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The purpose of this study was to investigate how age and 1 week of conventional resistance exercise affects commonly used housekeeping gene (HKG) messenger RNAs (mRNAs) in skeletal muscle. Ten college-aged (18-25 years) and 10 older (60-76 years) men completed 3 lower-body resistance exercise bouts on Monday, Wednesday, and Friday, and muscle samples were obtained before bout 1 (T1), 48 hours after the first (T2) and second bouts (T3), and 24 hours after the third bout (T4). Raw Ct values indicated that β-actin and cyclophilin were more highly expressed in older vs. younger males (p < 0.01) at T1. When normalizing each HKG mRNA to the other 4 HKG mRNAs, CYC increased at T3 and glyceraldehyde-3-phosphate dehydrogenase decreased at T2 (p < 0.05) in younger men. This is one of the few studies to suggest that explicit HKG mRNAs should be used depending upon age group and resistance exercise intervention.

To determine the influence of age and resistance exercise on myostatin pathway-related genes, younger (n = 10; 28 ± 5 years) and older (n = 10; 68 ± 6 years) men underwent four testing conditions (T1-T4). A baseline (T1) muscle sample was obtained, whereas the second and third biopsies were obtained 48 hours following the first and second training sessions (T2, T3), and a final biopsy was taken 24 hours following T3. The training sessions consisted of 3 sets of 10 repetitions (80% of one repetition maximum) on leg press, hack squat, and leg extension exercises. Follistatin (FST) messenger RNA was greater in older compared with younger men at T1 and T2 (p < .05). Follistatin-like 3 (FSTL3) messenger RNA was greater in older compared with younger men at T1 and T4 (p < .05). In older men, there was a significant decrease in myostatin (MSTN) messenger RNA at T4 (p < .05). Older men contained less active (Ser-425 phosphorylated) SMAD3 (p-SMAD3) protein than younger men at T3 and T4 (p < .05).Although it is well known that younger individuals possess a greater hypertrophic potential to resistance exercise, it appears that older individuals may paradoxically possess a more favorable resistance exercise response regarding myostatin pathway-related genes and a protein marker of pathway activity. Future research is warranted to examine the physiological significance of this age-dependent mechanism.

Androgen signaling occurs primarily via the androgen receptor. Megalin, a low-density lipoprotein endocytic receptor located in various mammalian tissues, has been recently shown to facilitate sex hormone–binding globulin (SHBG) steroid complexes across cell membranes. The purpose of this investigation is to determine if the megalin gene is expressed in human skeletal muscle and if present to determine how megalin and androgen receptor mRNA expression change in response to sequential exercise bouts with respect to aging. Ten younger (age: 18-25 years) and 10 older (age: 60-75 years) men completed 3 workouts (M, W, F) each consisting of 9 sets of lower-body exercises with 10 repetitions per set at 80% 1 repetition maximum. Vastus lateralis muscle biopsies were extracted at baseline (T1), 48 hours after workout 1 (T2) and 2 (T3), and 24 hours after workout 3 (T4), and blood samples were collected before and 5 minutes after each workout. Muscle was analyzed for megalin and androgen receptor expression using gene-specific primers and SYBR green chemistry, and blood was analyzed for serum testosterone, SHBG, and the free androgen index. Megalin was expressed in both young and old subjects across all time points, although no between- or within-group mean differences were detected at any time point. Androgen receptor was expressed higher in young men at all time points compared to in old men (p < 0.05), and a significant correlation (p < 0.05; r = 0.506) was found between serum testosterone and androgen receptor after workout 1. Based on our data, the gene coding for megalin is expressed inside skeletal muscle, but its role, if any, in steroid cellular transport cannot be determined. This finding could lay the groundwork for more mechanistic investigations to better delineate its functional role and its potential as a therapeutic adjunct for androgen-related disorders in healthy and aged populations.

The current study examined muscle DNA and protein concentrations ([ ]) and the [RNA] (assumed to represent translational capacity), [RNA]:[DNA] (assumed to represent transcriptional efficiency) and [protein]:[RNA] (assumed to represent translational efficiency) in younger vs. older participants during a resting state. Further, changes in muscle [DNA], translational capacity, and transcriptional efficiency were analyzed 24 hours after an unaccustomed resistance exercise bout. Younger (20.9 +/- 0.5 years, 84.0 +/- 5.2 kg, 26.6 +/- 1.8 kg x m(-2); n = 13) and older men (67.6 +/- 1.3 years, 88.7 +/- 4.8 kg, 28.6 +/- 1.4 kg x m(-2); n = 13) reported to the laboratory and completed an unaccustomed bout of lower-body resistance training (i.e., 3 sets of 10 repetitions at 80% 1 repetition maximum for Smith squat, leg press, and leg extensions). Muscle biopsies from the vastus lateralis were obtained before and 24 hours after exercise. Baseline [RNA], [DNA], [protein], and [RNA]:[DNA] were not different between age groups (p > 0.05). Baseline [protein]:[RNA] was greater in younger vs. older men (p = 0.045), whereas 24-hour postexercise [RNA]:[DNA] tended to be greater in older men (p = 0.087). These findings suggest that a decrease in the efficiency of translational processes occurs in older human skeletal muscle, whereas global transcriptional processes appear to be unaltered when compared with those in younger men. In lieu of these data, it remains apparent that muscle-protein synthesis is impaired in aging skeletal muscle and effective countermeasures such as resistance exercise and nutritional adequacy must be undertaken by older populations to offset this phenomenon.

This cross-sectional study examined aging and resistance exercise-related changes in intramuscular gene expression in younger (21.3 +/- 0.6 years, 84.8 +/- 6.0 kg, 26.6 +/- 2.1 kg x m(-2); n = 11) and older men (67.6 +/- 1.3 years, 88.7 +/- 4.8 kg, 28.6 +/- 1.4 kg x m(-2); n = 13) surrounding a single bout of resistance exercise. Participants completed 3 x 10 repetitions at 80% of their 1 repetition maximum for Smith squat, leg press, and leg extension. Muscle biopsies were obtained before and 24 hours after exercise, whereas venous blood was collected before, immediately after and 24 hours after exercise. Free testosterone levels were greater in younger participants at all time points (p < 0.05), in addition to a greater increase in the younger men immediately post exercise (p < 0.01). Preexercise human growth hormone levels between age groups were similar (p > 0.05). Human growth hormone increased immediately post exercise in both groups (p < 0.05) with a greater response occurring in the younger (p < 0.001) men. Older men expressed greater levels of androgen receptor (AR) at rest (p = 0.02). A significant correlation existed between preexercise free testosterone levels basal AR gene expression (r = -0.59, p < 0.01). These data suggest that AR expression patterns may be related to circulating free testosterone levels. Although these findings do not fully unveil the genomic effects of androgen signaling and its relationship to muscle wasting conditions, these results provide a platform for future researchers seeking to employ gene therapy to remedy muscle loss.