X-Message-Number: 13376 Date: Thu, 9 Mar 2000 17:14:32 -0800 (PST) From: Doug Skrecky <> Subject: drosophila longevity experiments Citations: 1-4 <1> Authors Mockett RJ. Sohal RS. Orr WC. Institution Department of Biological Sciences, Southern Methodist University, Dallas, Texas 75275, USA. Title Overexpression of glutathione reductase extends survival in transgenic Drosophila melanogaster under hyperoxia but not normoxia. Source FASEB Journal. 13(13):1733-42, 1999 Oct. Abstract The purpose of this study was to test the hypothesis that overexpression of glutathione reductase in transgenic Drosophila melanogaster increases resistance to oxidative stress and retards the aging process. Transgenic flies were generated by microinjection and subsequent mobilization of a P element construct containing the genomic glutathione reductase gene of Drosophila, with 4 kb upstream and 1.5 kb downstream of the coding region. Transgenic animals stably overexpressed glutathione reductase by up to 100% throughout adult life and under continuous exposure to 100% oxygen or air. Under hyperoxic conditions, overexpressors had increased longevity, decreased accrual of protein carbonyls, and dramatically increased survival rates after recovery from a semi-lethal dose of 100% oxygen. Under normoxic conditions, overexpression of glutathione reductase had no effect on longevity, protein carbonyl content, reduced glutathione, or glutathione disulfide content, although the total consumption of oxygen was slightly decreased. Glutathione reductase activity does not appear to be a rate-limiting factor in anti-aging defenses under normoxic conditions, but it may become a limiting factor when the level of oxidative stress is elevated. <2> Authors Brack C. Bechter-Thuring E. Labuhn M. Institution Laboratory of Molecular Gerontology, University of Basel, Switzerland. Title N-acetylcysteine slows down ageing and increases the life span of Drosophila melanogaster. Source Cellular & Molecular Life Sciences. 53(11-12):960-6, 1997 Dec. Abstract Ageing can be defined as the time-dependent decline of physiological functions of an organism. The molecular causes for the ageing process are multiple, involving both genetic and environmental factors. It has been proposed that antioxidants may positively influence the ageing process, protecting the organism against free radical-induced damage. Here we show that the antioxidant N-acetylcysteine (NAC) has a life-extending effect on Drosophila melanogaster. Dietary uptake of NAC results in a dose-dependent increase in median and maximum life span. Flies fed on 1 mg/ml NAC food live 16.6% longer; at 10 mg/ml, life span increases by 26.6%. We have examined the effect of NAC treatment on protein and RNA levels: we observe an NAC-dependent increase in absolute amounts of total RNA and ribosomal RNA, but no differences in protein levels. The NAC effect on longevity may involve differential expression of specific mRNA genes, as suggested by RNA finger-printing experiments. <3> Authors Anisimov VN. Mylnikov SV. Oparina TI. Khavinson VK. Institution Laboratory of Experimental Tumors, N.N. Petrov Research Institute of Oncology, St. Petersburg, Russia. Title Effect of melatonin and pineal peptide preparation epithalamin on life span and free radical oxidation in Drosophila melanogaster. Source Mechanisms of Ageing & Development. 97(2):81-91, 1997 Aug. Abstract It was shown previously that epithalamin delays age-related changes in reproductive and immune systems and increases the life span of mice and rats. These effects could be mediated by stimulating influences of epithalamin on synthesis and secretion of melatonin and on free radical processes. A comparative study on the effect of epithalamin and melatonin on both the life span of Drosophila melanogaster (strain HEM) and on the intensity of lipid peroxidation and activity of antioxidative enzymes in their tissues was the main aim of this work. Melatonin and epithalamin was added to the nutrition medium (100 micrograms/ml) during 2-3rd age of larvas. For survival analysis the flies were passed (five coupes per vessel) each 3-7 days. Lipid peroxidation was evaluated as the level of ketodienes (KD) and conjugated hydroperoxides (CHP) in fly tissues at the age of 11 days. Activity of Cu, Zn-superoxide dismuatse (SOD) and catalase was evaluated as well. The mean, median and maximum life span (MLS) were estimated. Mortality rate (MR) was calculated as alpha in the Gompertz equation (R = Ro (exp alpha t) and mortality rate doubling time (MRDT) as in 2/alpha. These parameters in groups of male and female flies exposed to melatonin and in male flies exposed to epithalamin were no different from the parameters for controls. However, exposure to epithalamin was followed in females by a significant increase in mean life span (by 17%, P < 0.02), of median (by 26%), of MLS by 14% and by a 2.12 times decrease of MR (P < 0.01) and MRDT (by 32%) compared with female controls. The level of CHP and KD in the tissues of male control flies was 40 and 49% less than that in females and indirectly correlates with male life span. Exposure to melatonin was followed by a decrease in the level of CHP and KD in females and the deletion of sex differences in them. Exposure to epithalamin significantly decreased the level of CHP and KD in female flies compared to controls (2.3 and 3.4 times, respectively, P < 0.001). Exposure to melatonin failed to influence the activity of catalase in males but increased it in females by 24% (P < 0.02) and failed to influence SOD activity both in males and females. Exposure to epithalamin was followed by a significant increase in activity of catalse, 20% in males and 7% in females and by an increase in SOD activity in males (41%). Thus, it was shown that exposure to epithalamin significantly increases the mean life span and MLS of female D.melanogaster and slowed down their aging rate by 2.12 times. This effect is in good agreement with the inhibiting effect of epithalamin in lipid peroxidation processes in fly tissues. <4> Authors Le Bourg E. Minois N. Institution Laboratoire d'Ethologie et de Psychologie Animale, Universite Paul Sabatier, Toulouse, France. Title Failure to confirm increased longevity in Drosophila melanogaster submitted to a food restriction procedure. Source Journals of Gerontology. Series A, Biological Sciences & Medical Sciences. 51(4):B280-3, 1996 Jul. Abstract Several studies have shown that, contrary to what occurs in rodents and in some invertebrate species, food restriction has no positive effect on longevity in Drosophila melanogaster. However, Chippindale et al. (1993) reported that flies subjected to food restriction, by modulating the yeast level, could live longer. In the present study we used the same yeast levels as Chippindale et al. in an attempt to confirm these results. No positive effect of food restriction on longevity could be observed in either sex in mated and virgin flies. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=13376