Why NAD+ Levels Matter
If you are interested in anti-aging, you have likely heard about NAD+.
NAD+ (Nicotinamide Adenine Dinucleotide) is a vital coenzyme found in all living cells, central to numerous metabolic processes, including energy production and cellular repair. Unfortunately, its levels decline with age, contributing to cellular dysfunction and an increased susceptibility to diseases associated with aging.
The Key Roles of NAD+
Energy Metabolism: NAD+ is essential for ATP production in mitochondria, supporting cellular energy needs.
DNA Repair: NAD+ activates enzymes like PARPs (Poly(ADP-ribose) polymerases), which repair DNA damage—a critical function for preventing mutations and cancer.
Sirtuin Activation: NAD+ is a cofactor for sirtuins, enzymes involved in regulating inflammation, metabolism, and longevity.
Redox Balance: The NAD+/NADH balance is vital for oxidative stress regulation, protecting cells from damage.
Why Does NAD+ Drop With Age?
As we age, our metabolism slows, and we struggle to produce new NAD+ or recycle it effectively from NADH. Compounding the issue, an enzyme called CD38 becomes overactive with age as part of the systemic inflammatory phenomenon known as inflammaging. CD38 actively degrades or consumes NAD+.
Other factors, such as cumulative environmental toxicity and epigenetic changes associated with aging, further reduce NAD+ production.
As NAD+ levels drop, several detrimental effects emerge:
Mitochondrial Dysfunction: Reduced energy production due to impaired mitochondrial function.
DNA Damage Accumulation: Increased cancer risk and accelerated aging processes.
Inflammation: Elevated due to impaired sirtuin activity.
Immune Dysfunction: Heightened susceptibility to infections and chronic diseases.
What Strategies Exist to Counteract Age-Related NAD+ Decline?
1. Supplementation
NAD+ precursors, such as NR (Nicotinamide Riboside) and NMN (Nicotinamide Mononucleotide), can boost NAD+ levels. These supplements show promise in improving mitochondrial function, reducing inflammation, and delaying age-related diseases.
2. CD38 Inhibition
CD38 and NAD+ Decline: CD38 is a major enzyme that degrades NAD+, and its activity increases with age. Research is actively exploring CD38 inhibitors as a strategy to preserve NAD+ levels, particularly in aging and age-related conditions.
Apigenin: This flavonoid, found in foods like parsley, chamomile, and celery, is a natural inhibitor of CD38. By reducing CD38 activity, apigenin helps protect NAD+ levels.
Evidence and Outlook
Animal and early human studies suggest that restoring NAD+ levels can improve metabolism, reduce neurodegeneration, and enhance cardiovascular health. Clinical trials are ongoing to explore the effects of NAD+ precursors on aging, chronic diseases, and overall healthspan.
In essence, targeting NAD+ levels holds significant potential for combating the hallmarks of aging, rejuvenating cellular energy, enhancing repair mechanisms, and reducing systemic inflammation.
What's Next?
In coming articles I will discuss the role of NAD+ precursor supplementaiton and CD38 inhibitors in more detail.
Copyright Dr Christopher Maclay 2024. All rights reserved. This article does not represent medical advice and should not be construed to do so.