title: The influence of pro-longevity gene Gclc overexpression on the age-dependent changes in Drosophila transcriptome and biological functions.
abstract: Transcriptional changes that contribute to the organism's longevity and prevent the age-dependent decline of biological functions are not well understood. Here, we overexpressed pro-longevity gene encoding glutamate-cysteine ligase catalytic subunit (Gclc) and analyzed age-dependent changes in transcriptome that associated with the longevity, stress resistance, locomotor activity, circadian rhythmicity, and fertility.
  
  
  
  Here we reproduced the life extension effect of neuronal overexpression of the Gclc gene and investigated its influence on the age-depended dynamics of transcriptome and biological functions such as fecundity, spontaneous locomotor activity and circadian rhythmicity, as well as on the resistance to oxidative, proteotoxic and osmotic stresses. It was shown that Gclc overexpression reduces locomotor activity in the young and middle ages compared to control flies. Gclc overexpression slowed down the age-dependent decline of locomotor activity and circadian rhythmicity, and resistance to stress treatments. Gclc level demonstrated associations with the expression of genes involved in a variety of cellular processes including Jak-STAT, MAPK, FOXO, Notch, mTOR, TGF-beta signaling pathways, translation, protein processing in endoplasmic reticulum, proteasomal degradation, glycolysis, oxidative phosphorylation, apoptosis, regulation of circadian rhythms, differentiation of neurons, synaptic plasticity and transmission.
  
  
  
  Our study revealed that Gclc overexpression induces transcriptional changes associated with the lifespan extension and uncovered pathways that may be associated with the age-dependent decline of biological functions.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia. amoskalev@list.ru.|Institute of Biology of Komi Science Center of Ural Branch of RAS, Syktyvkar, Russia. amoskalev@list.ru.|Moscow Institute of Physics and Technology, Dolgoprudny, Russia. amoskalev@list.ru.|Syktyvkar State University, Syktyvkar, Russia. amoskalev@list.ru.
authors.forename: Alexey
authors.initials: A
authors.lastname: Moskalev
authors.affiliation: Institute of Biology of Komi Science Center of Ural Branch of RAS, Syktyvkar, Russia.|Syktyvkar State University, Syktyvkar, Russia.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Shaposhnikov
authors.affiliation: Institute of Biology of Komi Science Center of Ural Branch of RAS, Syktyvkar, Russia.|Syktyvkar State University, Syktyvkar, Russia.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Proshkina
authors.affiliation: Institute of Biology of Komi Science Center of Ural Branch of RAS, Syktyvkar, Russia.|Syktyvkar State University, Syktyvkar, Russia.
authors.forename: Alexey
authors.initials: A
authors.lastname: Belyi
authors.affiliation: Moscow Institute of Physics and Technology, Dolgoprudny, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Fedintsev
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Zhikrivetskaya
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Zulfiya
authors.initials: Z
authors.lastname: Guvatova
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Asiya
authors.initials: A
authors.lastname: Sadritdinova
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Snezhkina
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: George
authors.initials: G
authors.lastname: Krasnov
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia. rhizamoeba@mail.ru.
authors.forename: Anna
authors.initials: A
authors.lastname: Kudryavtseva
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics; D004330:Drosophila / Q000502:physiology*; D004331:Drosophila melanogaster; D005260:Female; D005298:Fertility; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005721:Glutamate-Cysteine Ligase / Q000235:genetics*; D005978:Glutathione / Q000378:metabolism; D008124:Locomotion / Q000235:genetics; D008136:Longevity / Q000235:genetics*; D008297:Male; D009474:Neurons / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics; D059467:Transcriptome
chemical_list: D005721:Glutamate-Cysteine Ligase; D005978:Glutathione
keywords: Circadian rhythmicity; Drosophila melanogaster; Fertility; Gene expression; Glutathione; Lifespan; Locomotor activity