Anti-Aging Research and NAD+

One of the hallmark effects of normal aging is a decline in both the quality and efficiency of mitochondria, the body’s energy powerhouses responsible for fueling processes like neuron activity, digestion, and muscle function. Reduced mitochondrial performance is linked to typical aging but also plays a role in various age-related diseases. Studies indicate that mitochondrial aging contributes to cellular senescence, inflammation, and diminished stem cell activity, which slows healing and recovery from injury in older age [1].

Nuo Sun, from the National Heart, Lung, and Blood Institute at the National Institutes of Health, emphasizes that mitochondria are not merely energy factories but “platforms for intracellular signaling, regulators of innate immunity, and modulators of stem cell activity.” He notes that mitochondria are tied to numerous aging-related processes, including senescence, inflammation, and the broader decline in tissue and organ function with age. In essence, mitochondria are central to cellular aging, and understanding how to preserve their function is a critical step toward slowing, halting, or potentially reversing aging.

Emerging research suggests that some age-related mitochondrial decline can be reversed through dietary NAD+ supplementation. This discovery, which gained prominence in research circles, is credited to David Sinclair of Harvard University, the same scientist who identified the anti-aging benefits of resveratrol (a compound found in red wine). In 2013, Sinclair demonstrated that mitochondrial function in the muscles of mice could be rejuvenated to a more youthful state by injecting a precursor to NAD+ [2].

Research from 2013 revealed that declining NAD+ levels create a pseudohypoxic state within cells, disrupting normal communication between the nucleus (where DNA is stored) and the mitochondria. Supplementing older mice with NAD+ restores mitochondrial function and reestablishes this critical signaling [3]. A key reason NAD+ counters aging is its ability to activate SIRT1 function in the nucleus, preventing the typical age-related reduction in expression of this gene. SIRT1 encodes sirtuin 1 (or NAD-dependent deacetylase sirtuin-1), an enzyme that regulates proteins involved in cellular metabolism, stress response, longevity, and inflammation [4].

NAD+ in Neurodegenerative Disease

Much of the knowledge about NAD+ and aging also applies to various diseases, particularly those affecting the central nervous system. Changes in NAD+ levels have profound effects and are associated with neurodegenerative conditions like Alzheimer’s and Huntington’s diseases. A 2019 review article summarized the current understanding of NAD+’s role in the central nervous system, noting its neuroprotective properties in mouse models of human diseases, such as Huntington’s. NAD+ appears to enhance mitochondrial function, reducing the production of reactive oxygen species (ROS), which are known to damage cells in inflammatory and disease states and accelerate aging. There’s growing interest in potential synergistic effects of NAD+ supplementation with PARP inhibitors, a class of drugs targeting Poly-ADP-ribose polymerase proteins involved in DNA repair and programmed cell death. While activated PARP is vital for DNA repair, excessive activity can deplete cellular energy and trigger programmed cell death [5].

In mouse models of Parkinson’s disease, NAD+ supplementation has been shown to protect against motor deficits and the loss of dopaminergic neurons in the substantia nigra, suggesting it could not only alleviate symptoms but also slow or prevent the disease’s onset [6].

Intriguing research on the kynurenine pathway (KP)—a metabolic process—indicates that NAD+ supplementation may help prevent disease by reducing neurotransmitter breakdown and minimizing the diversion of protein precursors to NAD+ production. Tryptophan, an essential amino acid and building block for neurotransmitters and proteins, is metabolized via the KP to produce NAD+, which can deplete essential neurotransmitters. Imbalances in KP activity have been linked to Parkinson’s, Alzheimer’s, Huntington’s, and psychiatric disorders like schizophrenia and bipolar disorder [7]. Ongoing research is exploring whether NAD+ supplementation can correct KP imbalances and mitigate or prevent these neurodegenerative conditions.

The Role of NAD+ in Reducing Inflammation

NAD+ levels are influenced by various factors, including the enzyme NAMPT, which is associated with inflammation and often overexpressed in certain cancers—making it a target for potential anti-cancer therapies. NAMPT is also linked to obesity, type 2 diabetes, and nonalcoholic fatty liver disease. It strongly promotes inflammation, with its levels rising as NAD+ levels fall. NAD+ supplementation is thought to reduce NAMPT activation, thereby modulating inflammation [8].

Evidence suggests that the NAD+/NAMPT dynamic drives insulin resistance, a condition tied to obesity and often leading to type 2 diabetes and heart disease. Obesity triggers inflammation, which lowers NAD+ levels, increasing free fatty acids in the blood due to reduced adiponectin activity. This causes the liver to produce excess glucose while impairing insulin-mediated glucose uptake in skeletal muscle, resulting in insulin resistance. The pancreas responds by overproducing insulin, eventually leading to high blood glucose and diabetes over time [9].

NAD+ in Addiction Treatment

It’s well-established that drugs and alcohol negatively impact NAD+ levels, causing nutritional deficiencies and mood disturbances. NAD+ supplementation to address these deficits began in the 1960s and has recently regained attention due to studies showing that combining NAD+ with specific amino acid complexes can enhance recovery and provide more significant, lasting results in addiction rehabilitation. Research indicates this combination can reduce cravings and improve stress and anxiety levels [10].

NAD+ Supplementation and the Future of Aging Research

Animal studies provide compelling evidence that NAD+ supplementation can mitigate some effects of mitochondrial aging. However, most of this data comes from animal models, prompting a push for clinical trials in neurodegenerative diseases and chronic type 2 diabetes. NAD+ holds great promise for at least slowing the progression of these debilitating conditions, with hopes it might, alone or with other therapies, reverse certain disease processes or even regulate aging itself.

NAD+ exhibits minimal side effects, low oral bioavailability, and excellent subcutaneous bioavailability in mice. Per-kilogram dosages in mice do not directly scale to humans. NAD+ available for purchase at Peptide Sciences is strictly for educational and scientific research purposes, not for human consumption, and should only be bought by licensed researchers.