Extension of life span and stress resistance of Drosophila melanogaster by long-term supplementation with melatonin Ernesto Bonilla a,b, * , Shirley Medina-Leendertz b , Solangel Dõ Âaz b a Instituto de Investigaciones Clõ Ânicas ªDr Ame Ârico Negretteº, Facultad de Medicina, Universidad del Zulia, Apartado Postal 1151 Maracaibo, Venezuela b Instituto de Investigaciones Biome Âdicas INBIOMED), Fundacite Zulia, Apartado Postal 121 Maracaibo, Venezuela Received 7 August 2001; received in revised form 19 November 2001; accepted 20 November 2001 Abstract According to the free radical theory of aging, free radicals are involved in the production of changes in cellular metabolism that lead to a time-dependent functional decline in all living beings. Consequently, antioxidant and/or free radicals scavengers may retard the aging process. We explored the effect of melatonin on the life span of Drosophila melanogaster Oregon wild strain). It was presumed that given the antioxidant and free radicals scavenger properties of melatonin, this hormone would prevent oxidative damage to the ¯y tissues and slow down the process of aging. Melatonin, added daily to the nutrition medium at a concentration of 100 ug/ml, increased signi®cantly the life span of D. melanogaster. The maximum life span was 61.2 days in controls and 81.5 days in melatonin fed ¯ies. Relative to the controls, the percentage increase in the melatonin fed ¯ies was 33.2% in maximum life span, 19.3% in the onset of 90% mortality, and 13.5% in median life span. Furthermore, in a test of superoxide mediated toxicity it was shown that melatonin treatment increased the resistance of D. melanogaster to paraquat. Finally, the augmented resistance to an ambient temperature of 36 8C was also a demonstration of the antioxidative protection provided by the hormone. q 2002 Elsevier Science Inc. All rights reserved. Keywords: Drosophila melanogaster; Melatonin; Aging; Longevity; Paraquat; Free radicals 1. Introduction Although it is doubtful that a single theory can explain all the mechanisms of aging, the `free radical theory of aging' proposed by Harman 1956) is currently being supported by the majority of published reports. This theory is based on the premise that a single common process, modi®able by genetic and environmental factors, is responsible for the aging and death of all living beings Harman, 1981). The theory postulates that aging is caused by free radicals reactions that may be involved in the production of the aging changes associated with the environment, disease, and the intrinsic aging process. Reactive oxygen species oxygen free radicals and hydroperoxides) are initially produced by the univa- lent reduction of dioxygen to generate sequentially superoxide anion radical and hydrogen peroxide. The latter, if not eliminated, generates the highly reac- tive hydroxyl free radical, which is widely believed to be the main agent of oxidative damage Fridovich, 1978). The main assumption of the free radicals Experimental Gerontology 37 2002) 629±638 0531-5565/02/$ - see front matter q 2002 Elsevier Science Inc. All rights reserved. PII: S0531-556501)00229-7 www.elsevier.com/locate/expgero * Corresponding author. Address: Instituto de Investigaciones Clõ Ânicas ªDr Ame Ârico Negretteº, Facultad de Medicina, Universi- dad del Zulia, Apartado Postal 1151, Maracaibo, Venezuela. Tel.: 158-261-7597247; fax: 185-261-7838857. E-mail address: ebonillaro@yahoo.com E. Bonilla).