N. Ya. Weisman

Haploadaptivity of tumor suppressor lgl and ontogenesis in Drosophila melanogaster: Increased survival rate and life span under stress conditions

Mutations of tumor suppressor lgl induce neuroblastoma and malignant transformation of epithelial larval tissues in Drosophila. We have already shown that heterozygotes for lethal null variants lgl/+ are widespread in natural populations. In order to elucidate this paradox, we analyzed the parameters of biological adaptation of the carriers of one dose of the tumor suppressor. We studied the patterns of embryonic survival rate of lgl/+ flies under the conditions of competition for life resources and development at elevated and lowered temperatures (29 and 16°C), influence of stress thermal conditions on longevity, influence of short-term temperature stress during prezygotic period in the course of oogenesis of mothers on survival rate of F1 progenies, and resistance of heterozygotes for different lethal lgl alleles against RNA virus DCV. The loss of one dose of tumor suppressor lgl provided for increased survival rate and longevity of lgl/+ heterozygotes under stress conditions. This phenomenon was called haploadaptivity. Important features of adaptogenesis were established in lgl/+ heterozygotes: dependence on the maternal genotype and critical periods in development. The increased survival rate of F1 progenies was determined already during early oogenesis of their lgl/+ mothers at the proembryo stage. With respect to humans, this conclusion draws attention to the oogenesis-dependent transgeneration aspect of determination and expression of mutant factors of risk, including tumor suppressors. The data obtained are essential for understanding of the causes of spreading null variants for the genes related to multiple pathologies, including cancer, in human populations.

Terahertz radiation influence on number and development dynamics of offspring F1 of fruit fly females under stress

Virgin fruit fly females were stressed by placement into a confined space without food for 2.5 hours. Some flies were subjected to terahertz radiation (0.1–2.2 THz) for the last 30 min. Then females were copulated with males. Offspring F1 from oocytes which were mature or immature at exposure (oviposition in 1–2 or 9–10 days after irradiation) was studied. Stress induces a rejection of the offspring maturation dynamics to imago from external control (offspring of flies which was maintained in standard conditions). In offsping from mature oocytes of irradiated flies the dynamics of male maturation to imago was different from internal control (offspring of stressed unirradiated flies). The number of imago males decreased. The dynamics of female maturation to imago coincides with laboratory control. In offsping from immature oocytes of irradiated flies the dynamics of female and male maturation and the number of flies were not significantly different from the internal control. It was concluded that only mature oocytes are sensitive to THz radiation influence.

Parallelism and paradoxes on viability and the life span of two loss-of-function mutations: Heat shock protein transcriptional regulator hsf 1 and l(2)gl tumor suppressor in Drosophila melanogaster

In this study we analyzed how a dosage decrease in mono- and diheterozygotes on both lethal alleles of the lgl-gene and hsf heat shock regulator influences viability and life span at optimal and high temperature 29°C conditions. We found that hsf1/+ (1 dosage of active hsf -factor) heterozygote animals had significantly increased viability (up to 30–39%) in case of its development from egg to imago under the stress of 29°C. However, this stress-protective effect of a decreased dosage of HSF1 was suppressed in diheterozygotes, while the dosage of tumor suppressor lgl was simultaneously decreased. Under stress temperature conditions, a decrease in dosage of one of the alleles also increased the average life span and delayed aging, especially in the case of maternal inheritance of each of the loss-of-function mutations. In diheterozygotes the average life span had intermediate meanings. However, in diheterozygote males under stress conditions the positive longevity effect of hsf was suppressed in the presence of the lgl-mutation. Paradoxically, that decrease of expression of each of the studied vital genes provided a positive effect on both viability and life span under stress conditions. However, a simultaneous dosage decrease of two loss-of-function alleles in diheterozygotes resulted in disbalanced effects on the organism level. The received data indicate interaction between HSF1 and LGL gene products during ontogenesis and stress-defending processes.

Survival and life span of Drosophila melanogaster in response to terahertz radiation

Life span control is realized by the interaction of many genetic factors with the environment. Due to the development of modern technologies based on nonionized terahertz radiation (0.1–10 THz), the investigation of the influence of this radiation on living organisms is urgent. In our study, the effects of terahertz radiation on the survival and lifespan of the Oregon R line of Drosophila melanogaster were multidirectional, depending on the age of the insects. The terahertz effect on survival was negative or neutral in early life and positive in later life. In the drosophila response to terahertz radiation, sex differences were manifested. Males were not very sensitive to terahertz radiation. The survival of irradiated females increased significantly in the second half of the imago life. Irradiation of the drosophila did not significantly affect mean and maximal values of lifespan, but the gap between the values of the mean lifespans of males and females in this group of insects was increased. The mechanisms for the effects of terahertz radiation on survival and lifespan might be associated with changes in the cellular membrane, gene expression, and signaling pathways controlling these features.

Effect of phenol inducing antioxidant responsive element on D. melanogaster lifespan

The effect of hydrophilic synthetic antioxidant TS-13 (sodium 3-(3′-tert-butyl-4′-hydroxyphenyl)propyl thiosulfonate) on the lifespan of different lines of Drosophila melanogaster under normal conditions and the survival in the oxidative stress induced by hydrogen peroxide and paraquat were studied. The addition of 1% TS-13 to diets extended the lifespan of males and females of the long-living Canton S line of D. melanogaster, had no effect on the lifespan of short-living Oregon R line and shortened the average lifespan of males of the lgl558OR/Cy line of D. melanogaster containing a heterozygous recessive lethal mutation of tumor suppressor. Under the conditions of oxidative stress induced by hydrogen peroxide, TS-13 increased the survival of Canton S males and Oregon R females; under the action of paraquat, the protective effect of antioxidant was manifested toward Canton S females and Oregon R flies of both sexes. Despite the fact that anti-aging and protective properties of synthetic phenolic antioxidant TS-13 strongly depend on the genotype and gender, under extreme conditions of oxidative stress. its positive effect is pronounced.

The lifespan of the F1 progeny of drosophila females exposed to terahertz radiation of low intensity

Virgin drosophila females were stressed by placing them in a limited space without food for 3 h. Some of the flies were exposed to terahertz radiation for 30 min in the 0.1–2.2 THz frequency range. Irradiated and unirradiated flies were then mated with males. The F1 progeny of egg cells that were mature or immature at the time of radiation (laying at the first–second and ninth–tenth days after the radiation) were studied. The lifespan of separate individuals were registered. It was demonstrated that terahertz radiation has no effect on the average and absolute lifespan of F1 progeny of both sexes. Sexual dimorphism was found in the survival response to terahertz radiation. The survival curves of males that were developed from egg cells that were immature or mature at the time of radiation significantly differ from the appropriate control, while the survival curves for females are similar to the control. It was concluded that terahertz radiation has a longterm influence on the survival of F1 male progeny.

Effect of Phenol Inducing the Antioxidant Responsive Element on Drosophila Melanogaster Lifespan

The effect of hydrophilic synthetic antioxidant TC-13 (3-(3’-tert-butyl-4’-hydroxyphenyl) propylthiosulfonate sodium) inducing the antioxidant-responsive element on the lifespan of Drosophila melanogaster was studied. Addition of 1% TC-13 to diets prolonged the lifespan of long-lived D. melanogaster Canton S strain females and males, but not of short-lived Oregon R insects and reduced the mean lifespan of D. melanogaster males of the lgl558OR/Cy strain containing a recessive lethal mutation of tumor suppressor in the heterozygotic state. The geroprotective effects of TC-13 synthetic phenol antioxidant depended on D. melanogaster genotype and gender.

Terahertz radiation improves adaptation characteristics in Drosophila melanogaster

An investigation into the effect of nonionizing terahertz radiation (0.1–10 THz) on living organisms is urgent due to the recent development of modern technologies employing such radiation. The aim of this study was to establish the impact of terahertz radiation on successive generations of fruit flies. The effects of terahertz radiation on the survival ability and lifespan of the Oregon-R strain of Drosophila melanogaster proved to be diverse: they were negative or neutral at early life stages and positive at late stages. The female flies exposed to the radiation showed increased survival rate during the second half of the life of imago. The males demonstrated low sensitivity to the radiation. There were no significant differences noted in the dynamics of maturation and total number of offspring between the female flies that were exposed to the radiation and those that were not. The results of the study practically did not depend on the sex and maturity stage of the oocytes irradiated.

Unexpected effects of tumor-suppressing genes on fruit fly development

Numerous commonly known suppressor genes not only prevent unrestricted cell division or neoplasia but also produce various effects on animal development, vital functions, and fitness. The pleiotropic effects of these genes are related to their primary role in controlling key cell processes. In cooperation with other proteins, products of suppressor genes form cell junctions and polarity; take part in the transduction of molecular signals that govern important processes in a developing organism; control the cell cycle, growth, and proliferation; and modulate the signaling paths of cell survival and preprogrammed death, which protect the body from abnormal structures in critical situations. In spite of the vital importance of tumor suppressors, their lethal mutations are widespread in animal populations, and their presence in a heterozygous state confers better fitness in nature.

Variability of the antioxidant effect on survival: Modeling in drosophila lines with different lifespan and lgl-tumor suppressor dosage

Different exogenic antioxidants and geroprotectors are used to decrease age abnormalities and enhance the human life span. However, the antioxidant effect on lifespan is variable and requires detailed analysis. In the present report, we modeled in Drosophila the peculiar character of action of various doses of a new phenol antioxidant TC-13. We studied the TC-13 effect on aging of two Drosophila lines with genetically determined contrast lifespan dynamics. In addition, we tested the TC-13 antioxidant influence on the background of heterozygozity on the loss-of-function mutation of the l(2)gl tumor suppressor. The differing effect of TS-13 on LS, the character of which depends on the antioxidant dosage, genotype of line, and sex of Drosophila, was found. TS-13 in the concentration 0.2% did not affect the lifespan in all studied lines and decreased survival, whereas the antioxidant in a concentration of 1% positively affected the lifespan in both males and females of long-living lines. The antioxidant effect on animal lines with a smaller dose of tumor suppressor l(2)gl resulted in a decrease of the lifespan.