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

Abstract

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 (approximately 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.

Expression of growth-related genes in young and older human skeletal muscle following an acute stimulation of protein synthesis

“…4) are consistent with the work of others that have shown elevations in myogenic regulatory factor mRNA in the old at rest and that resistance exercise alters the expression of human skeletal muscle mRNAs associated with satellite cell regulation in both young and older subjects (8,28,33,34,45). We also report for the first time in human skeletal muscle, an age-related differential expression pattern post REϩEAA of a novel gene known as mindbomb 2 (mib2; Fig.…”

Elevated SOCS3 and altered IL-6 signaling is associated with age-related human muscle stem cell dysfunction

“…SOCS1 and SOCS3 proteins may also interfere with IGF-1 receptor signaling (13). The inhibition or dysregulation of IGF-1 signaling in older adults following resistance exercise has been shown previously and may also contribute to the impaired myogenic response (26,41). Elevated SOCS3 in cultured myoblasts as a result of treatment with IL-6 has been shown to block IGF-1 signaling through the ERK1/2 and Akt pathways via inhibitory interactions with IRS-1, suggesting IL-6 and specifically SOCS3 may inhibit classic growth factor signaling in skeletal muscle (1).…”

Neuromuscular stimulation causes muscle phenotype‐dependent changes in the expression of the IGFs and their binding proteins in developing slow and fast muscle of chick embryos

“…RT-PCR was performed using LightCycler technology as described by Hameed et al (2003) and further developed according to Bayol et al (2004). A 20-l reaction mix contained 10 l of a SYBR green mix (QuantiTect, Qiagen, Crawley, UK), 10 pMol of each forward and reverse primer, 2 l of cDNA (made from 1 g of RNA), and nuclease-free water to make up the reaction volume.…”