Stephen E. Alway, Ph.D.
	Professor and Chair, Exercise Physiology Graduate Training: McMaster University Fellowship: University of Waterloo; University of Texas Southwestern Medical School
	Office: -HSS Lab: 212, 214, 215 HSN (Annex) PO Box 9227 Morgantown, WV 26506	Email: salway@hsc.wvu.edu Phone:304-293-0772  304-293-7767 Fax: 304-293-7105

Research Interests:

Congestive heart failure (CHF) is a syndrome that is characterized by cardiac dysfunction and symptoms of exercise intolerance, including breathlessness or fatigue. Peripheral pathological changes in skeletal muscle, including muscle wasting/atrophy, and a reduction in oxidative fibers, play important roles in exercise intolerance. The incidence of CHF increases with age, and the clinical outcomes of CHF in aging are exacerbated by aging-associated muscle loss (sarcopenia). Both elevated oxidative stress and increased cellular apoptosis have been strongly implicated in the pathogenesis of sarcopenia, a muscle-wasting disease of significant importance in the elderly. Sarcopenia results in a loss of function and reduces the quality of life in the aged, especially in individuals with restricted mobility or extended hospitalization. Mitochondrial dysfunction and loss of mitochondria may contribute to elevated oxidative stress and apoptosis and underlie sarcopenia.

Our  research program is targeted to understand muscle growth and loss in conditions that include CHF, aging, denervation and disuse. The three broad areas of inquiry in our laboratory include: (i) understanding cellular and molecular adaptations to muscle hypertrophy/growth and aging , (ii) the role of apoptosis in skeletal and cardiac muscle remodeling during aging (iii) the role of oxidative stress in regulating adaptation and maladaptation to exercise and loading.  In addition to studies in human subjects, these projects have included examining several animal models including birds, rats and mice. Our approach has been to utilize various perturbations including resistance exercise, stretch and aerobic exercise to challenge the skeletal and cardiac muscle systems, and to utilize cellular and molecular probes, genetically modified animals and aged animals to evaluate the responses from the level of the gene to the whole muscle. Our recent work has shown that oxidative stress is elevated with aging and various muscle wasting conditions, and this can be offset via nutritional approaches. In addition, reducing oxidative stress may lead to reduced apoptotic-associated loss of muscle nuclei, thereby reducing the effects of aging-induced muscle loss (sarcopenia). This work has been funded by NIH for almost 20 years.

Selected References from publications in the past 3 years:

Apoptosis (most recent 5 years)

1. Wang Y, Hao Y. and ALWAY SE.  Suppression of Glycogen Synthase Kinase 3 beta (GSK-3ß) Activation by M-cadherin protects C2C12 Myoblasts against mitochondrial-associated Apoptosis during Myogenic Differentiation. J. Cell Science 124 (22):3835-3847, 2011.
2. Hao Y,  Jackson JR, Wang Y, Edens N, Pereira SL, and ALWAYS SE.  β-Hydroxy-β-methylbutyrate reduces muscle mass loss and myonuclear apoptosis following hindlimb suspension and reloading in aged rats.  Am J Physiol Regul Integr Comp Physiol. 301(3):R701-715,  2011. PMID: 21697520
3. Quadrilatero J, ALWAY SE and Dupont-Versteegden E.  Muscle Apoptotic Response to Physical Activity: Potential Mechanisms for Protection. Appl. Physiol. Met. Nutr. 36: 608-617, 2011. PMID: 21936642
4. Ryan MJ, Jackson JR, Hao Y, Leonard SS and ALWAY SE. Inhibition of xanthine oxidase reduces oxidative stress and improves skeletal muscle function in response to electrically stimulated isometric contractions in aged mice. Free Radic Biol Med  51(1):38-52, 2011. PMID: 21530649
5. Jackson JR, Ryan MJ, and ALWAY SE.  Long-Term Supplementation with Resveratrol Alleviates Oxidative Stress, but does not Attenuate Sarcopenia in Aged Mice.  J. Gerontol: Biological Sciences  66 (7):751-764, 2011.  PMID: 21454355
6. ALWAY SE and Siu PM.  Nuclear apoptosis and sarcopenia. Sarcopenia-Age-Related Muscle Wasting and Weakness: Mechanisms and Treatments. G. Lynch, (Editor). Springer, 2011, pp. 173-206
7. ALWAY SE.  Chapter 11. Apoptosis in Skeletal Muscle Health and Conditions of Muscle Wasting. In: Modern Insights into Disease from Molecules to Man: APOPTOSIS, Victor R. Preedy (Editor.): Science Publishers, CRC Press. 2010 pp 167-182. ISBN: 1578085837
8. Williamson CL, Dabkowski ER, Baseler WA, Croston TL, ALWAY SE and Hollander JM.  Enhanced Apoptotic Propensity in Diabetic Cardiac Mitochondria: Influence of Subcellular Spatial Location. Am J Physiol Heart Circ Physiol 298(2): H633-H642, 2010
9. ALWAY SE and Morissette MR. Chapter 4,   Apoptosis in aging muscle. Handbook of Aging.  E. J. Masoro and Steven Austad (Editors) Elsevier. 7th Edition. 2011, pp. 64-139.
10. Butler DC,  Haramizu S, Williamson DL and ALWAY SE.  Phospho-ablated Id2 is growth suppressive and pro-apoptotic in proliferating myoblasts. PLoS One, July 2009 | Volume 4 | Issue 7 | e6302-e6302, 2009
11. Siu PM and ALWAY SE.  Response and adaptation of skeletal muscle to denervation stress: the role of apoptosis in muscle loss. Front Biosci, 14:432-452, 2009.
12. Peterson JM, Wang Y, Bryner R, Williamson DL and ALWAY SE.  Bax signaling mediates palmitate-induced apoptosis in C2C12 myotubes. Am J Physiol Endocrinol Metab: 295:E1307-E1314, 2008.
13. Peterson JM, Bryner RW, Sindler A, Frisbee JC and ALWAY SE.  Mitochondria apoptotic signaling is elevated in cardiac but not skeletal muscle in the obese Zucker rat and is reduced with aerobic exercise. J Appl Physiol  105:1934-1943, 2008.
14. Pistilli EE and ALWAYS SE.  Systemic elevation of interleukin-15 in vivo promotes apoptosis in skeletal muscles of young adult and aged rats. Biochem Biophys Res Commun 373:20-24, 2008.
15. Siu PM and ALWAYS SE.  Denervation-induced apoptosis and oxidative stress in skeletal muscle Front. Biosci. Free Radicals in Biology and Medicine, 2008: Chapter 9 pp 1-31, 2008  ISBN: 978-81-308-0267-1.
16. ALWAY SE, and Siu PM. Nuclear apoptosis contributes to sarcopenia. Exerc. Sport Sci. Rev., Vol. 36, No. 2, pp. 51-57, 2008
17. ALWAY SE "Pathways of Apoptosis in Muscle", in Hood, D. (ed.), Mitochondrial Biogenesis: Processes, Regulation, Functions and Disease, 2007. The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London  (online at http://www.hstalks.com/?t=BL0151480-Alway)
18. ALWAY, SE "Pathways of Apoptosis in Muscle", in Hood, D. (ed.), Mitochondrial Biogenesis: Processes, Regulation, Functions and Disease, 2007. The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London.
19. Degens H, Swisher AK, Heijdra YF, Siu PM, Dekhuijzen PNR, ALWAY SE.  Apoptosis and Id2 expression in diaphragm and soleus muscle from the emphysematous hamster. Am. J. Physiol: Cell Physiol.  293:R135-R144, 2007.
20. Pistilli EE, Siu PM, and ALWAYS SE.  Responses of interleukin-15 to aging and skeletal muscle unloading-induced apoptosis in rats and quails. Am. J. Physiol: Cell Physiol.  292 (4):C1298-C1304, 2007.
    • Smith CA, Stauber FD, Waters CL, ALWAY SE and Stauber WT. Transforming growth factor-β following skeletal muscle strain injury in rats. J Appl Physiol  102 (2):755-761, 2007.

Oxidative Stress (most recent 4 years)

1. ALWAY SE, Cutlip RG.  Resistance loading and signaling assays for oxidative stress in rodent skeletal muscle. Methods in Molecular Biology 798:185-211, 2012.
2. Jackson JR, Ryan MJ, Hao Y, ALWAY SE.  Mediation of Antioxidant Capacity and Apoptotic Signaling by Resveratrol Following Muscle Disuse in the Gastrocnemius Muscles of Young and Old Rats" Am J Physiol Regul Integr Comp Physiol.  299 (6): R1572-R1581, 2010.
3. Ryan MJ, Dudash HJ, Docherty D, Geronilla KB, Baker BA, Haff GG, Cutlip RG, and ALWAY SE. Vitamin E and C supplementation reduces oxidative stress and improves antioxidant enzymes and positive muscle work in chronically loaded dorsiflexor muscles of aged rats. Exp Gerontol  45: 882-895, 2010.
4. Ryan MJ, Jackson JR, Hao Y, Williamson, C., Hollander JM and ALWAY SE. Suppression of oxidative stress by resveratrol after isometric contractions in gastrocnemius muscles of aged rats. J Gerontol A Biol Sci Med Sci 65:815-831, 2010.
5. Siu PM, Wang Y, and ALWAY SE.  Caspase-independent and caspase-dependent apoptotic signaling coordinate apoptosis induced by H2O2-mediated oxidative stress in differentiated C2C12 myotubes  Life Sci. Res.  84:468-481,2009.
6. Siu PM, Pistilli EE, ALWAY SE. Age-dependent increase in oxidative stress in gastrocnemius muscle with unloading. J Appl Physiol :105:1695-1705, 2008.
7. Ryan MJ, Dudash HJ, Docherty M, Geronilla KB, Baker BA, Cutlip RG, and ALWAY SE.  Aging-dependent regulation of antioxidant enzymes and redox status in chronically loaded rat dorsiflexor muscles . J Gerontol A Biol Sci Med Sci 63: 1015-1026, 2008.
8. Siu PM, and ALWAY SE.  Denervation-induced apoptosis and oxidative stress in skeletal muscle Front. Biosci. Free Radicals in Biology and Medicine, 2008: Chapter 9 pp 1-31, 2008  ISBN: 978-81-308-0267-1.

Muscle Adaptations (most recent 4 years)

1. Sharif S, Thomas JM, Donley DA, Gilleland DL, Bonner DE, McCrory JL, Hornsby WG, Zhao H, Lively MW, Hornsby JA and ALWAY SE. Resistance exercise reduces skeletal muscle cachexia and improves muscle function in rheumatoid arthritis. Case Rep Med 2011: 1-7,2011. Article ID 205691, PMID: 3235946
2. Drake J, ALWAY SE, Hollander JM, and Williamson DL.  AICAR treatment for 14 days normalizes obesity-induced dysregulation of TORC1 signaling and translational capacity in fasted skeletal muscle.Am J Physiol Regul Integr Comp Physiol.  299 (6):R1546-R1554, 2010
3. Williamson DL, Butler DC and ALWAY SE.  AMPK inhibits myoblast differentiation through a PGC-1α -dependent mechanism. Am J Physiol Endocrinol Metab 297(2):E304-E314,2009.
4. Siu PM, Pistilli EE, ALWAY SE.  Age-dependent increase in oxidative stress in gastrocnemius muscle with unloading. J Appl Physiol 105:1695-1705, 2008.
5. Peterson JM, Bryner R and ALWAY SE.   Satellite cell proliferation is reduced in muscles of obese Zucker rats, but restored with loading. Am J Physiol Cell Physiol  295:C521-C528, 2008.
6. Peterson JM, Bryner R, Frisbee JC and ALWAY SE. Effects of Exercise and Obesity on UCP3. Content in Rat Hindlimb Muscles. Med. Sci. Sports Exerc. 40 (9) 1616–1622, 2008.
7. Velan SS, Raylman R, Frisbee JC, Spencer R and ALWAY SE.  Distinct Patterns of Fat Metabolism in Skeletal Muscle of Normal Weight, Overweight, and Obese Humans. Am J Physiol Regul Integr Comp Physiol.  295: R1060-R1065, 2008.

Personnel

• Brian Bennett, Graduate Student
• Joseph Wilson, Graduate Student

Dr. Stephen Alway, Brian Bennett, Joseph Wilson