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

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 ß-alanine (ß-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) ß-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 ß-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.

Exercise but not (-)-epigallocatechin-3-gallate or ß-alanine enhances physical fitness, brain plasticity, and behavioral performance in mice.

Nutrition and physical exercise can enhance cognitive function but the specific combinations of dietary bioactives that maximize pro-cognitive effects are not known nor are the contributing neurobiological mechanisms. Epigallocatechin-3-gallate (EGCG) is a flavonoid constituent of many plants with high levels found in green tea. EGCG has anti-inflammatory and anti-oxidant properties and is known to cross the blood brain barrier where it can affect brain chemistry and physiology. ß-Alanine (B-ALA) is a naturally occurring ß-amino acid that could increase cognitive functioning by increasing levels of exercise via increased capacity of skeletal muscle, by crossing the blood brain barrier and acting as a neurotransmitter, or by free radical scavenging in muscle and brain after conversion into carnosine. The objective of this study was to determine the effects of EGCG (~250mg/kg/day), B-ALA (~550mg/kg/day), and their combination with voluntary wheel running exercise on the following outcome measures: body composition, time to fatigue, production of new cells in the granule layer of the dentate gyrus of the hippocampus as a marker for neuronal plasticity, and behavioral performance on the contextual and cued fear conditioning tasks, as measures of associative learning and memory. Young adult male BALB/cJ mice approximately 2months old were randomized into 8 groups varying the nutritional supplement in their diet and access to running wheels over a 39day study period. Running increased food intake, decreased fat mass, increased time to exhaustive fatigue, increased numbers of new cells in the granule layer of the hippocampus, and enhanced retrieval of both contextual and cued fear memories. The diets had no effect on their own or in combination with exercise on any of the fitness, plasticity, and behavioral outcome measures other than B-ALA decreased percent body fat whereas EGCG increased lean body mass slightly. Results suggest that, in young adult BALB/cJ mice, a 39day treatment of exercise but not dietary supplementation with B-ALA or EGCG enhances measures of fitness, neuroplasticity and cognition.

Voluntary wheel running, but not a diet containing (-)-epigallocatechin-3-gallate and ß-alanine, improves learning, memory and hippocampal neurogenesis in aged mice.

Aging is associated with impaired learning and memory accompanied by reductions in adult hippocampal neurogenesis and brain expression of neurotrophic factors among other processes. Epigallocatechin-3-gallate (EGCG, a green tea catechin), ß-alanine (ß-ala, the precursor of carnosine), and exercise have independently been shown to be neuroprotective and to reduce inflammation and oxidative stress in the central nervous system. We hypothesized that EGCG, ß-ala supplementation or exercise alone would improve learning and memory and increase neurogenesis in aged mice, and the combined intervention would be better than either treatment alone. Male Balb/cByJ mice (19 months) were given AIN-93M diet with or without EGCG (182mg/kg/d) and ß-ala (417mg/kg/d). Half of the mice were given access to a running wheel (VWR). The first 10 days, animals received 50mg/kg bromodeoxyuridine (BrdU) daily. After 28 days, learning and memory was assessed by Morris water maze (MWM) and contextual fear conditioning (CFC). Brains were collected for immunohistochemical detection of BrdU and quantitative mRNA expression in the hippocampus. VWR increased the number of BrdU cells in the dentate gyrus, increased expression of brain-derived neurotrophic factor, decreased expression of the inflammatory cytokine interleukin-1ß, and improved performance in the MWM and CFC tests. The dietary intervention reduced brain oxidative stress as measured by 4-hydroxynonenal in the cerebellum, but had no effect on BrdU labeling or behavioral performance. These results suggest that exercise, but not a diet containing EGCG and ß-ala, exhibit pro-cognitive effects in aged mice when given at these doses in this relatively short time frame.