Abstract
Accumulation of connective tissue, particularly extracellular matrix (ECM) proteins, has been observed in skeletal muscles with advancing age. Resistance training (RT) has been widely recommended to attenuate age-induced sarcopenia, even though its effects on the components that control ECM turnover in skeletal muscles remain to be elucidated. Thus, the aim of this study was to determine the effects of RT on connective tissue content and gene expression of key components of ECM in the skeletal muscles of aged rats. Young (3 mo.) and older (21 mo.) adult male Wistar rats were submitted to a RT protocol (ladder climbing with 65, 85, 95, and 100% load), 3 times a week for 12 weeks. Forty-eight hours post-training, the soleus (SOL) and gastrocnemius (GAS) muscles were dissected for histological and mRNA analysis. RT mitigated the age-associated increase of connective tissue content in both muscles, even though mRNA levels of COL-1 and−3 were elevated in older trained rats. Overall, RT significantly elevated the gene expression of key components of connective tissue deposition (TGFβ and CTGF; MMP-2 and-9; TIMP-1 and−2) in the GAS and SOL muscles of older rats. In conclusion, RT blunted the age-induced accumulation of connective tissue concomitant to the upregulation of genes related to synthesis and degradation of the ECM network in the SOL and GAS muscles of older rats. Although our findings indicate that RT plays a crucial role reducing connective tissue accumulation in aged hindlimb muscles, key components of ECM turnover were paradoxically elevated. The phenotypic responses induced by RT were not accompanied by the gene expression of those components related to ECM turnover.
Highlights
Connective tissue surrounds skeletal muscle fibers and contributes to the protection of fibers against contractile damage (Kragstrup et al, 2011)
Resistance training (RT) led to marked increases in COL-3A1, TGF-β, CTGF, MMP-2, MMP-9, tissue inhibitors of metalloproteinase (TIMPs)-1, and TIMP-2 transcripts when compared with their agematched counterparts (OT vs. young sedentary (YS); older trained (OT) vs. older sedentary (OS)) (Figures 2C–H)
While COL3A1 was unchanged, COL1A1 transcript was lower in the SOL muscle of OS rats than in the YS group, even though TGF-β and CTGF transcripts increased in OS rats when compared with the YS group (Figures 2A–D)
Summary
Connective tissue surrounds skeletal muscle fibers and contributes to the protection of fibers against contractile damage (Kragstrup et al, 2011). Accumulation of connective tissue, proteins of the extracellular matrix (ECM), has been observed in skeletal muscles with advancing age (Alnaqeeb et al, 1984; Wood et al, 2014). Degradation is orchestrated by a fine balance between the proteolytic activity of metalloproteinases (MMPs) and their endogenous tissue inhibitors of metalloproteinase (TIMPs) (Alameddine and Morgan, 2016). Even though the proteolytic activity of gelatinases is essentially to degrade denatured collagens (Chen and Li, 2009), MMP-2 and MMP-9 have been shown to be involved in the degeneration and regeneration of skeletal muscles (Kherif et al, 1999; Fukushima et al, 2007). TIMP-2 is involved in MMP-2 activation (Wang et al, 2000)
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