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

ABSTRACT: 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.

SUBMITTER: Thalacker-Mercer AE

PROVIDER: S-EPMC2891367 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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

Thalacker-Mercer Anna E AE Fleet James C JC Craig Bruce A BA Campbell Wayne W WW

The Journal of nutritional biochemistry 20100209 11

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 int ...[more]

PMID: 20149619

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Project description:Inadequate protein intake initiates an accommodative response with adverse changes in skeletal muscle function and structure. mRNA level changes due to short-term inadequate dietary protein might be an early indicator of accommodation. The aims of this study were to assess the effects of dietary protein and the diet-by-age interaction on the skeletal muscle transcript profile. Self-organizing maps were used to determine expression patterns across protein trials. 958 transcripts were differentially expressed (P<0.05) with diet and 853 had a diet-by-age interaction (P<0.05) using ANOVA. The results for diet alone revealed that P63 was associated with up-regulation of transcripts related to ubiquitin-dependent protein catabolism and muscle contraction and P63 and P94 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 expression patterns demonstrated that across the three protein trials transcripts related to protein metabolism were affected by age. Changes in skeletal muscle mRNA levels in the younger and older males to protein intake near or below the RDA are indicative of an early accommodative response. 5052 transcripts were determined as differentially expressed (P<0.05) between the younger and older males, of which 2556 met the False Discovery Rate correction (P=0.0081). The age-related changes in the transcript profile were consistent with aging skeletal muscle phenotypes including; mitochondrial dysfunction (UP- and DOWN-regulation), RNA splicing (UP), oxidative stress (UP), apoptosis (UP), and energy metabolism (DOWN). Experiment Overall Design: 22 healthy free-living younger (21-43 y, n=12) and older (63-79 y, n=10) males completed three controlled feeding trials with protein intakes of 63% (P63: 0.50 g/kg), 94% (P94: 0.75 g/kg), and 125% (P125: 1.00 g/kg) of the recommended dietary allowance (RDA). A fasting state vastus lateralis biopsy was taken from the dominant leg of each subject on day 12 of each trial following an overnight fast. Total RNA was isolated from the muscle samples using Tri-Reagent and the manufacture's protocol.

Project description:BACKGROUND:Inadequate dietary protein intake causes adverse changes in the morphology and function of skeletal muscle. These changes may be reflected in early alterations in muscle messenger RNA levels. OBJECTIVE:This study assessed whether inadequate protein intake differentially affects skeletal muscle transcript concentrations and expression profiles in older adults. DESIGN:Twenty-one older men and women (aged 55-80 y) consumed controlled diets that provided 1.2 g protein x kg(-1) x d(-1) (adequate protein) for 1 wk and then were randomly assigned to consume either 0.5 g protein x kg(-1) x d(-1) [inadequate protein (IP) group; n=11] or 1.2 g protein x kg(-1) x d(-1) (control group; n=10) for a second week. RNA was isolated from fasting-state vastus lateralis biopsy samples obtained at the end of each period, and transcript levels in the IP group were measured by using microarray analysis. Changes in selected transcript levels were confirmed by real-time polymerase chain reaction in both groups. RESULTS:Analysis of variance showed 529 differentially expressed transcripts (P<0.05) after inadequate protein intake. Using the false discovery rate (FDR) correction to adjust for multiple comparisons, we observed that 85 transcripts were differentially expressed: 54 were up-regulated and 31 were down-regulated. The differentially expressed transcripts were in functional classes for immune, inflammatory, and stress responses (predominantly up-regulated); contraction, movement, and development (up-regulated); extracellular connective tissue (up-regulated); energy metabolism (down-regulated); protein synthesis (down-regulated); and proliferation (down-regulated). Diet-related differences in the expression of 9 transcripts were cross-validated by using real-time polymerase chain reaction. CONCLUSION:The results document changes in skeletal muscle transcript levels induced by short-term inadequate protein intakes in older humans that might precede adverse metabolic, functional, and structural events, including muscle wasting.

Project description:BackgroundDue to the interaction between skeletal muscle ageing and lifestyle factors, it is often challenging to attribute the decline in muscle mass and quality to either changes in lifestyle or to advancing age itself. Because many of the physiological factors affecting muscle mass and quality are modulated by physical activity and physical activity declines with age, the aim of this study is to better understand the effects of early ageing on muscle function by comparing a population of healthy older and young males with similar physical activity patterns.MethodsEighteen older (69 ± 2.0 years) and 20 young (22 ± 2.0 years) males were recruited based on similar self-reported physical activity, which was verified using accelerometry measurements. Gene expression profiles of vastus lateralis biopsies obtained by RNA sequencing were compared, and key results were validated using quantitative polymerase chain reaction and western blot.ResultsTotal physical activity energy expenditure was similar between the young and old group (404 ± 215 vs. 411 ± 189 kcal/day, P = 0.11). Three thousand seven hundred ninety-seven differentially expressed coding genes (DEGs) were identified (adjusted P-value cut-off of <0.05), of which 1891 were higher and 1906 were lower expressed in the older muscle. The matrisome, innervation and inflammation were the main upregulated processes, and oxidative metabolism was the main downregulated process in old compared with young muscle. Lower protein levels of mitochondrial transcription factor A (TFAM, P = 0.030) and mitochondrial respiratory Complexes IV and II (P = 0.011 and P = 0.0009, respectively) were observed, whereas a trend was observed for Complex I (P = 0.062), in older compared with young muscle. Protein expression of Complexes I and IV was significantly correlated to mitochondrial capacity in the vastus lateralis as measured in vivo (P = 0.017, R2 = 0.42 and P = 0.030, R2 = 0.36). A trend for higher muscle-specific receptor kinase (MUSK) protein levels in the older group was observed (P = 0.08).ConclusionsThere are clear differences in the transcriptome signatures of the vastus lateralis muscle of healthy older and young males with similar physical activity levels, including significant differences at the protein level. By disentangling physical activity and ageing, we appoint early skeletal muscle ageing processes that occur despite similar physical activity. Improved understanding of these processes will be key to design targeted anti-ageing therapies.

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

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

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