Coenzyme NAD+ Can Restore Age-Related Muscle Deterioration, Study Finds

New research has found that Alzheimer’s-like protein aggregates underlie the muscle deterioration seen in ageing. We know the older we grow, the weaker our muscles get. Yet it is still unknown as to what is the cause for this muscle ageing.   

A team of scientists from the lab of Johan Auwerx at EPFL’s School of Life Sciences have studied this issue by looking through the similarities between muscle ageing and degenerative muscle diseases. What they found was that the protein aggregates that deposit in skeletal muscles during natural ageing and that blocking this can prevent the detrimental features of muscle ageing. 

Auwerx explains us that the body cells struggle to maintain correct protein folding during age-associated muscle diseases thus leading these misfolded proteins to precipitate and forming toxic protein aggregates within the muscles.

Beta-amyloid is the most prominent component of these protein aggregates, which is just like in the amyloid plaques in the brains of patients with Alzheimer’s disease.

The study identified amyloid-like protein aggregates in aged muscles from different species from the nematode C. elegans all the way to humans. They also found that these aggregates impair mitochondrial function. It is the first time that aggregated proteins have been shown to contribute to muscle ageing and to directly damage mitochondria. “These abnormal proteotoxic aggregates could serve as novel biomarkers for the ageing process, beyond the brain and muscle,” says Auwerx.

The question is can the formation of these protein aggregates be reversed. The researchers fed worms with nicotinamide riboside and the antitumor agent Olaparib, both of which boost the levels of nicotinamide adenine dinucleotide (NAD+), a biomolecule that is essential for maintaining the mitochondrial function, and whose levels decline during ageing.

In the worms, the two compounds turned on the defence systems of the mitochondria, even when provided at an advanced age. Turning on the so-called “mitochondrial quality control system” reduced the age-related amyloid protein aggregates and improved the worms’ fitness and lifespan.

They then moved on to human muscle tissue, which was taken from aged subjects and IBM patients. The encouraging results led the researchers to test nicotinamide riboside in aged mice. The treatment also activated the mitochondrial defence systems and reduced the number and size of amyloid aggregates in different skeletal muscle tissues.

“Drugs that boost mitochondrial quality control could therefore be tested in the clinic to reverse these age-related proteotoxic aggregates and rejuvenate tissues,” says Mario Romani, the first author of the study.

Journal Reference:
Mario Romani, Vincenzo Sorrentino, Chang-Myung Oh, Hao Li, Tanes Imamura de Lima, Hongbo Zhang, Minho Shong, Johan Auwerx. NAD+ boosting reduces age-associated amyloidosis and restores mitochondrial homeostasis in muscle. Cell Reports, 2021; 34 (3): 108660 DOI: 10.1016/j.celrep.2020.108660

Press Release: Ecole Polytechnique Fédérale de Lausanne