Assessment of biomarkers of protein anabolism in skeletal muscle during the life span of the rat: sarcopenia despite elevated protein synthesis

Abstract

. Assessment of biomarkers of protein anabolism in skeletal muscle during the life span of the rat: sarcopenia despite elevated protein synthesis. Am J Physiol Endocrinol Metab 287: E772-E780, 2004. First published June 8, 2004 10.1152/ajpendo.00535.2003.-Loss of muscle strength is a principal factor in the development of physical frailty, a condition clinically associated with increased risk of bone fractures, impairments in the activities of daily living, and loss of independence in older humans. A primary determinant in the decline in muscle strength that occurs during aging is a loss of muscle mass, which could occur through a reduction in the rate of protein synthesis, an elevation in protein degradation, or a combination of both. In the present study, rates of protein synthesis and the relative expression and function of various biomarkers involved in the initiation of mRNA translation in skeletal muscle were examined at different times throughout the life span of the rat. It was found that between 1 and 6 mo of age, body weight increased fourfold. However, by 6 mo, gastrocnemius protein synthesis and RNA content per gram of muscle were lower than values observed in 1-mo-old rats. Moreover, the relative expression of two proteins involved in the binding of initiator methionyl-tRNA to the 40S ribosomal subunit, eukaryotic initiation factors (eIF)2 and eIF2B, as well as the 70-kDa ribosomal protein S6 kinase, S6K1, was lower at 6 mo compared with 1 mo of age. Muscle mass, protein synthesis, and the aforementioned biomarkers remained unchanged until ϳ21 mo. Between 21 and 24 mo of age, muscle mass decreased precipitously. Surprisingly, during this period protein synthesis, relative RNA content, eIF2B activity, relative eIF2 expression, and S6K1 phosphorylation all increased. The results are consistent with a model wherein protein synthesis is enhanced during aging in a futile attempt to maintain muscle mass. translation initiation; eukaryotic initiation factor; ribosomal protein S6 kinase; aging SARCOPENIA, the disproportionate loss of skeletal muscle that occurs during the last quartile of the life span, has been well documented in many species, including humans (4, 33). A number of physiological factors have been suggested to be involved in sarcopenia, including an age-related reduction of hormones such as growth hormone (22), thyroxine (30), and, in women and men, estrogen and testosterone (29), respectively.

Resistance training and sarcopenia

“…However, although in individuals <80 years of age current research has established the efficacy of progressive resistance training as a method to enhance muscle mass and functional capacity; in older population (≥80 years old) additional evidence is needed examining interThere is some evidence suggesting that during the early phase of sarcopenia, muscle protein synthesis increases, perhaps because the accelerated catabolism makes aminoacids available [3]. This early state is characterized by impaired oxidative defense, decreased activity of mitochondrial enzymes activity and dysregulation of genes implicated in energy metabolism, DNA repair, stress response, immune response, and proteasome-mediated protein degradation [3].…”

“…This early state is characterized by impaired oxidative defense, decreased activity of mitochondrial enzymes activity and dysregulation of genes implicated in energy metabolism, DNA repair, stress response, immune response, and proteasome-mediated protein degradation [3].…”

Human Sarcopenia Reveals an Increase in SOCS-3 and Myostatin and a Reduced Efficiency of Akt Phosphorylation

“…48 In line with this is the recent suggestion that muscle protein synthesis rates may be increased in a futile attempt to maintain muscle mass; however increased levels of protein degradation is the determining factor during sarcopenia. 49 Sarcopenia, unlike severe acute muscle-wasting disorders, such as ALS, is a gradual process. This gradual loss of muscle mass with age may be due to a number of attempted "survival" feedback mechanisms, including increases in the total pool of Akt and GSK-3␤, as well as GSK-3␤ phosphorylation.…”

The Effects of Aging on Muscle Loss and Nuclear Factor Kappa-B Levels in Rats Fed a Diet Containing Suboptimal Leucine Levels

“…Tibialis anterior muscle appeared smaller, but the difference was not significant. Age related decreases in gastrocnemius weight/total body weight have also been found by other investigators (Kimball et al, 2004). Gastrocnemius and soleus muscle size did not increase proportionally with increased body mass during aging.…”

“…(50% smaller gastrocnemius weight/body weight in 27 vs. 12 month old rats). This indicates that muscle loss is occurring without the complete reduction in muscle synthesis potential, and that sarcopenia cannot be completely explained by changes in anabolic conditions (Kimball et al, 2004). Therefore, it is likely that sarcopenia may be due to increased proteolysis.…”