Can an NAD+ Precursor Change Biological Age? What Epigenetic Clocks Measure

Short answer: no trial we found establishes that an NAD+ precursor changes biological age. Epigenetic clocks estimate age from patterns in DNA methylation, and they remain research tools. One randomized pilot of nicotinamide riboside (NR) in 20 older adults with mild cognitive impairment reported a modest reduction in two clock estimates as an exploratory outcome. A 2026 systematic review counted that same result as not significant under its own rule. This is a company white paper from Mt. Angel Vitamins, not a peer-reviewed article. PubMed searches were run 20 October 2026.

If you're not a researcher

  • The question: Can an NAD+ precursor such as NMN or NR change biological age, as an epigenetic clock would measure it?
  • The answer: Not shown. The one NR trial with a clock outcome was a 20-person pilot, and the clock was not its main outcome.
  • How strong: Insufficient. The pilot's authors describe a modest reduction. A 2026 systematic review counted the same result as not significant.
  • Doses studied: NR, escalated to 1 g a day for 10 weeks, in the clock pilot. NMN at 300, 600 or 900 mg a day for 60 days in an 80-person trial whose biological age measure was not an epigenetic clock.
  • What to do: Do not choose a supplement on the strength of a clock result. If you are considering NMN or NR, read the dose and safety evidence first and talk to your clinician, especially if you take medication.
  • Go deeper: the NR monograph and the NMN monograph.

The surprise: more than 100 clock formulas exist

A 2026 database of published aging clocks lists more than 100 formulas drawn from 95 publications. Its authors also note there is no universal formula for biological age ([8]). Two clocks can answer different questions, which is why the names matter.

What an epigenetic clock measures

DNA methylation is a chemical tag on DNA that shifts with age. An epigenetic clock is a formula that reads methylation at a set of CpG sites (places where a cytosine is followed by a guanine) and returns an estimate. The first widely used clock was built from 8,000 samples across 82 datasets, covering 51 healthy tissues and cell types, and it uses 353 CpG sites ([1]). Later clocks were built around different targets.

Clock Year What it was built to estimate Source
Horvath 2013 Chronological age across 51 healthy tissues and cell types [1]
Hannum 2013 Chronological age from whole blood, 656 people aged 19 to 101 [2]
DNAm PhenoAge 2018 A composite of clinical blood measures that tracks mortality and healthspan [3]
DNAm GrimAge 2019 Time to death, using seven methylation-based protein estimators and a smoking estimate [4]
DunedinPACE 2022 The pace of aging as a rate, from one blood test [5]

Telomeres are repeating DNA caps at chromosome ends, and their length is a different kind of measure. Our NAD+ and telomeres post covers that side, so this page does not repeat it.

The limits of clock measures

The 2026 review describes clocks as investigational biomarkers that have not yet been thoroughly validated as clinical surrogate endpoints ([14]). Three limits matter most here.

  • Measurement noise. In one reliability study, technical noise produced deviations of up to 9 years between replicates for six prominent clocks. Principal-component versions brought most replicates within 1.5 years ([7]). DunedinPACE's developers also excluded probes with low test-retest reliability before building the measure ([5]).
  • Cell type and tissue. Methylation signatures can estimate the mix of white blood cells in a sample ([6]). The review notes that cell-type composition influences age prediction, and that circadian rhythms and acute stress can cause temporary changes ([14]). A blood clock can move when the cell mix moves.
  • What a change means. A clock change after an intervention "is not necessarily indicative of responsiveness or an improved clinical outcome," and reported effect sizes "do not directly translate into a change in whole-body biological aging or expected lifespan" ([14]).

Two author affiliations matter when reading these sources. PubMed lists a Tally Health affiliation for one author of the 2026 review, and an Elysium Health affiliation for one author of the 2022 reliability study. This page relies on their methods and data, not on their product statements.

What the NR pilot measured

Orr and colleagues ran a placebo-controlled randomized pilot in 20 older adults with mild cognitive impairment. Participants reached 1 g of NR a day through dose escalation, over 10 weeks. The primary outcome was cognition on the Montreal Cognitive Assessment. DNA methylation in peripheral blood mononuclear cells (PBMCs) was an exploratory outcome. The authors report a 2.6-fold rise in blood NAD+ (p < 0.001), and they report "a modest NR-associated increase in DNA methylation and concomitant reduction in epigenetic age as measured by PhenoAge and GrimAge epigenetic clock analyses" ([11]).

The limits are plain:

  • The study had 20 people. Its stated primary objective was safety.
  • The clock result was exploratory. The abstract gives no p-value or confidence interval for it. The PubMed full-text tool returned no article text for this paper, so the clock statistics are not confirmed here.
  • The 2026 review scored the same PhenoAge and GrimAge results as non-significant. Its rule counted a result only when p was below 0.05 at the end of the intervention ([14]). It summarizes NR as having "no detectable effect" on next-generation clocks. The two abstracts cannot be reconciled, and this page does not try to reconcile them.
  • The authors also note that a cerebral blood flow finding would not have survived correction for multiple comparisons ([11]).

The NMN trial and its biological age measure

Yi and colleagues randomized 80 healthy middle-aged adults to placebo or to 300, 600 or 900 mg of NMN a day for 60 days. The primary objective was blood NAD+. The abstract reports that "blood biological age (Aging.Ai 3.0 calculator)" rose significantly in the placebo group and stayed unchanged in every NMN group at day 60, and that the treated groups differed from placebo (all p < 0.05) ([9]). The abstract does not describe this measure as a DNA methylation clock, so this page does not count it as an epigenetic clock result. Author affiliations include Abinopharm, Huzhou Yihui Biotechnology and ABA Chemicals ([9]).

A post-hoc analysis of the same 80 people reports a dose-related rise in NAD+, with wide variation between individuals (coefficient of variation 29.2% to 113.3%). Its abstract reports no clock result ([10]).

Other human findings

  • A 2018 randomized crossover trial found NR well tolerated and reported that it stimulated NAD metabolism in healthy middle-aged and older adults. Its authors suggested that future trials assess blood pressure and arterial stiffness ([12]).
  • A 2026 protocol for a phase 2a trial of NMN, 1,000 mg twice daily for 24 weeks, in diabetic kidney disease lists "biomarkers of kidney injury and biological age" among its secondary outcomes. It reports no results ([13]).

Has any NMN or NR trial reported an epigenetic clock outcome?

Yes, once, for NR. The result was exploratory, in a 20-person pilot ([11]). The NMN trial we found reports a biological age estimate that its abstract does not describe as a methylation clock ([9]). The 2026 review's tables of 41 human intervention studies with next-generation clocks list one NAD+ precursor, NR, and no NMN study ([14]).

Search method: PubMed, run 20 October 2026. Query A used the brief's terms: ("nicotinamide riboside" OR "nicotinamide mononucleotide" OR NMN) AND ("epigenetic clock" OR "epigenetic age" OR "DNA methylation age" OR "biological age") AND (randomized OR trial). It returned 7 records. Query B paired NR, NMN and NAD with clock names. It returned 224 records, too many to screen for trials. Query C added randomized and clinical-trial publication types to the NR, NMN and clock terms. It returned 14 records: the two trials above and 12 unrelated papers, such as GrimAge in veterans with PTSD and vitamin C in myeloid cancer. Query A's excluded records were a 2026 review of male reproductive aging (PMID 41714893), whose one clinical sentence on biological age cites no study in its abstract, and the diabetic kidney disease protocol, which has no results.

This search covers NMN and NR only. We did not search urolithin A for clock outcomes in this run. The search may have missed records.

The product, where it fits

Mt. Angel Vitamins sells NMN + NR with Resveratrol and TMG, 60 capsules. Each 2-capsule serving, with 30 servings per bottle, provides 500 mg β-NMN and 200 mg NR, plus 250 mg resveratrol, 50 mg TMG, 50 mg Bioperine and 10 mg zinc, as stated on the live product page checked 20 October 2026. The price there is $59.99, which is $2.00 per day. View the product. The studies above tested NMN or NR alone. None tested this combination, and none measured an epigenetic clock on this product.

What is established, what is proposed, what would settle it

  • Established. NMN and NR raise blood NAD+ in randomized trials, with large differences between people ([9], [10], [11], [12]). Evidence grade: Moderate, since several small randomized trials point the same way.
  • Proposed. That an NAD+ precursor changes epigenetic age. Evidence grade: Insufficient. One exploratory clock result in 20 people stands against a 2026 review that counted the same result as not significant ([11], [14]).
  • What would settle it. A placebo-controlled trial with a named clock as its primary outcome, reported with at least two clocks. It would measure the clock's technical noise in the same trial ([7]), adjust for blood cell mix ([6]), run long enough for a change to stand out from noise, and link any clock change to a clinical outcome. Independent replication would follow.

For how NAD+ supports mitochondrial energy, see the mitochondrial health guide. For how trial doses compare, see our dose analysis.

How to read a biological age test result

  • A clock output is an estimate with error. Technical noise moved repeated results by up to 9 years in six prominent clocks ([7]).
  • The review notes that clocks have not yet been thoroughly validated as clinical surrogate endpoints ([14]). A result is not a diagnosis.
  • One result says little about whether anything changed. Repeated results on the same lab platform, read against that clock's known error, say more.
  • Do not change a medication or treatment because of a clock result. Bring the result to your clinician.

Next reads

Glossary

  • NAD+: nicotinamide adenine dinucleotide, a coenzyme cells use to move energy and to run repair enzymes.
  • NMN: nicotinamide mononucleotide, a precursor that cells can convert into NAD+.
  • NR: nicotinamide riboside, a form of vitamin B3 that cells can convert into NAD+.
  • DNA methylation: chemical tags on DNA that change with age and with cell type.
  • CpG site: a place on DNA where a cytosine is followed by a guanine. Clocks read methylation at these sites.
  • Epigenetic clock: a formula that turns methylation levels into an age or rate estimate.
  • PhenoAge, GrimAge, DunedinPACE: named clocks built around clinical measures, time to death, and the pace of aging.
  • PBMC: peripheral blood mononuclear cells, the white blood cells drawn from a blood sample.
  • Exploratory outcome: a measure a study collects without being powered to confirm it.
  • Post-hoc analysis: an analysis run after the trial, often on data the trial was not designed to test.
  • Systematic review: a review that searches defined sources under stated rules.
  • Placebo-controlled trial: a trial that compares the treatment against an inactive comparator.
  • PMID and DOI: PubMed's record number and the digital object identifier for a paper.

References

  1. Horvath S. DNA methylation age of human tissues and cell types. Genome Biology. 2013. PMID 24138928. PubMed. DOI
  2. Hannum G, et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Molecular Cell. 2013. PMID 23177740. PubMed. DOI
  3. Levine ME, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018. PMID 29676998. PubMed. DOI
  4. Lu AT, et al. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (Albany NY). 2019. PMID 30669119. PubMed. DOI
  5. Belsky DW, et al. DunedinPACE, a DNA methylation biomarker of the pace of aging. eLife. 2022. PMID 35029144. PubMed. DOI
  6. Houseman EA, et al. DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinformatics. 2012. PMID 22568884. PubMed. DOI
  7. Higgins-Chen AT, et al. A computational solution for bolstering reliability of epigenetic clocks: Implications for clinical trials and longitudinal tracking. Nature Aging. 2022. PMID 36277076. PubMed. DOI
  8. Kobelyatskaya A, et al. exBAClock: A comprehensive database of published clocks for age quantification and age-related diseases. Ageing Research Reviews. 2026. PMID 41577039. PubMed. DOI
  9. Yi L, et al. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. GeroScience. 2023 (epub 2022). PMID 36482258. PubMed. DOI
  10. Kuerec AH, et al. Towards personalized nicotinamide mononucleotide (NMN) supplementation: Nicotinamide adenine dinucleotide (NAD) concentration. Mechanisms of Ageing and Development. 2024. PMID 38430946. PubMed. DOI
  11. Orr ME, et al. A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment. GeroScience. 2024 (epub 2023). PMID 37994989. PubMed. DOI
  12. Martens CR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature Communications. 2018. PMID 29599478. PubMed. DOI
  13. Chandra MS, et al. Nicotinamide Adenine Dinucleotide Augmentation in Diabetic Kidney Disease: Randomized Trial Study Protocol. Kidney International Reports. 2026. PMID 42603990. PubMed. DOI
  14. Johnson AA, Sinclair DA. Turning back time: a comprehensive list of interventions that decrease next-generation epigenetic aging clocks in humans. Frontiers in Genetics. 2026. PMID 42294499. PubMed. DOI

Related reading

The Bottom Line

No trial we found shows that an NAD+ precursor changes biological age. The one clock signal for NR came from a 20-person pilot, was exploratory, and a 2026 review counted it as not significant. If you are weighing NMN or NR, start with the dose and safety evidence in our NR monograph, not with a clock result, and check with your clinician if you take medication.

FAQ

What is an epigenetic clock and what does it measure?

An epigenetic clock is a formula that reads DNA methylation, which are chemical tags on DNA that shift with age, at a set of CpG sites, then returns an age or rate estimate. The first widely used clock, published by Horvath in 2013, uses 353 CpG sites and was built to predict chronological age across 51 healthy tissues and cell types (PMID 24138928). Newer clocks are built around health outcomes or the pace of aging. A clock output is a model estimate, not a direct count of how old a body is.

How do the common clocks differ, such as Horvath, PhenoAge, GrimAge and DunedinPACE?

Horvath and Hannum were built to predict chronological age, the first from 51 tissues and cell types and the second from whole blood (PMIDs 24138928 and 23177740). PhenoAge tracks a composite of clinical blood measures linked to mortality and healthspan (PMID 29676998). GrimAge predicts time to death using methylation-based protein estimators and a smoking estimate (PMID 30669119). DunedinPACE outputs a rate, the pace of aging, from a single blood test (PMID 35029144). A 2026 database counts more than 100 clock formulas from 95 publications (PMID 41577039).

Has any NMN or NR trial reported an epigenetic clock outcome?

One NR trial has. A 2023 randomized pilot in 20 older adults reported a modest reduction in PhenoAge and GrimAge as an exploratory outcome, and its abstract gives no p-value for that result (PMID 37994989). A 2026 systematic review counted the same result as not significant under its own rule (PMID 42294499). The NMN trial we found measured a biological age estimate from a calculator named in its abstract, not a methylation clock (PMID 36482258). In the records we screened, no NMN trial reported a methylation clock outcome.

What do NAD+ precursor trials measure instead?

Most measure blood NAD+ first, then safety and function. The NMN trial in 80 adults measured blood NAD+, six-minute walk distance, insulin resistance, a general health survey and a biological age estimate (PMID 36482258). The NR pilot measured NAD+, cognition, cerebral blood flow and safety (PMID 37994989). A 2018 NR crossover trial reported tolerability and NAD metabolism, and its authors suggested measuring blood pressure and arterial stiffness next (PMID 29599478).

What would a trial need to show before anyone could say a supplement changes biological age?

It would need a pre-specified clock as its primary outcome, a placebo group, and at least two clocks reported. It would measure the clock's own technical noise in the same trial and adjust for blood cell mix, and it would run long enough for a change to stand out from that noise (PMIDs 36277076 and 22568884). It would also link any clock change to a clinical outcome, and an independent group would need to replicate it. A single exploratory clock signal does not meet that bar.

How should a reader interpret a biological age test result?

Treat it as an estimate with error, not a diagnosis. Technical noise between repeated measurements can be large, with deviations of up to 9 years between replicates for six prominent clocks (PMID 36277076). One result says little about whether anything changed. Repeated results on the same lab platform, read against that clock's known error, say more. The 2026 review notes that clocks have not yet been thoroughly validated as clinical surrogate endpoints (PMID 42294499). Do not change a medication or treatment because of a clock result.

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