Alexey Moskalev1,2,3, Ekaterina Proshkina4, Alex Zhavoronkov5, Mikhail Shaposhnikov4. 1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia. amoskalev@ib.komisc.ru. 2. Institute of Biology, Komi Scientific Center, Ural Division, Russian Academy of Sciences, Syktyvkar, 167982, Russia. amoskalev@ib.komisc.ru. 3. Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia. amoskalev@ib.komisc.ru. 4. Institute of Biology, Komi Scientific Center, Ural Division, Russian Academy of Sciences, Syktyvkar, 167982, Russia. 5. Insilico Medicine, Rockville, MD, USA.
Abstract
BACKGROUND: The JAK/STAT signaling pathway is involved in many aging-related cellular functions. However, effects of overexpression of genes controlling JAK/STAT signal transduction on longevity of model organisms have not been studied. Here we evaluate the effect of overexpression of the unpaired 1 (upd1) gene, which encodes an activating ligand for JAK/STAT pathway, on the lifespan of Drosophila melanogaster. RESULTS: Overexpression of upd1 in the intestine caused a pronounced shortening of the median lifespan by 54.1-18.9%, and the age of 90% mortality by 40.9-19.1% in males and females, respectively. In fat body and in nervous system of male flies, an induction of upd1 overexpression increased the age of 90% mortality and median lifespan, respectively. An increase in upd1 expression enhanced mRNA levels of the JAK/STAT target genes domeless and Socs36E. CONCLUSIONS: Conditional overexpression of upd1 in different tissues of Drosophila imago induces pro-aging or pro-longevity effects in tissue-dependent manner. The effects of upd1 overexpression on lifespan are accompanied by the transcription activation of genes for the components of JAK/STAT pathway.
BACKGROUND: The JAK/STAT signaling pathway is involved in many aging-related cellular functions. However, effects of overexpression of genes controlling JAK/STAT signal transduction on longevity of model organisms have not been studied. Here we evaluate the effect of overexpression of the unpaired 1 (upd1) gene, which encodes an activating ligand for JAK/STAT pathway, on the lifespan of Drosophila melanogaster. RESULTS: Overexpression of upd1 in the intestine caused a pronounced shortening of the median lifespan by 54.1-18.9%, and the age of 90% mortality by 40.9-19.1% in males and females, respectively. In fat body and in nervous system of male flies, an induction of upd1 overexpression increased the age of 90% mortality and median lifespan, respectively. An increase in upd1 expression enhanced mRNA levels of the JAK/STAT target genes domeless and Socs36E. CONCLUSIONS: Conditional overexpression of upd1 in different tissues of Drosophila imago induces pro-aging or pro-longevity effects in tissue-dependent manner. The effects of upd1 overexpression on lifespan are accompanied by the transcription activation of genes for the components of JAK/STAT pathway.
Authors: Hervé Agaisse; Ulla Maja Petersen; Michael Boutros; Bernard Mathey-Prevot; Norbert Perrimon Journal: Dev Cell Date: 2003-09 Impact factor: 12.270