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

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

SUBMITTER: Romani M 

PROVIDER: S-EPMC7816122 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature