Maintenance of type 2 glycolytic myofibers with age by Mib1-Actn3 axis
Open Access
- 26 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 12 (1), 1-15
- https://doi.org/10.1038/s41467-021-21621-6
Abstract
Age-associated muscle atrophy is a debilitating condition associated with loss of muscle mass and function with age that contributes to limitation of mobility and locomotion. However, the underlying mechanisms of how intrinsic muscle changes with age are largely unknown. Here we report that, with age, Mind bomb-1 (Mib1) plays important role in skeletal muscle maintenance via proteasomal degradation-dependent regulation of α-actinin 3 (Actn3). The disruption of Mib1 in myofibers (Mib1ΔMF) results in alteration of type 2 glycolytic myofibers, muscle atrophy, impaired muscle function, and Actn3 accumulation. After chronic exercise, Mib1ΔMF mice show muscle atrophy even at young age. However, when Actn3 level is downregulated, chronic exercise-induced muscle atrophy is ameliorated. Importantly, the Mib1 and Actn3 levels show clinical relevance in human skeletal muscles accompanied by decrease in skeletal muscle function with age. Together, these findings reveal the significance of the Mib1-Actn3 axis in skeletal muscle maintenance with age and suggest the therapeutic potential for the treatment or amelioration of age-related muscle atrophy.This publication has 77 references indexed in Scilit:
- Identification of morphological markers of sarcopenia at early stage of aging in skeletal muscle of miceExperimental Gerontology, 2016
- Analysis of theACTN3heterozygous genotype suggests that α-actinin-3 controls sarcomeric composition and muscle function in a dose-dependent fashionHuman Molecular Genetics, 2015
- The role of protein clearance mechanisms in organismal ageing and age-related diseasesNature Communications, 2014
- SMASH – semi-automatic muscle analysis using segmentation of histology: a MATLAB applicationSkeletal Muscle, 2014
- Sex hormones and skeletal muscle weaknessBiogerontology, 2013
- Murine models of atrophy, cachexia, and sarcopenia in skeletal muscleBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2013
- Aging and the aggregating proteomeFrontiers in Genetics, 2012
- Sequential stages in the age-dependent gradual formation and accumulation of tubular aggregates in fast twitch muscle fibers: SERCA and calsequestrin involvementAGE, 2011
- An Obligatory Role of Mind Bomb-1 in Notch Signaling of Mammalian DevelopmentPLOS ONE, 2007
- Identification of Ubiquitin Ligases Required for Skeletal Muscle AtrophyScience, 2001