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Regulation of Amino Acid Transporters and Sensors in Response to a High protein Diet: A Randomized Controlled Trial in Elderly Men.

The journal of nutrition, health & aging
May 5, 2019
N Zeng et al. (13 authors)
Journal ArticleRandomized Controlled TrialResearch Support, Non-U.S. Gov'tHuman StudyClinical
Study Details

Study Goal

The researchers aimed to determine whether consuming twice the recommended daily allowance (RDA) of protein affects the expression of amino acid transporters, sensors, and mTORC1 activity in older men.

Results Summary

Consuming twice the RDA of protein reduced LAT1 expression but did not alter mTORC1 activity or plasma leucine levels. Total RPS6 increased, suggesting potential improvements in muscular translational capacity.

Population

Older men aged 70-81 years.

Effective Dosage

0.8 g/kg/d (RDA) and 1.6 g/kg/d (2RDA).

Duration

10 weeks.

Interactions

None mentioned.

Extracted Claims (7)
InterventionDirectionEndpointPopulationDosageImpactClaim #
consumption of a diet containing twice the recommended daily allowance (RDA) of protein intake (2RDA) for ten weeks
decrease
protein expression of L-type amino acid transporter 1 (LAT1)
26 older men (70-81 years)
-
reduced
#1
consumption of a diet containing twice the recommended daily allowance (RDA) of protein intake (2RDA) for ten weeks
no change
plasma leucine concentration
26 older men (70-81 years)
-
unaltered
#2
consumption of a diet containing twice the recommended daily allowance (RDA) of protein intake (2RDA) for ten weeks
no change
basal mTORC1 activity
26 older men (70-81 years)
-
unaltered
#3
consumption of a diet containing twice the recommended daily allowance (RDA) of protein intake (2RDA) for ten weeks
no change
expression of AA sensors and mediators, including leucyl tRNA synthetase (LRS), cytosolic arginine sensor for mTORC1 (CASTOR1), Sestrin2 and Rag proteins
26 older men (70-81 years)
-
did not affect
#4
consumption of a diet containing twice the recommended daily allowance (RDA) of protein intake (2RDA) for ten weeks
increase
total ribosomal protein S6 (RPS6)
26 older men (70-81 years)
-
upregulated
#5
Ten weeks of 2RDA diet
no change
fasting mTORC1 signaling
26 older men (70-81 years)
-
did not affect
#6
Ten weeks of 2RDA diet
increase
total RPS6
26 older men (70-81 years)
-
increased
#7
Abstract

BACKGROUND: The mammalian target of rapamycin complex 1 (mTORC1) is fundamental for many cellular processes, yet it is often dysregulated with aging. Increased amino acid (AA) availability is correlated with the expression of AA transporters (AAT) and mTORC1 activity. Although many AA sensors and mediators have been proposed to relay the AA signal to mTORC1, it has not yet been determined if chronic dietary intervention affects the expression of AAT, sensors and mediators and their relationships with mTORC1 activity. OBJECTIVE AND DESIGN: This study investigated whether the consumption of a diet containing either the current recommended daily allowance (RDA) of protein intake (0.8 g/kg/d) or twice the RDA (2RDA) for ten weeks affected the expression of targets associated with AA transport, sensing and mTORC1 regulation in 26 older men (70-81 years). METHOD: Muscle biopsies were collected before and after the intervention under fasting conditions. Diets were controlled by providing fully prepared meals and snacks. Western blot and quantitative polymerase chain reaction were used to measure protein and gene expression respectively. RESULTS: Consumption of 2RDA reduced the protein expression of L-type amino acid transporter 1 (LAT1). However, plasma leucine concentration and basal mTORC1 activity were unaltered. The downregulation of LAT1 did not affect the expression of AA sensors and mediators, including leucyl tRNA synthetase (LRS), cytosolic arginine sensor for mTORC1 (CASTOR1), Sestrin2 and Rag proteins. Instead, total ribosomal protein S6 (RPS6) was upregulated with 2RDA. CONCLUSION: Ten weeks of 2RDA diet did not affect the fasting mTORC1 signaling, but increased total RPS6 might suggest improved muscular translational capacity to maintain muscular mass.

Medical Subject Headings (MeSH)
AgedAged, 80 and overAgingBody Mass IndexDiet, High-ProteinHumansIntracellular Signaling Peptides and ProteinsLarge Neutral Amino Acid-Transporter 1LeucineMaleMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesMuscle, SkeletalRecommended Dietary AllowancesRibosomal Protein S6Signal Transduction
Study Links
Quality Scores
Safety85
Efficacy70/10
Quality80/10
Citation Metrics
Total Citations5
Citations/Year0.8
Relative Citation Ratio0.29
NIH Percentile15.2%
Research Impact Scores
APT Score0.25
Weight Score2.06
Normalized Score0.78
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