Shuttle craft Gene Affects Lifespan of Drosophila melanogaster by Controlling Early Development and Modifying Aging Program.

Fundamental mechanisms underlying genetic control of lifespan are intensively studied and discussed due to the increasing importance of extending healthy human life. The stc gene of the model organism Drosophila melanogaster encodes a transcription factor, homolog of the human transcription factor NF-X1, involved in regulation of neuronal development and other processes, as well as in control of lifespan. In this work, we demonstrate that the stc knockdown in embryonic and nerve cells leads to changes in lifespan, with the nature of changes depending on the cell type and sex of individuals.

Modulated Expression of the Protein Kinase GSK3 in Motor and Dopaminergic Neurons Increases Female Lifespan in .

Most eukaryotic genes express multiple transcripts and proteins, and a sophisticated gene expression strategy plays a crucial role in ensuring the cell-specificity of genetic information and the correctness of phenotypes. The gene encodes several isoforms of the conserved glycogen synthase kinase 3 (GSK3), which is vitally important for multiple biological processes. To characterize the phenotypic effects of differential expression, we explored how the multidirectional modulation of the expression of the main GSK3 isoform, Shaggy-PB, in different tissues and cells affects lifespan.

Knockdown of the neuronal gene Lim3 at the early stages of development affects mitochondrial function and lifespan in Drosophila.

Understanding the molecular mechanisms underlying variation in lifespan is central to ensure long life. Lim3 encoding a homolog of the vertebrate Lhx3/4 transcription factors plays a key role in Drosophila neuron development. Here, we demonstrated that Lim3 knockdown early in life decreased survival of adult flies.

Disordered Expression of , the Gene Encoding a Serine-Threonine Protein Kinase GSK3, Affects the Lifespan in a Transcript-, Stage-, and Tissue-Specific Manner.

GSK3 (glycogen synthase kinase 3) is a conserved protein kinase governing numerous regulatory pathways. In , GSK3 is encoded by (), which forms 17 annotated transcripts corresponding to 10 protein isoforms. Our goal was to demonstrate how differential transcription affects lifespan, which GSK3 isoforms are important for the nervous system, and which changes in the nervous system accompany accelerated aging.

Reduced Neuronal Transcription of , the Gene Encoding a Snail-Type Transcription Factor, Promotes Longevity.

In recent years, several genes involved in complex neuron specification networks have been shown to control life span. However, information on these genes is scattered, and studies to discover new neuronal genes and gene cascades contributing to life span control are needed, especially because of the recognized role of the nervous system in governing homeostasis, aging, and longevity. Previously, we demonstrated that several genes that encode RNA polymerase II transcription factors and that are involved in the development of the nervous system affect life span in .

Tissue-specific transcription of the neuronal gene Lim3 affects Drosophila melanogaster lifespan and locomotion.

The identity of neuronal cell types is established and maintained by the expression of neuronal genes coding for ion channels, neurotransmitters, and neuropeptides, among others. Some of these genes have been shown to affect lifespan; however, their role in lifespan control remains largely unclear. The Drosophila melanogaster gene Lim3 encodes a transcription factor involved in complicated motor neuron specification networks.

The Mitochondria-Targeted Plastoquinone-Derivative SkQ1 Promotes Health and Increases Drosophila melanogaster Longevity in Various Environments.

Mitochondria play an important role in aging. Strongly reduced function of the mitochondria shortens life span, whereas moderate reduction prolongs life span, with reactive oxygen species production being the major factor contributing to life span changes. Previously, picomolar concentrations of the mitochondria-targeted antioxidant SkQ1 were shown to increase the life span of Drosophila by approximately 10%.

Embryonic expression of shuttle craft, a Drosophila gene involved in neuron development, is associated with adult lifespan.

Despite the progress in aging research that highlights the role of the nervous system in longevity, whether genes that control development and consequently structure of the nervous system affect lifespan is unclear. We demonstrated that a mutation inshuttle craft, a gene involved in the nervous system development, increased the lifespan of unmated females and decreased the lifespan of mated females, without affecting males. Precise reversions of the mutation lead to the restoration of the lifespan specific to control females.

Reproducible effects of the mitochondria-targeted plastoquinone derivative SkQ1 on Drosophila melanogaster lifespan under different experimental scenarios.

Previously, extremely low, nanomolar concentrations of the mitochondria-targeted plastoquinone derivative SkQ1 (10-(6'-plastoquinonyl) decyltriphenylphosphonium) were shown to prolong the lifespan of male and female Drosophila melanogaster by about 10 % (Anisimov et al., Biochemistry (Moscow) 73:1329-1342, 2008). Using long-term monitoring of SkQ1 effects on the Drosophila lifespan, we analyzed different integral parameters of Drosophila survival and mortality under SkQ1 treatment.

[The effect of volatile antioxidants of plant origin on leukemogenesis in mice].

The effect of savory essential oil added with drinking water (150 ng/ml) or with feed (2.5 microg/g) on the lifetime of AKR mice and the parameters of oxidative stress in animal blood were investigated. It was found for the first time that long-term administration of an essential oil in low doses increased the average lifetime of mice by 20-35% and was accompanied by a decrease in the hemolysis level and the content of lipid peroxidation products in erythrocytes of mice, as well as alteration in the structural state of their membranes and stabilization of polyunsaturated fatty acids level in mice liver cells.

[Effect of antioxidant beta-(4-hydroxy-3,5-ditertbutylphenyl) propionic acid (phenosan) on the development of malignant neoplasms].

The effect of different doses of synthetic antioxidant beta-(4-hydroxy-3,5-ditertbutylphenyl)propionic acid (phenosan) on the development of spontaneous leukemia in AKR mice was studied. The drug efficiency was determined from the survival curves, animal life spans, and the incidence of leukemia. Phenosan exhibited a pronounced antitumor activity at therapeutic (10(-4) mol/kg, 4 administrations) and ultra-low (10(-14) mol/kg, 4 administrations) doses.

[The differences and regularities of life-span dynamics for human and animal populations].

The dynamics of mortality of several generations of man, Wistar rats and line Canton-S fruit flies Drosophila melanogaster was investigated. The result was, that the correlation between sample mean and sample variance was negative for man, positive for flies and was absent for rats. To fit the survival curve we chose two-parametric Gompertz function.

[Historical dynamics of life-span distribution of Man].

In this activity the historical dynamics of life-span distribution parameters of the people was investigated in 12 developed countries encompassing the period of 1750-1998 years, it is treated about 1200 life tables. The approximately of a linear segment of a curve of age-specific death rate by the Gompertz function allows getting an analytical view of the life-span distribution. It is shown that the decreasing of the lower age range since 35 years till 10 years a little bit augments an approximation error.

[A possible mechanism of action of biologically active substances in extra-low concentrations at cellular and subcellular levels].

A model of interaction between biologically active substances and macromolecular structures is proposed. The solutions of kinetic equations of discrete and continuous cases were obtained which predict nonmonotonous dose dependences.