The skeletal muscle transcript profile reflects accommodative responses to inadequate protein intake in younger and older males.

Inadequate protein intake initiates adverse changes in skeletal muscle function and structure (i.e., an accommodative response). mRNA level changes due to short-term inadequate dietary protein might be an early indication of subsequent accommodation. The aims of this study were to assess the effects of dietary protein and the diet-by-age interaction on the skeletal muscle transcriptome. Twelve younger (21-43 y) and 10 older (63-79 y) men completed three controlled feeding trials with protein intakes of 0.50 (LPro: lower protein), 0.75 (MPro: medium protein) and 1.00 g protein·kg body weight⁻¹·day⁻¹ (HPro: higher protein). A fasting state biopsy was taken on Day 12 of each trial. Global changes in transcript levels were assessed with Affymetrix genechips and expression patterns determined using self-organizing maps. Nine hundred fifty-eight transcripts were differentially expressed (P<.05) by diet and 853 had a diet-by-age interaction (P<.05). The results for diet alone revealed that LPro was associated with up-regulation of transcripts related to ubiquitin-dependent protein catabolism and muscle contraction and LPro and MPro resulted in up-regulation of transcripts related to apoptosis and down-regulation of transcripts related to cell differentiation, muscle and organ development, extracellular space and responses to stimuli and stress. The diet-by-age effect on protein modification transcripts was consistent with the older males being less responsive to anabolic stimuli (lower protein synthesis at HPro) and more responsive to a catabolic state (protein breakdown at LPro). Changes in skeletal muscle mRNA levels in younger and older males to protein intake near or below the recommended dietary allowance are indicative of an early accommodative response.