The genetic mechanisms of the influence of the light regime on the lifespan of Drosophila melanogaster

Light is a crucial environmental factor influencing living organisms during their whole lives. It contributes to the regulation of circadian rhythms, affects growth, metabolic rate, locomotor activity and reproduction. The mechanisms of the influence of light on longevity are poorly understood. We have suggested that there are two relatively independent genetic mechanisms of the influence of light on lifespan (Moskalev and Malysheva, 2010). The first mechanism is related to the damaging effects of light, leading to a reduced lifespan (Figure 1A), the second mechanism is related to the influence of the dark as a mild stressor, which can stimulate the body’s defense system and lead to an increased lifespan (Figure 1B). It is known that an increase in the photoperiod usually decreases the lifespan of experimental animals (Massie and Whitney, 1991; Massie et al., 1993; Sheeba et al., 2000; Majercak, 2002; Anisimov et al., 2004; Vinogradova et al., 2009). An increase in day length promotes a higher level of metabolism due to the intensification of locomotor activity and changes in body temperature of Drosophila (Sheeba et al., 2000, 2002). An increase in metabolic rate, in turn, leads to the additional formation of toxic by-products—free radicals (Massie and Whitney, 1991; Helfand and Rogina, 2003), damaging the cell’s mitochondrial and nuclear DNA, membranes and proteins (Le Bourg, 2001), and as a result this can lead to accelerated aging and a reduced lifespan. In our works (Moskalev et al., 2006, 2008) we investigated the strain Drosophila melanogaster with the defective cytoplasmic superoxide dismutase gene (Sod) which has only 36.7% of the normal activity of the Cu/Zn Sod enzyme (Phillips et al., 1995) and the strain with the defective mutagen-sensitive 210 gene (mus210), protein-coding, involved in nucleotideexcision repair (homolog of the XPC protein in mammals) (Isaenko et al., 1994). This gene group contributes directly to the elimination of oxidative damage— through free radical detoxication (gene Sod) and DNA repair (gene mus210). It has been shown that mutations in genes responsible for the removal of oxidative damage can alter the lifespan of animal models. In particular, in Drosophila with zero Cu/Zn-superoxide dismutase activity, the lifespan is reduced by 80% (Staveley et al., 1990), and injecting into the short-lived strain Drosophila genome additional superoxide dismutase and catalase genes, basic antiradical protection enzymes, resulted in a lifespan increase (Orr and Sohal, 1994, 2003). Sod overexpression in Drosophila’s motor neurons only prolonged the lifespan by 40% and made Drosophila more resistant to agents stimulating active oxygen formation such as ionizing radiation and paraquat (Mattson et al., 2002). We also know that the ability to repair oxidized DNA bases decreases in XPC-deficient cells (D’Errico et al., 2006). In our experiments, the median lifespan of flies with an impaired Sod gene function also decreased compared with the lifespan of CantonS wild-type flies by 41% for males and 38% for females (Moskalev et al., 2006). In the strain with the defective mus210 gene the median lifespan was reduced by 48% in males and 21% females compared with wild-type flies (Moskalev et al., 2006). We hypothesized that in strains with a dysfunction of Sod and mus210 genes there will be a significant reduction in lifespan if subject to lighting round the clock, as compared to the wild-type strain. According to our results, in strains with Sod and mus210 gene mutations, there was a significant increase in the difference between the median and maximum lifespan in the dark and in the light compared with the Canton-S wild-type strain (Moskalev et al., 2006). In the strain with a free radical detoxication defect, the gap in the median lifespan in the dark and in the light was 36% for males and 14% for females; the maximum lifespan was 11% for males and 24% for females. At the same time, the addition of the antioxidant melatonin into the food for Drosophila with this defect reduced this variation (Moskalev et al., 2008). In the strain with the DNA repair defect, the gap in the median lifespan in the dark and in the light was 11% for males and 23% for females; and the maximum lifespan was 21% for males and 9% for females. The lifespan parameters of wild-type flies varied insignificantly (within 0–7%). Thus, our results confirm our hypothesis about the importance of detoxification and DNA repair genes in the regulation of lifespan under a changing day length (Moskalev et al., 2006, 2008). It is known that in the regulation of the oxidative stress response and lifespan a key role is played by sirtuin family proteins (Guarente and Kenyon, 2000; Balaban et al., 2005). In response to stress sirtuins deacylate histones and various transcription factors (including p53, FOXO, HSPs), activating the expression of the stress response genes and inactivating and inhibiting apoptosis, thus contributing to the cell survival rate and lifespan increase (Tanno et al., 2007; Niedernhofer and Robbins, 2008). It is known that sirtuins play a key role in the regulation of the aging rate and longevity. In particular,