Peptide Protocol

Nicotinamide adenine dinucleotide (NAD+) has emerged as one of the most critical molecules in aging research. This coenzyme, present in every living cell, plays a fundamental role in energy metabolism, DNA repair, and cellular signaling—processes that become increasingly impaired as we age.

The NAD+ Decline

Research has consistently demonstrated that NAD+ levels decline significantly with age. By middle age, NAD+ levels can drop to half of what they were in youth. This decline is associated with:

Mitochondrial dysfunction - Reduced energy production at the cellular level
DNA damage accumulation - Impaired repair mechanisms lead to genomic instability
Sirtuin deactivation - These longevity proteins require NAD+ to function
Chronic inflammation - NAD+ depletion contributes to inflammaging
Cellular senescence - Accelerated accumulation of senescent cells

NAD+ and the Hallmarks of Aging

The significance of NAD+ extends to nearly all recognized hallmarks of aging. As a critical substrate for sirtuins (SIRT1-7), NAD+ directly influences:

Epigenetic regulation and gene expression
Autophagy and cellular cleanup mechanisms
Circadian rhythm maintenance
Metabolic homeostasis
Stem cell function and regeneration

PARP and CD38: The NAD+ Consumers

Understanding why NAD+ declines requires examining its major consumers. Poly(ADP-ribose) polymerases (PARPs), particularly PARP1, use NAD+ for DNA repair. While essential, chronic DNA damage with age leads to excessive PARP activation and NAD+ depletion.

CD38, an enzyme that increases with age and inflammation, is another significant NAD+ consumer. Studies in mice have shown that CD38 inhibition can restore NAD+ levels and improve metabolic function in aged animals.

Therapeutic Strategies for NAD+ Restoration

Multiple approaches are being investigated to restore NAD+ levels:

NAD+ precursors - NMN and NR supplementation to boost NAD+ synthesis
Direct NAD+ administration - IV NAD+ therapy for rapid restoration
CD38 inhibitors - Reducing NAD+ degradation
NAMPT activators - Enhancing the salvage pathway
Lifestyle interventions - Exercise, fasting, and circadian optimization

Clinical Evidence

Human clinical trials are increasingly supporting the benefits of NAD+ restoration:

Improved insulin sensitivity and metabolic markers
Enhanced muscle function and exercise capacity
Better sleep quality and circadian rhythm
Reduced markers of inflammation
Improved cognitive function in preliminary studies

The Future of NAD+ Therapy

As research advances, several exciting developments are emerging:

Tissue-specific NAD+ delivery systems
Combination therapies targeting multiple pathways
Biomarker-guided personalized protocols
Novel NAD+ boosting compounds with improved bioavailability

The evidence increasingly suggests that maintaining optimal NAD+ levels may be one of the most impactful interventions for healthy aging. While more research is needed to optimize protocols and understand long-term effects, NAD+ restoration represents a promising frontier in longevity medicine.