Does NAD+ In Fact Decline With Age Sufficiently to be a Useful Target for Interventions?

Nicotinamide adenine dinucleotide (NAD) is an important part of the mechanisms by which mitochondria produce chemical energy store molecules to power cellular processes. NAD levels fall with age, concurrent with growing mitochondrial dysfunction. There is some enthusiasm for approaches - such as supplementation with vitamin B3 derivatives - that might compensate for this issue and thereby improve mitochondrial function in later life.

Researchers here suggest that in fact the quality and quantity of evidence for NAD+ levels to decline with age doesn't rise to the level that the scientific community should by using as a basis to proceed towards the development of interventions. I think it most likely that more rigorous work will confirm the existing evidence. More pertinent objections to sizable investment in NAD upregulation are that (a) exercise increases NAD levels to a greater degree than any of the other approaches assessed to date, and (b) the results of clinical trials of NAD upregulation are decidedly mediocre.

Nicotinamide adenine dinucleotide (NAD+) is an essential molecule involved in various metabolic reactions, acting as an electron donor in the electron transport chain and as a co-factor for NAD+-dependent enzymes. In the early 2000s, reports that NAD+ declines with aging introduced the notion that NAD+ metabolism is globally and progressively impaired with age. Since then, NAD+ became an attractive target for potential pharmacological therapies aiming to increase NAD+ levels to promote vitality and protect against age-related diseases.

This review summarizes and discusses a collection of studies that report the levels of NAD+ with aging in different species (i.e., yeast, C. elegans, rat, mouse, monkey, and human), to determine whether the notion that overall NAD+ levels decrease with aging stands true. We find that, despite systematic claims of overall changes in NAD+ levels with aging, the evidence to support such claims is very limited and often restricted to a single tissue or cell type. This is particularly true in humans, where the development of NAD+ levels during aging is still poorly characterized. There is a need for much larger, preferably longitudinal, studies to assess how NAD+ levels develop with aging in various tissues. This will strengthen our conclusions on NAD metabolism during aging and should provide a foundation for better pharmacological targeting of relevant tissues.



But I just spent $1500 on a year supply of NR! /s

Posted by: Matt at January 24th, 2022 6:49 PM

Based on conversations with others I must be an outlier concerning my experience with NAD precursors. At age 74, seven years ago, I struggled to maintain a brisk walking speed which had been a life long habit but at 74 my glutes now burned and neuropathy ran down to my left leg causing my left foot to scuff. To compensate I would lift my left knee slightly which gave me a gimpy gate. .I could tell I was in a downward spiral but looking like an old duffer was an unacceptable insult to my vanity despite my infirmities. At the time NAD precursors were just becoming available so I thought I would give one a try. For me the results were stunning. Within three days my effortless fast walking gate returned and my neuropathy totally disappeared never to return. Thus began a quest to see what else I could do having achieved what a considered to be a new normal. I am now a full fledged science based biohacker involving a number of pharmacological interventions while always evaluating risk versus reward. I know I am just an anecdote but enough anecdotes and enough time can become real science.

Posted by: Christopher Burden at January 25th, 2022 9:01 AM

@Christopher Burden: Would you mind telling me what brand and dosage of NAD precursors you used? Thanks.

Posted by: Kel at January 26th, 2022 3:32 PM

I just recently started on NMN (alivebyscience brand) 1g/d in the AM. They have a bulk option (100 g) for $125 w/ Happynewyear22 discount. I don't buy the liposomal stuff. The studies were done using oral lavage. I just mix it in water.

I have reached new records on all my Peleton 15, 30, 45 and 60 min rides and 15, 20 and 30 min runs (I don't run further than that) + an increase in my VO2max test of 2 pts using my polar watch.

My husband has commented several times that my skin looks great.

Posted by: Kay at January 27th, 2022 1:56 PM
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