Effects of exercise and dietary epigallocatechin gallate and β-alanine on skeletal muscle in aged mice

Abstract

Aging leads to sarcopenia and loss of physical function. We examined whether voluntary wheel running, when combined with dietary supplementation with (-)-epigallocatechin-3-gallate (EGCG) and β-alanine (β-ALA), could improve muscle function and alter gene expression in the gastrocnemius of aged mice. Seventeen-month-old BALB/cByJ mice were given access to a running wheel or remained sedentary for 41 days while receiving either AIN-93M (standard feed) or AIN-93M containing 1.5 mg·kg(-1) EGCG and 3.43 mg·kg(-1) β-ALA. Mice underwent tests over 11 days from day 29 to day 39 of the study period, including muscle function testing (grip strength, treadmill exhaustive fatigue, rotarod). Following a rest day, mice were euthanized and gastrocnemii were collected for analysis of gene expression by quantitative PCR. Voluntary wheel running (VWR) improved rotarod and treadmill exhaustive fatigue performance and maintained grip strength in aged mice, while dietary intervention had no effect. VWR increased gastrocnemius expression of several genes, including those encoding interleukin-6 (Il6, p = 0.001), superoxide dismutase 1 (Sod1, p = 0.046), peroxisome proliferator-activated receptor gamma coactivator 1-α (Ppargc1a, p = 0.013), forkhead box protein O3 (Foxo3, p = 0.005), and brain-derived neurotrophic factor (Bdnf, p = 0.008), while reducing gastrocnemius levels of the lipid peroxidation marker 4-hydroxynonenal (p = 0.019). Dietary intervention alone increased gastrocnemius expression of Ppargc1a (p = 0.033) and genes encoding NAD-dependent protein deacetylase sirtuin-1 (Sirt1, p = 0.039), insulin-like growth factor I (Igf1, p = 0.003), and macrophage marker CD11b (Itgam, p = 0.016). Exercise and a diet containing β-ALA and EGCG differentially regulated gene expression in the gastrocnemius of aged mice, while VWR but not dietary intervention improved muscle function. We found no synergistic effects between dietary intervention and VWR.

Voluntary running depreciates the requirement of Ca2+-stimulated cAMP signaling in synaptic potentiation and memory formation

“…Conversely, increased blood flow and circulating hormones to the brain during exercise would affect many aspects of neuronal function. As reported by previous studies, exercise also increases BDNF in the peripheral tissues including the skeletal muscle [ (Pence et al 2016) but also see (Jimenez-Maldonado et al 2016)]. Although previous works and our data show local increase of BDNF mRNA in brain tissues, it remains unclear on whether exercise-induced peripheral BDNF protein can circulate, cross the blood brain barrier, and affect brain neuron function.…”

Dose-dependent decrease in mortality with no cognitive or muscle function improvements due to dietary EGCG supplementation in aged mice

“…However, in aged mice, the dietary intervention caused several molecular changes in both brain and muscle tissues. Feeding the combination of both EGCG and ␤-Ala increased expression of several genes in the gastrocnemius of aged mice (Pence et al 2016), including Ppargc1a and Sirt1, both of which are involved in mitochondrial biogenesis (Jornayvaz and Shulman 2010). This dietary intervention also reduced oxidative stress, as measured by 4-hydroxynonenal, in the cerebellum of aged mice (Gibbons et al 2014).…”

“…We previously established that 40 days of feeding a diet consisting of 0.15% EGCG (1.5 mg·g −1 diet) and 0.343% ␤-Alanine (␤-Ala, 3.43 mg·g −1 diet) has no effect on muscle function (Pence et al 2016) or cognitive performance (Gibbons et al 2014) in aged Balb/ cByJ mice as well as adult C57Bl/6J mice (Bhattacharya et al 2015). However, in aged mice, the dietary intervention caused several molecular changes in both brain and muscle tissues.…”

“…In our previous aging studies (Gibbons et al 2014;Pence et al 2016), mice ingested an average of 182 mg EGCG per kilogram body weight per day. Based on the generally negative findings in our previous work, we considered that a change in either dose of EGCG or duration of feeding might yield more positive outcomes.…”

“…For the purpose of this study, we chose doses of EGCG corresponding generally to the highest (Friedrich et al 2012) and lowest (Chen et al 2009) reported doses that were successful in modulating cognitive or skeletal muscle function in previous studies. Because the positive effects due to the dietary intervention in the previous studies (Gibbons et al 2014;Pence et al 2016) are more likely to be associated with EGCG than ␤-Ala, we examined only EGCG. We hypothesized that EGCG supplementation would improve both cognitive and muscle performance in aged mice, possibly in a dose-dependent fashion.…”