Higher Protein Diets Oppose Changes in Skeletal Muscle Transcriptome with Age (OR18-03-19)

Abstract

ObjectivesAdvancing age during adulthood is associated with deterioration of skeletal muscle (SkM) structure and function (i.e., sarcopenia). Currently, high-protein diets are one of the few recommended therapies to attenuate sarcopenia. However, the mechanisms by which high-protein diets may improve SkM health are not fully understood. The objective of this study was to compare changes in the SkM transcriptome that occur with age (AGE: old vs. young adults) to changes in the SkM transcriptome of older adults in response to protein diets (PROTEIN: high protein vs. low protein diet). MethodsTwo previously published microarray datasets were used for this analysis. The AGE dataset included SkM transcriptomic data from 15 young (25 ± 1 years) and 21 older (78 ± 1 years) adults. The PROTEIN dataset included SkM transcriptomic data obtained from 10 older (72 ± 6 years) adults who consumed either a high (1.0 g protein x kg body wt–1x d–1) or a low (0.5 g protein x kg body wt–1x d–1) protein diet for 18 days. For both studies, morning fasting SkM biopsies were obtained from the vastus lateralis. RNA was extracted, and RNA quality and quantity was checked prior to microarray analysis. A False Discovery Rate correction was used to adjust for multiple comparisons. Differentially expressed genes were uploaded into Ingenuity Pathway Analysis (IPA), and upstream regulators, canonical pathways, and cellular and molecular functions were compared between the AGE and PROTEIN. ResultsThere were 11 common upstream regulators between the AGE and PROTEIN, including TGFB1, CREB1, TP53, ATF4, and FOXO1 that had opposing differences in regulation with the higher protein diet (Table 1). Similarly, there were 4 common canonical pathways between AGE and PROTEIN. Three of the four pathways had opposing changes in regulation including the Sirtuin Signaling, Nucleotide Excision Repair, and Integrin Signaling pathways. Lastly, there were three common Cellular and Molecular Functions (Organismal Death, Apoptosis, Cell Movement), all of which had opposing changes AGE vs. PROTEIN. ConclusionsThese results suggest that high protein diets alter the SkM transcriptome in older adults and may oppose age-related changes in the SkM, particularly those of tissue remodeling, nutrient sensing, and inflammation. Additionally, inadequate protein intake may promote age-related changes in SkM. Funding SourcesNA Supporting Tables, Images and/or Graphs▪