Deleterious effect of suboptimal diet on rest-activity cycle in Anastrepha ludens manifests itself with age.

Activity patterns and sleep-wake cycles are among the physiological processes that change most prominently as animals age, and are often good indicators of healthspan. In this study, we used the video-based high-resolution behavioral monitoring system (BMS) to monitor the daily activity cycle of tephritid fruit flies Anastrepha ludens over their lifetime. Surprisingly, there was no dramatic change in activity profile with respect to age if flies were consistently fed with a nutritionally balanced diet. However, if flies were fed with sugar-only diet, their activity profile decreased in amplitude at old age, suggesting that suboptimal diet affected activity patterns, and its detrimental effect may not manifest itself until the animal ages. Moreover, by simulating different modes of behavior monitoring with a range of resolution and comparing the resulting conclusions, we confirmed the superior performance of video-based monitoring using high-resolution BMS in accurately representing activity patterns in an insect model

Term-tissue specific models for prediction of gene ontology biological processes using transcriptional profiles of aging in drosophila melanogaster

Predictive classification on the base of gene expression profiles appeared recently as an attractive strategy for identifying the biological functions of genes. Gene Ontology (GO) provides a valuable source of knowledge for model training and validation. The increasing collection of microarray data represents a valuable source for generating functional hypotheses of uncharacterized genes. This study focused on using support vector machines (SVM) to predict GO biological processes from individual or multiple-tissue transcriptional profiles of aging in Drosophila melanogaster. Ten-fold cross validation was implemented to evaluate the prediction. One-tail Fisher's exact test was conducted on each cross validation and multiple testing was addressed using BH FDR procedure. The results showed that, of the 148 pursued GO biological processes, fifteen terms each had at least one model with FDR-adjusted p-value (Adj.p) <0.05 and six had the values between 0.05 and 0.25. Furthermore, all these models had the prediction sensitivity (SN) over 30% and specificity (SP) over 80%. We proposed the concept of term-tissue specific models indicating the fact that the major part of the optimized prediction models was trained from individual tissue data. Furthermore, we observed that the memberships of the genes involved in all the three pursued children biological processes on mitochondrial electron transport could be predicted from the transcriptional profiles of aging (Adj.p < 0.01). This finding may be important in biology because the genes of mitochondria play a critical role in the longevity of C. elegans and D. melanogaster.https://doi.org/10.1186/1471-2105-9-12

Nectarine promotes longevity in Drosophila melanogaster.

Fruits containing high antioxidant capacities and other bioactivities are ideal for promoting longevity and health span. However, few fruits are known to improve the survival and health span in animals, let alone the underlying mechanisms. Here we investigate the effects of nectarine, a globally consumed fruit, on life span and health span in Drosophila melanogaster. Wild-type flies were fed standard, dietary restriction (DR), or high-fat diet supplemented with 0-4% nectarine extract. We measured life span, food intake, locomotor activity, fecundity, gene expression changes, and oxidative damage indicated by the level of 4-hydroxynonenal-protein adduct in these flies. We also measured life span, locomotor activity, and oxidative damage in sod1 mutant flies on the standard diet supplemented with 0-4% nectarine. Supplementation with 4% nectarine extended life span, increased fecundity, and decreased expression of some metabolic genes, including a key gluconeogenesis gene, PEPCK, and oxidative stress-response genes, including peroxiredoxins, in female wild-type flies fed the standard, DR, or high-fat diet. Nectarine reduced oxidative damage in wild-type females fed the high-fat diet. Moreover, nectarine improved the survival of and reduced oxidative damage in female sod1 mutant flies. Together, these findings suggest that nectarine promotes longevity and health span partly by modulating glucose metabolism and reducing oxidative damage

A Multi-Scale Approach to Study Biochemical and Biophysical Aspects of Resveratrol on Diesel Exhaust Particle-Human Primary Lung Cell Interaction

Diesel exhaust particles (DEPs) are major air pollutants that lead to numerous human disorders, especially pulmonary diseases, partly through the induction of oxidative stress. Resveratrol is a polyphenol that ameliorates the production of reactive oxygen species (ROS) and delays aging-related processes. Herein we studied the cytoprotective effect of resveratrol on DEP-exposed human lung cells in a factorial experimental design. This work investigates biophysical features including cellular compositions and biomechanical properties, which were measured at the single-cell level using confocal Raman microspectroscopy (RM) and atomic force microscopy (AFM), respectively. Principal component analysis (PCA), hierarchical cluster analysis (HCA) and partial least square regression (PLS) analysis were applied to analyze Raman spectra with and without resveratrol protection. The health status of individual cells could be effectively predicted using an index derived from characteristic Raman spectral peak (e.g., 1006 cm−1) based on PLS model. AFM measurements indicated that cellular adhesion force was greatly reduced, while Young’s modulus was highly elevated in resveratrol treated DEP-exposed cells. Anti-oxidant resveratrol reduced DEP-induced ROS production and suppressed releases of several cytokines and chemokines. These findings suggest resveratrol may enhance resistance of human lung cells (e.g., SAEC) to air pollutants (e.g. DEPs)

Recording Lifetime Behavior and Movement in an Invertebrate Model

Characterization of lifetime behavioral changes is essential for understanding aging and aging-related diseases. However, such studies are scarce partly due to the lack of efficient tools. Here we describe and provide proof of concept for a stereo vision system that classifies and sequentially records at an extremely fine scale six different behaviors (resting, micro-movement, walking, flying, feeding and drinking) and the within-cage (3D) location of individual tephritid fruit flies by time-of-day throughout their lives. Using flies fed on two different diets, full sugar-yeast and sugar-only diets, we report for the first time their behavioral changes throughout their lives at a high resolution. We have found that the daily activity peaks at the age of 15–20 days and then gradually declines with age for flies on both diets. However, the overall daily activity is higher for flies on sugar-only diet than those on the full diet. Flies on sugar-only diet show a stronger diurnal localization pattern with higher preference to staying on the top of the cage during the period of light-off when compared to flies on the full diet. Clustering analyses of age-specific behavior patterns reveal three distinct young, middle-aged and old clusters for flies on each of the two diets. The middle-aged groups for flies on sugar-only diet consist of much younger age groups when compared to flies on full diet. This technology provides research opportunities for using a behavioral informatics approach for understanding different ways in which behavior, movement, and aging in model organisms are mutually affecting

RNA topoisomerase is prevalent in all domains of life and associates with polyribosomes in animals

DNA Topoisomerases are essential to resolve topological problems during DNA metabolism in all species. However, the prevalence and function of RNA topoisomerases remain uncertain. Here, we show that RNA topoisomerase activity is prevalent in Type IA topoisomerases from bacteria, archaea, and eukarya. Moreover, this activity always requires the conserved Type IA core domains and the same catalytic residue used in DNA topoisomerase reaction; however, it does not absolutely require the non-conserved carboxyl-terminal domain (CTD), which is necessary for relaxation reactions of supercoiled DNA. The RNA topoisomerase activity of human Top3β differs from that of Escherichia coli topoisomerase I in that the former but not the latter requires the CTD, indicating that topoisomerases have developed distinct mechanisms during evolution to catalyze RNA topoisomerase reactions. Notably, Top3β proteins from several animals associate with polyribosomes, which are units of mRNA translation, whereas the Top3 homologs from E. coli and yeast lack the association. The Top3β-polyribosome association requires TDRD3, which directly interacts with Top3β and is present in animals but not bacteria or yeast. We propose that RNA topoisomerases arose in the early RNA world, and that they are retained through all domains of DNA-based life, where they mediate mRNA translation as part of polyribosomes in animals

Integration specificity of the retrovirus-like transposable element Ty5 of Saccharomyces

The retrotransposons and retroviruses display a strong preference in selecting integration sites. The molecular mechanisms underlying this process, however, are largely unknown. I have characterized a new retrotransposon, called Ty5, in diverse strains of Saccharomyces cerevisiae and related species. A functional element, Ty5-6p, was identified from S. paradoxus. To investigate Ty5 target preference, the locations of 13 native insertions were determined in S. cerevisiae and S. paradoxus. Twelve were found near the telomeres and the mating locus HMR. To determine if this distribution is a consequence of targeted integration, a Ty5 transposition assay was developed in S. cerevisiae using Ty5-6p. The locations of 19 elements on chromosome III and six on other chromosomes were mapped. Twenty-two were near the telomeres and transcriptional silencers flanking HML and HMR, which share a common chromatin structure that represses transcription of adjacent genes (silent chromatin). These observations indicate that Ty5 preferentially transposes to silent chromatin. This target preference has likely had consequences for the genomic organization of chromosome ends. Recombination between elements is evidenced by the lack of target site duplications among native Ty5 insertions. In addition, native elements mark telomeric regions that have been duplicated and rearranged in S. cerevisiae and S. paradoxus. Molecular mechanisms of Ty5 targeting were investigated in various mutants that affect silent chromatin. HMR-E is the cis-sequence required for assembly of silent chromatin at HMR and accounts for approximately 2% of de novo transpositions. Mutations at HMR-E, which disrupt silent chromatin, abolish Ty5 transposition to this region. Deletion of SIR3, a gene that encodes a protein component of silent chromatin, resulted in an approximately six fold decrease in transposition. By analogy to Ty3 and HIV, we hypothesize that Ty5 target preference is due to interactions between its integration complex and protein components of silent chromatin. Ty5 target preference extends the link between telomere structure and reverse transcription as carried out by telomerase and Drosophila retrotransposons.</p