The Impact Of Age On The Transcriptional And Morphological Profile Of Skeletal Muscle

Abstract

Aging is associated with many physiological changes that impact physical function. Most notably, older adults experience a progressive loss of skeletal muscle mass and function, termed sarcopenia. A better understanding of the molecular and phenotypical changes associated with advancing age may provide therapeutic targets for interventions to slow the progression of sarcopenia. PURPOSE: To characterize the transcriptional and morphological profile of aging skeletal muscle. METHODS: Resting vastus lateralis muscle biopsies were collected from 9 young (Y; 27±3yr, 179±7cm, 82±10kg, 26±3BMI) and 9 older adults (O; 68±5yr, 172±8cm, 77±19kg, 26±5BMI) following an overnight fast. Whole transcriptome next-generation RNA sequencing was performed on cDNA synthesized from skeletal muscle RNA. Differentially expressed genes (FDR-adjusted P-value ≤ 0.05) were identified through DESeq2 and subjected to bioinformatic analyses using DAVID (v6.8). Skeletal muscle morphology including fiber type, satellite cell (SC) content, and capillarization was assessed through immunofluorescent microscopy RESULTS: In total, 900 differentially expressed genes were identified in the skeletal muscle of O versus Y (+1.5 fold change = 213; -1.5 fold change = 127). DAVID functional analyses indicated that aging was associated with functions related to glycogen metabolism, amino acid metabolism, ubiquitination, and transition between fast and slow fibers. Consistent with the latter, a significant difference (P=0.048) in myosin heavy chain (MyHC) fiber type profile was identified (Y = MyHCI: 29±4%, MyHCII: 71±4%; O = MyHCI: 46±7%, MyHCII: 54±7%). Moreover, aging was associated with a numerical reduction in SC specific to MyHCI (Y = 0.13±0.02, O = 0.07±0.02 SC/MyHCI fiber, P=0.07) but not MyHCII fibers (Y=0.12±0.03, O=0.08±0.02 P=0.373). Independent of fiber type, capillaries per fiber was significantly lower (P=0.015) in O (1.53±0.34) vs. Y (4.59±0.85). CONCLUSION: Advancing age is associated with changes in the transcriptional and morphological profile of skeletal muscle. These findings highlight potential therapeutic targets for the preservation of skeletal muscle mass and function with advancing age. Supported by a JumpStart Grant, CHS, ASU.