Effects of exercise on mitochondrial content and function in aging human skeletal muscle.

Skeletal muscle mitochondria are implicated with age-related loss of function and insulin resistance. We examined the effects of exercise on skeletal muscle mitochondria in older (age = 67.3 +/- 0.6 years) men (n = 5) and women (n = 3). Similar increases in (p <.01) cardiolipin (88.2 +/- 9.0 to 130.6 +/- 7.5 microg/mU creatine kinase activity [CK]) and the total mitochondrial DNA (1264 +/- 170 to 1895 +/- 273 copies per diploid of nuclear genome) reflected increased mitochondria content. Succinate oxidase activity, complexes 2-4 of the electron transport chain (ETC), increased from 0.13 +/- 0.02 to 0.20 +/- 0.02 U/mU CK (p <.01). This improvement was more pronounced (p <.05) in subsarcolemmal (127 +/- 48%) compared to intermyofibrillar (56 +/- 12%) mitochondria. NADH oxidase activity, representing total ETC activity, increased from 0.51 +/- 0.09 to 1.00 +/- 0.09 U/mU CK (p <.01). In conclusion, exercise enhances mitochondria ETC activity in older human skeletal muscle, particularly in subsarcolemmal mitochondria, which is likely related to the concomitant increases in mitochondrial biogenesis.

[1]  D. Muoio,et al.  Subsarcolemmal and intermyofibrillar mitochondria play distinct roles in regulating skeletal muscle fatty acid metabolism. , 2005, American journal of physiology. Cell physiology.

[2]  K. Nair,et al.  Decline in skeletal muscle mitochondrial function with aging in humans. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[3]  E. V. Menshikova,et al.  Effects of weight loss and physical activity on skeletal muscle mitochondrial function in obesity. , 2005, American journal of physiology. Endocrinology and metabolism.

[4]  B. Goodpaster,et al.  Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes. , 2005, Diabetes.

[5]  B. Goodpaster,et al.  Exercise training increases intramyocellular lipid and oxidative capacity in older adults. , 2004, American journal of physiology. Endocrinology and metabolism.

[6]  D. Kelley,et al.  High-performance liquid chromatography-based methods of enzymatic analysis: electron transport chain activity in mitochondria from human skeletal muscle. , 2004, Analytical biochemistry.

[7]  P. Ritz,et al.  Muscle fat oxidative capacity is not impaired by age but by physical inactivity: association with insulin sensitivity , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  Ewald R. Weibel,et al.  The ultrastructure of the normal human skeletal muscle , 1973, Pflügers Archiv.

[9]  D. G. Newman,et al.  Muscle oxidative capacity is a better predictor of insulin sensitivity than lipid status. , 2003, The Journal of clinical endocrinology and metabolism.

[10]  B. Goodpaster,et al.  Enhanced fat oxidation through physical activity is associated with improvements in insulin sensitivity in obesity. , 2003, Diabetes.

[11]  K. Nair,et al.  Impact of aerobic exercise training on age-related changes in insulin sensitivity and muscle oxidative capacity. , 2003, Diabetes.

[12]  M. Daly,et al.  PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes , 2003, Nature Genetics.

[13]  A. Butte,et al.  Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1 , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Phillip Nagley,et al.  Precise determination of mitochondrial DNA copy number in human skeletal and cardiac muscle by a PCR-based assay: lack of change of copy number with age. , 2003, Nucleic acids research.

[15]  Douglas L. Rothman,et al.  Mitochondrial Dysfunction in the Elderly: Possible Role in Insulin Resistance , 2003, Science.

[16]  A. Vinogradov,et al.  In situ assay of the intramitochondrial enzymes: use of alamethicin for permeabilization of mitochondria. , 2003, Analytical biochemistry.

[17]  D. Hood,et al.  Plasticity of Skeletal Muscle Mitochondria in Response to Contractile Activity , 2003, Experimental physiology.

[18]  Jing He,et al.  Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. , 2002, Diabetes.

[19]  G. Hunter,et al.  Age is independently related to muscle metabolic capacity in premenopausal women. , 2002, Journal of applied physiology.

[20]  Eli Carmeli,et al.  The biochemistry of aging muscle , 2002, Experimental Gerontology.

[21]  M. Jackson,et al.  Exercise and skeletal muscle ageing: cellular and molecular mechanisms , 2002, Ageing Research Reviews.

[22]  G. Bell,et al.  The effect of concurrent endurance and strength training on quantitative estimates of subsarcolemmal and intermyofibrillar mitochondria. , 2002, International journal of sports medicine.

[23]  H. C. Ong,et al.  Effect of a microstructure on the formation of self-assembled laser cavities in polycrystalline ZnO , 2001 .

[24]  D. Kelley,et al.  Hexokinase isozyme distribution in human skeletal muscle. , 2001, Diabetes.

[25]  M. E. Cress,et al.  Large energetic adaptations of elderly muscle to resistance and endurance training. , 2001, Journal of applied physiology.

[26]  D. Hood.  Plasticity in Skeletal, Cardiac, and Smooth Muscle Invited Review: Contractile activity-induced mitochondrial biogenesis in skeletal muscle , 2001 .

[27]  H Tanke,et al.  Simultaneous A8344G heteroplasmy and mitochondrial DNA copy number quantification in myoclonus epilepsy and ragged-red fibers (MERRF) syndrome by a multiplex molecular beacon based real-time fluorescence PCR. , 2001, Nucleic acids research.

[28]  D A Follmann,et al.  The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2000 by The Endocrine Society Quantitative Insulin Sensitivity Check Index: A Simple, Accurate Method for Assessing Insulin Sensitivity In Humans , 2022 .

[29]  S. Dimauro,et al.  Microanalysis of cardiolipin in small biopsies including skeletal muscle from patients with mitochondrial disease. , 1999, Journal of lipid research.

[30]  W. Willis,et al.  Differential responses to endurance training in subsarcolemmal and intermyofibrillar mitochondria. , 1998, Journal of applied physiology.

[31]  G. Bell,et al.  The effect of aerobic exercise training on the distribution of succinate dehydrogenase activity throughout muscle fibres. , 1998, Canadian journal of applied physiology = Revue canadienne de physiologie appliquee.

[32]  D. Turnbull,et al.  Effects of physical activity and age on mitochondrial function. , 1996, QJM : monthly journal of the Association of Physicians.

[33]  J. Simoneau,et al.  Skeletal muscle glycolytic and oxidative enzyme capacities are determinants of insulin sensitivity and muscle composition in obese women , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[34]  S. Papa,et al.  Decline with age of the respiratory chain activity in human skeletal muscle. , 1994, Biochimica et biophysica acta.

[35]  D. Hood,et al.  Properties of skeletal muscle mitochondria isolated from subsarcolemmal and intermyofibrillar regions. , 1993, The American journal of physiology.

[36]  J. Cooper,et al.  Analyses of mitochondrial respiratory chain function and mitochondrial DNA deletion in human skeletal muscle: Effect of ageing , 1992, Journal of the Neurological Sciences.

[37]  M. Brown,et al.  Histochemical and enzymatic comparison of the gastrocnemius muscle of young and elderly men and women. , 1992, Journal of gerontology.

[38]  M. Brown,et al.  Skeletal muscle adaptations to endurance training in 60- to 70-yr-old men and women. , 1992, Journal of applied physiology.

[39]  Edward Byrne,et al.  DECLINE IN SKELETAL MUSCLE MITOCHONDRIAL RESPIRATORY CHAIN FUNCTION: POSSIBLE FACTOR IN AGEING , 1989, The Lancet.

[40]  M. Sjöström,et al.  Biochemical and morphometric properties of mitochondrial populations in human muscle fibres. , 1985, Clinical science.

[41]  W. Evans,et al.  Suction applied to a muscle biopsy maximizes sample size. , 1982, Medicine and science in sports and exercise.

[42]  F. Booth,et al.  Populations of rat skeletal muscle mitochondria after exercise and immobilization. , 1980, Journal of applied physiology: respiratory, environmental and exercise physiology.

[43]  C. Hoppel,et al.  Biochemical properties of subsarcolemmal and interfibrillar mitochondria isolated from rat cardiac muscle. , 1977, The Journal of biological chemistry.

[44]  J. A. V Pritchard,et al.  CANCER DETECTION , 1976, The Lancet.

[45]  R. Huston,et al.  Effects of exercise, training, and diet on muscle citric acid cycle enzyme activity. , 1973, Canadian journal of biochemistry.

[46]  J. Holloszy,et al.  Mitochondrial citric acid cycle and related enzymes: adaptive response to exercise. , 1970, Biochemical and biophysical research communications.