What is NAD+ and why does it decline as you age?
NAD+ is an indispensable energy carrier and guardian of your DNA, and your body produces less of it as you age. The mechanisms behind that decline are reasonably well understood, but what you can practically do about it is still very much under investigation.
NAD+ is a coenzyme that is active in virtually every cell of your body. Its first role is to convert nutrients into usable energy. It also acts as a helper molecule for a range of proteins that repair DNA damage, regulate gene activity, clear out aged cells and direct the immune system. Without sufficient NAD+, all of those processes falter at the same time.
NAD+ levels decline steadily as you get older. This has been measured in tissues from both mice and humans, and the pattern is consistent. One important cause lies in a chain reaction of low-grade inflammation. Senescent cells accumulate in fat tissue and the liver and secrete inflammatory substances. Those substances attract a particular type of immune cell (a pro-inflammatory macrophage), and that type contains high levels of an enzyme that actively breaks down NAD+. The result: the more of those cells are present in your tissue, the faster NAD+ is used up.
A second mechanism is that NAD+-dependent proteins themselves function less effectively as the NAD+ supply shrinks. For instance, the activity of a specific protein that normally slows cellular ageing also falls. This in turn reinforces the accumulation of senescent cells, which fans the flames of inflammation further. It is therefore a self-reinforcing downward spiral.
The declining NAD+ levels are linked in animal research to cognitive decline, muscle loss, metabolic problems and general frailty. Whether that causal link holds just as tightly in humans has not yet been proven. In humans, the evidence so far consists of statistical associations. Animal research shows that restoring NAD+ levels, for example through supplements such as NMN, can slow ageing-related problems. Whether that works the same way in humans and whether it is safe in the long term is still the subject of ongoing research.
All claims are based on PMID 33353981, 37848251, 29514064, 29249689, 33199924, 40343916 and 32467649. The basic biology of NAD+ and its age-related decline are well supported. The mechanistic explanation via CD38-positive macrophages is moderately supported (one study). The link to disease and the effect of supplements in humans remains uncertain.
Does NAD+ cause weight gain?
Research into NAD+ supplements such as NMN and NR shows that they do not cause weight gain. In people with overweight or obesity, there are early indications of a small weight loss.
What is the relation between NAD+ and vitamin B3?
Vitamin B3 is the only dietary building block for NAD+ in your body; that relationship is causal and well supported. Whether NAD+ supplements such as NMN or NR genuinely deliver health benefits has yet to be proven.
Does my metabolism really slow down as I get older?
Your metabolism does not slow down from your thirties onward, but after your sixties energy expenditure does decline noticeably. Muscle loss and reduced physical activity are the biggest culprits, and these are also the areas where you have the most influence yourself.
Why is it harder for me to lose weight than it used to be?
Ageing lowers your energy expenditure through muscle loss and a slower metabolism, making weight loss objectively harder. Strength training two to three times per week is the best-supported way to slow that process and support weight loss, ideally with professional guidance.
What is NAD+ and what does it do in your body?
NAD+ is an indispensable molecule for energy, DNA repair and cell maintenance, and its levels measurably decline with age. Whether that decline can be corrected with supplements, and what benefit that would bring, is a separate question.
At what age does taking NAD+ supplements make sense?
There is no established age at which NAD+ supplementation becomes worthwhile. Studies focus on middle-aged and older adults, but a measurable functional benefit in humans has not yet been demonstrated.