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1 Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA
2 Geriatric Research, Education, and Clinical Center, Veterans Affairs Medical Center, Birmingham, AL, USA
* To whom correspondence should be addressed. E-mail: mbamman{at}physiology.uab.edu.
Increasing evidence suggests the regenerative capacity consequent to mechanical overload is impaired in sarcopenic muscle. Because local growth factors and myogenic regulatory factors (MRFs) are thought to modulate repair/regeneration responses following overload, we hypothesized that resistance loading (RL)-induced expression of MRFs and muscle IGF-I related genes would be blunted in older (O) males (M) and females (F) with demonstrable sarcopenia compared to younger (Y) adults. Twenty young (Y) (20-35 yr, 10 YF, 10 YM) and 18 O (60-75 yr, 9 OF, 9 OM) consented to vastus lateralis biopsy before and 24 h after a bout of RL (3 sets x 8-12 repetitions to volitional fatigue of squat, leg press, knee extension). The magnitude of sarcopenia was assessed by immunofluorescence microscopydetermined cross-sectional area (CSA) and distribution of type I, IIa, and IIx myofibers. Gene expression levels were determined by relative RT-PCR with 18S as an internal standard and analyzed by age x gender x load repeated measures ANOVA. Older muscles were sarcopenic as quantified by type II myofiber atrophy, displaying significantly smaller type IIa (P<0.05) and IIx (P<0.001) myofibers. Within-gender myofiber size differences were more marked in women (OF < YF: IIa 21%, IIx 42%). Main load effects (P<0.05) were found for 4 of 7 transcripts as mRNA levels increased for IGF-IEa (34%), myogenin (53%), and MyoD (20%) and decreased for myf-6 (-10%). The load-mediated increase in IGF-IEa appeared to be mainly driven by O (+48%) and/or M (+43%). An age x gender x load interaction was also observed in the levels of MyoD expression (P<0.05). An age x load interaction for IGFR1 (P<0.05) appeared to be driven primarily by a small but significant load-induced increase in O (16%, P<0.05). Main age effects (P<0.05) resulted from higher MyoD (54%), myf-5 (21%), and IGFBP4 (17%) in O. The main age effects for MyoD and myf-5 expression were primarily driven by women at baseline (MyoD, OF 94% > YF; myf-5, OF 47% > YF, P<0.05). Higher IGFBP4 levels in OF vs. YF (17%, P<0.01) contributed to a main age effect and a gender x load interaction (P<0.05). We conclude that mechanical load acutely increases mRNA expression of IGF-IEa and myogenin, which may promote growth/regeneration in both Y and O. Higher resting levels of MyoD and myf-5 mRNAs in OF versus YF suggest heightened basal regenerative activity in the sarcopenic muscles of older women.
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