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Biological age & clocks
Research brief

Nicotinamide riboside and HIIT showed opposing epigenetic-age effects in human skeletal muscle

Across three independent studies, 5-month nicotinamide riboside supplementation was associated with reduced epigenetic age acceleration in human skeletal muscle, while 4–6 weeks of high-intensity interval training showed opposite effects in some clocks. These are associations, not proven causes. [1]

Automatic summary · not editorially reviewed

The key findings

  1. The abstract examined epigenetic age acceleration in human skeletal muscle across three independent studies of NR supplementation and HIIT. [1]

  2. Five-month NR supplementation was associated with reduced muscle epigenetic age acceleration, while 4–6 weeks of HIIT showed opposite effects in some clocks. [1]

  3. Changes in skeletal muscle mitochondrial content correlated with changes in MEAT-derived epigenetic age acceleration after NR and 6 weeks of HIIT. [1]

The source at a glance

Study type / format
Abstract of three independent intervention studies
Population / context
Human skeletal muscle in three independent studies of NR supplementation and HIIT
Summary based on
Study abstract
Original publication
August 1, 2026

Muscle epigenetic age after NR and HIIT

The abstract describes aging as involving declining physiological function and greater disease vulnerability, with mitochondrial dysfunction and epigenetic changes named as key hallmarks. Nicotinamide riboside (NR), a vitamin B3 precursor to NAD, and high-intensity interval training (HIIT) have both been proposed to counter aging-related mitochondrial decline. However, the authors state that their effects on epigenetic aging in skeletal muscle were not fully clarified. They therefore examined epigenetic age acceleration (EAA), measured with seven epigenetic clocks, in human skeletal muscle across three independent studies.

Supporting source [1]

Opposing clock results for NR versus HIIT

NR supplementation over 5 months was associated with reduced muscle EAA, particularly with the PCHannum, MEAT and DunedinPACE clocks. HIIT lasting 4–6 weeks produced opposite effects in some clocks, notably increasing the pace of aging by DunedinPACE. Correlation analyses found that changes in skeletal muscle mitochondrial content correlated with changes in MEAT-derived EAA after NR and after 6 weeks of HIIT. The authors interpret this as a possible link between mitochondrial abundance and epigenetic clocks, while noting that further studies are needed to clarify how NR and exercise regulate epigenetic aging.

Supporting source [1]

Abstract-only scope and open questions

This explainer is based only on the abstract; the full text was not reviewed. The abstract reports three independent studies but gives no participant numbers, ages, sex distribution, randomization details or follow-up beyond the stated intervention lengths. It reports associations between interventions and clock-based measures, not proof that NR or HIIT cause changes in epigenetic aging or in health outcomes. The authors themselves call for further studies and describe the results as new insights toward strategies for epigenetic outcomes and healthy aging, not as established benefits.

Supporting source [1]

How to interpret this

Abstract only; the full text was not reviewed. Participant numbers, ages, sex distribution, randomization and longer follow-up are not reported in the abstract. Findings are associations, not proof of causation or of health benefits.

Based on the study abstract; the full paper, tables and supplementary data were not reviewed.

Source & supporting passages

[1]
The Divergent Effects of Nicotinamide Riboside and High-Intensity Exercise Training on Skeletal Muscle Epigenetic Aging.

Heikkinen A, Uusitalo-Kylmälä L, Blom I, Helge JW, Gillberg L, Seaborne R, Larsen S, Jacques M, Grolaux R, Aaltonen S, Kaprio J, van der Kolk BW, Heinonen S, Eynon N, Pietiläinen KH, Kivelä R, Pirinen E, Ollikainen M. · europepmc.org · August 1, 2026

Read the quoted passagesIn the language of the original source
  1. Finding 1 ↑

    across three independent studies
  2. Finding 2 ↑

    HIIT produced opposite effects in some clocks
  3. Finding 3 ↑

    correlated with changes in MEAT-derived EAA

AI-assisted summary with linked source passages. No independent editorial or clinical review.

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