Protein Metabolism and Age: Influence of Insulin and Resistance Exercise

2001 ◽  
Vol 11 (s1) ◽  
pp. S150-S163 ◽  
Author(s):  
Peter A. Farrell
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Resistance Exercise ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mrna Translation ◽  
Bed Rest ◽  
Skeletal Muscle Protein ◽  
Amino Acid Availability ◽  
Effects Of Aging

Skeletal muscle proteins are constantly being synthesized and degraded, and the net balance between synthesis and degradation determines the resultant muscle mass. Biochemical pathways that control protein synthesis are complex, and the following must be considered: gene transcription, mRNA splicing, and transport to the cytoplasm; specific amino acyl-tRNA, messenger (mRNA), ribosomal (rRNA) availability; amino acid availability within the cell; the hormonal milieu; rates of mRNA translation; packaging in vesicles for some types of proteins; and post-translational processing such as glycation and phosphorylation/dephosphorylation. Each of these processes is responsive to the need for greater or lesser production of new proteins, and many states such as sepsis, uncontrolled diabetes, prolonged bed-rest, aging, chronic alcohol treatment, and starvation cause marked reductions in rates of skeletal muscle protein synthesis. In contrast, acute and chronic resistance exercise cause elevations in rates of muscle protein synthesis above rates found in nondiseased rested organisms, which are normally fed. Resistance exercise may be unique in this capacity. This chapter focuses on studies that have used exercise to elucidate mechanisms that explain elevations in rates of protein synthesis. Very few studies have investigated the effects of aging on these mechanisms; however, the literature that is available is reviewed.

scholarly journals Resistance exercise maintains skeletal muscle protein synthesis during bed rest

1997 ◽  
Vol 82 (3) ◽  
pp. 807-810 ◽  
Author(s):  
Arny A. Ferrando ◽  
Kevin D. Tipton ◽  
Marcas M. Bamman ◽  
Robert R. Wolfe
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Resistance Training ◽  
Resistance Exercise ◽  
Lean Body Mass ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Bed Rest ◽  
Skeletal Muscle Protein ◽  
Skeletal Muscle Protein Synthesis

Ferrando, Arny A., Kevin D. Tipton, Marcas M. Bamman, and Robert R. Wolfe. Resistance exercise maintains skeletal muscle protein synthesis during bed rest. J. Appl. Physiol. 82(3): 807–810, 1997.—Spaceflight results in a loss of lean body mass and muscular strength. A ground-based model for microgravity, bed rest, results in a loss of lean body mass due to a decrease in muscle protein synthesis (MPS). Resistance training is suggested as a proposed countermeasure for spaceflight-induced atrophy because it is known to increase both MPS and skeletal muscle strength. We therefore hypothesized that scheduled resistance training throughout bed rest would ameliorate the decrease in MPS. Two groups of healthy volunteers were studied during 14 days of simulated microgravity. One group adhered to strict bed rest (BR; n = 5), whereas a second group engaged in leg resistance exercise every other day throughout bed rest (BREx; n = 6). MPS was determined directly by the incorporation of infusedl-[ ring-13C6]phenylalanine into vastus lateralis protein. After 14 days of bed rest, MPS in the BREx group did not change and was significantly greater than in the BR group. Thus moderate-resistance exercise can counteract the decrease in MPS during bed rest.

Prolonged bed rest decreases skeletal muscle and whole body protein synthesis

1996 ◽  
Vol 270 (4) ◽  
pp. E627-E633 ◽  
Author(s):  
A. A. Ferrando ◽  
H. W. Lane ◽  
C. A. Stuart ◽  
J. Davis-Street ◽  
R. R. Wolfe
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Bed Rest ◽  
Whole Body ◽  
Protein Breakdown ◽  
Skeletal Muscle Protein ◽  
Model Calculations ◽  
Body Protein

We sought to determine the extent to which the loss of lean body mass and nitrogen during inactivity was due to alterations in skeletal muscle protein metabolism. Six male subjects were studied during 7 days of diet stabilization and after 14 days of stimulated microgravity (-6 degrees bed rest). Nitrogen balance became more negative (P < 0.03) during the 2nd wk of bed rest. Leg and whole body lean mass decreased after bed rest (P < 0.05). Serum cortisol, insulin, insulin-like growth factor I, and testosterone values did not change. Arteriovenous model calculations based on the infusion of L-[ring-13C6]-phenylalanine in five subjects revealed a 50% decrease in muscle protein synthesis (PS; P < 0.03). Fractional PS by tracer incorporation into muscle protein also decreased by 46% (P < 0.05). The decrease in PS was related to a corresponding decrease in the sum of intracellular amino acid appearance from protein breakdown and inward transport. Whole body protein synthesis determined by [15N]alanine ingestion on six subjects also revealed a 14% decrease (P < 0.01). Neither model-derived nor whole body values for protein breakdown change significantly. These results indicate that the loss of body protein with inactivity is predominantly due to a decrease in muscle PS and that this decrease is reflected in both whole body and skeletal muscle measures.

TNF-α impairs heart and skeletal muscle protein synthesis by altering translation initiation

2002 ◽  
Vol 282 (2) ◽  
pp. E336-E347 ◽  
Author(s):  
Charles H. Lang ◽  
Robert A. Frost ◽  
Angus C. Nairn ◽  
David A. MacLean ◽  
Thomas C. Vary
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Translation Initiation ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mrna Translation ◽  
Translational Efficiency ◽  
Skeletal Muscle Protein ◽  
Phosphorylation State ◽  
Tnf Α

This study examined potential mechanisms contributing to the inhibition of protein synthesis in skeletal muscle and heart after administration of tumor necrosis factor (TNF)-α. Rats had vascular catheters implanted, and TNF-α was infused continuously for 24 h. TNF-α decreased in vivo-determined rates of global protein synthesis in gastrocnemius (39%) and heart (25%). The TNF-α-induced decrease in protein synthesis in the gastrocnemius involved a reduction in the synthesis of both myofibrillar and sarcoplasmic proteins. To identify potential mechanisms responsible for regulating mRNA translation, we examined several eukaryotic initiation factors (eIFs) and elongation factors (eEFs). TNF-α decreased the activity of eIF-2B in muscle (39%) but not in heart. This diminished activity was not caused by a reduction in the content of eIF-2Bε or the content and phosphorylation state of eIF-2α. Skeletal muscle and heart from TNF-α-treated rats demonstrated 1) an increased binding of the translation repressor 4E-binding protein-1 (4E-BP1) with eIF-4E, 2) a decreased amount of eIF-4E associated with eIF-4G, and 3) a decreased content of the hyperphosphorylated γ-form of 4E-BP1. In contrast, the infusion of TNF-α did not alter the content of eEF-1α or eEF-2, or the phosphorylation state of eEF-2. In summary, these data suggest that TNF-α impairs skeletal muscle and heart protein synthesis, at least in part, by decreasing mRNA translational efficiency resulting from an impairment in translation initiation associated with alterations in eIF-4E availability.

scholarly journals Nutritional and contractile regulation of human skeletal muscle protein synthesis and mTORC1 signaling

2009 ◽  
Vol 106 (4) ◽  
pp. 1374-1384 ◽  
Author(s):  
Micah J. Drummond ◽  
Hans C. Dreyer ◽  
Christopher S. Fry ◽  
Erin L. Glynn ◽  
Blake B. Rasmussen
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Resistance Exercise ◽  
Human Skeletal Muscle ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Essential Amino Acids ◽  
Skeletal Muscle Protein ◽  
Mtorc1 Signaling

In this review we discuss current findings in the human skeletal muscle literature describing the acute influence of nutrients (leucine-enriched essential amino acids in particular) and resistance exercise on muscle protein synthesis and mammalian target of rapamycin complex 1 (mTORC1) signaling. We show that essential amino acids and an acute bout of resistance exercise independently stimulate human skeletal muscle protein synthesis. It also appears that ingestion of essential amino acids following resistance exercise leads to an even larger increase in the rate of muscle protein synthesis compared with the independent effects of nutrients or muscle contraction. Until recently the cellular mechanisms responsible for controlling the rate of muscle protein synthesis in humans were unknown. In this review, we highlight new studies in humans that have clearly shown the mTORC1 signaling pathway is playing an important regulatory role in controlling muscle protein synthesis in response to nutrients and/or muscle contraction. We propose that essential amino acid ingestion shortly following a bout of resistance exercise is beneficial in promoting skeletal muscle growth and may be useful in counteracting muscle wasting in a variety of conditions such as aging, cancer cachexia, physical inactivity, and perhaps during rehabilitation following trauma or surgery.

Skeletal muscle protein synthesis and the abundance of the mRNA translation initiation repressor PDCD4 are inversely regulated by fasting and refeeding in rats

2011 ◽  
Vol 300 (6) ◽  
pp. E986-E992 ◽  
Author(s):  
Sana Zargar ◽  
Tracy S. Moreira ◽  
Helena Samimi-Seisan ◽  
Senthure Jeganathan ◽  
Dhanshri Kakade ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mammalian Target Of Rapamycin ◽  
Mrna Translation ◽  
Male Rats ◽  
Skeletal Muscle Protein ◽  
Programmed Cell Death 4 ◽  
In Cells

Optimal skeletal muscle mass is vital to human health, because defects in muscle protein metabolism underlie or exacerbate human diseases. The mammalian target of rapamycin complex 1 is critical in the regulation of mRNA translation and protein synthesis. These functions are mediated in part by the ribosomal protein S6 kinase 1 (S6K1) through mechanisms that are poorly understood. The tumor suppressor programmed cell death 4 (PDCD4) has been identified as a novel substrate of S6K1. Here, we examined 1) the expression of PDCD4 in skeletal muscle and 2) its regulation by feed deprivation (FD) and refeeding. Male rats (∼100 g; n = 6) were subjected to FD for 48 h; some rats were refed for 2 h. FD suppressed muscle fractional rates of protein synthesis and Ser67 phosphorylation of PDCD4 (−50%) but increased PDCD4 abundance ( P < 0.05); refeeding reversed these changes ( P < 0.05). Consistent with these effects being regulated by S6K1, activation of this kinase was suppressed by FD (−91%, P < 0.05) but was increased by refeeding. Gavaging rats subjected to FD with a mixture of amino acids partially restored muscle fractional rates of protein synthesis and reduced PDCD4 abundance relative to FD. Finally, when myoblasts were grown in amino acid- and serum-free medium, phenylalanine incorporation into proteins in cells depleted of PDCD4 more than doubled the values in cells with a normal level of PDCD4 ( P < 0.0001). Thus feeding stimulates fractional protein synthesis in skeletal muscle in parallel with the reduction of the abundance of this mRNA translation inhibitor.

scholarly journals Artificial gravity maintains skeletal muscle protein synthesis during 21 days of simulated microgravity

2009 ◽  
Vol 107 (1) ◽  
pp. 34-38 ◽  
Author(s):  
T. B. Symons ◽  
M. Sheffield-Moore ◽  
D. L. Chinkes ◽  
A. A. Ferrando ◽  
D. Paddon-Jones
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Vastus Lateralis ◽  
Bed Rest ◽  
Artificial Gravity ◽  
Skeletal Muscle Protein ◽  
Longitudinal Loading ◽  
Breakdown Rates

We sought to determine the effects of longitudinal loading (artificial gravity) on skeletal muscle protein kinetics in 15 healthy young males after 21 days of 6° head-down tilt bed rest [experimental treatment (Exp) group: n = 8, 31 ± 1 yr; control (Con) group; n = 7, 28 ± 1 yr, means ± SE]. On days 1 and 21 of bed rest, postabsorptive venous blood samples and muscle biopsies (vastus lateralis and soleus) were obtained during a 1-h pulse bolus infusion protocol (0 min, l-[ ring-13C6]phenylalanine, 35 μmol/kg; 30 min, l-[ ring-15N]phenylalanine, 35 μmol/kg). Outcome measures included mixed muscle fractional synthesis (FSR) and breakdown rates (FBR). The Exp group experienced 1 h of longitudinal loading (2.5G at the feet) via a short-radius centrifuge during each day of bed rest. Mixed muscle FSR in the Con group was reduced by 48.5% ( day 1, 0.081 ± 0.000%/h vs. day 21, 0.042 ± 0.000%/h; P = 0.001) in vastus lateralis after 21 days of bed rest, whereas the Exp group maintained their rate of protein synthesis. A similar but nonsignificant change in FSR was noted for the soleus muscle (Exp, −7%; Con, −22%). No changes in muscle protein breakdown were observed. In conclusion, 1 h of daily exposure to artificial gravity maintained the rate of protein synthesis of the vastus lateralis and may represent an effective adjunct countermeasure to combat the loss of muscle mass and functional during extended spaceflight.

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