Ribosome profiling analysis of human skeletal muscle identifies reduced translation of mitochondrial proteins with age

RNA Biol. 2021 Nov;18(11):1555-1559. doi: 10.1080/15476286.2021.1875647. Epub 2021 Jan 21.

Abstract

With advancing age, human muscle loses strength and function, but the molecular causes of these losses are unknown. Skeletal muscle shows an age-dependent decline in the levels of different proteins, but whether such decline is associated with reduced translation has not been studied. To address this gap of knowledge, we used the technique of ribosome profiling to study translation in muscle from middle-aged and old individuals. Using ribosome occupancy as a measure of translation status, several mRNAs showed differential translation with age. Older age was associated with lower translation of myosin and titin isoforms and more broadly with the translation of proteins involved in oxidative phosphorylation encoded by the mitochondrial genome. Based on our findings, we propose that mitochondrial proteins are less translated in old skeletal muscle.

Keywords: Ageing; ribosome profiling; skeletal muscle; translation regulation.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Age Factors
  • Aged, 80 and over
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology*
  • Oxidative Phosphorylation
  • Protein Biosynthesis*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Ribosomes / genetics
  • Ribosomes / metabolism*

Substances

  • Mitochondrial Proteins
  • RNA, Messenger

Grants and funding

This research was supported by the Intramural Program of the National Institutes of Aging.