THE ROLE OF NAD+ AND NMN PRECURSORS IN MUSCLE DEVELOPMENT AND LIMITING MYASTHENIA GRAVIS

The consequence of NAD+ deficiency is muscle aging

The hallmark of aging is reduced mitochondrial function, evidenced by reduced metabolic fuel utilization, ATP production, and subsequent oxygen consumption. Mitochondrial volume is reduced in aged muscle, largely explained by reduced mitochondrial biogenesis controlled by the SIRT/PGC-1α/Tfam axis. The enzymes most affected by decreasing NAD+ levels with aging are SIRT, specifically SIRT1 and SIRT3. SIRT activity systematically decreases with aging although the enzyme protein content remains relatively stable. This depletion may directly affect its ability to deacetylate PGC-1α, leading to lower Tfam, which is the key nuclear factor for activating mitochondrial biogenesis.

In addition, reduced NAD+ also inactivates SIRT3, the mitochondrial sirtuin, thereby inhibiting enzymes in the TCA cycle through increased acetylation. Furthermore, low NAD+ levels may cause age-related loss of mitochondrial homeostasis, leading to loss of muscle function and sarcopenia. Indeed, a recent study demonstrated that NAD+ deficiency in 24-month-old mice was associated with increased acetylation of multiple proteins in mouse hindlimb muscle and the heart.

Another serious consequence of reduced NAD+ levels in the aging body is impaired antioxidant defenses, leading to increased oxidative stress and inflammatory responses. Furthermore, reduced NAD+ levels limit the ability to repair DNA damage that occurs in old age.

The impact of NAD+ on muscle growth and regeneration

NAD+ plays an important role in a variety of cellular functions related to metabolism, signal transduction and redox balance. In yeast and invertebrates, NAD+ supplementation increases lifespan while counteracting age-related functional decline. In mammals and humans, supplementation with NAD+ precursors such as Nicotinamide Mononucleotide (NMN) significantly improves age-related mitochondrial degradation, metabolic dysfunction, insulin resistance, neurological and motor impairment. It can be said that NAD+ plays an important role in developing muscle health through the process of maintaining muscle fibers in an organized manner.

Mitochondrial dysfunction is considered a hallmark of muscle aging, so much of the research has linked NAD+ precursor supplementation to mitochondrial function. In general, scientists agree that improving NAD+ levels and minimizing the effects of aging in muscle is due to increased SIRT1 activity while improving mitochondrial homeostasis. Increased NAD+ concentrations alone have increased endurance performance in laboratory rats, so combining NAD+ supplementation with exercise has shown some positive results through experiments. More specifically, some scientists have added NAD+ precursors to the drinking water of young and old mice in combination with endurance training, which increased SIRT1 deacetylation activity in both age groups, along with according to increased PGC-1α levels in aged mouse muscle.

Supplementing NAD+ increases blood flow and increases physical endurance.

Recently, another study also demonstrated that NAD+ supplementation increased blood flow and increased physical endurance in aged mice by promoting capillary density. The role of blood flow in muscle aging is also emphasized throughout the report. In fact, NAD+ has the ability to promote muscle regeneration , increase muscle strength, running time and longevity in old mice. This study sheds new light on the role of NAD+ in improving not only existing aged muscle cell function but also the ability to reverse age-related decline in muscle morphology and physiology through cell rejuvenation. origin.

Supplementing NAD+ plays an important role in muscle regeneration and development. Many people choose to supplement the NAD+ precursor Nicotinamide Mononucleotide (NMN) to limit muscle weakness and sarcopenia and start the journey of healthy aging.