Key Points
- NMN extended lifespan in mice by up to 8 weeks
- Restored NAD+ levels in cells and tissues
- Improved mitochondrial function and antioxidant defenses
- Reduced cellular senescence and DNA damage
- Supported reproductive organ structure and hormone balance
Methods
This study used both mice and human-derived cells to mimic accelerated aging.
In vivo (mouse model):
- Control (WT): healthy mice received saline placebo daily for four weeks
- G608G: progeria mice received saline placebo daily for four weeks
- G608G+NMN: progeria mice received 300 mg/kg NMN orally daily for four weeks
In vitro (cell model):
- Mesenchymal stem cells (MSCs) derived from HGPS patients
- Cells were treated with 200 µM NMN for 72 hours
Lifespan Significantly Increased in Mice
Treatment with NMN prolonged lifespan in G608G progeria mice.
This figure shows NMN-treated G608G mice (blue line) had a higher survival rate compared to the untreated G608G control (orange line).
When analyzed by sex:
- Females lived over 8 weeks longer on average
- Males lived 3–5 weeks longer
"In female G608G mice, the average lifespan was approximately 35 weeks, and NMN supplementation significantly extended it by nearly 8 weeks…"
"Male G608G mice exhibited a baseline lifespan of 40 weeks… NMN administration extended their lifespan by 3–5 weeks."
The NMN-treated group showed a consistently higher survival rate, with the greatest benefit seen in females.
"NMN administration extended the median and maximum lifespan of G608G mice, highlighting its potential to improve systemic health and delay the onset of age-related pathologies."
NMN Reduced Progeria-Related Aging Symptoms
NMN supplementation improved multiple markers associated with accelerated aging.
Researchers observed increased levels of NAD⁺, NADH, and ATP in several organs, including the liver, kidney, muscle, and spleen.
"Long-term NMN oral administration elevated their concentrations in tissues."
Cardiovascular structure also improved. NMN partially restored vascular smooth muscle cells, suggesting healthier and more resilient blood vessels.
"NMN administration partially ameliorated vascular smooth muscle cell degeneration… in the medial layer of the aortic arch."
Physical performance and appearance improved as well.
"Long-term NMN supplementation has been shown to partially ameliorate these motor deficits… G608G mice exhibited smoother and thicker coats after long-term NMN supplementation."
Rescued Reproductive Organs
NMN supported reproductive health in both male and female progeria mice.
In females, NMN helped restore ovarian follicle number toward healthy levels. In males, NMN improved the structure of seminiferous tubules, which are involved in sperm production.
*This illustrates the significant reduction in ovarian follicle number in female G608G mice (orange) compared to healthy mice (green), and how NMN treatment rescued these numbers to near normal levels (blue).*
"These findings suggest that NMN partially ameliorates reproductive deficits in HGPS mice by mitigating specific cellular and molecular features of aging-related decline."
Hormone measurements showed a healthier balance after NMN treatment.
"Following NMN treatment, FSH [follicle-stimulating hormone] levels decreased significantly, while estradiol (E2) and anti-Müllerian hormone (AMH) levels were partially rescued."
Cellular and Genomic Health Improved With NAD⁺ Restoration
To better understand how NMN produced these whole-body effects, researchers examined patient-derived stem cells.
Cells from HGPS patients had lower NAD⁺ levels and higher levels of senescent cells (old, damaged cells that no longer function properly). NMN treatment restored NAD⁺ and reduced senescence and cell death.
Here, cells from HGPS patients (orange) had ~15% more senescent cells than healthy cells (green), but NMN treatment (blue) reduced this to near-healthy levels.
"NMN treatment led to the marked recovery of NAD⁺ and NADH levels… effectively attenuated all observed senescence markers… and significantly reduced apoptosis in G608G MSCs."
NMN also lowered the number of dangerous double-strand DNA breaks, which are difficult for cells to repair and increase mutation risk.
"Immunostaining quantification demonstrated a 20% reduction in DNA double-strand breaks following NMN treatment."
Restored heterochromatin (neatly packed and stored DNA) indicated improved genetic stability and tighter control over gene expression.
"NMN contributed to the re-establishment of constitutive heterochromatin."
*This shows the growth pattern of the different groups over four days. The control and NMN treated cells nearly tripled in number, while the G608G cells showed little to no growth.
Cell growth patterns further showed recovery.
Healthy and NMN-treated cells nearly tripled in number over four days, while untreated G608G cells showed little to no growth.
"These results provide strong evidence that NMN supplementation effectively mitigates multiple cellular defects associated with premature aging."
Understanding how senescent cells accumulate and disrupt tissue function helps explain why reducing senescence markers is strongly associated with improved lifespan and genomic stability in accelerated aging models.
Precursor Enhanced Mitochondrial Balance (Cellular)
NMN also improved mitochondrial health, a central driver of aging.
Researchers found that NMN switched on genes involved in energy production and fuel use, while reducing activity in pathways linked to metabolic dysfunction.
"Genes upregulated by NMN were predominantly enriched in oxidative phosphorylation, the tricarboxylic acid cycle, and DNA repair pathways…"
"In contrast, downregulated genes were associated with insulin resistance, mTOR signaling, and the TP53 pathway."
HGPS cells showed fragmented, damaged mitochondria. NMN largely reversed this structural damage.
"These abnormalities were substantially reversed following NMN treatment."
Oxidative stress was reduced, and antioxidant defenses increased.
"Elevated reactive oxygen species (ROS) levels… were effectively normalized by NMN supplementation."
Key protective proteins involved in mitochondrial and stress regulation were also increased.
"NMN treatment upregulated the protein expression of SIRT1, PGC-1α, and FOXO3."
Comprehensive reviews of mitochondrial decline show why restoring mitochondrial structure, energy production, and antioxidant defenses is closely tied to improved cellular resilience and longevity outcomes.
Conclusion
This study showed that NMN supplementation produces, multi-system benefits in a severe model of accelerated aging. NMN improved lifespan, physical function, cardiovascular structure, reproductive health, mitochondrial performance, and cellular integrity.
"Four months of NMN administration in G608G transgenic mouse models resulted in significant improvements in gonadal function, cardiovascular parameters, skin pathology, and lifespan extension."
"These findings establish NAD⁺ precursor therapy as a promising preventive and therapeutic strategy for aging-related pathologies in HGPS."
Together, the results support further exploration of NAD⁺ restoration as a strategy for understanding and addressing both premature and normal aging.
