Two of the most popular anti-aging strategies just went head to head on the epigenetic clock, and they did not agree. In a new Aging Cell paper, nicotinamide riboside (NR) was associated with younger-looking human skeletal muscle. High-intensity interval training (HIIT) moved some of the same clocks in the opposite direction. One clock, DunedinPACE, showed HIIT increasing the pace of aging.
Before you cancel your gym membership or empty your cart of supplements, read the details. The result is more interesting, and more complicated, than the headline suggests.
The Short Version: Who "Won"?
On muscle epigenetic age acceleration (EAA), NR came out ahead. The study by Heikkinen and colleagues, published in Aging Cell, reports that NR supplementation was associated with reduced muscle EAA. The effect was clearest on three clocks: PCHannum, MEAT, and DunedinPACE.
HIIT "produced opposite effects in some clocks," in the authors' words. The most notable was a rise in the pace of aging as measured by DunedinPACE.
The paper's conclusion is that muscle epigenetic aging can be modulated by both interventions, but in opposing directions.
What the Researchers Actually Did
The team looked at human skeletal muscle across three independent studies. They assessed epigenetic age acceleration using seven epigenetic clocks. The interventions were:
- NR supplementation for 5 months
- HIIT for 4 to 6 weeks
NR is a vitamin B3 precursor to NAD+, a molecule central to cellular energy metabolism. HIIT is a well-known way to stimulate muscle mitochondria. Both had been proposed to counter the mitochondrial decline of aging, and mitochondrial dysfunction and epigenetic alteration are both recognized hallmarks of aging. This study asked a narrower question: what do these interventions do to the epigenetic clocks in muscle?
The Plot Twist: Mitochondria May Be the Link
The most intriguing finding may be the correlation analysis. Changes in skeletal muscle mitochondrial content correlated with changes in MEAT-derived EAA after NR and after 6 weeks of HIIT.
The abstract does not give the direction or strength of that relationship, so we should not overstate it. What it does suggest is a potential link between mitochondrial abundance and what epigenetic clocks read out in muscle. Two very different interventions may be touching the same machinery while producing different clock readings.
Why HIIT's Result Shouldn't Scare You
The "HIIT accelerates aging" reading is tempting, but the evidence doesn't support it. Here is why.
- The effect was clock-specific. HIIT produced opposite effects in some clocks, not all seven. DunedinPACE was the standout.
- Clocks are readouts, not outcomes. An epigenetic clock measures DNA methylation patterns. It does not measure strength, endurance, insulin sensitivity, or survival. The paper does not claim that HIIT harmed muscle function.
- Short intervention windows. HIIT lasted just 4 to 6 weeks. Acute training stress and tissue remodeling could plausibly affect methylation patterns differently than long-term training does. That is a hypothesis, not a finding of this paper.
- The authors call for more work. They state that further studies are needed to clarify how NR and exercise regulate epigenetic aging.
The cautious takeaway is that epigenetic clocks in muscle may respond to exercise in ways that don't map neatly onto "younger" or "older."
Practical Takeaways (Within What the Paper Supports)
Dose and timing
The abstract does not report NR dosing or time-of-day timing, so there is no dose to quote from this paper. What it does specify is duration:
- NR: 5 months of supplementation
- HIIT: 4 to 6 weeks of training
If you want exact protocols, check the full text and the three underlying studies rather than relying on a summary.
Who might find this interesting
- People curious about NR or NAD+ precursors and what they might do in muscle tissue
- Exercisers who track biological age markers and want context for conflicting readings
- Anyone following the epigenetic-clock field, where tissue-specific readouts are still being worked out
Who should be cautious
The paper offers no safety or eligibility guidance, so these are general sense-checks and not claims from the study:
- Don't treat this as a reason to drop exercise. The study did not test whether HIIT worsens health outcomes.
- Don't treat it as proof that NR improves function. The reported outcome is epigenetic age acceleration, not performance or disease risk.
- People with medical conditions, or those taking medications, should talk to a clinician before starting any supplement or intense training program.
The Bigger Picture
The study is a reminder that "anti-aging" interventions don't all move biomarkers the same way. A supplement and a training program that both target mitochondria produced divergent clock results in the same tissue. That suggests epigenetic clocks capture something about mitochondrial biology, but not a simple "good vs. bad" signal.
The authors say their results "offer new insights into development of strategies for promoting epigenetic outcomes and healthy aging." The key unknowns remain: how NR and exercise regulate epigenetic aging, and whether clock changes in muscle predict anything meaningful about health.
Bottom Line
- NR: associated with reduced muscle epigenetic age acceleration, especially on PCHannum, MEAT, and DunedinPACE
- HIIT: opposite effects on some clocks, including a higher DunedinPACE pace of aging
- Link: changes in muscle mitochondrial content correlated with changes in MEAT-derived EAA after NR and 6 weeks of HIIT
- Caveat: this is a biomarker finding, and more research is needed
Source: Heikkinen et al., "The Divergent Effects of Nicotinamide Riboside and High-Intensity Exercise Training on Skeletal Muscle Epigenetic Aging," Aging Cell. DOI: 10.1111/acel.70638. PubMed: 42481916.
