We present genome-wide microarray expression analysis of 11,000 genes in an aging potentially mitotic tissue, the liver. This organ has a major impact on health and homeostasis during aging. The effects life- health-span-extending caloric restriction (CR) gene among young old mice between long-term CR (LT-CR) short-term (ST-CR) were examined. experimental design allowed us to accurately distinguish from those expression. Aging was accompanied by changes associated with increased...

Small RNAs complex with proteins to mediate a variety of functions in animals and plants. Some small RNAs, particularly miRNAs, circulate mammalian blood may carry out signaling function by entering target cells modulating gene expression. The subject this study is set circulating 30–33 nt that are processed derivatives the 5′ ends subset tRNA genes, closely resemble cellular (tRFs, tiRNAs, half-tRNAs, halves) previously shown inhibit translation initiation response stress cultured cells. In...

Caloric restriction (CR), the consumption of fewer calories while avoiding malnutrition, decelerates rate aging and development age-related diseases. CR has been viewed as less effective in older animals acting incrementally to slow or prevent changes gene expression. Here we demonstrate that initiated 19-month-old mice begins within 2 months increase mean time death by 42% maximum lifespans 4.7 (P = 0.000017) 6.0 0.000056), respectively. The age-associated mortality was decreased 3.1-fold....

Small noncoding RNAs circulating in the blood may serve as signaling molecules because of their ability to carry out a variety cellular functions. We have previously described tRNA- and YRNA-derived small components larger complexes humans mice; characteristics these imply specific processing, secretion, physiological regulation. In this study, we asked if changes serum abundance tRNA YRNA fragments are associated with diagnosis cancer. used deep sequencing informatics analysis catalog sera...

Cytosine methylation in the genome of Drosophila melanogaster has been elusive and controversial: Its location function have not established. We used a novel highly sensitive genomewide cytosine assay to detect map stage 5 embryos. The we observe with this method is localized strand asymmetrical, limited regions covering ∼1% genome, dynamic early embryogenesis, concentrated specific 5-base sequence motifs that are CA- CT-rich but depleted guanine. Gene body associated lower expression, many...

Small noncoding RNAs carry out a variety of functions in eukaryotic cells, and multiple species they can travel between thus serving as signaling molecules. In mammals small have been found to circulate the blood, although most cases targets these RNAs, even their functions, are not well understood. YRNAs (84-112 nt) with poorly characterized best known because make up part Ro ribonucleoprotein autoantigens connective tissue diseases. surveying present serum healthy adult humans, we YRNA...

// Berta Victoria Martinez 1,* , Joseph M. Dhahbi 2,* Yury O. Nunez Lopez 3 Katarzyna Lamperska 4 Paweł Golusinski 5,6 Lukasz Luczewski 6 Tomasz Kolenda 4,7 Hani Atamna 8 Stephen R. Spindler 2 Wojciech and Michal Masternak 1,6 1 University of Central Florida, Burnett School Biomedical Sciences, College Medicine Orlando, FL, USA Department Biochemistry, California at Riverside, CA, Translational Research Institute for Metabolism Diabetes, Florida Hospital, Deptartment Cancer Genetics, Greater...

The obesity epidemic in the U.S. has led to extensive research into potential contributing dietary factors, especially fat and fructose. Recently, increased consumption of soybean oil, which is rich polyunsaturated fatty acids (PUFAs), been proposed play a causal role epidemic. Here, we designed series four isocaloric diets (HFD, SO-HFD, F-HFD, F-SO-HFD) investigate effects saturated versus unsaturated fat, as well fructose, on diabetes. C57/BL6 male mice fed diet moderately high from...

To facilitate the development of assays for discovery pharmaceuticals capable mimicking effects caloric restriction (CR) on life- and healthspan (CR mimetics), we evaluated effectiveness glucoregulatory putative cancer chemopreventatives in reproducing hepatic gene expression profile produced by long-term CR (LTCR), using Affymetrix microarrays. We have shown that initiated late life begins to extend lifespan, reduce as a cause death, reproduce approximately three-quarters genomic LTCR 8 wk...

Disrupted growth hormone/insulin-like factor-1 signaling (DF) and caloric restriction (CR) extend life span delay the onset of age-related diseases in rodents. In combination, these interventions additively span. To investigate molecular basis for effects, we performed genome-wide, microarray expression analysis liver from homozygous heterozygous Ames dwarf mice fed ad libitum or CR. CR DF affected a group 95 genes. Individually together, independently 212 77 genes, respectively. These...

In cell senescence, cultured cells cease proliferating and acquire aberrant gene expression patterns. MicroRNAs (miRNAs) modulate through translational repression or mRNA degradation have been implicated in senescence. We used deep sequencing to carry out a comprehensive survey of miRNA involvement Informatic analysis small RNA sequence datasets from young senescent IMR90 human fibroblasts identifies many miRNAs that are regulated (either up down) with Comparison profiles reveals potential...

We characterized the effects of calorie restriction (CR) on expression key glycolytic, gluconeogenic, and nitrogen-metabolizing enzymes in mice. Of gluconeogenic investigated, liver glucose-6-phosphatase mRNA increased 1.7- 2.3-fold young old CR Phospho enolpyruvate carboxykinase activity 2.5- 1.7-fold glycolytic enzymes, pyruvate kinase decreased ∼60% Hepatic phosphofructokinase-1 dehydrogenase 10–20% genes that detoxify ammonia generated from protein catabolism, hepatic glutaminase,...

Aging increases and caloric restriction (CR) decreases morbidity mortality associated with the cardiovascular system. Using Affymetrix microarrays, we identified changes in heart gene expression induced by aging CR male mice. Eight weeks of (CR8) reproduced 19% long-term (LTCR)-related changes. Because CR8 begins to extend life span these mice, genes may be keys its cardioprotective effects. LTCR changed a manner consistent reduced remodeling fibrosis, enhanced contractility energy...

Statins such as simvastatin are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and standard therapy for the prevention treatment of cardiovascular diseases in mammals. Here we show that significantly increased mean maximum lifespan Drosophila melanogaster (Drosophila) enhanced cardiac function aging flies by reducing heart arrhythmias increasing contraction proportion contraction/relaxation cycle. These results appeared independent internal changes ubiquinone or...

The nuclear receptor hepatocyte factor 4α (HNF4α) is tumor suppressive in the liver but amplified colon cancer, suggesting that it also might be oncogenic. To investigate whether this discrepancy due to different HNF4α isoforms derived from its two promoters (P1 and P2), we generated Tet-On-inducible human cancer (HCT116) cell lines express either P1-driven (HNF4α2) or P2-driven (HNF4α8) isoform analyzed them for growth global changes gene expression (transcriptome sequencing [RNA-seq]...

Summary Recent evidence demonstrates that serum levels of specific mi RNA s significantly change with age. The ability circulating snc to act as signaling molecules and regulate a broad spectrum cellular functions implicates them key players in the aging process. To discover impact long‐lived Ames dwarf mice, we conducted deep sequencing small extracted from young old mice. Our analysis showed genotype‐specific changes 21 during [genotype‐by‐age interaction (GbA)]. Genotype‐by‐age four...

The majority of the heme-binding proteins possess a "heme-pocket" that stably binds to heme. Usually known as housekeeping heme-proteins, they participate in variety metabolic reactions (e.g., catalase). Heme also with lower affinity "Heme-Regulatory Motifs" (HRM) specific regulatory proteins. This type heme binding is exchangeable or (RH). HRM regulates their function Bach1). Although there are well-established methods for assaying total cellular heme-proteins plus RH), currently no method...

We have determined methylation state differences in the epigenomes of uncultured cells purified from human, chimpanzee, and orangutan, using digestion with a methylation-sensitive enzyme, deep sequencing, computational analysis sequence data. The methylomes show high degree conservation, but states ∼10% CpG island-like regions differ significantly between human chimp. are not associated changes CG content recapitulate known phylogenetic relationship three species, indicating that they stably...