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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: CELL REPORTS; v. 34, n. 3 JAN 19 2021.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 19/11171-7 - Plataforma de triagem para a identificação de alvos moleculares envolvidos na homeostase mitocondrial
• Beneficiário: Tanes Imamura de Lima
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado