Key Points
- NMN increased physical activity
- Glucose tolerance improved by nearly 17%
- Combined group enhance fat burning
- Key NAD+ pathways NAMPT and SIRT1 were upregulated
Methods
Forty male mice were assigned to five groups:
- Young Sedentary (YS): young control mice that did not exercise or receive NMN.
- Aged Sedentary (AS): older mice that remained inactive and received no treatment.
- Aged + Exercise (AE): followed treadmill protocol
- Aged + MNM (ASNMN): received 300 mg/kg/day NMN
- Aged + Exercise + NMN (AENMN): received 300 mg/kg/day NMN and followed treadmill protocol
The intervention lasted six weeks, with treadmill speed and incline gradually increased to build endurance.
Metabolic Efficiency Increased
VO2 levels, or oxygen consumption reflects how much energy is being used in activity or how efficient mitochondria are working. NMN elevated VO₂ and total energy expenditure, with the combined group showing the greatest values.
"VO2 levels were significantly higher in the AE, ASNMN, and AENMN groups compared to the AS group, with the AENMN group showing greater VO2 levels than both the AE and ASNMN groups."
Energy use followed the same pattern. The NMN + exercise group had the lowest RER (respiratory exchange rate) reflecting a shift towards fat metabolism.
"The AENMN group showed a significantly lower RER than the AS, AE, and ASNMN groups."
Levels of NAMPT and SirT1, enzymes linked to NAD⁺ production and healthy aging, were both elevated, pointing to improved cellular efficiency.
"The AE, ASNMN, and AENMN groups had significantly increased NAMPT levels compared with AS… SirT1 expression…was significantly lower in the YS group than in the ASNMN and AENMN groups."
This shows that NMN helped support healthy NAD⁺ levels and made the mitochondria work more efficiently, with the biggest improvements when paired with exercise. Understanding how NMN works at the cellular level reveals that its conversion to NAD+ activates sirtuins and supports mitochondrial biogenesis, providing a mechanistic explanation for why combining NMN with exercise produces synergistic metabolic benefits.
Glucose Tolerance Markedly Improved
Mice receiving NMN alone or NMN combined with exercise showed blood-sugar levels fell more quickly after a glucose challenge, indicating better glucose handling after a standard glucose challenge.
"After the 6-week intervention, both the ASNMN and AENMN groups exhibited significantly lower glucose levels over time compared to the AS group."
The combined NMN + exercise group (AENMN) performed the best overall. Their total glucose exposure during the test was reduced by 17.48%.
"The AENMN group demonstrated improved glucose tolerance, as reflected by a 17.48%, 17.50%, and 14.95% reduction in AUC values compared to the YS, AS, and AE groups, respectively."
This suggests the combination of NMN and aerobic training helped aged mice handle glucose more efficiently than any other group and beyond what exercise alone achieved.
Daily Movement Improved
Older mice are usually far less active, yet the NMN-plus-exercise group moved almost three times more physical activity than the sedentary group.
- ASNMN: 1.37× higher wheel activity vs AS
- AENMN: 2.85× higher vs AS (nearly triple)
"The AE, ASNMN, and AENMN groups all displayed significantly improved activity compared to the AS group… Notably, the AENMN group showed the greatest recovery, with a 2.85-fold increase over the AS group."
This shows that NMN counteracted age-related hypoactivity, with the combined group showing the largest improvement.
Conclusion
This study shows that NMN and regular aerobic exercise work well together to support healthy energy use and physical activity with age.
"In conclusion, this study provides evidence that six weeks of NMN supplementation combined with aerobic exercise improved aerobic endurance, glucose tolerance, and systemic energy metabolism in naturally aged mice."
"These outcomes, which include enhanced aerobic capacity, better glucose regulation, and favorable shifts in fat metabolism, are all relevant to mitigating age-related metabolic and functional decline."
The mice used oxygen more efficiently, burned more fat, and handled glucose better, all signs of healthier mitochondria. These findings suggest that pairing NMN with exercise may help maintain metabolic health and physique later in life.
"Together, these outcomes support the presence of a synergistic effect between NMN and exercise in restoring metabolic resilience during aging."
Research on NMN and exercise performance continues to validate that NAD+ precursor supplementation enhances training adaptations across multiple domains—from mitochondrial function to glucose metabolism—positioning NMN as a promising adjunct for optimizing both athletic performance and healthy aging trajectories.
