Downregulation of Rpd3, a homologue of mammalian Histone Deacetylase 1 (HDAC1), extends lifespan in Drosophila melanogaster. Once revealed that long-lived fruit flies exhibit limited cardiac decline, we investigated whether Rpd3 downregulation would improve stress resistance and/or lifespan when targeted in the heart. Contested against three different stressors (oxidation, starvation and heat), heart-specific Rpd3 downregulation significantly enhanced stress resistance in flies. However, these higher levels of resistance were not observed when Rpd3 downregulation was targeted in other tissues or when other long-lived flies were tested in the heart-specific manner. Interestingly, the expressions of anti-aging genes such as sod2, foxo and Thor, were systemically increased as a consequence of heart-specific Rpd3 downregulation. Showing higher resistance to oxidative stress, the heart-specific Rpd3 downregulation concurrently exhibited improved cardiac functions, demonstrating an increased heart rate, decreased heart failure and accelerated heart recovery. Conversely, Rpd3 upregulation in cardiac tissue reduced systemic resistance against heat stress with decreased heart function, also specifying phosphorylated Rpd3 levels as a significant modulator. Continual downregulation of Rpd3 throughout aging increased lifespan, implicating that Rpd3 deacetylase in the heart plays a significant role in cardiac function and longevity to systemically modulate the fly's response to the environment.

Biological behaviors and longevity of ectothermic animals are remarkably influenced by ambient temperature. Development at 18°C significantly enhances the stress resistance of adult flies with more accumulation of nutrients (especially fat) in the body than development at 25°C. Gene expression analysis between the flies developed at 18°C and 25°C revealed that the Immune deficiency (Imd) pathway, including the downstream antimicrobial peptides (AMPs), is downregulated in the flies developed at 18°C. When hypomorphic imd mutant flies with reduced AMP expressions were developed at 25°C, they showed induced stress resistance with higher fat content in the body similar to the wild-type flies developed at 18°C. However, severe hypomorphic imd mutants could not enhance stress resistance due to the downregulation of another downstream JNK pathway that expresses stress tolerance genes. Interestingly, the downregulation of AMP genes, itself, extended lifespan with increased stress resistance. Especially, fat body-specific downregulation of Imd AMP genes exhibited a longer lifespan with higher heat resistance. The fat body is known to function in metabolic homeostasis, stress tolerance, growth, and longevity in Drosophila. Here, we provide the first evidence that mild downregulation of the Imd pathway with AMP genes increases fat content, stress resistance, and lifespan in adult flies.

Mucin type O-glycosylation is a widespread modification of eukaryotic proteins, but its functional requirements remain incompletely understood. It is initiated by the attachment of N-acetylgalactosamine (GalNAc) to Ser or Thr residues, and then elongated by additional sugars. We have examined requirements for mucin-type glycosylation in Drosophila by characterizing the expression and phenotypes of core 1 galactosyltransferases (core 1 GalTs), which elongate O-GalNAc by adding galactose in a beta1,3 linkage. Drosophila encode several putative core 1 GalTs, each expressed in distinct patterns. CG9520 (C1GalTA) is expressed in the amnioserosa and central nervous system. A null mutation in C1GalTA is lethal, and mutant animals exhibit a striking morphogenetic defect in which the ventral nerve cord is greatly elongated and the brain hemispheres are misshapen. Lectin staining and blotting experiments confirmed that C1GalTA contributes to the synthesis of Gal-beta1,3-GalNAc in vivo. Our results identify a role for mucin-type O-glycosylation during neural development in Drosophila.

Ambient temperature affects the lifespan of cold-blooded organisms such as Drosophila melanogaster. To better understand what influences the lifespan of an adult fruit fly, we tested whether developmental temperature could affect stress responses used as surrogate markers for the aging process. When 2-day-old adult flies developed at two representative temperatures (18°C and 25°C) were challenged with three stresses (starvation, oxidation, and heat), both male and female flies developed at 18°C exhibited stronger resistance to all three stresses compared to those developed at 25°C. Nutrient composition analyses showed that fat, protein, and glycogen levels increased when male flies were developed at 18°C. These differences in stress resistance by developmental temperature were sustained even between 30-day-old male flies of two groups aged at the same temperature. We also showed that development at a lower temperature represented by 18°C significantly downregulates anti-microbial peptide genes, AttA and DptB, of Imd pathway.