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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Romani, Mario [1] ; Sorrentino, Vincenzo [1] ; Oh, Chang-Myung [1, 2, 3] ; Li, Hao [1] ; de Lima, Tanes Imamura [1] ; Zhang, Hongbo [1] ; Shong, Minho [4] ; Auwerx, Johan [1]
Total Authors: 8
Affiliation:
[1] Ecole Polytech Fed Lausanne, Lab Integrat Syst Physiol, CH-1015 Lausanne - Switzerland
[2] CHA Univ, CHA Bundang Med Ctr, Dept Endocrinol & Metab, Sch Med, Seongnam 13497 - South Korea
[3] Gwangju Inst Sci & Technol, Dept Biomed Sci & Engn, Gwangju 61005 - South Korea
[4] Chungnam Natl Univ, Res Ctr Endocrine & Metab Dis, Sch Med, Daejeon 35015 - South Korea
Total Affiliations: 4
Document type: Journal article
Source: CELL REPORTS; v. 34, n. 3 JAN 19 2021.
Web of Science Citations: 0
Abstract

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. (AU)

FAPESP's process: 19/11171-7 - Screening platform for the identification of molecular targets involved in mitochondrial homeostasis
Grantee:Tanes Imamura de Lima
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor