TY - JOUR
T1 - Discovery proteomics in aging human skeletal muscle finds change in spliceosome, immunity, proteostasis and mitochondria
AU - Ubaida-Mohien, Ceereena
AU - Lyashkov, Alexey
AU - Gonzalez-Freire, Marta
AU - Tharakan, Ravi
AU - Shardell, Michelle
AU - Moaddel, Ruin
AU - Semba, Richard D.
AU - Chia, Chee Wei
AU - Gorospe, Myriam
AU - Sen, Ranjan
AU - Ferrucci, Luigi
N1 - Funding Information:
1Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, United States; 2Johns Hopkins Medical Institute, Baltimore, United States
Funding Information:
This work was supported by the Intramural Research Program of the National Institute on Aging, NIH, Baltimore, MD, USA, NIH R01 AG027012, and R01 AG057723. We are grateful to the GESTALT participants and the GESTALT Study Team at Harbor Hospital and NIA, Linda Zukely, and Mary Kaila for sample collection and project coordination. We thank Supriyo De, Yulan Piao and the NIA Sequencing Core Facility for the RNA sample sequencing, library preparation and data generation. We also thank Lauren Brick for assistance with figure design.
Publisher Copyright:
© 2019, eLife Sciences Publications Ltd. All rights reserved.
PY - 2019/10
Y1 - 2019/10
N2 - 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.
AB - 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.
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U2 - 10.7554/eLife.49874
DO - 10.7554/eLife.49874
M3 - Article
C2 - 31642809
AN - SCOPUS:85073760410
SN - 2050-084X
VL - 8
JO - eLife
JF - eLife
M1 - e49874
ER -