Age-related muscle wasting and increased frailty are major socioeconomic as well as medical problems. In the quest to extend quality of life it is important to increase the strength of elderly people sufficiently so they can carry out everyday tasks and to prevent them falling and breaking bones that are brittle due to osteoporosis. Muscles generate the mechanical strain that contributes to the maintenance of other musculoskeletal tissues, and a vicious circle is established as muscle loss results in bone loss and weakening of tendons. Molecular and proteomic approaches now provide strategies for preventing age-related muscle wasting. Here, attention is paid to the role of the GH/IGF-1 axis and the special role of the IGFI-Ec (mechano growth factor/MGF) which is derived from the IGF-I gene by alternative splicing. During aging MGF levels decline but when administered MGF activates the muscle satellite (stem) cells that “kick start” local muscle repair and induces hypertrophy. 1. Introduction When our hominid species evolved from several millions of years ago, ancient man was a hunter-gatherer, and survival required covering long distances. As well as stamina, homosapiens had to have sufficient strength to kill large animals for food. Ancient man would have sustained muscle injuries during hunting and tribal confrontations, and, from a Darwinian viewpoint, natural selection would have resulted in generations of offspring with strong and adaptable musculature; this includes rapid and effective tissue repair as this was also a requisite for survival and the continuation of the species. However, over most of this time the average life expectancy for most homosapiens was only about 25 years, that is to say a little beyond the age of reproduction. For example, in ancient Egypt the average life span was 24 years but now with developments in science and medicine this has increased by over 3-fold which presents problems for human society. In the more affluence society of today there are other factors such as overconsumption of food and alcohol and the failure to maintain an active, healthy life style. In Scandinavian countries family doctors prescribe exercise to improve the general fitness which enables individuals to maintain an active life style and to live longer. Longevity and the increasing percentage of elderly in the populations in many developed countries including the USA, Europe, and Japan present its own major socioeconomic as well as medical care problems. Therefore maintaining independence has now to be very much focused on the aging processes of
References
[1]
C. Kenyon, J. Chang, E. Gensch, A. Rudner, and R. Tabtiang, “A C. elegans mutant that lives twice as long as wild type,” Nature, vol. 366, no. 6454, pp. 461–464, 1993.
[2]
C. T. Murphy, S. A. McCarroll, C. I. Bargmann et al., “Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans,” Nature, vol. 424, no. 6946, pp. 277–283, 2003.
[3]
S. V. Brooks and J. A. Faulkner, “Severity of contraction-induced injury is affected by velocity only during stretches of large strain,” Journal of Applied Physiology, vol. 91, no. 2, pp. 661–666, 2001.
[4]
F. R. Sattler, S. Bhasin, J. He et al., “Durability of the effects of testosterone and growth hormone supplementation in older community-dwelling men: the HORMA trial,” Clinical Endocrinology, vol. 75, no. 1, pp. 103–111, 2011.
[5]
G. Goldspink, S. Y. Yang, M. Skarli, and G. Vrbova, “Local growth regulation is associated with an isoform of IGF-I that is expressed in normal muscles but not in dystrophic muscles,” The Journal of Physiology, vol. 495, pp. 162–163, 1996.
[6]
C. de Bari, F. Dell'Accio, F. Vandenabeele, J. R. Vermeesch, J. M. Raymackers, and F. P. Luyten, “Skeletal muscle repair by adult human mesenchymal stem cells from synovial membrane,” Journal of Cell Biology, vol. 160, no. 6, pp. 909–918, 2003.
[7]
M. J. Campbell, A. J. McComas, and F. Petito, “Physiological changes in ageing muscles,” Journal of Neurology Neurosurgery and Psychiatry, vol. 36, no. 2, pp. 174–182, 1973.
[8]
W. R. Frontera, K. F. Reid, E. M. Phillips et al., “Muscle fiber size and function in elderly humans: a longitudinal study,” Journal of Applied Physiology, vol. 105, no. 2, pp. 637–642, 2008.
[9]
D. Rudman, M. H. Kutner, C. M. Rogers, M. F. Lubin, and A. Flemming, “Impaired growth hormone secretion in the adult population,” Journal of Clinical Investigation, vol. 67, no. 5, pp. 1361–1369, 1981.
[10]
G. Goldspink and S. D. R. Harridge, “Mini-review. Growth factors and muscle ageing,” Experimental Gerontology, vol. 39, no. 10, pp. 1433–1438, 2004.
[11]
A. Yamaguchi, T. Fujikawa, S. Shimada et al., “Muscle IGF-I Ea, MGF, and myostatin mRNA expressions after compensatory overload in hypophysectomized rats,” Pflugers Archiv, vol. 45, no. 2, pp. 203–210, 2006.
[12]
A. L. Goldberg, “Work-induced growth of skeletal muscle in normal and hypophysectomized rats,” The American journal of physiology, vol. 213, no. 5, pp. 1193–1198, 1967.
[13]
J. M. Sacheck, A. Ohtsuka, S. C. McLary, and A. L. Goldberg, “IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1,” American Journal of Physiology, Endocrinology and Metabolism, vol. 287, no. 4, pp. E591–E601, 2004.
[14]
A. C. McPherron and S. J. Lee, “Double muscling in cattle due to mutations in the myostatin gene,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 23, pp. 12457–12461, 1997.
[15]
M. Schuelke, K. R. Wagner, L. E. Stolz et al., “Myostatin mutation associated with gross muscle hypertrophy in a child,” New England Journal of Medicine, vol. 350, no. 26, pp. 2682–2688, 2004.
[16]
C. D. McMahon, L. Popovic, J. M. Oldham et al., “Myostatin-deficient mice lose more skeletal muscle mass than wild-type controls during hindlimb suspension,” American Journal of Physiology, Endocrinology and Metabolism, vol. 285, no. 1, pp. E377–E381, 2003.
[17]
L. Grobet, D. Pirottin, F. Farnir et al., “Modulating skeletal muscle mass by postnatal, muscle-specific inactivation of the myostatin gene,” Genesis, vol. 35, no. 4, pp. 227–238, 2003.
[18]
H. Amthor, A. Otto, R. Macharia, I. McKinnell, and K. Patel, “Myostatin imposes reversible quiescence on embryonic muscle precursors,” Developmental Dynamics, vol. 235, no. 3, pp. 672–680, 2006.
[19]
H. Amthor, R. Macharia, R. Navarrete et al., “Lack of myostatin results in excessive muscle growth but impaired force generation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 6, pp. 1835–1840, 2007.
[20]
P. F. Arthur, “Double muscling in cattle: a review,” Australian Journal of Agricultural Research, vol. 46, pp. 1493–1515, 1995.
[21]
G. Goldspink, A. Scutt, P. Loughna, D. Wells, T. Jaenicke, and G.-F. Gerlach, “Gene expression in skeletal muscle in response to mechanical signals,” American Journal of Physiology, vol. 262, pp. R326–R363, 1990.
[22]
S. Yang, M. Alnaqeeb, H. Simpson, and G. Goldspink, “Cloning and characterization of an IGF-1 isoform expressed in skeletal muscle subjected to stretch,” Journal of Muscle Research and Cell Motility, vol. 17, no. 4, pp. 487–495, 1996.
[23]
M. Hill and G. Goldspink, “Expression and splicing of the insulin-like growth factor gene in rodent muscle is associated with muscle satellite (stem) cell activation following local tissue damage,” Journal of Physiology, vol. 549, no. 2, pp. 409–418, 2003.
[24]
M. Hill, A. Wernig, and G. Goldspink, “Muscle satellite (stem) cell activation during local tissue injury and repair,” Journal of Anatomy, vol. 203, no. 1, pp. 89–99, 2003.
[25]
S. Y. Yang and G. Goldspink, “Different roles of the IGF-I Ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation,” FEBS Letters, vol. 522, no. 1-3, pp. 156–160, 2002.
[26]
G. Goldspink and S. Y. Yang, “The splicing of the IGF-I gene to yield different muscle growth factors,” Advances in Genetics, vol. 52, pp. 23–49, 2004.
[27]
V. Owino, S. Y. Yang, and G. Goldspink, “Age-related loss of skeletal muscle function and the inability to express the autocrine form of insulin-like growth factor-1 (MGF) in response to mechanical overload,” FEBS Letters, vol. 505, no. 2, pp. 259–263, 2001.
[28]
M. Hameed, R. W. Orrell, M. Cubbold, G. Goldspink, and S. D.R. Harridge, “Expression of IGF-I splice variants in young and old human skeletal muscle after high resistance exercise,” Journal of Physiology, vol. 547, no. 1, pp. 247–254, 2003.
[29]
P. K. Kandalla, G. Goldspink, G. Butler-Browne, and V. Mouly, “Mechano Growth Factor E peptide (MGF-E), derived from an isoform of IGF-1, activates human muscle progenitor cells and induces an increase in their fusion potential at different ages,” Mechanisms of Ageing and Development, vol. 132, no. 4, pp. 154–162, 2011.
[30]
M. A. Alnaqeeb, N. S. Al Zaid, and G. Goldspink, “Connective tissue changes and physical properties of developing and ageing skeletal muscle,” Journal of Anatomy, vol. 139, no. 4, pp. 677–689, 1984.
[31]
M. Hameed, K. H. W. Lange, J. L. Andersen et al., “The effect of recombinant human growth hormone and resistance training on IGF-I mRNA expression in the muscles of elderly men,” Journal of Physiology, vol. 555, no. 1, pp. 231–240, 2004.
[32]
S. Klossner, A. C. Durieux, D. Freyssenet, and M. Flueck, “Mechano-transduction to muscle protein synthesis is modulated by FAK,” European Journal of Applied Physiology, vol. 106, no. 3, pp. 389–398, 2009.
[33]
F. P. Moss and C. P. Leblond, “Satellite cells as the source of nuclei in muscles of growing rats,” Anatomical Record, vol. 170, no. 4, pp. 421–435, 1971.
[34]
M. D. Grounds, “Age-associated changes in the response of skeletal muscle cells to exercise and regeneration,” Annals of the New York Academy of Sciences, vol. 854, pp. 78–91, 1998.
[35]
G. S. Butler-Browne, V. Jacquemin, D. Furling, A. Bigot, and V. Mouly, “IGF-1 induces human myotube hypertrophy by increasing cell recruitment,” Experimental Cell Research, vol. 299, no. 1, pp. 148–158, 2004.
[36]
M. Hill and G. Goldspink, “Expression and splicing of the insulin-like growth factor gene in rodent muscle is associated with muscle satellite (stem) cell activation following local tissue damage,” Journal of Physiology, vol. 549, no. 2, pp. 409–418, 2003.
[37]
M. Hill, A. Wernig, and G. Goldspink, “Muscle satellite (stem) cell activation during local tissue injury and repair,” Journal of Anatomy, vol. 203, no. 1, pp. 89–99, 2003.
[38]
R. M. Crameri, L. Henning, P. Magnusson et al., “Changes in satellite cells in human skeletal muscle after a single bout of high intensity exercise,” Journal of Physiology, vol. 558, no. 1, pp. 333–340, 2004.
[39]
J. S. Kim, J. M. Cross, and M. M. Bamman, “Impact of resistance loading on myostatin expression and cell cycle regulation in young and older men and women,” American Journal of Physiology, vol. 288, no. 6, pp. E1110–E1119, 2005.
[40]
M. D. Grounds, “Reasons for the degeneration of ageing skeletal muscle: a central role for IGF-1 signalling,” Biogerontology, vol. 3, no. 1-2, pp. 19–24, 2002.
[41]
G. Goldspink and S. D. R. Harridge, “Growth factors and muscle ageing,” Experimental Gerontology, vol. 39, no. 10, pp. 1433–1438, 2004.
[42]
K. Ates, S. Y. Yang, R. W. Orrell et al., “The IGF-I splice variant MGF increases progenitor cells in ALS, dystrophic, and normal muscle,” FEBS Letters, vol. 581, no. 14, pp. 2727–2732, 2007.
[43]
M. Flueck and G. Goldspink, “Point:Counterpoint: IGF is/is not the major physiological regulator of muscle mass,” Journal of Applied Physiology, vol. 108, no. 6, pp. 1821–1833, 2010.
[44]
K. M. Heinemeier, J. L. Olesen, P. Scherling, et al., “Short term strength duration and the expression of myostatin and IGF-I isoforms in rat muscle tendons: dfferential effects of specific contraction types,” Journal of Applied Physiology, vol. 102, pp. 573–581, 2007.
[45]
B. R. McKay, C. E. O'Reilly, S. M. Phillips, M. A. Tarnopolsky, and G. Parise, “Co-expression of IGF-1 family members with myogenic regulatory factors following acute damaging muscle-lengthening contractions in humans,” Journal of Physiology, vol. 586, no. 22, pp. 5549–5560, 2008.
[46]
H. Roschel, C. Ugrinowistch, R Barrosa, et al., “Effect of eccentric exercise velocity on akt/mtor/p70(s6k) signaling in human skeletal muscle,” Applied Physiology, Nutrition, and Metabolism, vol. 36, no. 2, pp. 283–290, 2011.
[47]
I. V. Kravchenko, V. A. Furalyov, E. S. Lisitsina, and V. O. Popov, “Stimulation of mechano-growth factor expression by second messengers,” Archives of Biochemistry and Biophysics, vol. 507, no. 2, pp. 323–331, 2011.
[48]
M. Roberts, V. Dalbo, K. Sunderderland, et al., “Stout IGF-I slice vatiant and IGF-I peptide expression pterns in young and old human skeletal muscle following sequential exercise bouts,” European Journal of Applied Physiology, vol. 110, no. 5, pp. 961–969, 2010.
[49]
Z. Dai, F. Wu, E. W. Yeung, and Y. Li, “IGF-IEc expression, regulation and biological function in different tissues,” Growth Hormone and IGF Research, vol. 20, no. 4, pp. 275–281, 2010.
[50]
P. Mills, J. C. Dominique, J. F. Lafrenière, M. Bouchentouf, and J. P. Tremblay, “A synthetic mechano growth factor E peptide enhances myogenic precursor cell transplantation success,” American Journal of Transplantation, vol. 7, no. 10, pp. 2247–2259, 2007.
[51]
L. L. Tang, C. Y. Xian, and Y. L. Wang, “The MGF expression of osteoblasts in response to mechanical overload,” Archives of Oral Biology, vol. 51, no. 12, pp. 1080–1085, 2006.
[52]
M. Aperghis, I. P. Johnson, J. Cannon, S. Y. Yang, and G. Goldspink, “Different levels of neuroprotection by two insulin-like growth factor-I splice variants,” Brain Research, vol. 1009, no. 1-2, pp. 213–218, 2004.
[53]
V. Carpenter, K. Matthews, G. Devlin et al., “Mechano-growth factor reduces loss of cardiac function in acute myocardial infarction,” Heart Lung and Circulation, vol. 117, no. 1, pp. 97–104, 2007.
[54]
J. M. Collins, P. H. Goldspink, and B. Russell, “Migration and proliferation of human mesenchymal stem cells is stimulated by different regions of the mechano-growth factor prohormone,” Journal of Molecular and Cellular Cardiology, vol. 49, no. 6, pp. 1042–1045, 2010.
[55]
J. D？zniewska, A. Sarnowska, M. Beresewicz et al., “A strong neuroprotective effect of the autonomous C-terminal peptide of IGF-1 Ec (MGF) in brain ischemia,” FASEB Journal, vol. 19, no. 13, pp. 1896–1898, 2005.
[56]
A. Stavropoulou, A. Halapas, A. Sourla et al., “IGF-1 expression in infarcted myocardium and MGF E peptide actions in rat cardiomyocytes in vitro,” Molecular Medicine, vol. 15, no. 5-6, pp. 127–135, 2009.
[57]
T. V. Kuznetsova, A. A. Schulga, A. N. Wulfson et al., “Producing human mechano growth factor (MGF) in Escherichia coli,” Protein Expression and Purification, vol. 58, no. 1, pp. 70–77, 2008.
[58]
I. V. Kravchenko, V. A. Furalyov, E. S. Lisitsina, and V. O. Popov, “Stimulation of mechano-growth factor expression by second messengers,” Archives of Biochemistry and Biophysics, vol. 507, no. 2, pp. 323–331, 2011.
[59]
L. Song, W.-S. Zhu, J. L. Dong, Z. Y. Li, and X. H. Liu, “Expression and purification of two alternative peptides for mechano-growth factor in Escherichia coli,” Biotechnology Letters, vol. 34, no. 2, pp. 231–237, 2012.
