Muscle aging improved by NAD+


The older we grow, the weaker our muscles get, riddling old age with frailty and physical disability. However, this does not only influence the individual, it also creates a significant burden on public healthcare. And research efforts to the biological processes and biomarkers that specify muscle aging have not yet defined the underlying causes.

Now, a group of scientists from laboratory of Johan Auwerx at EPFL’s School Of Life Sciences looked at the issue from a different angle: the similarities between muscle aging and degenerative muscle diseases. They’ve found protein aggregates that deposit in skeletal muscles through natural aging, and that blocking this can prevent the harmful characteristics of muscle aging. The study is published in Cell Reports.

“During age-associated muscle diseases, such as inclusion body myositis (IBM), our cells struggle to maintain correct protein folding, leading these misfolded proteins to precipitate and forming toxic protein aggregates within the muscles,” explains Auwerx. “The most prominent component of these protein aggregates is beta-amyloid, just like in the amyloid plaques in the brains of patients with Alzheimer’s disease.”

In the study, the scientists recognize amyloid-like protein aggregates in aged muscles from different species, from the nematode C. elegans all of the way to people. Additionally, they also discovered these aggregates also impair mitochondrial function. Although aggregated proteins are suggested to lead to brain aging, this is actually the first time they have been shown to bring about muscle aging and to immediately damage mitochondria. “These abnormal proteotoxic aggregates could serve as novel biomarkers for the aging process, beyond the brain and muscle,” says Auwerx. 

But can the creation of this protein aggregates be reversed? To answer this, the investigators fed rats the vitamin nicotinamide riboside and the antitumor agent Olaparib, each of which boost the degree of nicotinamide adenine dinucleotide (NAD+), a biomolecule that’s essential for maintaining mitochondrial function, and whose levels decrease during aging.

In the worms, both chemicals turned on the defense mechanisms of the mitochondria, even if supplied at advanced age. Spinning on the so-called “mitochondrial quality control system” decreased the age-related amyloid protein aggregates and improved the rats’ fitness and lifespan.

The scientists then proceeded on to individual muscle tissue, taken from elderly and IBM patients. Turning on exactly the same mitochondrial excellent control systems produced comparable improvements in protein and mitochondrial homeostasis. The encouraging results led the researchers to check nicotinamide riboside in aged mice. The treatment also triggered the mitochondrial defense mechanisms and reduced the amount and size of amyloid aggregates in different skeletal muscle cells.

“Drugs that boost mitochondrial Excellent control could therefore be tested in the clinic to reverse those age-related proteotoxic aggregates And rejuvenate cells,” says Mario Romani, the first writer of the study.

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