Supplement and exercise differed on some muscle aging measures
A before-and-after analysis of 30 adults linked five months of nicotinamide riboside supplementation to lower muscle aging estimates on three clocks.
Non-randomized trial, placebo-controlled, multicenter, registered NCT03951285
Limit: Different methylation arrays were used for NR and exercise, potentially distorting comparisons
Stake: Novo Nordisk funded the study.
Edited by Boris Djordjevic · AgingResearch.News
Researchers analyzed skeletal muscle in three before-and-after intervention studies of adults. The supplement analysis included 30 people from a mostly identical-twin cohort averaging 40 years old, predominantly with overweight or obesity. They took nicotinamide riboside for five months, reaching 1,000 milligrams daily. Exercise analyses included 39 adults aged 21–42 or 55–74 with overweight or obesity, and 37 healthy, moderately fit adults aged 19–47. They trained three times weekly for six and four weeks, respectively. Women comprised 44%–48% across the studies.
Seven epigenetic clocks estimated aging from chemical marks on DNA. Supplement use was associated with lower muscle aging estimates on three clocks; one showed an increase. Exercise was linked to a faster estimated aging pace on one clock in both studies. Other clock results varied.
Why it matters
Mitochondria supply energy to cells, and problems with them are a hallmark of aging. The authors suggest their abundance may be linked to muscle aging clocks.
Caveats
The analyses compared participants with their own earlier measurements, rather than testing the interventions against each other. The outcomes were aging estimates, mostly from clocks developed for blood rather than muscle, not measures of health or lifespan.
From the paper
- Participants
In the current study, we utilized data on adult twin individuals (30–65 years) who were administered NR supplementation with available DNA methylation samples from both timepoints (before and after NR) from either of the two tissues: blood (n = 36 individuals) and muscle (n = 30 individuals).
- Who took part
The human NR trial was originally performed to investigate the effect of 5‐month NR supplementation (with the final dose of 1000 mg/day) on muscle and adipose tissue mitochondrial biogenesis (clinicaltrials.gov entry NCT03951285) using monozygotic twin pairs, targeting twin pairs discordant for body mass index (BMI …
- Sex
Mean ages ranged from 33 years in Gene SMART to 40 in NR study and 48 in EpiH, while female participants comprised 44%–48%.
- Analyzed for DunedinPACE
Given that exercise training has been shown to increase the skeletal muscle NAD⁺ metabolome in humans (de Guia et al. ), we explored whether HIIT interventions induced changes in muscle EAA using data from two studies, EpiH (n = 39 individuals) and Gene SMART (n = 37 individuals).
- Limitation
First, modest sample sizes may limit statistical power and generalizability, particularly given the known random biological and technical variation in EAA estimates, contributing to limited individual replicability.
- DunedinPACE
After a 4‐week HIIT intervention (Gene SMART), the only significant change in EAA we observed was an increase in DunedinPACE (ß = 0.02, p = 0.034) before versus after the exercise intervention similarly to what was observed in EpiH.
- MEAT-derived epigenetic age acceleration
Additionally, we noticed a positive correlation between changes in MEAT EAA and mtDNAq (r = 0.45, p = 0.02; Figure ) after NR, indicating that individuals with a greater increase in muscle mtDNAq tended to exhibit a larger increase in MEAT epigenetic aging.
- MEAT-derived epigenetic age acceleration
However, the decrease was statistically significant only when measured with DunedinPACE (ß = −0.04, p < 0.001), PCHannum (ß = −0.69, p = 0.013), and MEAT (ß = −2.39, p < 0.001).
Quoted word for word from the full text on PubMed Central.
- Nicotinamide riboside
- High-intensity interval training
- Epigenetic regulation of gene expression
- DunedinPACE
- MEAT
- Humans
The paper
University of Helsinki
Aging Cell, Jul 22, 2026, Open access
