Project description:Sir2 is the most intensively discussed longevity gene in current aging research. Although the gene encoding for a NAD+-dependent histone deacetylase initially was found to extend lifespan of various organisms ranging from yeast to mammals, serious doubts regarding its role in longevity have been expressed recently. In this study, we tested whether tissue-specific overexpression of Sir2 in the adult fat body can extend lifespan when compared to genetically identical controls. We also wanted to elucidate the mechanisms by which fat body Sir2 promotes longevity by studying the phenotypic and transcriptional changes in the fat body. We found that moderate (3-fold) Sir2 overexpression in the fat body during adulthood only can promote longevity in both sexes by roughly 13 %. In addition, we obtained transcriptional profiles elicited by this overexpression and propose a role for Sir2 in lipid droplet biology especially under conditions of starvation. Furthermore, our data do not support the idea of Sir2 mediating the response to dietary restriction (DR) because transcriptional profiles of fat bodies after DR or Sir2 overexpression do not match. This study provides additional independent evidence for the concept of Sir2 as a longevity gene and as a promising pharmacological target to cure age-related diseases. 6 groups of sample types were included in the experiment: a) females overexpressing Sir2 in the fat body b) female controls c) males overexpressing Sir2 in the fat body d) male controls e) wildtype females subjected to DR f) wildtype females feeding on a normal diet. 3 biological replicates were included per group.
Project description:Sir2 is the most intensively discussed longevity gene in current aging research. Although the gene encoding for a NAD+-dependent histone deacetylase initially was found to extend lifespan of various organisms ranging from yeast to mammals, serious doubts regarding its role in longevity have been expressed recently. In this study, we tested whether tissue-specific overexpression of Sir2 in the adult fat body can extend lifespan when compared to genetically identical controls. We also wanted to elucidate the mechanisms by which fat body Sir2 promotes longevity by studying the phenotypic and transcriptional changes in the fat body. We found that moderate (3-fold) Sir2 overexpression in the fat body during adulthood only can promote longevity in both sexes by roughly 13 %. In addition, we obtained transcriptional profiles elicited by this overexpression and propose a role for Sir2 in lipid droplet biology especially under conditions of starvation. Furthermore, our data do not support the idea of Sir2 mediating the response to dietary restriction (DR) because transcriptional profiles of fat bodies after DR or Sir2 overexpression do not match. This study provides additional independent evidence for the concept of Sir2 as a longevity gene and as a promising pharmacological target to cure age-related diseases.
Project description:Feeding resveratrol to Drosophila melanogaster extends lifespan. Studies of microarray show similarities between calorie/dietary restriction and resveratrol on both a gene expression and biological pathway level.
Project description:Expression data from four different lifespan-extending conditions: dietary restriction in two different genetic backgrounds (canton-s and a yw, w1118 combination), sir2 overexpression and p53 knockdown (+/-). Comparison of significantly over and under-expressed genes reveals a signature for dietary restriction and lifespan extension. Abstract A major challenge in translating the positive effects of dietary restriction (DR) for the improvement of human health is the development of therapeutic mimics. One approach to finding DR mimics is based upon identification of the proximal effectors of DR life span extension. Whole genome profiling of DR in Drosophila shows a large number of changes in gene expression, making it difficult to establish which changes are involved in life span determination as opposed to other unrelated physiological changes. We used comparative whole genome expression profiling to discover genes whose change in expression is shared between DR and two molecular genetic life span extending interventions related to DR, increased dSir2 and decreased Dmp53 activity. We find twenty-one genes shared among the three related life span extending interventions. One of these genes, takeout, thought to be involved in circadian rhythms, feeding behavior and juvenile hormone binding is also increased in four other life span extending conditions: Rpd3, Indy, chico and methuselah. We demonstrate takeout is involved in longevity determination by specifically increasing adult takeout expression and extending life span. These studies demonstrate the power of comparative whole genome transcriptional profiling for identifying specific downstream elements of the DR life span extending pathway. 42 samples were used in the analysis. Sir2 overexpression flies and the yw, w1118 background DR flies had the same control. Flies were collected at ages 10 and 40 days. Tissue is whole body females.
Project description:we performed proteome sequencing in Drosophila at day 7 (young) and day 42 (old) under dietary restriction (DR)and ad libitum (AL) conditions.
Project description:Feeding resveratrol to Drosophila melanogaster extends lifespan. Studies of microarray show similarities between calorie/dietary restriction and resveratrol on both a gene expression and biological pathway level. 9 samples: 3 biological replicates each of normal diet, restricted diet and normal diet plus resveratrol
Project description:Dietary restriction is a nutritional intervention that consistently increases life span in animals. To identify alternative, more acceptable nutritional regimes that nevertheless extend life span, we used the fruit fly Drosophila melanogaster as a model. We tested if weekly recurring nutritional regimes composed of phases of ad libitum feeding and dietary restriction can increase life span. Short periods of dietary restriction (up to 2 days) followed by longer ad libitum phases increased life span only marginally, whereas regimes comprising longer contiguous periods (3 days and more) became clearly positive, reaching similar life span extensions as those seen if dietary restriction was applied persistently. Female flies were substantially more responsive to these interventions than males. The finding that a minimal period of 3-4 days of dietary restriction is required to induce robust life span extensions was mirrored by the observation that substantial physiological and transcriptional changes occurred in a similar temporal pattern. Moreover, these dietary restriction induced changes were also detectable after switching to ad libitum feeding. Among the physiological changes induced by these phases of dietary restriction, a reduced metabolic rate and a substantial and long-lasting reduction in insulin signaling were most compelling. Age associated molecular signatures comprising mechanisms that reduce insulin signaling showed up after longer periods of dietary restriction in the fly’s fat body, thus showing how molecular alterations transduce into life span related physiological changes.