Academy

NAD+ Metabolism and Aging

Nicotinamide adenine dinucleotide (NAD+) is a vital coenzyme found in all living cells, acting as a key regulator of metabolism and energy production. As we age, NAD+ levels naturally decline, compromising mitochondrial function and DNA repair. Maintaining adequate NAD+ is crucial for healthy aging because it powers enzymes like sirtuins and PARPs that control gene expression, stress resistance, and genomic stability.

NAD+ Precursors and Pathways

• Nicotinamide mononucleotide (NMN): A direct NAD+ precursor that bypasses rate-limiting steps in the salvage pathway to quickly restore coenzyme levels.
• Urolithin A: A mitochondrial quality-control agent derived from gut microbiota metabolism of ellagitannins, enhancing mitophagy.
• Ca-AKG (Calcium alpha-ketoglutarate): An intermediate in the Krebs cycle that supports energy metabolism and epigenetic regulation.
• Additional precursors: Nicotinamide riboside (NR) and tryptophan provide alternative biosynthetic routes to NAD+.

Impact on Cellular Health

By replenishing NAD+, cells improve their ability to generate ATP, repair DNA damage, and regulate inflammatory responses. Enhanced sirtuin activity leads to more efficient mitochondrial turnover and stress resistance. When combined with senolytic compounds like quercetin and fisetin, the approach both restores bioenergetics and clears harmful senescent cells, reducing chronic inflammation.

Practical Applications in Longevity Science

1. Supplementation: Daily NMN and precursor intake aims to sustain NAD+ levels, as seen in animal studies exhibiting improved muscle performance and cognitive function.
2. Mitophagy activation: Urolithin A supports mitochondrial cleaning, promoting endurance and reducing age-related decline in muscle tissue.
3. Senescence management: Senolytics target aging cells, preventing them from secreting pro-inflammatory factors.

Conclusion: NAD+ metabolism lies at the heart of longevity interventions. By combining targeted precursors, mitochondrial activators, and senolytics, modern supplements offer a multifaceted strategy to support cellular energy, tissue health, and overall vitality common to aging research.