4.5 Article

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

Journal

RNA BIOLOGY
Volume 18, Issue 11, Pages 1555-1559

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/15476286.2021.1875647

Keywords

Ageing; skeletal muscle; translation regulation; ribosome profiling

Funding

  1. Intramural Program of the National Institutes of Aging

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As human muscle ages, the translation of proteins related to oxidative phosphorylation, especially those encoded by the mitochondrial genome, decreases, potentially leading to reduced strength and function in old skeletal muscle.
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.

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