Effect of PARP-1 overexpression and pharmacological inhibition of NF-kB on the lifespan of Drosophila melanogaster.

Age-dependent accumulation of genome rearrangements leads to cellular senescence, overall aging and lifespan decreasing of the organism. In this respect, it is important to study the effect of overexpression of DNA repair genes on the lifespan and aging parameters (rates of age-related decline of fertility and locomotor activity). The present work investigates how the overexpression of the PARP-1 gene, which is involved in various mechanisms of DNA repair (base excision repair and DNA double-strand breaks repair), combined with a pharmacological inhibition of the NF-kB transcription factor that controls the genes of inflammatory response, affects the lifespan of Drosophila melanogaster. It is demonstrated that in males, constitutive activation of PARP-1 overexpression in the nervous system throughout the lifetime results in reduced median (by 14%) and maximum (by 8%) lifespan, whereas in females the median (by 14%) and maximum (by 20%) lifespan increases. Activation of PARP-1 overexpression in the imago (conditionally) results in extension of the median (by 3-16%) and the maximum (by 10-15%) lifespan in females and males, respectively. The lifespan increase in females with PARP-1 conditional overexpression was accompanied by decrease of fertility. Selective pharmacological inhibition of transcription factor NF-kB with pyrrolidine dithiocarbamate increases the median (by 13-20%) and the maximum (by 11-14%) lifespan in females and males, respectively. No synergic effect between conditionally activated PARP-1 expression and NF-kB inhibition is observed. The geroprotective effect of PARP-1 overexpression depends on the sex and the life history stage of overexpression induction.