Effects of exercise and dietary epigallocatechin gallate and β-alanine on skeletal muscle in aged mice.

Aging leads to sarcopenia and loss of physical function. We examined whether voluntary wheel running, when combined with dietary supplementation with (-)-epigallocatechin-3-gallate (EGCG) and β-alanine (β-ALA), could improve muscle function and alter gene expression in the gastrocnemius of aged mice. Seventeen-month-old BALB/cByJ mice were given access to a running wheel or remained sedentary for 41 days while receiving either AIN-93M (standard feed) or AIN-93M containing 1.5 mg·kg(-1) EGCG and 3.43 mg·kg(-1) β-ALA. Mice underwent tests over 11 days from day 29 to day 39 of the study period, including muscle function testing (grip strength, treadmill exhaustive fatigue, rotarod). Following a rest day, mice were euthanized and gastrocnemii were collected for analysis of gene expression by quantitative PCR. Voluntary wheel running (VWR) improved rotarod and treadmill exhaustive fatigue performance and maintained grip strength in aged mice, while dietary intervention had no effect. VWR increased gastrocnemius expression of several genes, including those encoding interleukin-6 (Il6, p = 0.001), superoxide dismutase 1 (Sod1, p = 0.046), peroxisome proliferator-activated receptor gamma coactivator 1-α (Ppargc1a, p = 0.013), forkhead box protein O3 (Foxo3, p = 0.005), and brain-derived neurotrophic factor (Bdnf, p = 0.008), while reducing gastrocnemius levels of the lipid peroxidation marker 4-hydroxynonenal (p = 0.019). Dietary intervention alone increased gastrocnemius expression of Ppargc1a (p = 0.033) and genes encoding NAD-dependent protein deacetylase sirtuin-1 (Sirt1, p = 0.039), insulin-like growth factor I (Igf1, p = 0.003), and macrophage marker CD11b (Itgam, p = 0.016). Exercise and a diet containing β-ALA and EGCG differentially regulated gene expression in the gastrocnemius of aged mice, while VWR but not dietary intervention improved muscle function. We found no synergistic effects between dietary intervention and VWR.

[1]  M. Tarnopolsky,et al.  β-Alanine Supplementation Does Not Augment the Skeletal Muscle Adaptive Response to 6 Weeks of Sprint Interval Training. , 2015, International Journal of Sport Nutrition & Exercise Metabolism.

[2]  Ted G. Graber,et al.  Voluntary Aerobic Exercise Reverses Frailty in Old Mice. , 2015, The journals of gerontology. Series A, Biological sciences and medical sciences.

[3]  A. Kalinkovich,et al.  Sarcopenia – The search for emerging biomarkers , 2015, Ageing Research Reviews.

[4]  B. Pence,et al.  Exercise but not (–)-epigallocatechin-3-gallate or β-alanine enhances physical fitness, brain plasticity, and behavioral performance in mice , 2015, Physiology & Behavior.

[5]  C. Stewart,et al.  Longevity and skeletal muscle mass: the role of IGF signalling, the sirtuins, dietary restriction and protein intake , 2015, Aging cell.

[6]  J. Rhodes,et al.  Mouse genetic differences in voluntary wheel running, adult hippocampal neurogenesis and learning on the multi-strain-adapted plus water maze , 2015, Behavioural Brain Research.

[7]  Junaith S Mohamed,et al.  Green tea extract attenuates muscle loss and improves muscle function during disuse, but fails to improve muscle recovery following unloading in aged rats. , 2015, Journal of applied physiology.

[8]  Stephen A. Martin,et al.  Voluntary wheel running, but not a diet containing (−)-epigallocatechin-3-gallate and β-alanine, improves learning, memory and hippocampal neurogenesis in aged mice , 2014, Behavioural Brain Research.

[9]  S. Pereira,et al.  Epigallocatechin-3-gallate improves plantaris muscle recovery after disuse in aged rats , 2014, Experimental Gerontology.

[10]  J. Oliver,et al.  Effects of 28 days of beta-alanine and creatine supplementation on muscle carnosine, body composition and exercise performance in recreationally active females , 2012, Journal of the International Society of Sports Nutrition.

[11]  M. Cesari,et al.  Mitochondrial dysfunction and sarcopenia of aging: from signaling pathways to clinical trials. , 2013, The international journal of biochemistry & cell biology.

[12]  Stephen A. Martin,et al.  Forced treadmill exercise training exacerbates inflammation and causes mortality while voluntary wheel training is protective in a mouse model of colitis , 2013, Brain, Behavior, and Immunity.

[13]  B. Pedersen.  Muscle as a secretory organ. , 2013, Comprehensive Physiology.

[14]  R. Dantzer,et al.  Effects of voluntary wheel running on LPS-induced sickness behavior in aged mice , 2013, Brain, Behavior, and Immunity.

[15]  W. Derave,et al.  Effect of Beta-Alanine and Carnosine Supplementation on Muscle Contractility in Mice , 2012 .

[16]  R. LaMotte,et al.  Mechanisms of Itch Evoked by β-Alanine , 2012, The Journal of Neuroscience.

[17]  R. Basu,et al.  Endurance exercise as a countermeasure for aging. Diabetes 2008;57:2933–2942 , 2012, Diabetes.

[18]  S. Klaus,et al.  Acute effects of epigallocatechin gallate from green tea on oxidation and tissue incorporation of dietary lipids in mice fed a high-fat diet , 2012, International Journal of Obesity.

[19]  M. McKenna,et al.  Effects of carnosine on contractile apparatus Ca²⁺ sensitivity and sarcoplasmic reticulum Ca²⁺ release in human skeletal muscle fibers. , 2012, Journal of applied physiology.

[20]  Herman I. May,et al.  Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis , 2012, Nature.

[21]  H. Roschel,et al.  Beta-alanine (Carnosyn™) supplementation in elderly subjects (60–80 years): effects on muscle carnosine content and physical capacity , 2011, Amino Acids.

[22]  B. Rasmussen,et al.  Skeletal muscle protein balance and metabolism in the elderly. , 2011, Current aging science.

[23]  Luigi Ferrucci,et al.  Sarcopenia with limited mobility: an international consensus. , 2011, Journal of the American Medical Directors Association.

[24]  J. Lambert,et al.  (-)-Epigallocatechin-3-gallate increases the expression of genes related to fat oxidation in the skeletal muscle of high fat-fed mice. , 2011, Food & function.

[25]  R. Ransohoff,et al.  Macrophages recruited via CCR2 produce insulin‐like growth factor‐1 to repair acute skeletal muscle injury , 2011, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[26]  K. Petersen,et al.  Targeted expression of catalase to mitochondria prevents age-associated reductions in mitochondrial function and insulin resistance. , 2010, Cell metabolism.

[27]  B. Zhu,et al.  Mitochondrial superoxide dismutase SOD2, but not cytosolic SOD1, plays a critical role in protection against glutamate-induced oxidative stress and cell death in HT22 neuronal cells. , 2010, Free radical biology & medicine.

[28]  W. Derave,et al.  Muscle Carnosine Metabolism and β-Alanine Supplementation in Relation to Exercise and Training , 2010, Sports medicine.

[29]  C. Leeuwenburgh,et al.  Skeletal muscle autophagy and apoptosis during aging: Effects of calorie restriction and life-long exercise , 2010, Experimental Gerontology.

[30]  M. Jois,et al.  Green tea, black tea, and epigallocatechin modify body composition, improve glucose tolerance, and differentially alter metabolic gene expression in rats fed a high-fat diet. , 2009, Nutrition research.

[31]  Q. Li,et al.  Long-term administration of green tea catechins prevents age-related spatial learning and memory decline in C57BL/6 J mice by regulating hippocampal cyclic amp-response element binding protein signaling cascade , 2009, Neuroscience.

[32]  M. J. Hartman,et al.  The effect of beta-alanine supplementation on neuromuscular fatigue in elderly (55–92 Years): a double-blind randomized study , 2008, Journal of the International Society of Sports Nutrition.

[33]  I. Papet,et al.  Antioxidant supplementation restores defective leucine stimulation of protein synthesis in skeletal muscle from old rats. , 2008, The Journal of nutrition.

[34]  Ian R. Lanza,et al.  Endurance Exercise as a Countermeasure for Aging , 2008, Diabetes.

[35]  W. Derave,et al.  Creatine supplementation augments skeletal muscle carnosine content in senescence-accelerated mice (SAMP8). , 2008, Rejuvenation research.

[36]  P. Kalaiselvi,et al.  Repletion of antioxidant status by EGCG and retardation of oxidative damage induced macromolecular anomalies in aged rats , 2008, Experimental Gerontology.

[37]  A. Goldberg,et al.  FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. , 2007, Cell metabolism.

[38]  S. Clément,et al.  Novel application of flow cytometry: determination of muscle fiber types and protein levels in whole murine skeletal muscles and heart. , 2007, Cell Motility and the Cytoskeleton.

[39]  B. Hempstead,et al.  Brain-derived neurotrophic factor: a newly described mediator of angiogenesis. , 2007, Trends in cardiovascular medicine.

[40]  T. Luedde,et al.  Targeted ablation of IKK2 improves skeletal muscle strength, maintains mass, and promotes regeneration. , 2006, The Journal of clinical investigation.

[41]  T. Unterman,et al.  FoxO proteins in insulin action and metabolism , 2005, Trends in Endocrinology & Metabolism.

[42]  Y. Boirie,et al.  Due to reverse electron transfer, mitochondrial H2O2 release increases with age in human vastus lateralis muscle although oxidative capacity is preserved , 2005, Mechanisms of Ageing and Development.

[43]  E. Plow,et al.  Distinct Roles for the α and β Subunits in the Functions of Integrin αMβ2* , 2004, Journal of Biological Chemistry.

[44]  E. Plow,et al.  Distinct roles for the alpha and beta subunits in the functions of integrin alphaMbeta2. , 2005, The Journal of biological chemistry.

[45]  Oprs Alert.  Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers , 2005 .

[46]  P. Kloetzel,et al.  Green Tea Epigallocatechin-3-Gallate Mediates T Cellular NF-κB Inhibition and Exerts Neuroprotection in Autoimmune Encephalomyelitis1 , 2004, The Journal of Immunology.

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

[48]  Henriette Pilegaard,et al.  Exercise induces transient transcriptional activation of the PGC‐1α gene in human skeletal muscle , 2003, The Journal of physiology.

[49]  P. Puigserver,et al.  Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. , 2003, Endocrine reviews.

[50]  Geert J. P. L. Kops,et al.  Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress , 2002, Nature.

[51]  K. Nair,et al.  Effects of passive smoking on coronary circulation. , 2002 .

[52]  R. Wolfe,et al.  Basal muscle amino acid kinetics and protein synthesis in healthy young and older men. , 2001, JAMA.

[53]  C. Leeuwenburgh,et al.  Oxidative stress and antioxidants in exercise. , 2001, Current medicinal chemistry.

[54]  B. Harrison,et al.  Cardiac and skeletal muscle adaptations to voluntary wheel running in the mouse. , 2001, Journal of applied physiology.

[55]  J. Aiken,et al.  Mitochondrial DNA deletion mutations colocalize with segmental electron transport system abnormalities, muscle fiber atrophy, fiber splitting, and oxidative damage in sarcopenia , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[56]  S. Trevisanato,et al.  Tea and health. , 2009, Nutrition reviews.

[57]  K. Kunze,et al.  Concentrations of free carnosine (a putative membrane-protective antioxidant) in human muscle biopsies and rat muscles. , 1999, Archives of gerontology and geriatrics.

[58]  K. Nair,et al.  Effect of age on in vivo rates of mitochondrial protein synthesis in human skeletal muscle. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[59]  A. Boldyrev,et al.  Natural histidine-containing dipeptide carnosine as a potent hydrophilic antioxidant with membrane stabilizing function. A biomedical aspect. , 1993, Molecular and chemical neuropathology.

[60]  P. Johnson,et al.  Histidine dipeptide levels in ageing and hypertensive rat skeletal and cardiac muscles. , 1992, Comparative biochemistry and physiology. B, Comparative biochemistry.