Ten Weeks of Resistance Training in 60-Year-Olds Doubles NAD+ Levels in Muscle Tissue

When looking at any of the work presently taking place on improving metabolism in older individuals, whether by stress response upregulation, or by improving mitochondrial function, it is always worth checking the human data, where it exists, to compare the effect size with that of exercise. This open paper is a useful resource when comparing exercise to the class of approaches that fairly directly increase levels of NAD+/NADH. These molecules are involved in mitochondrial function, and for various reasons - decline in recycling, decline in synthesis - become less available with age.

A number of supplements and treatments are on the market or under development to increase NAD+ levels in older people, and an initial human trial has been published for nicotinamide riboside. In that trial, nicotinamide riboside supplementation boosted NAD+ by 60% or so in immune cells from a blood sample. In the paper here, NAD+ was more than doubled in muscle cells following ten weeks of resistance training, restoring levels in older people to that of collage-aged individuals. This is not an apples to apples comparison, but worth considering while thinking about the present enthusiasm for NAD+ upregulation. The long term effects of exercise and resistance training are quite well catalogued, and while beneficial, do not greatly extend life.

Nicotinamide adenine dinucleotide (NAD+) is a metabolite involved in numerous biochemical reactions. In particular, NAD+ is involved with electron transport where the reduced form (NADH) transfers electrons to other substrates and intermediates of metabolism. There is enthusiasm surrounding the role that tissue NAD+ concentrations play in the aging process, and researchers have determined skeletal muscle NAD+ concentrations are lower in older rodents and humans. These findings have led some to suggest that the age-associated loss in skeletal muscle NAD+ levels contributes to mitochondrial dysfunction. NAD+ biosynthesis can be catalyzed through the salvage/recycling pathway, and nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in this pathway. Beyond its involvement with redox reactions, NAD+ binds to and activates a class of enzymes that possess deacetylase activity called sirtuins (SIRTs).

Endurance training appears to be capable of increasing skeletal muscle markers related to NAD+ and SIRT signaling. For instance, endurance training in rodents and humans has been shown to modulate SIRT1 and SIRT3 protein levels and increase the activity of these enzymes in skeletal muscle. Additionally, skeletal muscle NAMPT protein levels have been reported to be higher in endurance-trained athletes versus untrained individuals. However, there is a paucity of research examining these biomarkers in response to resistance training. It remains plausible that resistance training can increase skeletal muscle markers related to NAD+ biosynthesis and SIRT signaling, and this may be an involved mechanism in facilitating training adaptations.

Given the paucity of data in this area, we sought to examine the effects of resistance training on skeletal muscle NAD+ concentrations as well as NAMPT protein levels, SIRT1/3 protein levels, and markers of SIRT activity in middle-aged, overweight, untrained individuals. In the middle-aged participants, the 10-week training intervention: i) promoted training adaptations (i.e., increased strength and localized hypertrophy), ii) robustly increased muscle NAD+ and NADH concentrations, iii) modestly (but significantly) increased NAMPT protein levels and global SIRT activity, and iv) robustly increased citrate synthase activity levels in muscle suggesting mitochondrial biogenesis occurred. This is the first evidence to suggest resistance training in middle-aged individuals restores muscle NAD+ and NADH concentrations to levels observed in recreationally-trained college-aged individuals.

Link: https://doi.org/10.18632/aging.103218

Comments

I have 2 questions regarding exercice vs supplement :

1) exercice seems to increase NAD+ levels only in muscles ?
2) oral supplement increase NAD+ levels in every cells/tissues in your body ?

So basically it's +50% in every tissue versus +100% only in muscles. Of course supplement + moderate exercice is better, but not all 60+ years old can do the amount exercice needed to double NAD+ levels.

Posted by: Jonathan Weaver at May 13th, 2020 7:18 AM

The trial on NR supplement found +50% in circulating NAD+ at a dosage of 1gr x day. Despite that it found very limited effect in partecipant phisiology, only moderate improvement in CV parameters. Not a very exciting result. Also too few participants, 12 NR and 12 Placebo.

Posted by: Marco S at May 13th, 2020 8:14 AM

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