Melatonin as a geroprotector: Experiments withDrosophila melanogaster

Abstract

The lifespan of D. melanogaster treated with melatonin in a concentration of 0.08% at the stage of development is studied. The geroprotective effect of melatonin is the most obvious (up to 12-18%) in comparison with controls with a short lifespan; if the controls' lifespan was relatively long, the hormone exerts negligible or toxic effect shortening the lifespan by up to 10%. Antioxidant mechanism of geroprotective effect of melatonin is discussed in light of the concept of fluctuations in the lifespan in successive D. melanogaster generations.Key Words: melatonin; lifespan; geroprotector; Drosophila melanogaster Melatonin (N-acetyl-5-methoxytryptamine), first known as a pineal hormone, attracts attention due to its numerous positive effects on biological systems of various complexity [3,13]. The efficacy of melatonin in vitro surpasses that of glutathion, mannitol, tx-tocopherol, and ascorbic acid [11,14]. Melatonin regulates circadian rhythms in live organisms [13].The geroprotective activity of melatonin has been little studied in experiments. Melatonin added to daily rations of mice during the whole life increased the mean lifespan (LS) by 25%. However, no geroprotective effect was detected after addition of the drug at the late larval stages of D. melanogaster development.All this necessitates further investigation of geroprotective properties of melatonin. We studied the LS of D. melanogaster treated with melatonin. MATERIALS AND METHODSCrystalline melatonin (Sigma) was used.Lipophilic substance dissolved in ethanol was added to ready nutrient medium cooled to 45~ For control groups, the same amount of ethanol was added into the nutrient medium (final ethanol concentration 0.1%/unit). Preliminary tests showed that this con- D. melanogaster, Canton-S wild strain, was used.All experimental procedures and growth conditions have been described in detail [5]. The LS distribution in the control and experimental groups was compared by pairs using the Kolmogorov--Smirnov test. Cot'relations between LS in the control population and the geroprotector efficacy was analyzed using Spearman's test [151. RESULTSThe LS in the control groups greatly varied: the extreme values differed by more than 40% in females and by almost 30% in males (Table 1). These results agree with previous reports on the natural fluctuations in LS of successive D. melanogaster generations [6,7].Paired differences in LS between the control and experimental groups varied: we observed a significant geroprotective effect of melatonin prolonging the LS by 10-18% and lack of the effect or even a 10% shortening of LS. For elucidating the relationship between LS in the control and experimental groups, each mean 0007-4888/99/0002-0186522.00 ~ Kluwer Academic/Plenum Publishers