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

Autor:	Romani M; Laboratory of Integrative Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland., Sorrentino V; Laboratory of Integrative Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland., Oh CM; Laboratory of Integrative Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland; Department of Endocrinology and Metabolism, CHA Bundang Medical Center, School of Medicine CHA University, Seongnam 13497, South Korea; Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, South Korea., Li H; Laboratory of Integrative Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland., de Lima TI; Laboratory of Integrative Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland., Zhang H; Laboratory of Integrative Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland., Shong M; Research Center for Endocrine and Metabolic Diseases, Chungnam National University School of Medicine, Daejeon 35015, South Korea., Auwerx J; Laboratory of Integrative Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland. Electronic address: admin.auwerx@epfl.ch.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Jan 19; Vol. 34 (3), pp. 108660.
DOI:	10.1016/j.celrep.2020.108660
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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