive dysfunction of patients.
Parkinson’s disease (PD) is also related to mitochondrial protein, lysosomal enzyme gene mutations and NAD+ metabolism changes, adding NR to the disease model can prevent neurons from “escaping” and improve movement disorders.
Now, a number of clinical trials for AD and PD are underway, hoping to determine how powerful NAD+ supplementation really is.
Improve NAD+ : Anti-aging “secret”
How to increase the level of NAD+ in our body? Scientists have come up with three big ideas.
Precursor supplementation is the most direct approach.
Niacinamide mononucleotide (NMN), which can be turned into NAD+ by Salvage route, can also be easily absorbed by oral administration. By feeding some mice, age-related diseases of many tissues have been improved.
Not to be outdone, nicotinamide ribose (NR) is rapidly converted into NMN, which is beneficial to mitochondrial function, neuronal protection, and stem cell regeneration.
Niacin (NA) takes the Preiss-Handler path, which can increase the level of NAD+ and improve lipid metabolism, which is easy to blush when the dose is large.
Although niacinamide (NAM) can be recycled to produce NAD+, eating too much may inhibit the activity of key enzymes, so be careful.
Regulation of enzyme activity is also critical.
The presence of CD38 inhibitors can increase the level of NAD+ and improve mitochondrial function;
PARP inhibitors can reduce the consumption of NAD+ and make DNA repair more effective.
NAMPT activators are like stepping on the accelerator for NAD+ biosynthesis.
Lifestyle interventions are also important.
Caloric restriction activated related pathways, NAD+ levels stabilized, mice lived longer, and human metabolic health improved.
Exercise is also a good way to increase NAD+ levels in skeletal muscles.
There are also foods rich in NAD+ precursors, as well as polyphenols, which, while indirectly helping, can slowly increase NAD+ levels.
However, there are also “stumbling blocks” on the way to improving NAD+.
High doses of NAM or NA may be disruptive, inhibiting the activity of important enzymes, NA eating too much blush like a ripe tomato, so we have to find the most appropriate dose, but also long-term observation has no side effects.
NAD+ enhancement is promising in neurodegenerative and metabolic diseases, but in cancer, it may become an “accomplice” of tumor cells and promote growth, which should be treated with caution.
Individual differences are also very large, different people’s absorption of NAD+ enhancement strategy, metabolic efficiency is not the same, genes, age, health status are “stirring up”, the future must develop a personalized program, accurate anti-aging.
