The effects of dietary protein and age on albumin and the skeletal muscle transcript profile
Abstract
Aging is associated with changes in protein metabolism and multiple physiological and functional alterations in the skeletal muscle which are accentuated by decreased dietary protein intake. Protein and its components, amino acids, play many functional, structural, and metabolic roles in the body; therefore, an adequate dietary protein intake is essential for overall health. Researchers have not definitively determined if the Recommended Dietary Allowance (RDA) for protein of 0.8 g protein•kg body weight-1•day -1 is adequate for older adults. Albumin has been used as a crude indicator of protein status, and transcript profiling is a potential tool to identify adverse changes in the skeletal muscle. To assess the effects of age and dietary protein intake on the hepatic fractional synthesis rate (FSR) of albumin, healthy younger (21-43 y) and older (63-79 y) males and females completed three, 18-d controlled feeding trials with protein intakes of 63% (P63), 94% (P94), and 125% (P125) of the RDA for protein. On day 12 of each trial, postabsorptive and postprandial albumin FSR were estimated from the rates of L-[1-13C] leucine incorporation into plasma albumin during an 8-h infusion. There were no age-related differences in postabsorptive and postprandial albumin FSR. Postprandial albumin FSR was higher than postabsorptive FSR (P<0.0001), and the change from postabsorptive to postprandial states was greater as dietary protein intake increased from P63 and P94 to P125 (P<0.05). Independent of protein intake, males had a higher albumin FSR (P<0.05) and a greater increase in albumin FSR with nutrient ingestion (P<0.05). Age and dietary protein intake did not affect serum albumin concentration. Males had a higher albumin concentration than females (P<0.0001). The results demonstrate that the FSR of albumin responds comparably to nutrient ingestion and dietary protein intake in younger and older adults. Males have a higher albumin concentration, which might be established by a greater albumin synthesis rate. The effect of dietary protein intake on the transcript profile was assessed in older (55-80 y) males and females who consumed controlled diets containing 1.20 g•kg-1•d-1 for one week followed by 0.50 g•kg-1•d-1 (inadequate protein intake) for one week. Diet-related differentially expressed transcripts were identified with ANOVA and false discovery rate correction (529: P<0.05 and 85: P=0.0006, respectively). There was up-regulation of transcripts related to immune, inflammatory, and stress responses; contraction, movement, and development; and extracellular connective tissue and down-regulation of transcripts related to energy metabolism, protein synthesis, and proliferation. Changes in skeletal muscle transcript levels following one week of inadequate dietary protein intake could precede adverse changes in skeletal muscle metabolism, function, and structure. A second transcript profiling study was conducted to assess the effects of dietary protein intake on the transcript profile and to determine how age affects the dietary protein related changes. Vastus lateralis muscle biopsies were taken in the fasting state on day 12 from the male subjects who participated in the albumin study (described above). ANOVA revealed 958 transcripts that were differentially expressed (P<0.05) with diet and 853 transcripts with a diet-by-age interaction (P<0.05). The results for diet revealed that lower protein intake was associated with up-regulation of transcripts related to ubiquitin-dependent protein catabolism, muscle contraction, and apoptosis and down-regulation of transcripts related to muscle and organ development, cell differentiation, extracellular space, and responses to stimuli and stress. The results from the diet-by-age interaction showed that younger and older males had comparable mean expression for transcripts related to protein metabolism after the P125 diet, but had a differential response to the P63 and P94 diets. Changes in skeletal muscle mRNA levels in the younger and older males to protein intakes near or below the RDA could be the first indication of an accommodative response to inadequate protein intake and the potential for preferred responses to protein intake above the RDA. The transcript profiles from one and two weeks of inadequate protein intake were not consistent and the transcript profile after two weeks of inadequate protein more closely resembled an accommodative response. In conclusion, younger and older adults have comparable changes in albumin synthesis rates with dietary protein intake and nutrient ingestion. The transcript profile for both studies suggests that protein intake near or below the RDA has the potential for adverse changes in skeletal muscle structure and function and, therefore, protein intake above the RDA might be advantageous.
Degree
Ph.D.
Advisors
Campbell, Purdue University.
Subject Area
Nutrition
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