Effects of Aging on Angiogenic and Muscle Growth-Related Factors in Naturally Aged Rat Skeletal Muscles

Abstract

Aging exacerbates muscle function, power, strength, and endurance; it also increases the incidence of falls and chronic metabolic diseases, which impact the quality of life. The reduction of muscle function in older adults is predominantly because of the decrease in muscle mass during aging, a process known as sarcopenia. 1) As aging progresses, skeletal muscles show decreased responsiveness to physical activity and other anabolic stimuli, resulting in a decrease in the muscle protein synthetic response referred to as anabolic resistance. 2) Background: This study explored the effects of aging on the expression of angiogenic and muscle protein synthesis factors, as well as the number of satellite cells affecting sarcopenia in naturally aged rat skeletal muscles. Methods: We divided 16 Sprague-Dawley rats into young (12 weeks old, n=8) and old (24 months old, n=8) groups and compared muscle and body weight (BW) between them. We also analyzed the expression levels of angiogenic and muscle growth proteins in soleus (slow-twitch) and extensor digitorum longus (EDL; fast-twitch) muscles by western blotting and assessed the number of skeletal muscle satellite cells and myonuclei and mean fiber cross-sectional area (CSA) using by immunofluorescence staining. Results: EDL/BW was significantly lower in old rats than in young rats (p=0.002). The vascular endothelial growth factor level in soleus muscles was significantly lower in old rats than in young rats (p=0.001). Hypoxia-inducible factor 1-alpha and fetal liver kinase 1 levels in EDL muscles were lower in old rats than in young rats (p=0.001). The mammalian target of rapamycin (mTOR), p70S6K, and 4E-BP1 levels were significantly lower in the soleus muscles of old rats than in those of young rats (p<0.01). Similarly, insulin growth factor-1, Akt, mTOR, and p70S6K levels were significantly lower in EDL muscles of old rats than in those of young rats (p<0.01). Additionally, myonuclei/fiber, Pax7/fiber, and mean fiber CSAs in both muscle types were significantly lower in old rats than in young rats (p<0.01). Conclusion: These data suggest different regulation of indices of angiogenic and muscle growth with aging in different muscle types.

Circulating Extracellular Vesicles and Particles Derived From Adipocytes: The Potential Role in Spreading MicroRNAs Associated With Cellular Senescence

“…Our results suggest that miRNAs profile in circulating adipocyte-derived EVPs obtained from aged Wistar rats collaborate at least in part with translation initiation impairment, which can impact cellular growth and development. Although to our knowledge the involvement of adipocytes-derived EVPs has not been evaluated, the reduced levels of IGF-1, AKT, mTOR, and P70 S6 kinase (p70S6K) levels were found in the muscles of aged rats ( Yeo et al, 2020 ). Moreover, our results indicate that protein degradation by CAPN8 (calpain 8), which is found especially in surface mucus in the stomach cells and in the goblet cells of the intestines ( Sorimachi et al, 1993 ; Hata et al, 2010 ), can be increased, because this is a predicted target of a downregulated miRNA, miR-210-5p.…”

The impact of aging and physical training on angiogenesis in the musculoskeletal system

“…Specifically, it has been reported that HIF-1 α mRNA expression is ∼44% lower in aged mice (22-month-old) when compared to young mice (6-month-old) ( Wagatsuma, 2006 ). Similarly, HIF-1 α protein expression decreases by ∼20% in old rats (20–24-month-old) when compared to young rats (3-month-old) ( Yeo, Lim & Ahn, 2020 ). Little is known about the mechanism of age-related changes of ECM remodelling in skeletal muscle.…”

“…Fast muscle fibres are more susceptible to age-related loss of capillaries when compared to slow muscle fibres ( Croley et al, 2005 ; Gavin et al, 2007 ). A recent report by Yeo, Lim & Ahn (2020) demonstrated that there are muscle type-dependent differences in the age-related mechanism of angiogenesis. It was found that VEGF expression was downregulated in slow-twitch muscle fibres (soleus) in aging, whereas the expression of VEGF receptor 2 (KDR) was unchanged.…”

“…In contrast, in aged fast-twitch muscle (EDL), VEGF expression was not altered, while KDR expression was strongly downregulated in slow-twitch muscles. Additionally, HIF-1 α expression during aging was well maintained in the soleus muscle while significantly decreased in the fast-twitch EDL muscle ( Yeo, Lim & Ahn, 2020 ). Therefore, based on this recent report, the mechanism of age-related attenuation of angiogenesis in varied muscle types needs further examination.…”

Role of hypoxia-inducible factor in postoperative delirium of aged patients: A review

“…Furthermore, a copper metabolism MURR domain 1 (COMMD1) was significantly elevated after MCAO only in the brains of aged rats, and suppression of COMMD1 by siRNA targeting COMMD1 restored HIF-1 transactivation and improved recovery from MCAO-induced damage in the aged brain. Ndubuizu OI [ 84 ] reported that HIF-1α accumulation and transcriptional activation of HIF target genes in aged rats are significantly attenuated during acute hypoxic exposure. Cortical HIF-1α accumulation and HIF-1 activation remain absent during chronic hypoxic exposure in the aged rat brain.…”