Mitochondrial Metabolism and Ageing
This group is focused on understanding how physiological stimuli such as exercise, inactivity and nutrition induce molecular signalling networks to remodel skeletal muscle in the context of health and disease. Current research at the Garvan is exploring the role of mitochondrial metabolism in the progression of muscle deterioration in diabetes and ageing, focusing on the therapeutic potential of exercise, pharmacology and nutraceuticals to maintain optimal muscle function across health span.
To achieve these goals, the group utilises cell, worm, rodent and human experimental models in combination with ‘omic’ platforms to provide detailed metabolic characterisation of skeletal muscle.
Dent, J.R. Martins, V.F. Svensson, K. LaBarge, S.A. Schlenk, N.C. Esparza, M.C. Buckner, E.H. Meyer, G.A. Hamilton, D.L. Schenk, S. Philp, A. (2017) Muscle-specific knockout of general control of amino acid synthesis 5 (GCN5) does not enhance basal or endurance exercise-induced mitochondrial adaptation. Mol Metab. Dec;6(12):1574-1584. doi: 10.1016/j.molmet.2017.10.004.
Pérez-Schindler, J. Kanhere, A. Edwards, L. Allwood, W.L. Dunn, W.B. Schenk, S. Philp, A. (2017) Exercise and high-fat feeding remodel transcript-metabolite interactive networks in mouse skeletal muscle. Scientific Reports. Oct 18;7(1):13485. doi: 10.1038/s41598-017-14081-w.
Song, S. Moore, DR. Hodson, N. Ward, C. Dent, JR. O’Leary, MF. Shaw, AM. Hamilton, DL. Sarkar, S. Gangloff, Y-G. Hornberger, TA. Spriet, LL. Heigenhauser, GJ. Philp, A. (2017) Resistance exercise initiates mechanistic target of rapamycin (mTOR) translocation and protein complex co-localisation in human skeletal muscle. Scientific Reports, Jul 10;7(1):5028. doi: 10.1038/s41598-017-05483-x.
Park,S-J. Gavrilova, O. Brown, AL. Soto, JE. Bremner, S. Kim, J. Xu, X. Yang, S. Um, J-H. Koch, LG. Britton, SL. Lieber, RL. Philp, A. Baar, K. Kohama, SG. Abel, DE. Kim, MK. Chung, JH. (2017) DNA-PK promotes the mitochondrial, metabolic and physical decline that occurs during aging. Cell Metabolism. Aug 1;26(2):447. doi: 10.1016/j.cmet.2017.07.005.
Philp, A. Schenk, S. Perez-Schindler, J. Hamilton, DL. Breen, L. Laverone, E. Jeromson, S. Phillips, SM. Baar, K. (2015) Rapamycin does not prevent increases in myofibrillar or mitochondrial protein synthesis following endurance exercise. J Physiol. Sep;593(18):4275-84.
Hamilton DL.* Philp A,* MacKenzie M, Patton A, Towler M, Gallagher I, Bodine S, and Baar K. (2014) Molecular brakes regulating mTORC1 activation in skeletal muscle following synergist ablation. Am J Physiol Endocrinol Metab. 307(4):E365-73.
Park, S-J. Ahmed, F. Philp, A. Baar, K. Williams, T. Luo, H. Ke, H. Rehmann, H. Taussig, R. Kim, M.K. Beaven, M.A. Manganiello, V. Chung, J.H. (2012). Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell. Feb 3;148(3):421-33.
Schenk, S. McCurdy, C.E. Philp, A. Chen, MZ. Holliday, MJ. Bandyopadhyay, GK. Osborn, O. Baar, K. Olefsky, JM. (2011). SIRT1 mediates enhanced skeletal muscle insulin sensitivity in calorie-restricted mice. J Clin Invest. Nov;121(11):4281-8.
Philp, A. Chen, A. Lan, D. Meyer, G.A. Murphy, A.N. Knapp, A.E. Olfert, I.M. McCurdy, C.E. Marcotte, G.R. Hogan, M.C. Baar, K. Schenk, S. (2011) Sirtuin 1 (SIRT1) deacetylase activity is not required for mitochondrial biogenesis or peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) deacetylation following endurance exercise. J. Biol. Chem. Sep 2;286(35):30561-70.
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