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Biomedical subjects

Stephen M Roth

Publications and source records attributed to Stephen M Roth.

26 records · Page 2Linked to original sources
PubMed2004

Association of interleukin-15 protein and interleukin-15 receptor genetic variation with resistance exercise training responses.

Interleukin-15 (IL-15) is an anabolic cytokine that is produced in skeletal muscle and directly affects muscle anabolism in animal and in vitro models. The contribution of IL-15 variability in muscle responses to 10 wk of resistance exercise training in young men and women was examined by measuring acute and chronic changes in IL-15 protein in plasma and characterizing genetic variation in the IL-15 receptor-alpha gene (IL15RA). Participants trained 3 days a week at 75% of one repetition maximum, performing three sets (6-10 repetitions) of 13 resistance exercises. Plasma IL-15 protein was significantly increased (P < 0.05) immediately after acute resistance exercise but did not change with training and was not associated with variability in muscle responses with training. A single nucleotide polymorphism in exon 7 of IL15RA was strongly associated with muscle hypertrophy and accounted for 7.1% of the variation in regression modeling. A polymorphism in exon 4 was also independently associated with muscle hypertrophy and accounted for an additional 3.5% of the variation in hypertrophy. These results suggest that IL-15 is an important mediator of muscle mass response to resistance exercise training in humans and that genetic variation in IL15RA accounts for a significant proportion of the variability in this response.

Adult↗
PubMed2003

Sequence variation in hypoxia-inducible factor 1alpha (HIF1A): association with maximal oxygen consumption.

Hypoxia-inducible factor 1 (HIF1) is a DNA transcription factor composed of two subunits, one of which is regulated by hypoxia (HIF1alpha, encoded by HIF1A). Genes regulated by HIF1 are involved in the processes of angiogenesis, erythropoiesis, and metabolism, making HIF1A a candidate gene in establishing maximal oxygen consumption (VO2 max) before and after aerobic exercise training. The purpose of the present study was to screen HIF1A for sequence variation and determine whether such variation is associated with VO2 max before and after aerobic exercise training. A total of 233 Caucasian and African-American subjects were available for screening of HIF1A and determination of allele frequencies, with 155 of those subjects used to study VO2 max in relation to identified variants. We measured VO2 max before and after 24 wk of aerobic exercise training. Screening revealed several rare and common polymorphisms in HIF1A with race-specific allele frequencies. African Americans with AT or TT genotype at the A-2500T locus exhibited significantly lower baseline VO2 max compared with those of AA genotype (21.9 +/- 0.99 vs. 25.1 +/- 1.0, P = 0.03). An age by P582S (C/T) genotype interaction was observed in Caucasian subjects, such that those of CT or TT genotype exhibited significantly lower change in VO2 max after training than those of CC genotype when compared at ages 65 and 60 yr, but not at age 55 yr. No other significant differences were noted among genotype groups at the A-2500T, P582S, or T+140C sites. Based on these findings, we conclude that HIF1A sequence variation is associated with VO2 max before and after aerobic exercise training in older humans.

Aging↗
PubMed2003

C174T polymorphism in the CNTF receptor gene is associated with fat-free mass in men and women.

We performed gene screening of the ciliary neurotrophic factor receptor (CNTFR) gene and genotyped three newly identified polymorphisms: C-1703T in the 5' promoter region, T1069A in intron 5, and C174T in exon 9. We studied the association of these CNTFR variants with muscle strength, mass, and body composition in 465 men and women (20-90 yr) from the Baltimore Longitudinal Study of Aging. Only the C174T variant was significantly associated with muscle-related phenotypes. In the entire cohort, when corrected for age, sex, race, physical activity, and height, homozygotes for the common C allele at C174T (CC) exhibited lower total body mass and body mass index than carriers of the rare T allele, which appeared to be due to significant differences in total nonosseous fat-free mass (FFM) (48.0 +/- 0.4 vs. 50.0 +/- 0.7 kg; P = 0.011) and lower limb FFM (16.5 +/- 0.1 vs. 17.2 +/- 0.2 kg; P = 0.002). The CC group also exhibited significantly lower quadriceps concentric and eccentric isokinetic strength values at both 30 and 180 degrees /s than the T allele carriers (all P < 0.04), but these differences were no longer significant after adjustment for lower limb FFM. There were no significant sex-by-genotype interactions. The results indicate that the C174T polymorphism in exon 9 of CNTFR is significantly associated with FFM in men and women, with concomitant differences in muscular strength.

Adult↗
PubMed2003

Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men.

Testosterone (T) supplementation in men induces muscle fiber hypertrophy. We hypothesized that T-induced increase in muscle fiber size is associated with a dose-dependent increase in satellite cell number. We quantitated satellite cell and myonuclear number by using direct counting and spatial orientation methods in biopsies of vastus lateralis obtained at baseline and after 20 wk of treatment with a gonadotropin-releasing hormone agonist and a 125-, 300-, or 600-mg weekly dose of T enanthate. T administration was associated with a significant increase in myonuclear number in men receiving 300- and 600-mg doses. The posttreatment percent satellite cell number, obtained by direct counting, differed significantly among the three groups (ANCOVA P < 0.000001); the mean posttreatment values (5.0 and 15.0%) in men treated with 300- and 600-mg doses were greater than baseline (2.5 and 2.5%, respectively, P < 0.05 vs. baseline). The absolute satellite cell number measured by spatial orientation at 20 wk (1.5 and 4.0/mm) was significantly greater than baseline (0.3 and 0.6/mm) in men receiving the 300- and 600-mg doses (P < 0.05). The change in percent satellite cell number correlated with changes in total (r = 0.548) and free T concentrations (r = 0.468). Satellite cell and mitochondrial areas were significantly higher and the nuclear-to-cytoplasmic ratio lower after treatment with 300- and 600-mg doses. We conclude that T-induced muscle fiber hypertrophy is associated with an increase in satellite cell number, a proportionate increase in myonuclear number, and changes in satellite cell ultrastructure.

Adult↗
PubMed2003

Interleukin-6 (IL6) genotype is associated with fat-free mass in men but not women.

We studied the association of the G-174C promoter polymorphism in the interleukin-6 gene (IL6) with total body fat and fat-free mass (FFM) in 242 men and women (IL6 genotypes: G/G, n = 87; G/C, n = 100; C/C, n = 55) across the adult age span (21-92 years). In men, but not women (significant genotype by sex interactions; p =.023-.048), the C/C group exhibited significantly lower total FFM than the G/G group (54.7 +/- 0.8 kg vs 57.2 +/- 0.7 kg, respectively, p =.020), as well as significantly lower FFM of the lower limbs compared with the G/G group (18.4 +/- 0.3 kg vs 19.8 +/- 0.3 kg, respectively, p =.004). No significant genotype differences were observed in total body fat mass in either men or women. The results indicate that the IL6 G-174C polymorphism is significantly associated with FFM in men but not women.

Adult↗
PubMed2003

Myostatin gene expression is reduced in humans with heavy-resistance strength training: a brief communication.

This study examined changes in myostatin gene expression in response to strength training (ST). Fifteen young and older men (n = 7) and women (n = 8) completed a 9-week heavy-resistance unilateral knee extension ST program. Muscle biopsies were obtained from the dominant vastus lateralis before and after ST. In addition to myostatin mRNA levels, muscle volume and strength were measured. Total RNA was reverse transcribed into cDNA, and myostatin mRNA was quantified using quantitative PCR by standard fluorescent chemistries and was normalized to 18S rRNA levels. A 37% decrease in myostatin expression was observed in response to ST in all subjects combined (2.70 +/- 0.36 vs 1.69 +/- 0.18 U, arbitrary units; P < 0.05). Though the decline in myostatin expression was similar regardless of age or gender, the small number of subjects in these subgroups suggests that this observation needs to be confirmed. No significant correlations were observed between myostatin expression and any muscle strength or volume measure. Although further work is necessary to clarify the findings, these data demonstrate that myostatin mRNA levels are reduced in response to heavy-resistance ST in humans.

Adult↗
PubMed2002

Influence of age, sex, and strength training on human muscle gene expression determined by microarray.

The purpose of this study was to determine the influence of age, sex, and strength training (ST) on large-scale gene expression patterns in vastus lateralis muscle biopsies using high-density cDNA microarrays and quantitative PCR. Muscle samples from sedentary young (20-30 yr) and older (65-75 yr) men and women (5 per group) were obtained before and after a 9-wk unilateral heavy resistance ST program. RNA was hybridized to cDNA filter microarrays representing approximately 4,000 known human genes and comparisons were made among arrays to determine differential gene expression as a result of age and sex differences, and/or response to ST. Sex had the strongest influence on muscle gene expression, with differential expression (>1.7-fold) observed for approximately 200 genes between men and women (approximately 75% with higher expression in men). Age contributed to differential expression as well, as approximately 50 genes were identified as differentially expressed (>1.7-fold) in relation to age, representing structural, metabolic, and regulatory gene classes. Sixty-nine genes were identified as being differentially expressed (>1.7-fold) in all groups in response to ST, and the majority of these were downregulated. Quantitative PCR was employed to validate expression levels for caldesmon, SWI/SNF (BAF60b), and four-and-a-half LIM domains 1. These significant differences suggest that in the analysis of skeletal muscle gene expression issues of sex, age, and habitual physical activity must be addressed, with sex being the most critical variable.

Adult↗