PT  - JOURNAL ARTICLE
AU  - Ceereena Ubaida-Mohien
AU  - Alexey Lyashkov
AU  - Marta Gonzalez-Freire
AU  - Ravi Tharakan
AU  - Michelle Shardell
AU  - Ruin Moaddel
AU  - Richard D. Semba
AU  - Chee W. Chia
AU  - Myriam Gorospe
AU  - Ranjan Sen
AU  - Luigi Ferrucci
TI  - Aging Skeletal Muscle Proteomics Finds Changes in Spliceosome, Immune factors, Proteostasis and Mitochondria
AID  - 10.1101/700468
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 700468
4099  - http://biorxiv.org/content/early/2019/07/11/700468.short
4100  - http://biorxiv.org/content/early/2019/07/11/700468.full
AB  - A progressive 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 fully understood. Here, using quantitative discovery proteomic data from skeletal muscle specimens collected from 58 healthy persons aged 20 to 87 years show that ribosomal proteins and proteins related to energetic metabolism, including those related to the TCA cycle, mitochondria respiration, and glycolysis were underrepresented in older persons. Proteins with important roles in innate and adaptive immunity, involved in proteostasis and regulation of alternative splicing were all overrepresented in muscle from older persons. Changes with aging of alternative splicing were confirmed by RNA-seq. Overall, older muscle has a profound deficit of energetic metabolism, a pro-inflammatory environment and increased proteostasis. Upregulation of the splicing machinery maybe an attempt to compensate for these changes and this could be tested in future studies.