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- Timmons, James A., et al.
(författare)
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Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans
- 2010
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 108:6, s. 1487-1496
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Tidskriftsartikel (refereegranskat)abstract
- Timmons JA, Knudsen S, Rankinen T, Koch LG, Sarzynski M, Jensen T, Keller P, Scheele C, Vollaard NB, Nielsen S, Akerstrom T, MacDougald OA, Jansson E, Greenhaff PL, Tarnopolsky MA, van Loon LJ, Pedersen BK, Sundberg CJ, Wahlestedt C, Britton SL, Bouchard C. Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans. J Appl Physiol 108: 1487-1496, 2010. First published February 4, 2010; doi:10.1152/japplphysiol.01295.2009.-A low maximal oxygen consumption ((V) over dotO(2max)) is a strong risk factor for premature mortality. Supervised endurance exercise training increases (V) over dotO(2max) with a very wide range of effectiveness in humans. Discovering the DNA variants that contribute to this heterogeneity typically requires substantial sample sizes. In the present study, we first use RNA expression profiling to produce a molecular classifier that predicts (V) over dotO(2max) training response. We then hypothesized that the classifier genes would harbor DNA variants that contributed to the heterogeneous (V) over dotO(2max) response. Two independent preintervention RNA expression data sets were generated (n = 41 gene chips) from subjects that underwent supervised endurance training: one identified and the second blindly validated an RNA expression signature that predicted change in (V) over dotO(2max) (""predictor"" genes). The HERITAGE Family Study (n = 473) was used for genotyping. We discovered a 29-RNA signature that predicted (V) over dotO(2max) training response on a continuous scale; these genes contained similar to 6 new single-nucleotide polymorphisms associated with gains in (V) over dotO(2max) in the HERITAGE Family Study. Three of four novel candidate genes from the HERITAGE Family Study were confirmed as RNA predictor genes (i.e., ""reciprocal"" RNA validation of a quantitative trait locus genotype), enhancing the performance of the 29-RNA-based predictor. Notably, RNA abundance for the predictor genes was unchanged by exercise training, supporting the idea that expression was preset by genetic variation. Regression analysis yielded a model where 11 single-nucleotide polymorphisms explained 23% of the variance in gains in (V) over dotO(2max), corresponding to similar to 50% of the estimated genetic variance for (V) over dotO(2max). In conclusion, combining RNA profiling with single-gene DNA marker association analysis yields a strongly validated molecular predictor with meaningful explanatory power. (V) over dotO(2max) responses to endurance training can be predicted by measuring a similar to 30-gene RNA expression signature in muscle prior to training. The general approach taken could accelerate the discovery of genetic biomarkers, sufficiently discrete for diagnostic purposes, for a range of physiological and pharmacological phenotypes in humans.
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| 2. |
- Snijders, Tim, et al.
(författare)
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A single bout of exercise activates skeletal muscle satellite cells during subsequent overnight recovery
- 2012
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Ingår i: Experimental Physiology. - Hoboken, USA : Wiley-Blackwell. - 0958-0670 .- 1469-445X. ; 97:6, s. 762-773
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Tidskriftsartikel (refereegranskat)abstract
- Skeletal muscle satellite cell (SC) content has been reported to increase following a single bout of exercise. Data on muscle fibre type-specific SC content and/or SC activation status are presently lacking. The objective of the study was to determine the impact of a single bout of exercise on muscle fibre type-specific SC content and activation status following subsequent overnight recovery. Eight healthy men (age, 20 ± 1 years) performed a single bout of combined endurance- and resistance-type exercise. Muscle biopsies were collected before and immediately after exercise, and following 9 h of postexercise, overnight recovery. Muscle fibre type-specific SC and myonuclear content and SC activation status were determined by immunohistochemical analyses. Satellite cell activation status was assessed by immunohistochemical staining for both Delta-like homologue 1 (DLK1) and Ki-67. Muscle fibre size and fibre area per nucleus were greater in type II compared with type I muscle fibres (P < 0.05). At baseline, no differences were observed in the percentage of SCs staining positive for DLK1 and/or Ki67 between fibre types. No significant changes were observed in SC content following 9 h of postexercise, overnight recovery; however, the percentage of DLK1-positive SCs increased significantly during overnight recovery, from 22 ± 5 to 41 ± 5% and from 24 ± 6 to 51 ± 9% in the type I and II muscle fibres, respectively. No changes were observed in the percentage of Ki-67-positive SCs. A single bout of exercise activates both type I and II skeletal muscle fibre SCs within a single night of postexercise recovery, preceding the subsequent increase in SC content.
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| 3. |
- Verdijk, Lex B., et al.
(författare)
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Satellite cells in human skeletal muscle; from birth to old age
- 2014
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Ingår i: Age (Omaha). - Dordrecht : Springer Netherlands. - 0161-9152 .- 1574-4647. ; 36:2, s. 545-557
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Tidskriftsartikel (refereegranskat)abstract
- Changes in satellite cell content play a key role in regulating skeletal muscle growth and atrophy. Yet, there is little information on changes in satellite cell content from birth to old age in humans. The present study defines muscle fiber type-specific satellite cell content in human skeletal muscle tissue over the entire lifespan. Muscle biopsies were collected in 165 subjects, from different muscles of children undergoing surgery (< 18 years; n = 13) and from the vastus lateralis muscle of young adult (18-49 years; n = 50), older (50-69 years; n = 53), and senescent subjects (70-86 years; n = 49). In a subgroup of 51 aged subjects (71 +/- 6 years), additional biopsies were collected after 12 weeks of supervised resistance-type exercise training. Immunohistochemistry was applied to assess skeletal muscle fiber type-specific composition, size, and satellite cell content. From birth to adulthood, muscle fiber size increased tremendously with no major changes in muscle fiber satellite cell content, and no differences between type I and II muscle fibers. In contrast to type I muscle fibers, type II muscle fiber size was substantially smaller with increasing age in adults (r = -0.56; P < 0.001). This was accompanied by an age-related reduction in type II muscle fiber satellite cell content (r = -0.57; P < 0.001). Twelve weeks of resistance-type exercise training significantly increased type II muscle fiber size and satellite cell content. We conclude that type II muscle fiber atrophy with aging is accompanied by a specific decline in type II muscle fiber satellite cell content. Resistance-type exercise training represents an effective strategy to increase satellite cell content and reverse type II muscle fiber atrophy.
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