Background: During their life, multicellular organisms are challenged with oxidative stress. It is generated by several reactive oxygen species (ROS), may limit lifespan and has been related to several human diseases. ROS can generate a wide variety of defects in many cellular components and thus the response of the organism challenged with oxidative stress may share some features with other stress responses. Conversely, in spite of recent progress, a complete functional analysis of the transcriptional responses to different oxidative stresses in model organisms is still missing. In addition, the functional significance of observed transcriptional changes is still elusive. Results: We used oligonucleotide microarrays to address the specificities of transcriptional responses of adult Drosophila to different stresses induced by paraquat and H₂O₂, two oxidative stressors, and by tunicamycin which induces an endoplasmic reticulum (ER) stress. Both specific and common responses to the three stressors were observed and whole genome functional analysis identified several important classes of stress responsive genes. Within some functional classes, we observed that isozymes do not all behave similarly, which may reflect unsuspected functional specificities. Moreover, genetic experiments performed on a subset of lines bearing mutations in genes identified in microarray experiments showed that a significant number of these mutations may affect resistance of adult Drosophila to oxidative stress. Conclusions: A long term common stress response to paraquat- or H₂O₂-induced oxidative stresses and ER stress is observed for a significant number of genes. Besides this common response, the unexpected complexity of the stress responses to oxidative and ER stresses in Drosophila, suggest significant specificities in protective properties between genes associated to the same functional classes. According to our functional analysis, a large part of the genome may play a role in protective mechanisms against oxidative stress in Drosophila.

Aging’s most obvious characteristic is the time dependent increase of an individual’s probability to die. This lifelong process is accompanied by a large number of molecular and physiological changes. Although numerous genes involved in aging have been identified in the past decades its leading factors have yet to be determined. To identify the very processes driving aging we have developed in the past years an assay to identify physiologically old individuals in a synchronized population of Drosophila melanogaster. Those individuals show an age-dependent increase of intestinal permeability followed by a high risk of death. Here we show that this physiological marker of aging is conserved in 3 invertebrate species Drosophila mojavensis, Drosophila virilis, Caenorhabditis elegans as well as in 1 vertebrate species Danio rerio. Our findings suggest that intestinal barrier dysfunction may be an important event in the aging process conserved across a broad range of species, thus raising the possibility that it may also be the case in Homo sapiens.

Glia are important modulators of neural activity, yet few studies link glia to sleep regulation. We find that blocking activity of the endocytosis protein, dynamin, in adult Drosophila glia increases sleep and enhances sleep need, manifest as resistance to sleep deprivation. Surface glia comprising the fly equivalent of the blood-brain barrier (BBB) mediate the effect of dynamin on sleep. Blocking dynamin in the surface glia causes ultrastructural changes, albeit without compromising the integrity of the barrier. Supporting a role for endocytic trafficking in sleep, a screen of Rab GTPases identifies sleep-modulating effects of the recycling endosome Rab11 in surface glia. We also find that endocytosis is increased in BBB glia during sleep and reflects sleep need. We propose that endocytic trafficking through the BBB represents a function of sleep.

Background: During the last two decades progress in the genetics of aging in invertebrate models such as C. elegans and D. melanogaster has clearly demonstrated the existence of regulatory pathways that control the rate of aging in these organisms, such as the insulin-like pathway, the Jun kinase pathway and the Sir2 deacetylase pathway. Moreover, it was rapidly shown that some of these pathways are conserved from yeast to humans. In parallel to genetic studies, genomic expression approches have given us significant information on the gene expression modifications that occur during aging either in wild type or long-lived mutant animals. But most of the genomic studies of invertebrate models have been performed so far on whole animals, while several recent studies in mammals have shown that the effects of aging are tissue specific. Results: We used oligonucleotide microarrays to address the specificities of transcriptional responses in aging Drosophila in head, thorax or whole body. These fly parts are enriched in transcripts that represent different and complementary sets of genes. We present evidence for both specific and common transcriptional responses during the aging process in these tissues. About half of the genes described as downregulated with age are linked to reproduction and enriched in gonads. Greater downregulation of mitochondrial genes, activation of the JNK pathway and upregulation of proteasome subunits in the thorax of aged flies all suggest that muscle may be particularly sensitive to aging. Simultaneous age-related impairment of synaptic transmission gene expression is observed in fly heads. In addition, a detailed comparison with other microarray data indicates that in aged flies there are significant deviations from the canonical responses to oxidative stress and immune stress. Conclusion: Our data demonstrates the advantages and value of regionalized and comparative analysis of gene expression in aging animals. Adding to the age-regulated genes already identified in whole animal studies, it provides lists of new regionalized genes to be studied for their functional role in the aging process. This work also emphasizes the need for such experiments to reveal in greater detail the consequences of the transcriptional modifications induced by aging regulatory pathways.