Analysis of the role of tryptophan-kynurenine pathway in the life span control in Drosophila melanogaster
Abstract
Aim. To analyze life span in mutant Drosophila stocks with impaired tryptophan-kynurenine metabolism. Methods. Wild type stocks Canton-S and Oregon, stocks with mutations of the locus white: white, whiteapricot, whitesatsuma, and stocks with the mutation vermilion have been used. The average life span of imago has been determined, survival curves have been analyzed. Results. It has been shown that the average life span of Drosophila females with mutant alleles of the white gene does not differ from the wild-type stock; in males of the w(C-S) and wa(C-S) stocks the index is increased. The presence of the mutantion vermilion in the genotype also increases the average life span of imago of both sexes, but in males the extension is more pronounced. Conclusions. The results suggest that aging is associated with the regulation of tryptophan-kynurenine metabolism.
Keywords: Drosophila melanogaster, life span, kynurenine pathway of tryptophan metabolism.
References
Lуpez-Otin C., Blasco M.A., Partridge L. Serrano M., Kroemer G. The Hallmarks of Aging. Cell. 2013. Vol. 153 (6). P. 1194–1217. doi: 10.1016/j.cell.2013.05.039.
Greer E.L., Maures T.J., Ucar D., Hauswirth A.G., Mancini E., Lim J.P., Benayoun B.A., Shi Y., Brunet A. Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans. Nature. 2011. Vol. 479. P. 365–371. doi: 10.1038/nature10572.
Orentreich N., Matias J.R., DeFelice A., Zimmermann J.A. Low methionine ingestion by rats extends life span. J. Nutr. 1993. Vol. 123 (2). P. 269–274. doi: 10.1093/jn/123.2.269.
Zarse K., Schmeisser S., Groth M., Priebe S., Beuster G., Kuhlow D., Guthke R., Platzer M., Kahn C.R., Ristow M. Impaired insulin/IGF1 signaling extends life span by promoting mitochondrial L-proline catabolism to induce a transient ROS signal. Cell Metab. 2012. Vol. 15 (4). P. 451–465. doi: 10.1016/j.cmet.2012.02.013.
Van der Goot A.T., Wentao Zhu, Vбzquez-Manriqueet R.P., Seinstra R.I., Dettmer K., Michels H., Farina F., Krijnen J., Melki R., Buijsman R.C., Silva M.R., Thijssen K.L., Kema I.P., Neri Ch., Oefner P.J., Nollen E.A.A. Delaying aging and the aging as-sociated decline in protein homeostasis by inhibition of tryptophan degradation. Proc Natl Acad Sci USA. 2012. Vol. 109 (37). P. 14912–14917. doi: 10.1073/pnas.1203083109.
Savvateeva-Popova E.V., Popov A.V., Heinemann T., Riederer P. Drosophila mutants of the kynurenine pathway as a model for ageing studies. Adv. Exp. Med. Biol. 2003. Vol. 527. P. 713–722.
Oxenkrug G., Navrotskaya V., Vorobyova L., Summergrad P. Extension of life span of Drosophila melanogaster by the inhibitors of tryptophan – kynurenine metabolism. Fly (Austin). 2011. Vol. 5 (4). Р. 307–309. doi: 10.4161/fly.5.4.18414.
Navrotskaya V., Oxenkrug G., Vorobyova L.I., Summergrad P. Berberine attenuated aging-accelerating effect of high tempera-ture in drosophila model. Amer. J. Plant Sci. 2014. Vol. 5 (3). P. 275–278. doi: 10.4236/ajps.2014.53037.
Gorenskaya O.V., Kostenko V.V., Vorobyova L.I., Taglina O.V. The influence of allelic state of locus white on some parameters of fitness in Drosophila melanogaster. Bulletin of problems in biology and medicine. 2015. Issue 1. P. 74–79. [in Russian]
Mackenzie S.M., Brooker M.R., Gill T.R., Cox G.B., Howells A.J., Ewart G.D. Mutations in the white gene of Drosophila mel-anogaster affecting ABC transporters that determine eye colouration. Biochimica et Biophysica Acta. 1999. Vol. 1419. P. 173–185.
Kamyshev M.G. Longevity and its relation to the locomotor activity in tryptophan–xanthommatin metabolic pathway mutant of Drosophila. Dokl Acad Nauk USSR. 1980. Vol. 253. P. 1476–1480. [in Russian]
Oxenkrug G.F. The extended life span of Drosophila melanogaster eye-color (white and vermilion) mutants with impaired formation of kynurenine. J. Neural. Transm. 2010. Vol. 117. P. 23–26. doi: 10.1007/s00702-009-0341-7.
Frik B., Schroecksnadel K., Neurauter G., Leblhuber F., Fuchs D. Increasing production of homocysteine and neopterin and degradation of tryptophan with older age. Clin. Biochem. 2004. Vol. 37. P. 684–687. doi: 10.1016/j.clinbiochem.2004.02.007.
Sutphin G.L., Backer G., Sheehan S., Bean S., Corban C., Liu T., Peters M.J., van Meurs J.B.J., Murabito J.M., Johnson A.D., Korstanje R. Caenorhabditis elegans orthologs of human genes differentially expressed with age are enriched for determinants of longevity. Aging Cell. 2017. Vol. 16 (4). P. 672–682. doi: 10.1111/acel.12595.
Ocampo J.R., Huitrуn R.L., Gonzбlez-Esquivel D., Ugalde-Muсiz P., Jimйnez-Anguiano A., Pineda B., Pedraza-Chaverri J., Rнos C., Pйrez de la Cru V. Kynurenines with neuroactive and redox properties: relevance to aging and brain diseases. Oxidative Medicine and Cellular Longevity. 2014. Vol. 2014. Article ID 646909. doi: 10.1155/2014/646909.
Campesan S., Green E.W., Breda C., Sathyasaikumar K.V., Muchowski P.J., Schwarcz R., Kyriacou C.P., Giorgini F. The kynurenine pathway modulates neurodegeneration in a drosophila model of Huntington's disease. Curr. Biol. 2011. Vol. 21 (11). P. 961–966. doi: 10.1016/j.cub.2011.04.028.
Oxenkrug G.F. Increased plasma levels of xanthurenic and kynurenic acids in type 2 diabetes. Mol. Neurobiol. 2015. Vol. 52 (2). P. 805–810. doi: 10.1007/s12035-015-9232-0.