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NAD+ boosting reduces age-associated amyloidosis and restores mitochondrial homeostasis in muscle

Cell Reports

January 19, 2021

Romani, Mario

Summary

Aging is characterized by loss of proteostasis and mitochondrial homeostasis. Here, we provide bioinformatic evidence of dysregulation of mitochondrial and proteostasis pathways in muscle aging and diseases. Moreover, we show accumulation of amyloid-like deposits and mitochondrial dysfunction during natural aging in the body wall muscle of C. elegans, in human primary myotubes, and in mouse skeletal muscle, partially phenocopying inclusion body myositis (IBM). Importantly, NAD+ homeostasis is critical to control age-associated muscle amyloidosis. Treatment of either aged N2 worms, a nematode model of amyloid-beta muscle proteotoxicity, human aged myotubes, or old mice with the NAD+ boosters nicotinamide riboside (NR) and olaparib (AZD) increases mitochondrial function and muscle homeostasis while attenuating amyloid accumulation. Hence, our data reveal that age-related amyloidosis is a contributing factor to mitochondrial dysfunction and that both are features of the aging muscle that can be ameliorated by NAD+ metabolism-enhancing approaches, warranting further clinical studies.

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Original work © 2022 by Right of Assembly

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IMPORTANT DISCLOSURES

1. Health Supplements Are Not Medicines. Health Supplements that raise NAD levels, like nicotinamide riboside or other NAD precursors, are not intended to diagnose, treat, cure, or prevent any disease.

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2. No Medical Advice. I am a lawyer and a journalist, not a doctor, and I offer no medical advice. But I do follow the science, and I can bring to your attention some interesting studies. You can read more about me here. And check with your physician -- your physician can look at this research, too.

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