BackgroundThe molecular mechanisms that determine the organism's response to a variety of doses and modalities of stress factors are not well understood.ResultsWe studied effects of ionizing radiation (144, 360 and 864 Gy), entomopathogenic fungus (10 and 100 CFU), starvation (16 h), and cold shock (+4, 0 and -4°C) on an organism's viability indicators (survival and locomotor activity) and transcriptome changes in the Drosophila melanogaster model. All stress factors but cold shock resulted in a decrease of lifespan proportional to the dose of treatment. However, stress-factors affected locomotor activity without correlation with lifespan. Our data revealed both significant similarities and differences in differential gene expression and the activity of biological processes under the influence of stress factors.ConclusionsStudied doses of stress treatments deleteriously affect the organism's viability and lead to different changes of both general and specific cellular stress response mechanisms.

DNA repair declines with age and correlates with longevity in many animal species. In this study, we investigated the effects of GAL4-induced overexpression of genes implicated in DNA repair on lifespan and resistance to stress factors in Drosophila melanogaster. Stress factors included hyperthermia, oxidative stress, and starvation. Overexpression was either constitutive or conditional and either ubiquitous or tissue-specific (nervous system). Overexpressed genes included those involved in recognition of DNA damage (homologs of HUS1, CHK2), nucleotide and base excision repair (homologs of XPF, XPC and AP-endonuclease-1), and repair of double-stranded DNA breaks (homologs of BRCA2, XRCC3, KU80 and WRNexo). The overexpression of different DNA repair genes led to both positive and negative effects on lifespan and stress resistance. Effects were dependent on GAL4 driver, stage of induction, sex, and role of the gene in the DNA repair process. While the constitutive/neuron-specific and conditional/ubiquitous overexpression of DNA repair genes negatively impacted lifespan and stress resistance, the constitutive/ubiquitous and conditional/neuron-specific overexpression of Hus1, mnk, mei-9, mus210, and WRNexo had beneficial effects. This study demonstrates for the first time the effects of overexpression of these DNA repair genes on both lifespan and stress resistance in D. melanogaster.

There is a relationship between various cellular stress factors and aging. In earlier studies, we demonstrated that overexpression of the D-GADD45 gene increases the life span of Drosophila melanogaster. In this study, we investigate the relationship between D-GADD45 activity and resistance to oxidative, genotoxic and thermal stresses as well as starvation. In most cases, flies with constitutive and conditional D-GADD45 overexpression in the nervous system were more stress-resistant than ones without overexpression. At the same time, most of the studied stress factors increased D-GADD45 expression in the wild-type strain. The lifespan-extending effect of D-GADD45 overexpression was also retained after exposure to chronic and acute gamma-irradiation, with doses of 40 сGy and 30 Gy, respectively. However, knocking out D-GADD45 resulted in a significant reduction in lifespan, lack of radiation hormesis and radioadaptive response. A dramatic decrease in the spontaneous level of D-GADD45 expression was observed in the nervous system as age progressed, which may be one of the causes of the age-related deterioration of organismal stress resistance. Thus, D-GADD45 expression is activated by most of the studied stress factors, and D-GADD45 overexpression resulted in an increase of stress resistance.