Expression of IGF‐I splice variants in young and old human skeletal muscle after high resistance exercise

The mRNA expression of two splice variants of the insulin‐like growth factor‐I (IGF‐I) gene, IGF‐IEa and mechano growth factor (MGF), were studied in human skeletal muscle. Subjects (eight young, aged 25–36 years, and seven elderly, aged 70–82 years) completed 10 sets of six repetitions of single legged knee extensor exercise at 80 % of their one repetition maximum. Muscle biopsy samples were obtained from the quadriceps muscle of both the control and exercised legs 2.5 h after completion of the exercise bout. Expression levels of the IGF‐I mRNA transcripts were determined using real‐time quantitative RT‐PCR with specific primers. The resting levels of MGF were significantly (≈100‐fold) lower than those of the IGF‐IEa isoform. No difference was observed between the resting levels of the two isoforms between the two subject groups. High resistance exercise resulted in a significant increase in MGF mRNA in the young, but not in the elderly subjects. No changes in IGF‐IEa mRNA levels were observed as a result of exercise in either group. The mRNA levels of the transcription factor MyoD were greater at rest in the older subjects (P < 0.05), but there was no significant effect of the exercise bout. Electrophoretic separation of myosin heavy chain (MHC) isoforms showed the older subjects to have a lower (P < 0.05) percentage of MHC‐II isoforms than the young subjects. However, no association was observed between the composition of the muscle and changes in the IGF‐I isoforms with exercise. The data from this study show an attenuated MGF response to high resistance exercise in the older subjects, indicative of age‐related desensitivity to mechanical loading. The data in young subjects indicate that the MGF and IGF‐IEa isoforms are differentially regulated in human skeletal muscle.

[1]  F. Booth,et al.  Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats. , 1997, Journal of applied physiology.

[2]  F. Biering-Sørensen,et al.  Training by low‐frequency stimulation of tibialis anterior in spinal cord–injured men , 2002, Muscle & nerve.

[3]  C. Stewart,et al.  Growth, differentiation, and survival: multiple physiological functions for insulin-like growth factors. , 1996, Physiological reviews.

[4]  Hamish Simpson,et al.  Cloning and characterization of an IGF-1 isoform expressed in skeletal muscle subjected to stretch , 1996, Journal of Muscle Research & Cell Motility.

[5]  A. Musarò,et al.  Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[6]  S B Roberts,et al.  Exercise training and nutritional supplementation for physical frailty in very elderly people. , 1994, The New England journal of medicine.

[7]  S. Harridge,et al.  Knee extensor strength, activation, and size in very elderly people following strength training , 1999, Muscle & nerve.

[8]  L. Lipsitz,et al.  High-intensity strength training in nonagenarians. Effects on skeletal muscle. , 1990, JAMA.

[9]  P. Aagaard,et al.  Myosin heavy chain IIX overshoot in human skeletal muscle , 2000, Muscle & nerve.

[10]  P. Tesch,et al.  The influence of muscle metabolic characteristics on physical performance , 2004, European Journal of Applied Physiology and Occupational Physiology.

[11]  G R Hunter,et al.  Mechanical load increases muscle IGF-I and androgen receptor mRNA concentrations in humans. , 2001, American journal of physiology. Endocrinology and metabolism.

[12]  F. Haddad,et al.  The relationships among IGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy. , 1996, Journal of applied physiology.

[13]  D. Skelton,et al.  Exercise studies with elderly volunteers. , 1994, Age and ageing.

[14]  G. Goldspink,et al.  Different roles of the IGF‐I Ec peptide (MGF) and mature IGF‐I in myoblast proliferation and differentiation , 2002, FEBS letters.

[15]  J. Kehayias,et al.  Insulin-like growth factor I in skeletal muscle after weight-lifting exercise in frail elders. , 1999, American journal of physiology. Endocrinology and metabolism.

[16]  F. Biering-Sørensen,et al.  Myosin heavy chain isoform transformation in single fibres from m. vastus lateralis in spinal cord injured individuals: Effects of long-term functional electrical stimulation (FES) , 1996, Pflügers Archiv.

[17]  J. Faulkner,et al.  Contraction-induced injury: recovery of skeletal muscles in young and old mice. , 1990, The American journal of physiology.

[18]  G. Goldspink,et al.  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 , 2001, FEBS letters.

[19]  P. Bechtel,et al.  Activation of insulin-like growth factor gene expression during work-induced skeletal muscle growth. , 1990, The American journal of physiology.

[20]  Antonio Musarò,et al.  Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle , 2001, Nature Genetics.

[21]  E. Simonsen,et al.  A mechanism for increased contractile strength of human pennate muscle in response to strength training: changes in muscle architecture , 2001, The Journal of physiology.

[22]  F. Kadi,et al.  Concomitant increases in myonuclear and satellite cell content in female trapezius muscle following strength training , 2000, Histochemistry and Cell Biology.

[23]  A. Fry,et al.  Correlation between percentage fiber type area and myosin heavy chain content in human skeletal muscle , 2004, European Journal of Applied Physiology and Occupational Physiology.

[24]  B. Saltin,et al.  Ageing alters the myosin heavy chain composition of single fibres from human skeletal muscle. , 1990, Acta physiologica Scandinavica.

[25]  A. Musarò,et al.  Enhanced expression of myogenic regulatory genes in aging skeletal muscle. , 1995, Experimental cell research.

[26]  F. Haddad,et al.  Selected contribution: acute cellular and molecular responses to resistance exercise. , 2002, Journal of applied physiology.

[27]  G. Butler-Browne,et al.  Cellular adaptation of the trapezius muscle in strength-trained athletes , 1999, Histochemistry and Cell Biology.

[28]  W. Gonyea,et al.  Effect of radiation on satellite cell activity and protein expression in overloaded mammalian skeletal muscle , 1997, The Anatomical record.

[29]  V. Edgerton,et al.  Limited myogenic response to a single bout of weight-lifting exercise in old rats. , 2000, American Journal of Physiology - Cell Physiology.

[30]  G. Adams,et al.  Localized infusion of IGF-I results in skeletal muscle hypertrophy in rats. , 1998, Journal of applied physiology.

[31]  P. Bechtel,et al.  Modulation of IGF mRNA abundance during stretch-induced skeletal muscle hypertrophy and regression. , 1994, Journal of applied physiology.

[32]  B. Russell,et al.  Expression of insulin growth factor‐1 splice variants and structural genes in rabbit skeletal muscle induced by stretch and stimulation , 1999, The Journal of physiology.