Secondary Logo

Journal Logo

Original Article

Molecular Attributes of Human Skeletal Muscle at Rest and After Unaccustomed Exercise: An Age Comparison

Roberts, Michael D1; Kerksick, Chad M1,2,3; Dalbo, Vincent J4; Hassell, Scott E1; Tucker, Patrick S1; Brown, Ryan5

Author Information
Journal of Strength and Conditioning Research: May 2010 - Volume 24 - Issue 5 - p 1161-1168
doi: 10.1519/JSC.0b013e3181da786f
  • Free



As humans age, they lose a substantial amount of skeletal-muscle mass that becomes problematic in regards to maintaining an independent lifestyle during the later years of life. Mechanistically, skeletal muscle aging is associated with decrements in muscle-protein synthesis (19), potential increases in intramuscular proteolysis (20), and a dysfunction in type II fiber satellite cell activity (18). These events contribute to an estimated 20-30% decrease in lean body mass between the third and eighth decades in life (10). In regards to age-related differences in muscle physiology, recent experiments have indicated that muscle RNA, DNA, and fractional protein content is altered in older vs. younger animals (5,15). Of particular interest, researchers have determined that the skeletal muscle of older rodents contains a diminished protein-RNA ratio indicating that, per ribosome, less protein is capable of being translated in resting states (i.e., a decrement in translational efficiency). The authors of these papers suggest that the increased RNA content in older humans is a molecular signature of aging that may indicate a “decreased ribosomal efficiency for protein synthesis.” Simply stated, this evidence suggests that decrements in aging skeletal muscle mass may be largely because of the fact that the synthesis of muscle proteins from mRNA transcripts is inexplicitly constrained.

Given this evidence in rodents, it is compelling to speculate that sarcopenia may be partially driven by decrements in the protein-RNA ratio (or translational efficiency) in older humans. In this regard, aging has been shown to affect translational mechanisms that result in the accretion of myofibrillar protein. Hasten et al. (7) measured the incorporation rates of l-[1-13C]leucine into intramuscular protein fractions and reported that total protein synthetic and myosin fractional synthetic rates are decreased in sedentary older men compared with that in younger sedentary counterparts. Likewise, translation initiation mechanisms (specifically the assembly of eukaryotic initiation factor-4F) have been shown to be impaired in older rodents (4), which again indicates that translational decrements accompany skeletal-muscle aging. Nonetheless, although various researchers have put forward brilliant methodologies to determine that aging unfavorably impacts the transcriptomic and proteomic attributes of older mammals, no study to our knowledge has compared global skeletal muscle attributes including total RNA (assumed to represent translational capacity), DNA (assumed to represent the amount of genomic material that is able to transcribe protein messages), muscle protein and the [RNA]:[DNA] (assumed to represent global transcriptional efficiency) and [protein]:[RNA] (assumed to represent global translational efficiency) in younger vs. older human skeletal muscle. Although these variables undoubtedly serve as surrogate measures of transcriptional efficiency, translational efficiency, and translational capacity, these data can serve as beneficial age-related descriptive variables for future researchers delving into more complex human muscle physiology endeavors. Furthermore, these data will continue to outline the age-related discrepancies present in aging skeletal muscle that may be ameliorated with long-term resistance training and nutritional strategies. Therefore, the purpose of this study was an exploratory examination of skeletal muscle [DNA], [protein], translational capacity ([RNA]) and transcriptional efficiency ([RNA]:[DNA]) and translational efficiency ([protein]:[RNA]) indices during a resting state in younger and older men. Likewise, we sought to determine changes in muscle [DNA], translational capacity (i.e., changes in [RNA]), and transcriptional efficiency (i.e., [RNA]:[DNA]) 24 hours after an unaccustomed lower-body resistance training bout to determine how unaccustomed physical activity in untrained humans differentially impacts these variables in different age groups.


Experimental Approach to the Problem

As humans age, they lose a substantial amount of skeletal muscle mass that becomes problematic in regards to maintaining an independent lifestyle during the later years of life. Although various papers have discussed potential mechanisms attempting to explain the cause of age-related muscle loss, little research has focused on examining the age-related differences in transcriptional and translational efficiencies between young and older men. Thus, the primary objective of this study was to compare these intramuscular attributes in younger and older men at rest and after a single bout of unaccustomed resistance exercise. In accordance with previous rodent findings (5) and to stimulate a physiological response, muscle biopsies were obtained before and 24 hours after an unaccustomed resistance training bout.


Younger (20.9 ± 0.5 years, 84.0 ± 5.2 kg, 26.6 ± 1.8 kg·m−2; n = 13) and older (67.6 ± 1.3 years, 88.7 ± 4.8 kg, 28.6 ± 1.4 kg·m−2; n = 13) apparently healthy men volunteered to participate in this study. Subjects were informed of the experimental procedures and signed informed consent statements and medical history forms in adherence with the human subjects' guidelines of the University of Oklahoma Health Sciences Center Institutional Review Board and the American College of Sports Medicine (ACSM) before any data collection.


Entrance Criteria

Before participation, subjects had to (a) sign statements stating that they had no current or past use of anabolic steroids, human growth hormone, or other pharmaceutical drugs that affect muscle mass; (b) had not partaken in a structured lower-body resistance training program (i.e., one workout per week) for at least 1 year; (c) have not ingested or were not currently ingesting creatine, beta-hydroxy beta-methylbutyric acid (HMB), thermogenic aids, and other nutritional supplements (excluding multivitamins) for an 8-week period before beginning the study; (d) be classified as low risk according to ACSM criteria with no medical contraindications to resistance exercise if in the younger group; (e) be classified as moderate risk according to ACSM criteria with no medical contraindications to resistance exercise and be cleared by a physician to participate if in the older group.

Familiarization Session

Participants reported to the laboratory in a fasted state between 0600 and 0900. After anthropometric assessments of height and body mass, subjects had their 1 repetition maximum (1RM) determined on the Smith squat, bilateral leg press, and bilateral leg extension exercises. After a standardized warm-up (2 sets × 10 repetitions @ 50% 1RM), 1RM testing was completed by certified strength and conditioning specialists using previously published guidelines for proper exercise technique and maximal strength assessment (2). Because sarcopenia has been partially attributed to a decrement in energy and protein ingestion (8), participants completed a detailed 2-day food record before baseline testing to determine if age-related alterations in molecular variables may have been because of dietary deficiencies. Upon completion, participants were provided a copy and instructed to consume their normal dietary regimen during all follow-up testing.

Baseline Testing

Approximately 1 week after the familiarization session, participants reported to laboratory at a similar time (0600-0900) after a 12-hour fast. Participants were told to refrain from rigorous cardiovascular activities 48 hours before this session. Although hydration levels were not assessed, subjects were instructed to consume water before testing to be in a well-hydrated state before exercise. Before testing, muscle samples were collected from vastus lateralis of the dominant leg using a 16 gauge biopsy needle (Medical Devices Technologies Inc, Gainesville, FL). An estimated 15-30 mg skeletal muscle tissue was retrieved using these procedures. All visible fat and connective tissue were removed before being flash frozen in liquid nitrogen and stored at −80°C until later analysis. After sample collection, participants cycled at 60 rpm at a standardized work rate of 360 kg·m·min−1 on a cycle ergometer for 5 minutes. Using their previously determined 1RM, participants first completed one warm-up set of the Smith squat exercise at 50% 1RM. Participants then completed 3 sets of 10 repetitions at 80% 1RM using the Smith squat, bilateral leg press, and leg extension while observing a 3-minute rest period between sets and between exercises. Acceptable squat and leg press depths were established at 90° of knee flexion, this being visually gauged by the tester. Immediately after the training bout, participants were told to perform the following procedures: (a) refrain from further physical activity until the next laboratory visit, (b) refrain from ingesting over-the-counter anti-inflammatory drugs because of the potential alterations in RNA expression that could arise (21), and (c) maintain their normal diet before returning for their last testing session. Approximately 24 hours later, participants returned to the laboratory for their last testing session in a fasted state to donate a second skeletal-muscle sample using identical collection procedures.

Biochemical Analyses

Total RNA, DNA, and Protein Isolation

Approximately 10-12 mg of muscle was homogenized using the TRI-reagent method (Sigma Chemical Co., St. Louis, MO). All muscle samples were preweighed, placed into an autoclaved microcentrifuge tube, and homogenized using a micropestle and 500 μL of TRI reagent per 10 mg tissue. After homogenization, approximately 100 μL of chloroform was added to each sample, the samples were vortexed for 15 seconds, and allowed to stand at room temperature for 10 minutes. Samples were then centrifuged at 12,000 rpm at 4°C for 15 minutes. This homogenization procedure yields 3 phases including an upper aqueous phase containing total RNA, an interphase containing DNA, and an organic phase containing myofibrillar protein. The upper aqueous phase was transferred into a new autoclaved microcentrifuge tube, and the original tube containing the inter and organic phases were stored at 4°C for further DNA and protein isolation steps, respectively. All remaining isolation steps were completed on the same day as RNA isolation. Approximately 250 μL of 100% isopropanol per 500 μL of TRI reagent was used to precipitate the RNA from the aqueous phase. The RNA pellet was exposed to subsequent ethanol washes and finally dissolved in 30 μL of RNase-free water with repeated pipetting and vortexing. The diluted RNA samples were stored at −80°C until later analyses.

For DNA isolation, 150 μL of 100% ethanol per 500 μL TRI reagent was added to the original microcentrifuge tubes containing the inter and organic phases. Samples were then centrifuged, and the supernatant containing total muscle protein was placed into a new autoclaved microcentrifuge tube and stored at 4°C until subsequent protein isolation procedures later that same day. The remaining DNA pellets were washed with 500 μL of 0.1 M sodium citrate in 10% ethanol solution per 500 μL of TRI reagent used, centrifuged, and washed with 1,000 μL of 75% ethanol for a total of 2 washes. Finally, the DNA pellets were dissolved in 40 μL of 10 mM Tris-HCl, 1 mM ethylenediaminetetraacetic acid (EDTA), pH 8.2, heated overnight, and stored at −80°C until subsequent analysis.

The protein remaining from the total DNA isolation procedure was isolated with isopropanol, ethanol, and 0.3 M guanidine hydrochloride. The protein was then dissolved in 1 mL of 1.0% sodium dodecyl sulfate, and stored at −80°C until later protein analysis. It should be noted that this isolation procedure is designed to completely dissociate all nucleoprotein complexes (i.e., nucleosome dissociation from DNA, ribonuclear protein dissociation from messenger RNA, etc.) contained within the muscle sample. Furthermore, this isolation procedure yielded adequate protein as assessed by Bradford assay analyses from the current and previous investigations in our laboratory (17,25,26).

Total RNA and DNA Determination

Total RNA concentration was determined using a High-Sensitivity RNA analysis kit with the Experion Automated Electrophoresis platform (Bio-Rad, Hercules, CA). This method separates and quantitates RNA ranging from 50 to 6,000 nucleotides in length using a laser-excitable RNA stain and RNA ladder provided by the manufacturer. The reagents and the RNA ladder were prepared according to the manufacturer's instructions. Furthermore, all RNA samples and the RNA ladder were thawed on ice during the assay to preserve RNA integrity. Samples were assayed in duplicate, and the average CV for total RNA was 5.8%.

The presence of DNA was initially determined by running a 0.8% agarose gel at 200 V for 30 minutes. Because of the presence of large molecular weight DNA (fragments > 17,000 bp), samples were further diluted with Tris and EDTA (TE) buffer (10 mM Tris-HCl, 1 mM EDTA, pH 8.4) up to 100 μL volumes and were determined in duplicate using a spectrophotometer at an optical density of 260 (i.e., 5 μL of raw sample diluted into 495 μL of dH2O). Samples were assayed in duplicate, and the average CV for total DNA was 12.5%.

Protein Determination

Total protein content for each sample was determined spectrophotometrically in duplicate using a Bradford assay (Bio-Rad, Hercules, CA) at a wavelength of 595 nm as described previously (17). A standard curve (r2 range: 0.95-1.00) was generated using a serial dilution of bovine serum albumin (0.045, 0.091, 0.181, 0.363, 0.725, and 1.450 mg·mL−1). The average CV for myofibrillar protein content was 2.1%.

Statistical Analyses

All data are reported as means ± standard error of the mean (SEM). Participant demographics, total lifting volume during visit 2, and dietary intake were compared using independent samples t-tests. DNA concentrations were obtained in nanograms and were expressed as ng DNA/mg tissue. Similarly, protein concentrations were obtained in micrograms and were expressed as μg/mg tissue. Transcriptional efficiency was defined as [RNA]:[DNA] (ng RNA/ng DNA) as described by others (3,5). Translational capacity was defined as muscle [RNA] because most RNA in skeletal muscle is ribosomal RNA, which constitutes a large portion of the polyribosome fraction (5,13,15). Translational efficiency was defined as [protein]:[RNA] (ng protein/ng RNA) because muscle protein turnover (i.e., synthesis vs. breakdown) does not change with aging (22). Thus, a decrement in the amount of protein per unit of RNA would indicate that translational processes are disrupted. All dependent variables were compared between age groups using independent samples t-tests. Within-group pre-to-post exercise changes in muscle [DNA], translational capacity, and transcriptional efficiency were compared using paired sample t-tests. Significance for all statistical analyses was determined using an alpha level of 0.05.


Demographics, Total Lifting Volume, and Dietary Intake

Baseline demographics are presented in Table 1. As expected, the young group exhibited greater values for Smith squat 1RM, leg extension 1RM, and total lifting volume during visit 2 (p < 0.05) when compared with their older peers. There were no significant differences in energy and/or macronutrient intakes adjusted to body mass between age groups.

Table 1:
Demographics, strength, lifting volume, and dietary intake values.

Baseline [RNA], [DNA], [protein], [RNA]:[DNA], and [protein]:[RNA]

Figure 1 illustrates the baseline comparisons of skeletal muscle [DNA], [protein], translational capacity ([RNA]), the translational efficiency index ([RNA]:[DNA]), and the translational efficiency index ([protein]:[RNA]) of young vs. old participants that were compared using separate independent t-tests. Baseline skeletal muscle [DNA], [protein], and translational capacity were not statistically different between age groups (p > 0.05). Conversely, the transcriptional efficiency index tended to be greater (p = 0.082), and translational efficiency was significantly greater in the younger group when compared with that in the older group (p = 0.049).

Figure 1:
A-E) Comparison of baseline molecular attributes between young and old human skeletal muscle presented as means ± SE; ‡Significant difference between groups (p < 0.05).

Postexercise changes in [RNA], [DNA], and [RNA]:[DNA]

Figure 2 illustrates the 24-hour postexercise delta values for transcriptional capacity ([RNA]), [DNA], and the transcriptional efficiency index ([RNA]:[DNA]) between the young and old participants. Separate independent t-tests revealed that there were no differences between age groups concerning muscle [DNA] (p = 0.67), translational capacity ([RNA]; p = 0.14), or transcriptional efficiency ([RNA]:[DNA]) 24 hours after exercise, albeit the latter value tended to be greater in the older participants (p = 0.087). Paired-samples t-tests revealed that there were no pre-to-post exercise changes in muscle [DNA] (young, p = 0.14; old p = 0.20), transcriptional capacity (young, p = 0.23; old p = 0.38), and/or the transcriptional efficiency index (young, p = 0.26; old, p = 0.21) within both age groups.

Figure 2:
A-C) Comparison of pre-to-post exercise changes in molecular attributes between young and old human skeletal muscle (expressed as postexercise value − pre-exercise value means ± SE).


Although aging and/or exercise affects the expression patterns of various genes and/or proteins, limited data exist examining how these stressors impact crude markers of transcriptional and/or translational efficiency in humans. In this regard, the current data provide initial human evidence of these variables that may benefit muscle physiologists studying sarcopenia from a descriptive standpoint. Although [RNA], [DNA], and [protein] levels were not significantly different between younger and older men during resting conditions, our data suggest that aging may impact transcriptional efficiency ([RNA]:[DNA]) and seemingly impact translational efficiency ([protein]:[RNA]) in humans during resting states. In regards to the former, more total RNA tended to be transcribed per unit of DNA in younger skeletal muscle. In regards to the latter, more protein is apparently translated per unit of RNA in younger skeletal muscle, a finding that compliments recent literature contending that protein synthesis (specifically translation initiation) is impaired in older individuals (4,9). Finally, the tendency for transcriptional capacity to increase (or remain elevated) in older vs. younger muscle after exercise may indicate that a compensatory response is occurring postexercise because of the potential need for more rRNA and polyribosomes in accruing muscle protein after an exercise stimulus.

In resting states, translational capacity (i.e., RNA content) in skeletal muscle was not different between age groups; this being a finding that also indicates that the ability of RNA to be transcribed is not impaired in aging skeletal muscle. This finding is similar to the findings of Haddad and Adams (5) who demonstrated that aged rodents contain slightly greater but more significant muscle RNA concentrations compared with those in younger rodents. Likewise, Prod'homme et al. (15) demonstrated that RNA content was statistically similar in both the gastrocnemius and soleus muscles between adult and old rats. Welle et al. (24) similarly reported that older men contain a higher concentration of intramuscular mRNA transcripts. Hence, the 3 aforementioned studies and the current study suggest that global epigenetic patterns, transcription capabilities (i.e., RNA polymerase I-III-mediated transcription), and potentially translational capacity (i.e., the number of ribosomes) appear to remain intact with mammalian aging in disease-free conditions. In regards to the former conclusion, it remains speculative that isolated decrements in gene-specific transcription factor functions and/or age-associated epigenetic silencing (i.e., methylation of CpG islands within promoter regions and/or histone acetylation/methylation that is independent of translational capacity) appear to be a likely candidate that may account for age-related differences in the skeletal-muscle transcriptome (11). For instance, Marx et al. (12) revealed that the mRNA and protein expression of the MHC I/IIa/IIx isoforms did not differ between younger and older men, albeit other groups have demonstrated that transcripts and proteins related to the process of muscle hypertrophy (i.e., mechano growth factor as an example [6]) may exhibit some age-dependent differences. Thus, future gene-explicit DNA methylation analyses will be needed to confer which genes are transcriptionally silenced with skeletal-muscle aging.

In regards to similar total protein per milligram of muscle, our findings are in agreement with those of Haddad and Adams (5) and Prod'homme et al. (15) who also demonstrated that total protein (i.e., myofibrillar, sarcoplasmic, mitochondrial, and nuclear fractions) is not different between younger and older rodents. Further, absolute protein synthesis rates (milligram muscle protein synthesized per day) were similar in the gastrocnemius and soleus muscles of adult vs. older rats as reported by the latter research group. Interestingly, the former authors did reveal that myofibril proteins were diminished in aged rodents. In lieu of the current evidence, it seems plausible that a decrement in the synthetic rate of the myofibrillar fraction, and not the total protein pool, accompanies muscle aging. In this regard, future studies should determine myofibril protein content between younger vs. older humans and the potential mechanistic causes for age-associated decrements.

The similar muscle [DNA] content between age groups suggests that myonuclear content remains unaltered with aging. Some researchers contend that myonuclei counts are reduced with animal aging (1), whereas others suggest that this does not occur in humans (14). Although assessing muscle homogenate DNA provides a rough estimation of myonuclei (i.e., this measurement does not differentiate between muscle DNA and that from immune cells, fibroblasts, vascular cells, muscle precursor cells, etc.), our data suggest that aging minimally impacts myonuclei number in human skeletal muscle.

Our findings concerning a decrease in resting [protein]:[RNA] in older men suggests that younger men are seemingly able to translate more muscle protein per unit RNA. Haddad and Adams (5) reported that the protein-to-RNA ratio was lower during resting conditions in older vs. younger rats, a finding that parallels our findings. Similarly, Prod'homme et al. (15) reported that older rats contained more intramuscular RNA, less muscle protein, and greater impairments in protein synthetic signal transduction pathways leading to ribosomal assembly. As mentioned previously, the mechanism of translation initiation has been shown to be impaired in older rodents (4) and humans (9). Thus, our data support the aforementioned findings in that muscle protein synthesis, and not global transcriptional processes, are negatively affected with aging. From an exercise adaptation standpoint, it should be noted that a series of training bouts may actually improve translational efficiency in older individuals, but this is still largely unknown. For instance, Welle et al. (23) reported that 3 days of resistance exercise increases translational efficiency in 62- to 75-year-old participants because total mRNA levels after a 1-week intervention did not change, whereas myofibrillar protein synthesis rates increased. In this regard, it would be interesting to investigate how chronic training affects, if at all, the [protein]:[RNA] in older humans.

The increase in [RNA]:[DNA] (transcriptional efficiency) in older men approached significance 24 hours after resistance exercise when compared with young men. Our results are very similar to the findings of Haddad and Adams (5) who discovered that total RNA significantly increased to a greater degree in older vs. younger rats 48 hours after an electrical stimulation exercise protocol. These authors interpreted their findings as an indication that older skeletal muscle needs more ribosomes after an exercise stimulus to support adaptation given that the pre-exercise protein-to-RNA ratio (i.e., translational efficiency) reported in the same study, as in our study, was lower in older rodents. Thus, the presence of more postexercise RNA relative to DNA in older vs. younger humans may indicate one or more of the following: (a) the expression of numerous splice variants as described by Welle et al. (24) occurs to a greater extent in older vs. younger men after exercise (which is unlikely given that mRNA makes up ∼5% of the total RNA fraction); (b) there is an accelerated degradation in RNA in young individuals after an exercise stimulus; or, (c) the overexpression of myogenic RNA per unit DNA in old participants may act as a compensatory mechanism to offset decrements in muscle protein synthesis as mentioned by Raue et al. (16) and implied by Haddad and Adams above.

In summary, our findings indicate that global transcription capabilities likely remain intact with aging, whereas translational efficiency is seemingly impaired. Specifically, a decrement in resting [protein]:[RNA] values in older humans in the present study supports the contention that deficiencies in muscle protein synthesis and translation initiation and elongation is a molecular signature of muscle aging. The prolonged accumulation of myogenic RNA species per unit DNA in older men after an exercise stimulus is in agreement with previous exercise rodent literature (5) and is suggestive of a potential compensatory mechanism in an attempt to ameliorate decrements in translational efficiency. It should be noted that muscle fiber typing was not performed because of methodological constraints. It can be assumed that older individuals in the current study may have contained proportionally less type II fibers which, in turn, may have depressed the translational efficiency index. However, the transcriptional efficiency and protein synthetic rates of different muscle fiber types remain unknown. Therefore, future studies should examine the protein synthetic rates of different human skeletal muscle fiber types to further clarify this issue. Additional studies should also be conducted examining age-related changes over multiple bouts of resistance exercise followed by prolonged training studies to examine prolonged changes in transcriptional and translational efficiency.

Practical Applications

These findings illustrate that the rate at which skeletal muscle translates RNA into protein may be impaired with aging and support the notion that muscle protein synthesis is impaired with aging. Further, results from this study also show that efficiency changes in these markers can improve with resistance training and that all populations can benefit at the molecular level for regular resistance training. In this regard, these data continue to obviate the need for increasing translational mechanisms through resistance exercise and/or essential amino acid supplementation to potentially combat the loss of muscle mass. Therefore, based on current research illustrating that resistance training can increase skeletal muscle protein synthesis in younger and older individuals (9), athletic trainers and/or elder exercise trainees should employ an adequate resistance training regimen and proper nutritional adequacy (i.e., 1.5-2.0 g protein per kilogram bodyweight per day as suggested by the NSCA for active individuals [2]) to combat the aforementioned negative age-related changes in skeletal-muscle physiology.


We would like to thank the subjects that participated in this study and all laboratory assistants who assisted with data collection and analysis. We would also like to graciously thank the reviewers that took the time to critique this manuscript. Finally, we would like to thank Dr. Fadia Haddad at the University of California, Irvine for her technical assistance. The National Strength and Conditioning Foundation provided funds for this project through a Young Investigator Grant to the corresponding author and investigator (CK).


1. Always, SE and Siu, PM. Nuclear apoptosis contributes to sarcopenia. Exerc Sport Sci Rev 36: 51-57, 2008.
2. Baechle, T and Earle, R. Essentials of Strength and Conditioning. (2nd ed). Champaign, IL: Human Kinetics, 2000.
3. Booth, FW, Tseng, BS, Fluck, M, and Carson, JA. Molecular and cellular adaptation of muscle in response to physical training. Acta Physiol Scand 162: 343-350, 1998.
4. Funai, K, Parkington, JD, Carambula, S, and Fielding, RA. Age-associated decrease in contraction-induced activation of downstream targets of Akt/mTOR signaling in skeletal muscle. Am J Physiol Regul Integr Comp Physiol 290: R1080-R1086, 2006.
5. Haddad, F and Adams, GR. Aging-sensitive cellular and molecular mechanisms associated with skeletal muscle hypertrophy. J Appl Physiol 100: 1188-1203, 2006.
6. Hameed, M, Orrell, RW, Cobbold, M, Goldspink, G, and Harridge, SD. Expression of IGF-1 splice variants in young and old human skeletal muscle after high resistance exercise. J Physiol 547: 247-254, 2003.
7. Hasten, DL, Pak-Loduca, J, Obert, KA, and Yarasheski, KE. Resistance exercise acutely increases MHC and mixed muscle protein synthesis rates in 78-84 and 23-32 yr olds. Am J Physiol Endocrinol Metab 278: E620-E626, 2000.
8. Koopman, R and van Loon, LJ. Aging, exercise, and muscle protein metabolism. J Appl Physiol 106: 2040-2048, 2009.
9. Kumar, V, Selby, A, Rankin, D, Patel, R, Atherton, P, Hildebrandt, W, Williams, J, Smith, K, Seynnes, O, Hiscock, N, and Rennie, MJ. Age-related differences in the dose-response relationship of muscle protein synthesis to resistance exercise in young and old men. J Physiol 587: 211-217, 2009.
10. Kyle, UG, Genton, L, Hans, D, Karsegard, L, Slosman, DO, and Pichard, C. Age-related differences in fat-free mass, skeletal muscle, body cell mass and fat mass between 18 and 94 years. Eur J Clin Nutr 55: 663-672, 2001.
11. Martin, GM. The genetics and epigenetics of altered proliferative homeostasis in ageing and cancer. Mech Ageing Dev 128: 9-12, 2007.
12. Marx, JO, Kraemer, WJ, Nindl, BC, and Larsson, L. Effects of aging on human skeletal muscle myosin heavy-chain mrna content and protein isoform expression. J Gerontol A Biol Sci Med Sci 57: B232-B238, 2002.
13. Nader, GA, McLoughlin, TJ, and Esser, KA. mTOR function in skeletal muscle hypertrophy: increased ribosomal RNA via cell cycle regulators. Am J Physiol Cell Physiol 289: C1457-C1465, 2005.
14. Petrella, JK, Kim, JS, Cross, JM, Kosek, DJ, and Bamman, MM. Efficacy of myonuclear addition may explain differential myofiber growth among resistance-trained young and older men and women. Am J Physiol Endocrinol Metab 291: E937-E946, 2006.
15. Prod'homme, M, Balage, M, Debras, E, Farges, MC, Kimball, S, Jefferson, L, and Grizard, J. Differential effects of insulin and dietary amino acids on muscle protein synthesis in adult and old rats. J Physiol 563: 235-248, 2005.
16. Raue, U, Slivka, D, Jemiolo, B, Hollon, C, and Trappe S. Myogenic gene expression at rest and after a bout of resistance exercise in young (18-30 yr) and old (80-89 yr) women. J Appl Physiol 101: 53-59, 2006.
17. Roberts, MD, Iosia, M, Kerksick, CM, Taylor, LW, Campbell, B, Wilborn, CD, Harvey, T, Cooke, M, Rasmussen, C, Greenwood, M, Wilson, R, Jitomir, J, Willoughby, D, and Kreider, RB. Effects of arachidonic acid supplementation on training adaptations in resistance-trained males. J Int Soc Sports Nutr 4: 21, 2007.
18. Snijders, T, Verdijk, LB, and van Loon, LJ. The impact of sarcopenia and exercise training on skeletal muscle satellite cells. Ageing Res Rev 8: 328-338, 2009.
19. Toth, MJ, Matthews, DE, Tracy, RP, and Previs, MJ. Age-related differences in skeletal muscle protein synthesis: Relation to markers of immune activation. Am J Physiol Endocrinol Metab 288: E883-E891, 2005.
20. Trappe, T, Williams, R, Carrithers, J, Raue, U, Esmarck, B, Kjaer, M, and Hickner, R. Influence of age and resistance exercise on human skeletal muscle proteolysis: A microdialysis approach. J Physiol 554: 803-813, 2004.
21. Trappe, TA, Fluckey, JD, White, F, Lambert, CP, and Evans, WJ. Skeletal muscle PGF2(alpha) and PGE2 in response to eccentric resistance exercise: Influence of ibuprofen acetaminophen. J Clin Endocrinol Metab 86: 5067-5070, 2001.
22. Ward, WF. The relentless effects of the aging process on protein turnover. Biogerontology 1: 195-199, 2000.
23. Welle, S, Bhatt, K, and Thornton, CA. Stimulation of myofibrillar synthesis by exercise is mediated by more efficient translation of mrna. J Appl Physiol 86: 1220-1225, 1999.
24. Welle, S, Brooks, AI, Delehanty, JM, Needler, N, and Thornton, CA. Gene expression profile of aging in human muscle. Physiol Genomics 14: 149-159, 2003.
25. Willoughby, DS and Rosene, JM. Effects of oral creatine and resistance training on myogenic regulatory factor expression. Med Sci Sports Exerc 35: 923-929, 2003.
26. Willoughby, DS, Stout, JR, and Wilborn, CD. Effects of resistance training and protein plus amino acid supplementation on muscle anabolism, mass, and strength. Amino Acids 32: 467-477, 2007.

transcription; translation; aging; resistance exercise; efficiency

© 2010 National Strength and Conditioning Association