XPrize Healthspan convenes a global competition to reinvigorate aging biology, offering $101 million to teams that demonstrate a ten-year reversal in muscle mass, cognitive function, and immune response among 50- to 80-year-olds. Entrants are evaluated for scientific rigor, scalability, and affordability, with finalists gearing up for a one-year clinical validation, aiming to democratize accessible longevity interventions.
Key points
$101 million XPrize incentivizes ten-year reversal of sarcopenia, cognitive decline, and immunosenescence
Interventions include repurposed drugs (metformin, rapamycin), NMN/NAD+ augmentation, neuromodulation, and lifestyle regimens
Finalists undergo an $81 million, one-year clinical validation focusing on scalability, affordability, and robust biomarker outcomes
Why it matters:
By funding scalable aging reversal strategies targeting fundamental biology, this prize could transform healthcare by extending healthspan and reducing age-related disease burden.
Q&A
What does a ten-year rejuvenation mean?
How does NMN supplementation work?
Why is accessibility a competition criterion?
What role do repurposed drugs play?
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Academy
Nicotinamide Adenine Dinucleotide (NAD+) and Nicotinamide Mononucleotide (NMN)
Nicotinamide adenine dinucleotide (NAD+) is a vital coenzyme found in every cell, playing key roles in energy metabolism, DNA repair, and cellular signaling. It shuttles electrons in metabolic pathways, supporting mitochondrial function and helping maintain genomic stability. As organisms age, NAD+ levels decline, impairing cell function and contributing to age-related diseases.
Nicotinamide mononucleotide (NMN) is a direct precursor to NAD+ that cells can convert rapidly. Supplementation with NMN aims to restore intracellular NAD+ concentrations, boost sirtuin enzyme activity, and improve mitochondrial bioenergetics. Preclinical studies show NMN can enhance physical endurance, cognitive performance, and stress resilience in aging models.
Age-Related NAD+ Decline and Its Consequences
With advancing age, NAD+ synthesis pathways become less efficient, and consumption by DNA repair enzymes increases, leading to depleted NAD+ reserves. This NAD+ deficit disrupts cellular metabolism, weakens stress responses, and reduces the activity of sirtuin proteins that regulate gene expression, inflammation, and longevity pathways.
Mechanisms of Action: Sirtuins, DNA Repair, and Energy Metabolism
Sirtuin enzymes (SIRT1–SIRT7) depend on NAD+ to deacetylate target proteins, modulating gene regulation, mitochondrial biogenesis, and antioxidant defenses. Higher NAD+ levels also support PARP enzymes in DNA damage repair and fuel the electron transport chain for efficient ATP production, sustaining cellular vitality.
Sources and Supplementation of NMN
- Dietary Sources: Trace amounts of NMN are found in edamame, broccoli, cucumbers, and avocado, but natural intake is low.
- Supplement Forms: Pharmaceutical-grade NMN is formulated as capsules or powders with high purity. Proper storage and manufacturing standards are essential to maintain stability.
Safety and Regulatory Considerations
- Quality Control: Supplements are not regulated like drugs, so third-party testing for purity and absence of contaminants is critical.
- Dosage and Tolerance: Human studies exploring dose ranges from 250 mg to 1 g per day report minimal side effects, but long-term safety data are still emerging.
- Medical Guidance: Always consult a qualified healthcare professional before starting NMN, especially if you have underlying health conditions or take prescription medications.
Future Directions in NAD+ Research
- Clinical Trials: Ongoing studies aim to establish standardized biomarkers of NAD+ efficacy, optimal dosing regimens, and long-term outcomes in diverse populations.
- Combination Therapies: Research is exploring synergistic effects of NMN with exercise, caloric restriction mimetics, or other small molecules to maximize healthspan benefits.
- Personalized Nutrition: Integration of genetic profiling and metabolic analysis may allow individualized NMN dosing strategies for targeted improvements in energy metabolism and cellular repair.
Key Takeaways
- NMN supplementation restores NAD+ levels, supporting energy production and DNA repair.
- Boosting NAD+ activates sirtuins, enhancing stress resilience and metabolic health.
- Quality, dose, and medical oversight are crucial for safe and effective use of NMN.
