Epigallocatechin-3-gallate improves plantaris muscle recovery after disuse in aged rats

Abstract

Aging exacerbates muscle loss and slows the recovery of muscle mass and function after disuse. In this study we investigated the potential that epigallocatechin gallate (EGCg), an abundant catechin in green tea, would reduce signaling for apoptosis and promote skeletal muscle recovery in the fast plantaris muscle and the slow soleus muscle after hindlimb unloading (HLS) in senescent animals. Fischer 344 × Brown Norway inbred rats (age 34 mo.) received either EGCg (50 mg/kg body weight), or water daily by gavage. One group of animals received HLS for 14 days and a second group of rats received 14 days of HLS, then the HLS was removed and they recovered from this forced disuse for 2 weeks. Animals that received EGCg over the HLS followed by 14 days of recovery, had a 14% greater plantaris muscle weight (p <0.05) as compared to the animals treated with the vehicle over this same period. Plantaris fiber area was greater after recovery in EGCg (2715.2 ± 113.8 μm2) vs. vehicle treated animals (1953.0 ± 41.9 μm2). In addition, activation of myogenic progenitor cells was improved with EGCg over vehicle treatment (7.5% vs. 6.2%) in the recovery animals. Compared to vehicle treatment, the apoptotic index was lower (0.24% vs. 0.52%), and the abundance of pro-apoptotic proteins Bax (−22%), and FADD (−77%) were lower in EGCg treated plantaris muscles after recovery. While EGCg did not prevent unloading-induced atrophy, it improved muscle recovery after the atrophic stimulus in fast plantaris muscles. However, this effect was muscle specific because EGCg had no major impact in reversing HLS-induced atrophy in the slow soleus muscle of old rats.

Epigallocatechin-3-gallate increases autophagy signaling in resting and unloaded plantaris muscles but selectively suppresses autophagy protein abundance in reloaded muscles of aged rats

“…An abrupt decrease in physical activity leading to forced bedrest or hospitalization exacerbates muscle wasting in both middle aged (Arentson-Lantz et al, 2016) and elderly persons (Pisot et al, 2016), and significantly exacerbates their health problems (Inouye et al, 1993; Pisani et al, 2016). Furthermore, aging attenuates or delays recovery of muscle mass and function after disuse in elderly humans and aged animal models (Alway et al, 2014a; Hao et al, 2011; Pisot et al, 2016; Tanner et al, 2015; White et al, 2015; Zarzhevsky et al, 2001). …”

“…However, there is evidence that apoptotic signaling in myonuclei and satellite cells may have a role in regulating muscle loss in response to forced disuse (Alway et al, 2014a; Alway et al, 2015; Alway et al, 2011; Alway et al, 2014b; Hao et al, 2011; Marzetti et al, 2013a; Marzetti et al, 2012; Wang et al, 2011). Loss of autophagy signaling in satellite cells/muscle stem cells in aging muscle (Garcia-Prat et al, 2016; Sousa-Victor et al, 2014) might increase the susceptibility of satellite cells for apoptosis and reduce the regenerative capacity of muscle.…”

“…We hypothesized that part of the depressed recovery of muscle after forced inactivity such as that imposed by hindlimb suspension (HS) in aged rats (Alway et al, 2014a; Hao et al, 2011; Pisot et al, 2016; Tanner et al, 2015; White et al, 2015; Zarzhevsky et al, 2001) could be due to high levels of apoptosis and that increasing autophagy/mitophagy during reloading after disuse could remove dysfunctional mitochondria as the apoptotic initiators, thereby improving muscle recovery in aged animals or humans. However, the role of muscle autophagy/mitophagy during recovery from disuse-atrophy in aging is not clear because similar autophagy protein levels have been reported in hindlimb muscles of aged rats as compared to younger rats during recovery from disuse, despite a lower restoration of muscle mass in aging (White et al, 2015).…”

“…Green tea catechins were reported to reduce the loss of soleus muscle force during a period of HS in mice (Ota et al, 2011) and in aged rats (Alway et al, 2015). Epigallocatechin-3-gallate (EGCg) is the primary catechin found in green tea, and EGCg has been shown to improve muscle restoration after HS-induced inactivity in aged rats (Alway et al, 2014a). Both disuse and reloading greatly increase the oxidative stress in muscles (Andrianjafiniony et al, 2010; Jackson et al, 2010; Pellegrino et al, 2011) and oxidant stress is a powerful initiator of mitochondrial damage leading to apoptosis and muscle wasting (Herbst et al, 2016; Lee 2016; Wenz et al, 2009).…”

“…Thus, EGCg is a potential therapeutic candidate for improving muscle recovery after inactivity by suppressing apoptosis, potentially by mediating oxidative stress. Nevertheless, we did not know if the EGCg mediated attenuation of apoptotic signaling (Alway et al, 2014a), was accomplished in concert with altered autophagy signaling or if if EGCg had any effect in regulating autophagy during HS or recovery from disuse in aged muscles.…”