Effects of long-term physical exercise on skeletal muscles in senescence-accelerated mice (SAMP8).

We examined the effect of long-term exercise on the prevention of sarcopenia using a senescence-accelerated-prone mice (SAMP8) model. Mice were housed in a wheel cage for 25 weeks to increase voluntary exercise. At week 23, endurance running capacity was examined using a treadmill. In a treadmill running test, the wheel cage group had increased endurance running capacity, which suggests that aging-related loss of muscle function was recovered by long-term exercise. Mice were sacrificed and microarray analysis revealed that genes involved in protein synthesis and degradation were upregulated in the skeletal muscles of the wheel cage group, suggesting accelerated protein turnover. Total body and adipose tissue weights decreased following the use of the wheel cage. Thus, long-term, spontaneous physical exercise may assist in recovering from aging-related sarcopenia (loss of muscle function) and obesity.

Pore Structures for High-Throughput Nanopore Devices.

Nanopore devices are expected to advance the next-generation of nanobiodevices because of their strong sensing and analyzing capabilities for single molecules and bioparticles. However, the device throughputs are not sufficiently high. Although analytes pass through a nanopore by electrophoresis, the electric field gradient is localized inside and around a nanopore structure. Thus, analytes located far from a nanopore cannot be driven by electrophoresis. Here, we report nanopore structures for high-throughput sensing, namely, inverted pyramid (IP)-shaped nanopore structures. Silicon-based IP-shaped nanopore structures create a homogeneous electric field gradient within a nanopore device, indicating that most of the analytes can pass through a nanopore by electrophoresis, even though the analytes are suspended far from the nanopore entrance. In addition, the nanostructures can be fabricated only by photolithography. The present study suggests a high potential for inverted pyramid shapes to serve as nanopore devices for high-throughput sensing.

Metabolomic analysis of C2C12 myoblasts induced by the transcription factor FOXO1.

The transcription factor FOXO1 is considered to play roles in the regulation of energy metabolism in various tissues. To determine the metabolic changes occurring due to FOXO1 activation, we analyzed the metabolic profile of C2C12 myoblasts expressing a FOXO1-estrogen receptor fusion protein using capillary electrophoresis with electrospray ionization time-of-flight mass spectrometry (CE-TOFMS). In FOXO1-activated cells, the metabolite levels during glycolysis are higher and the gene expression of pyruvate dehydrogenase kinase, an enzyme that inhibits glucose utilization, is increased. In addition, the metabolite levels of numerous amino acids are decreased, with increased gene expression of branched chain amino acid metabolism enzymes. Our results suggest that FOXO1 suppresses glucose utilization and promotes the use of proteins/amino acids as energy sources in muscle cells, potentially during starvation.

Genistein, daidzein, and resveratrols stimulate PGC-1ß-mediated gene expression.

PGC-1ß is a transcriptional co-activator of nuclear receptors such as the estrogen receptor-related receptor (ERR). Transgenic overexpression of PGC-1ß in mice increases energy expenditure and suppresses high-fat diet-induced obesity. In this study, we screened various food-derived and natural compounds using a reporter assay system to measure the transcriptional activity of PGC-1ß. Soy-derived isoflavones, genistein and daidzein, and several resveratrols activated PGC-1ß. Genistein, daidzein, and trans-oxyresveratrol activated ERR-responsive element-mediated reporter activity in the presence of PGC-1ß. Stable overexpression of PGC-1ß in C2C12 myoblasts increased the expression of medium-chain acyl-CoA dehydrogenase (MCAD), an important enzyme in fatty acid ß-oxidation. Genistein and daidzein increased MCAD mRNA levels and mitochondrial content in PGC-1ß-expressing C2C12 cells. These compounds activated ERR/PGC-1ß complex-mediated gene expression, and our findings may be a practical foundation for developing functional foods targeting obesity.

Screening dataset of food components that enhance transcriptional activity of PGC1-beta.

PGC-1ß is a transcriptional co-activator of nuclear receptors, which acts to increase energy expenditure. PGC-1ß fused to GAL4 DNA-binding domain transfected in HEK293T cells showed a reporter luciferase activity. We screened food-derived and natural compounds using a reporter assay system to measure the transcriptional activity of PGC-1ß. We found that soy-derived isoflavones, genistein and daidzein, and several resveratrols activated PGC-1ß, see "Genistein, daidzein, and resveratrols stimulate PGC-1ß-mediated gene expression" [1]. The list of 166 compounds and their reporter activity is shown here.