Project description:Disruption of the circadian clock, which directs rhythmic expression of numerous genes, accelerates aging. To inquire how the circadian system protects organisms during aging, we compared circadian transcriptomes in heads of young and old Drosophila melanogaster. These data revealed a class of genes that adopt de novo rhythmicity during aging, termed "late life cyclers" (LLCs). We show that application of exogenous oxidative stress in young flies mimics aging by inducing robust, rhythmic LLC upregulation in a light- and CLOCK-dependent fashion. Additionally, we identified age-onset rhythmicity in some primary piRNA transcripts that overlap antisense transposable elements. To share our data, we developed a database for public viewing of graphical RNA-seq results for coding and non-coding RNAs in young and old flies. Taken together, our results suggest that aging organisms recruit the circadian system to launch a temporally coordinated defense to cope with their increasingly stressful cellular environments.
Project description:Gene expression changes in response to aging compared to heat stress, oxidative stress and ionizing radiation in Drosophila melanogaster
Project description:Gene expression changes in response to aging, hyperoxia, hydrogen peroxide, ionizing radiation, and heat stress were compared using microarrays. While aging shared features with each stress, aging was more similar to the stresses most associated with oxidative stress (hydrogen peroxide, hyperoxia, ionizing radiation) than to heat stress. Aging is associated with down-regulation of numerous mitochondrial genes, including electron-transport-chain (ETC) genes and mitochondrial metabolism genes, and a sub-set of these changes was also observed upon hydrogen peroxide stress and ionizing radiation stress. Aging shared the largest number of gene expression changes with hyperoxia. The extensive down-regulation of mitochondrial and ETC genes during aging is consistent with an aging-associated failure in mitochondrial maintenance, which may underlie the oxidative stress-like and proteotoxic stress-like responses observed during aging.
Project description:During oxidative stress, reactive oxygen species (ROS) can modify and damage cellular proteins. In particular, the thiol groups of cysteine residues can undergo reversible or irreversible oxidative post-translation modifications (PTMs). Identifying the redox-sensitive cysteines on a proteome-wide scale can provide insight into those proteins that act as redox sensors or become irreversibly damaged upon exposure to high levels of ROS. Aging is accompanied by oxidative stress, and oxygen-rich tissues such as the eye are particularly vulnerable because of its high energy demand and generation of ROS byproducts, which increases the risk for ocular disease. In this study, we profiled the redox proteome of the aging Drosophila eye to identify cysteine residues that are modified by age-associated ROS.
Project description:Gene expression changes in response to aging, hyperoxia, hydrogen peroxide, ionizing radiation, and heat stress were compared using microarrays. While aging shared features with each stress, aging was more similar to the stresses most associated with oxidative stress (hydrogen peroxide, hyperoxia, ionizing radiation) than to heat stress. Aging is associated with down-regulation of numerous mitochondrial genes, including electron-transport-chain (ETC) genes and mitochondrial metabolism genes, and a sub-set of these changes was also observed upon hydrogen peroxide stress and ionizing radiation stress. Aging shared the largest number of gene expression changes with hyperoxia. The extensive down-regulation of mitochondrial and ETC genes during aging is consistent with an aging-associated failure in mitochondrial maintenance, which may underlie the oxidative stress-like and proteotoxic stress-like responses observed during aging. Thirty five sample of RNA including Stress Controls (4 replicates), Heat Stress (3 replicates), Ionizing Radiation (4 replicates), Sugar (4 replicates), Hydrogen Peroxide (4 replicates), Young Controls (6 replicates) , Hyperoxia (6 replicates) and Old (4 replicates) adult Drosophila were analysed by Affymetrix microarrays. Stress Controls were used as controls for Heat Stress, Ionizing Radiation, Sugar and Hydrogen Peroxide samples. Young Controls were used as controls for Hyperoxia and Old samples. All flies were male progeny of a cross between Oregon-R wildtype and transgenic strain w[1118];P{w+ rtTA}(3)[E2]/ TM3. Flies lacking the balancer but bearing the transgene were used.
Project description:Curcumin, a yellow pigment extracted from the rhizome of the plant Curcuma longa (turmeric) has been widely used as a spice and herbal medicine in Asia. It has been suggested to have many biological activities such as anti-oxidative, anti-inflammatory, anti-cancer, chemopreventive, and anti-neurodegenerative properties. We evaluated the impact of curcumin on lifespan, fecundity, feeding rate, oxidative stress, locomotion and gene expression in two different wild type Drosophila melanogaster strains, Canton-S and Ives, under two different experimental conditions. We report that curcumin extended the lifespan of two different strains of Drosophila and was accompanied by protection against oxidative stress, improvement in locomotion and chemopreventive effects. Curcumin also modulated the expression of several aging related genes (genes with age-dependent changes in gene expression) such as mth, thor, InR, and JNK. In order to evaluate the impact of curcumin and aging on gene expression, we first determined which genes were affected by aging alone in Canton S flies. Age-related changes in gene expression were defined as changes in expression levels that occurred between 3 and 40 days of age (median lifespan). Among the 18,880 probe sets in the Affymetrix GeneChip® Drosophila Genome 2.0 Array, 1,383 genes (Data on file, 7.3%, P < 0.05) had statistically significant changes in expression levels during this time frame. We next determined the effect of curcumin on gene expression levels in young and aged Canton S flies. Gene expression were defined as changes in expression levels that occurred between 3 and 40 days of aged flies with or without curcumin-feeding.