NAD+ restores muscles
Researchers from the Federal Polytechnic School of Lausanne (EPFL) have found that protein aggregates similar to clusters of beta-amyloid in Alzheimer's disease provoke age-related destruction of muscle tissue. But these changes can be reversed by increasing the level of nicotinamide adenine dinucleotide (NAD+), which activates the protective systems of mitochondria in cells and restores muscle strength. NAD+ is a biomolecule that is necessary to maintain mitochondrial function and whose level decreases with age.
The older a person gets, the weaker his muscles, which is why old age is accompanied by infirmity and physical limitations. This affects not only the elderly and their relatives, but also public health. Numerous studies of biological processes and biomarkers associated with muscle aging have not yet identified the main causes of degenerative changes.
A group of scientists led by Johan Auwerks from the EPFL School of Natural Sciences looked at the problem from a different angle. They found similarities between muscle aging and degenerative muscle diseases and discovered protein aggregates that are deposited in skeletal muscles during natural aging. Blocking them can prevent signs of muscle aging.
In age-related muscle degenerative diseases, for example, sporadic myositis with inclusions (sMSV), cells try to maintain proper protein assembly, but this leads to the deposition of "wrong" proteins and the formation of toxic aggregates in the muscles. The main component of these protein aggregates is beta-amyloid, which forms amyloid plaques in the brains of patients with Alzheimer's disease.
During the study, scientists identified amyloid-like protein aggregates in aging muscles of various organisms, from the nematode C. elegans to humans. They also found that these aggregates disrupt mitochondrial function. Aggregated proteins are thought to contribute to brain aging, and this is the first time they have been shown to promote muscle aging and directly damage mitochondria. Is it possible to reverse the formation of protein aggregates? To answer this question, the researchers added nicotinamide riboside and the antitumor drug olaparib to the worms' diet – each of them increases the level of NAD+.
In experimental worms, regardless of age, protective systems in mitochondria were activated as a result of treatment. Activation of the so-called "mitochondrial quality control system" reduced the deposition of beta-amyloid aggregates and improved the fitness and lifespan of worms.
The researchers repeated the experiment on samples of human muscle tissue taken from healthy elderly people and patients with mSv. Activation of the same mitochondrial quality control systems led to a similar improvement in protein and mitochondrial homeostasis. The results prompted the researchers to test nicotinamide riboside on old mice. The treatment also activated mitochondrial defense systems and reduced the number and size of amyloid aggregates in skeletal muscles.
Thus, the authors were able to show that drugs that enhance the synthesis of NAD+ and lead to the activation of the mitochondrial protection system can reduce the number of age-related proteotoxic aggregates and rejuvenate tissues. It is planned to test them in clinical trials.
Article by M.Romani et al. NAD+ boosting reduces age-associated amyloidosis and restores mitochondrial homeostasis in muscle published in the journal Cell Reports.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on EPFL materials: NAD+ can restore age-related muscle determination.