Aging and the Skeletal Muscle Angiogenic Response to Exercise in Women.

Whether aging lowers skeletal muscle basal capillarization and angiogenesis remains controversial. To investigate the effects of aging on skeletal muscle capillarization, eight young (YW) and eight aged (AW) women completed 8 weeks of exercise training. The response and relationships of muscle capillarization, interstitial vascular endothelial growth factor (VEGF), and microvascular blood flow to aerobic exercise training were investigated. Vastus lateralis biopsies were obtained before and after exercise training for the measurement of capillarization. Muscle interstitial VEGF protein and microvascular blood flow were measured at rest and during submaximal exercise at PRE, 1-WK, and 8-WKS by microdialysis. Exercise training increased (20%-25%) capillary contacts of type I, IIA, and IIB fibers in YW and AW. Interstitial VEGF protein was higher in AW than YW at rest and was higher in YW than AW during exercise independent of training status. Differences in muscle capillarization were not explained by secreted VEGF nor were differences in VEGF explained by microvascular blood flow. These results confirm that aging (57-76 years age range) does not impair the muscle angiogenic response to exercise training, although sex differences may exist in similarly trained women and men.

No difference in the skeletal muscle angiogenic response to aerobic exercise training between young and aged men.

Ischaemia-induced skeletal muscle angiogenesis is impaired in aged compared with young mice. In humans, vascular endothelial growth factor (VEGF) mRNA and protein following an acute exercise bout are lower in aged compared with young untrained men. We hypothesized that exercise-induced skeletal muscle angiogenesis would be attenuated in aged compared with young men. In eight aged (mean age: 64 years) and six young (mean age: 25 years) sedentary men, muscle biopsies were obtained from the vastus lateralis prior to (Pre), after 1 week and after 8 weeks of an aerobic exercise training program for the measurement of capillarization and VEGF mRNA. Dialysate VEGF protein collected from the muscle interstitial space was measured at rest and during submaximal exercise at Pre, 1 week and 8 weeks. Exercise training increased capillary contacts (CC) and capillary-to-fibre perimeter exchange index (CFPE) of type I and IIA fibres similarly in young and aged. The CC of type IIA and IIB fibres was lower in aged compared with young independent of training status. Exercise-induced interstitial VEGF protein was lower in aged compared with young independent of training status. In untrained, greater exercise-induced interstitial VEGF protein during exercise was associated with greater type I, IIA and IIB CC. Exercise training increased VEGF mRNA similarly in young and aged. These results demonstrate that the angiogenic response to aerobic exercise training is not altered during the ageing process in humans. In addition, muscular activity-associated increases in interstitial VEGF protein may play an important role in the maintenance of skeletal muscle capillarization across the life span.

Collagen, cross-linking, and advanced glycation end products in aging human skeletal muscle.

We examined intramuscular endomysial collagen, cross-linking, and advanced glycation end products, as well as the general and contractile protein concentration of 20 young (25 +/- 3 yr) and 22 old (78 +/- 6 yr, range: 70-93 yr) sedentary men and women to better understand the underlying basis of changes in skeletal muscle mass and function that occur with aging. The old individuals had an impaired ability (increased time) (P < 0.05) to climb stairs (80%), rise from a chair (56%), and walk (44%), as well as lower (P < 0.05) quadriceps muscle volume (-29%), muscle strength (-35%), muscle power (-48%), and strength (-17%) and power (-33%) normalized to muscle size. Vastus lateralis muscle biopsies revealed that intramuscular endomysial collagen (young: 9.6 +/- 1.1, old: 10.2 +/- 1.2 microg/mg muscle wet wt) and collagen cross-linking (hydroxylysylpyridinoline) (young: 395 +/- 65, old: 351 +/- 45 mmol hydroxylysylpyridinoline/mol collagen) were unchanged (P > 0.05) with aging. The advanced glycation end product, pentosidine, was increased (P < 0.05) by approximately 200% (young: 5.2 +/- 1.3, old: 15.9 +/- 4.5 mmol pentosidine/mol collagen) with aging. While myofibrillar protein concentration was lower (-5%, P < 0.05), the concentration of the main contractile proteins myosin and actin were unchanged (P > 0.05) with aging. These data suggest that the synthesis and degradation of proteins responsible for the generation (myosin and actin) and transfer (collagen and pyridinoline cross-links) of muscle force are tightly regulated in aging muscle. Glycation-related cross-linking of intramuscular connective tissue may contribute to altered muscle force transmission and muscle function with healthy aging.

Contractile protein concentrations in human single muscle fibers.

The intent of this investigation was twofold: (1) to develop a convenient method for analyzing skeletal muscle protein concentrations in a large number of individual human single fibers and (2) to compare the myosin heavy chain (MHC) and actin concentrations in fibers expressing pure MHC I or MHC IIa. Individual vastus lateralis fibers were dissected from five individuals (3 M, 2 F; 24 +/- 1 years) and used to determine single fiber total protein (TP) concentration and MHC distribution. Fibers expressing pure MHC I and MHC IIa were further analyzed for MHC (252 fibers; mean of 50/subject) and actin (160 fibers; mean of 32/subject) concentration relative to TP. Single fiber MHC concentration was 26 +/- 4% greater (P < 0.05) in MHC IIa (364 +/- 39 micrograms MHC/mg TP) vs. MHC I (266 +/- 29 micrograms MHC/mg TP) fibers. No differences (P > 0.05) were noted in single fiber actin concentration (MHC I: 171 +/- 17 micrograms actin/mg TP; MHC IIa: 165 +/- 17 micrograms actin/mg TP). These data indicate that within the TP fraction, skeletal muscle fibers contain differing amounts of MHC, and this appears to be fiber type specific. These data and methods have implications for the study of human muscle fiber type specific alterations in various protein concentrations in response to exercise, models of unloading, and aging.

Influence of creatine monohydrate ingestion on muscle metabolites and intense exercise capacity in individuals with multiple sclerosis.

OBJECTIVE: To evaluate the effectiveness of ingesting creatine monohydrate in elevating intramuscular creatine stores and improving exercise capacity in individuals with multiple sclerosis (MS). DESIGN: Randomized, double-blind, placebo-controlled, pre-posttrial. SETTING: A university-based exercise physiology laboratory. PARTICIPANTS: Sixteen individuals with relapsing-remitting MS (median Expanded Disability Status Scale score, 4.75; range, 1.5-6.0). INTERVENTION: Eight individuals with MS were randomized to the creatine group (20g/d of creatine monohydrate for 5d), and 8 others were randomized to the placebo group. Needle biopsies were performed on the vastus lateralis at rest before and after treatment. Subjects performed 3 bouts of 30 maximal knee extensions and flexions at 180 degrees /s with 1 minute of recovery between bouts before and after treatment. MAIN OUTCOME MEASURES: Intramuscular total creatine, phosphocreatine, free creatine, and total work output. RESULTS: Creatine ingestion did not significantly elevate intramuscular total creatine, phosphocreatine, or free creatine or improve total work production. CONCLUSION: Creatine ingestion had no significant effect on muscle creatine stores or high-intensity exercise capacity in individuals with MS.