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 journalArticle

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 pro-inflammatory 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)
JournaleLife
Volume8
DOIs
StatePublished - Oct 23 2019

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Spliceosomes
Mitochondria
Proteomics
Muscle
Immunity
Skeletal Muscle
Aging of materials
Alternative Splicing
Muscles
Metabolism
Ribosomal Proteins
Muscle Strength
Adaptive Immunity
Glycolysis
Innate Immunity
Muscle Cells
Proteolysis
Respiration
Proteins
Animal Models

Keywords

  • aging
  • epidemiology
  • global health
  • human
  • human biology
  • medicine
  • mitochondria
  • proteomics
  • proteostasis
  • skeletal muscle
  • spliceosome

ASJC Scopus subject areas

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

Cite this

Ubaida-Mohien, C., Lyashkov, A., Gonzalez-Freire, M., Tharakan, R., Shardell, M., Moaddel, R., ... Ferrucci, L. (2019). Discovery proteomics in aging human skeletal muscle finds change in spliceosome, immunity, proteostasis and mitochondria. eLife, 8. https://doi.org/10.7554/eLife.49874

Discovery proteomics in aging human skeletal muscle finds change in spliceosome, immunity, proteostasis and mitochondria. / Ubaida-Mohien, Ceereena; Lyashkov, Alexey; Gonzalez-Freire, Marta; Tharakan, Ravi; Shardell, Michelle; Moaddel, Ruin; Semba, Richard D.; Chia, Chee W.; Gorospe, Myriam; Sen, Ranjan; Ferrucci, Luigi.

In: eLife, Vol. 8, 23.10.2019.

Research output: Contribution to journalArticle

Ubaida-Mohien, C, Lyashkov, A, Gonzalez-Freire, M, Tharakan, R, Shardell, M, Moaddel, R, Semba, RD, Chia, CW, Gorospe, M, Sen, R & Ferrucci, L 2019, 'Discovery proteomics in aging human skeletal muscle finds change in spliceosome, immunity, proteostasis and mitochondria', eLife, vol. 8. https://doi.org/10.7554/eLife.49874
Ubaida-Mohien C, Lyashkov A, Gonzalez-Freire M, Tharakan R, Shardell M, Moaddel R et al. Discovery proteomics in aging human skeletal muscle finds change in spliceosome, immunity, proteostasis and mitochondria. eLife. 2019 Oct 23;8. https://doi.org/10.7554/eLife.49874
Ubaida-Mohien, Ceereena ; Lyashkov, Alexey ; Gonzalez-Freire, Marta ; Tharakan, Ravi ; Shardell, Michelle ; Moaddel, Ruin ; Semba, Richard D. ; Chia, Chee W. ; Gorospe, Myriam ; Sen, Ranjan ; Ferrucci, Luigi. / Discovery proteomics in aging human skeletal muscle finds change in spliceosome, immunity, proteostasis and mitochondria. In: eLife. 2019 ; Vol. 8.
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