From: hubermanlab

NAD Pathway and Its Role in Longevity

The NAD (Nicotinamide Adenine Dinucleotide) pathway has emerged as a significant area of interest within the longevity and anti-aging research community. This article delves into the biochemical significance of NAD, its association with cellular processes critical for longevity, and the current understanding of its supplementation impact based on a discussion between Dr. Andrew Huberman and Dr. Peter Attia on the Huberman Lab podcast.

Overview of NAD

NAD is a crucial coenzyme found in all living cells, except red blood cells, that plays a vital role in redox reactions, transferring electrons from one reaction to another [[00:26:18]]. It exists in two states: NAD+ (oxidized) and NADH (reduced), constantly shuttling between these forms to facilitate hundreds of biochemical reactions, including those involved in cellular energy production and mitochondrial function [[00:27:02]].

NAD’s Role in Longevity

The interest in NAD within the context of longevity primarily stems from its involvement in cellular energy metabolism and its interaction with sirtuins—proteins that have been implicated in aging and regulation of cellular health. NAD acts as a substrate for sirtuins, which are enzymes that help repair DNA and regulate gene expression, impacting aging impacting aging [[00:45:00]].

Decline of NAD with Age

It is well-documented that NAD levels decline with age, correlating with reduced cellular function and increased vulnerability to diseases associated with aging associated with aging [[00:57:03]]. Lower NAD levels have been linked to mitochondrial dysfunction, reduced DNA repair capacity, and an increase in inflammatory markers, all of which are markers of aging markers of aging [[01:06:09]].

NAD Augmentation Strategies

Several strategies have been proposed to augment NAD levels in the body, primarily focusing on supplementation with precursors such as Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN), or direct NAD infusions direct NAD infusions [[00:56:16]].

NR vs. NMN vs. NAD Infusions

  • Nicotinamide Riboside (NR): NR is a precursor to NAD that can easily penetrate the cell membrane, making it a favored option for oral supplementation. It is thought to raise NAD levels effectively in some tissues, especially the liver and blood supplementation [[01:23:14]].

  • Nicotinamide Mononucleotide (NMN): While NMN is also a precursor to NAD, it must be converted into NR to permeate the cell membrane, making high dosing possibly necessary for comparable effects [[01:11:37]].

  • NAD Direct Infusions: Although intravenous NAD can directly increase NAD levels, the process can be uncomfortable and expensive, and the long-term benefits specifically related to longevity remain unproven specifically related to longevity [[01:09:01]].

Current Scientific Consensus

While there are anecdotal reports and some studies suggesting health span benefits from NAD-augmenting interventions, the scientific consensus on their efficacy, especially concerning human longevity, is cautious NAD-augmenting interventions. Several interventions have shown promise in model organisms, but translating these findings into conclusive human benefits requires further research [[01:41:01]].

Conclusion

The NAD pathway continues to be a focal point of research into aging and longevity. Despite the potential mechanisms through which NAD could affect aging processes, the efficacy of NAD-enhancing supplements or interventions for extending human lifespan remains to be definitively proven. Both Dr. Huberman and Dr. Attia emphasize focusing on foundational aspects of health, such as sleep, nutrition, and exercise health, while remaining open to the evolving science of NAD and its implications.