Nicotinamide adenine dinucleotide, or “NAD” to its friends, is a coenzyme produced in the human body (amongst other places), and it is critical for cellular energy metabolism, but there’s more to it than that.

Today we’ll be looking mostly at NAD⁺, of which the + indicates the positive formal charge of one of its nitrogen atoms. We won’t get too much into the chemistry of this, but we will mention that it’s a cofactor with NADH—the former accepting electrons and the latter donating electrons.

Both NAD⁺ and NADH are critical to good health, but we’re going to focus on NAD⁺ for the simple reason that it gets depleted with aging.

Note: it gets depleted with aging.

Chronological age is not so important here, but there is a direct relationship between biological aging and NAD⁺ depletion.

For example, healthy centenarians tend not to have depleted NAD⁺ levels. Further, its depletion (in those in whom it is depleted) is then a causal factor for many age-related diseases:

❝Remarkably, ageing is accompanied by a gradual decline in tissue and cellular NAD⁺ levels in multiple model organisms, including rodents and humans.

This decline in NAD⁺ levels is linked causally to numerous ageing-associated diseases, including cognitive decline, cancer, metabolic disease, sarcopenia and frailty.

Many of these ageing-associated diseases can be slowed down and even reversed by restoring NAD⁺ levels.❞

~ Dr. Rosalba Perrone et al.

Read in full: NAD⁺ metabolism and its roles in cellular processes during ageing

As for restoring those NADᐩ levels, that does help in interventional trials, whether by supplementing directly, or with NAD precursors*:

❝NAD⁺ levels steadily decline with age, resulting in altered metabolism and increased disease susceptibility.

Restoration of NAD⁺ levels in old or diseased animals can promote health and extend lifespan, prompting a search for safe and efficacious NAD-boosting molecules that hold the promise of increasing the body’s resilience, not just to one disease, but to many, thereby extending healthy human lifespan.❞

~ Dr. David Sinclair et al.

Read more: Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence

*There are actually also other NAD-boosting molecules besides NAD itself and its precursors. For example, the liver will not produce NADᐩ unless it has aminocarboxymuconate-semialdehyde decarboxylase (or “ACMSD”, to its friends), which limits the production of NADᐩ. Why, you ask? The theory is that it is a kind of evolutionary conservativism, much like not lighting a fire without the ability to put it out. In any case, taking ACMSD-blockers will thus result in an increased endogenous production of NADᐩ.

You can read about this here:

De novo NAD⁺ synthesis enhances mitochondrial function and improves health

Nor is taking supplements or drugs the only way to get more of it; there’s an enzyme nicotinamide phosphoribosyltransferase (“NAMPT”, to its friends) involved in the synthesis of NADᐩ, and exercise boosts levels by 127% (i.e., it more than doubles the levels), based on a modest three-week exercise bike regimen:

Skeletal muscle NAMPT is induced by exercise in humans

And to underline that point, another study found that resistance training (so, a different kind of exercise from that of the previous study) boosts levels of NADᐩ itself by the same 127%:

Resistance training increases muscle NAD⁺ and NADH concentrations as well as NAMPT protein levels and global sirtuin activity in middle-aged, overweight, untrained individuals

One way to get more out of NADᐩ

We’ll get straight to the point: it works very well paired with a senolytic agent, i.e. something that kills aging cells so that they get recycled sooner:

NAD+, Senolytics, or Pyruvate for Healthy Aging?

To read more about senolytics, check out:

Fisetin: The Anti-Aging Assassin

Want to try some?

We don’t sell it, but here for your convenience is an example product on Amazon 😎

Enjoy!