Associate Professor Phil Sheard
Department of Physiology
Otago School of Medical Sciences
University of Otago
PO Box 913
Fax: +64 3 479 7323
Member of Cellular & Molecular Neuroscience.
Sarcopenia - age-related loss of muscle mass and strength.
Sarcopenia is the widely described phenomenon of age-related loss of muscle mass and strength. The functional impairments that arise from progressive weakness have profound implications for the elderly, and therefore for modern society. Sarcopenia manifests as a death of muscle fibers and decrease in cross sectional area of surviving fibers, the triggers for this progressive loss of muscle remain largely unknown. We are particularly interested in the role the motor nerve terminal may play in driving sarcopenia, since progressive withdrawal of the motor nerve from the muscle fibre also seems to be a conspicuous feature of elderly muscle. We are currently examining age-related changes to the neuromuscular junction with a view to using this information to establish whether motor nerve withdrawal is a cause of muscle fibre death, or a consequence of it.
We use electrophysiology, electron microscopy, confocal microscopy, fluorescence and transmitted light microscopy, histochemistry, immunohistochemistry, and anterograde and retrograde cell tracing techniques.
- Cornwall, J.C., S.F. Farrell, & P.W. Sheard. Fiber types of human suboccipital muscles. Eur J Anat (2016) 20(1): 31-36.
- Gillon, A.P. & P.W. Sheard. Elderly mouse skeletal muscle fibres have a diminished capacity to upregulate NCAM production in response to denervation. Biogerontology (2015) 16:811-823.
- Thaung, H.P.A., J C Baldi, H-Y Wang, G Hughes, RF Cook, CT Bussey, PW Sheard, A Bahn, PP Jones, DO Schwenke & RR Lamberts. Increased efferent cardiac sympathetic nerve activity and defective intrinsic heart rate regulation in type 2 diabetes. Diabetes (2015) 64(8):2944-2956.
- N.N. Lal & P.W. Sheard. The emergence of dying myofibers with abnormal dystrophin-encircled vacuolar inclusions in elderly mouse skeletal muscles. Biogerontology (2015) 16:443-459.
- D Rowlands, R Page, W Sukala, M Giri, I Hayat, B Cheema, I Lys, M Leikis, P Sheard, St. J Wakefield, B Breier, Y Hathout, K Brown, R Marathi, F Orkunoglu-Suer, J Devaney, S Ghimbovschi, B Leiken, J Krebs, W Hopkins, & E Hoffman. Multi-Omic integrated networks connect DNA methylation and microRNA with skeletal muscle plasticity to chronic exercise in type 2 diabetic obesity. Physiological Genomics (2014) 46 (20): 747-765. 10.1152/physiolgenomics.00024.2014
- S Hellyer, A Selwood, R van Ginkel, R Munday, P Sheard, C Miles, L Rhodes & D S Kerr. In vitro labeling of muscle type nicotinic receptors using a fluorophore-conjugated pinnatoxin F derivative. Toxicon (2014) 87: 17-25.
- C. D. McMahon, R. Chai, H. Radley-Crabb, T. Watson, K. G. Matthews, P. W. Sheard, Z. Soffe, M. D. Grounds & T. Shavlakadze. Life-long exercise and locally produced IGF-1 have a modest influence on reducing age-related muscle wasting in mice. Scan. J. Med. Sci. Sports (2014) e423-435
- Davis, T.M., J. Cornwall, & P.W. Sheard. Modelling dichotomously-marked muscle fibre configurations. Stat Med (2013) 32:4240-4258. DOI:10.1002/sim.5806
- Sheard, P.W. & R.D. Anderson. Age-related loss of muscle fibres is highly variable amongst mouse skeletal muscles. Biogerontology 13:157-167 (2012)
- Sheard, P.W., G.S. Bewick, A.G. Woolley, J, Shaw, L. Fisher, S.W. Fong & M. J. Duxson. Investigation of neuromuscular abnormalities in neurotrophin-3 deficient mice. Eur. J. Neuroscience 31:29-41 (2010).
- Woolley, A.G., K.J. Tait, P.W. Sheard & M.J. Duxson. Developmental loss of NT-3 in vivo results in reduced levels of myelin-specific proteins and a reduced extent of myelination. Glia 56: 306-317 (2008).
- Li, C., J.L. Stanton, T.M. Robertson, J.M. Suttie, P.W. Sheard, A.J. Harris & D.E. Clark. Nerve Growth Factor mRNA Expression in the Regenerating Antler Tip of Red Deer (Cervus elaphus). PLoS ONE 2(1): e148. doi:10.1371/journal.pone.0000148 (2007).
- Sun, C-K., X-Y. Zhang, P.W. Sheard, A.I. Mabuchi, & A.M. Wheatley. Change in mitochondrial membrane potential is the key mechanism involved in early warm hepatic ischemia-reperfusion injury. Microvasc. Res. 70(1-2): 102-110 (2005).
- Homer, C., D.A.Knight, L. Hananeia, P. Sheard, J. Risk, A, Lasham, J. Royds & A.M. Braithwaite. Y-box factor YB1 controls p53 apoptotic function. Oncogene 24: 8314-8325, 2005. (on line doi:10.1038/sj.onc.1208998) (2005).
- Woolley, A.G., P.W. Sheard, & M.J. Duxson. Neurotrophin-3 null mutant mice display a postnatal motor neuropathy. Eur. J. Neuroscience 21: 2100-2110 (2005).
- Paul, A.C., P.W. Sheard, & M.J. Duxson. Development of a mammalian series-fibred muscle. Anatomical Record 287A: 571-578 (2004).
- Mabuchi, A., I. Mullaney, P.W. Sheard, P. Hessian, B.L. Mallard, M.N. Tawadrous, A. Zimmermann, H. Senoo & A.M. Wheatley. Role of hepatic stellate cell/hepatocyte interaction in the early phase of liver regeneration in the rat. J. Hepatology 40: 910-916 (2004).
- Mabuchi, A., Mullaney, I., Sheard, P., Hessian, P., Zimmerman, A., Senoo, H., and Wheatley, A. Role of hepatic stellate cells in the early phase of liver regeneration in rat: Formation of tight adhesion to parenchymal cells. Comparative Hepatology 3 S1: S29-32 (2004).
- Zhang, Y-F, C. Homer, S.J. Edwards, L. Hananeia, A. Lasham, J. Royds, P.W. Sheard & A.M. Braithwaite. Nuclear localization of Y-box factor YB1 requires wild type p53. Oncogene 22: 2782-2794 (2003).
- Maclennan, K., Y. Zheng, P.W. Sheard, S. Williams, C.L. Darlington & P.M. Smith. Adrenalectomy-induced cell death in the dentate gyrus: further characterisation using TUNEL and effects of the Ginko Biloba extract, EGb 761, and Ginkgolide B. Hippocampus 13: 212-225 (2003).
- Sheard, P.W., Paul, A., and Duxson, M.J. Intramuscular force transmission. Advances in Experimental Medicine and Biology 508: 495-499 (2002).
- Paul, A.C., P.W. Sheard, S.J. Kaufman, M.J. Duxson. Localization of alpha-7 integrins and dystrophin suggest potential for both lateral and longitudinal transmission of tension in large mammalian muscles. Cell and Tissue Research 308: 255-265 (2002).
- Sheard, P.W., K. Musaad, & M.J. Duxson. Distribution of neurotrophin receptors in the mouse neuromuscular system. International Journal of Developmental Biology 46: 569-575 (2002).