Discovery proteomics in aging human skeletal muscle finds change in spliceosome, immunity, proteostasis and mitochondria

Ceereena Ubaida-Mohien, Alexey Lyashkov, Marta Gonzalez-Freire, Ravi Tharakan, Michelle Shardell, Ruin Moaddel, Richard D. Semba, Chee W. Chia, Myriam Gorospe, Ranjan Sen, Luigi Ferrucci

Research output: Contribution to journalArticlepeer-review

Abstract

A decline of skeletal muscle strength with aging is a primary cause of mobility loss and frailty in older persons, but the molecular mechanisms of such decline are not understood. Here, we performed quantitative proteomic analysis from skeletal muscle collected from 58 healthy persons aged 20 to 87 years. In muscle from older persons, ribosomal proteins and proteins related to energetic metabolism, including those related to the TCA cycle, mitochondria respiration, and glycolysis, were underrepresented, while proteins implicated in innate and adaptive immunity, proteostasis, and alternative splicing were overrepresented. Consistent with reports in animal models, older human muscle was characterized by deranged energetic metabolism, a proinflammatory environment and increased proteolysis. Changes in alternative splicing with aging were confirmed by RNA-seq analysis. We propose that changes in the splicing machinery enables muscle cells to respond to a rise in damage with aging.

Original languageEnglish (US)
Article numbere49874
JournaleLife
Volume8
DOIs
StatePublished - Oct 2019

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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