Using nuclear envelope mutations to explore age-related skeletal muscle weakness.

Edmund Battey,Julien Ochala,Matthew J Stroud

doi:10.1042/cs20190066

Edmund Battey, Julien Ochala + Show 1 more

Open Access

https://doi.org/10.1042/cs20190066

Copy DOI

Journal: Clinical Science	Publication Date: Aug 26, 2020
Citations: 17	License type: CC BY 4.0

Affiliation: King's College London, University of Copenhagen

Abstract

Skeletal muscle weakness is an important determinant of age-related declines in independence and quality of life but its causes remain unclear. Accelerated ageing syndromes such as Hutchinson–Gilford Progerin Syndrome, caused by mutations in genes encoding nuclear envelope proteins, have been extensively studied to aid our understanding of the normal biological ageing process. Like several other pathologies associated with genetic defects to nuclear envelope proteins including Emery–Dreifuss muscular dystrophy, Limb–Girdle muscular dystrophy and congenital muscular dystrophy, these disorders can lead to severe muscle dysfunction. Here, we first describe the structure and function of nuclear envelope proteins, and then review the mechanisms by which mutations in genes encoding nuclear envelope proteins induce premature ageing diseases and muscle pathologies. In doing so, we highlight the potential importance of such genes in processes leading to skeletal muscle weakness in old age.

Highlights

The human lifespan has increased substantially over the past half-century and this trend is projected to continue well into the 21st century [1]
We describe the mechanisms by which mutations in genes encoding these nuclear envelope proteins induce premature ageing diseases and muscle pathologies
We suggest how this knowledge could be used to unveil the key determinants of skeletal muscle weakness in old age

Summary

Introduction

The human lifespan has increased substantially over the past half-century and this trend is projected to continue well into the 21st century [1]. HGPS and other related disorders such as Emery–Dreifuss muscular dystrophy, Limb–Girdle muscular dystrophy and congenital muscular dystrophy can lead to severe muscle pathologies resembling muscle weakness in old age, suggesting how modifications in the nuclear envelope may alter skeletal muscle development and function. We describe the mechanisms by which mutations in genes encoding these nuclear envelope proteins induce premature ageing diseases and muscle pathologies.

Results

Conclusion