Life span extension in Drosophila melanogaster induced by morphine.

The influence of morphine on the life span of Drosophila melanogaster fruit flies has been investigated. Morphine hydrochloride (MH) at concentrations of 0.01, 0.05 and 0.25 mg/ml was added to a medium starting from day 5 or 54 of imaginal life. Supplementation with MH starting from day 5 of imaginal life has resulted in significant increases in the mean life span of males at all concentrations studied. In females, a significant increase in life span compared with control was obtained only for those treated with 0.25 mg/ml MH. In flies with MH feeding from day 54, residual life span was significantly increased in both males and females after treatment with 0.05 mg/ml MH. The present data, together with those of our earlier study in mice (Dubiley et al. Probl Aging Longvity 9:331­332, 2000) suggest that morphine supplementation can result in life extension in both vertebrate and invertebrate animal species.

Life extension in Drosophila maintained under lengthened light/dark regime.

In the present study, we investigated whether the length of light/dark cycle could influence the pre-adult developmental time and adult life span in Drosophila melanogaster. Flies were reared to adulthood and maintained as adults under both 24-h (light/dark 12:12 h) and 48-h (light/dark 24:24 h) cycles. The flies reared during pre-adult stages at the 48-h light/dark cycle had significantly prolonged developmental time compared to those in flies reared at normal 24-h cycle. Irrespective of the duration of pre-adult light/dark period, the males maintained as adults at prolonged 48-h cycle had a 13-16% longer mean adult life span than those maintained at normal 24-h cycle (P<0.001 in all cases). In females reared under normal 24-h cycle such differences were lower but also significant (P=0.03); no significant difference in life span was found in females reared under prolonged 48-h cycle. The results are interpreted to demonstrate that pre-adult developmental time and adult life span in Drosophila melanogaster are both influenced by the length of light/dark cycle.

Cross-life stage and cross-generational effects of gamma irradiations at the egg stage on Drosophila melanogaster life histories.

The long-term effects of X-irradiation with 0.25, 0.5, 0.75 and 1 Gy of 1 h eggs on the fitness-related life history traits in adult Drosophila melanogaster fruit flies and their offspring were investigated. Following irradiation with 0.25, 0.5 and 0.75 Gy, both F0 and F1 flies have decreased adult body weight and increased locomotor (photo- and geotactic) activity, whereas metabolic rate measured as the rate of CO2 production was unchanged or even increased, and female fecundity was slightly reduced compared to appropriate controls. In some cases, irradiation resulted in hormetic effects increased resistance to both starvation and heat shock stresses as well as life extension. An explanation of the beneficial long lasting effects induced by early irradiation is offered, which suggests that these effects are due to cross-life stage and cross-generational adaptive phenotypic plasticity.

Effect of X-irradiation at larval stage on adult lifespan in Drosophila melanogaster.

The effects of X-ray irradiation at larval stage with doses of 1.2, 2.1, 4.2, 7.5 and 17.1 Gy on adult longevity and fecundity in Drosophila melanogaster fruit flies were studied. A significant negative trend with increasing dose of irradiation was detected for the median lifespan in both sexes. In all experimental groups, both male and female mortality rates in irradiated flies were above control levels approximately for one month after emergence, and below control levels at older ages. The irradiation with 1.2 and 2.1 Gy resulted in 11.5% and 12.7% increase of male maximum lifespan, respectively. Irradiated females had in most cases a lower fecundity than control females. In all studied age groups, the decrease of fecundity was dose-related, and the negative effect of irradiation on fecundity was no longer observed in flies older than two weeks of age. Mean fecundity for the 4-25-day period of the irradiated females was shortened and dose-related [one-way ANOVA: F(5,414) = 10.56, P < 0.001], but significant differences from control were observed only for flies irradiated with doses of 4.2, 7.5 and 17.1 Gy. Mean fecundity for females irradiated with doses of 1.2 and 2.1 Gy did not differ from that of control females.

Variation of mortality rate during the individual annual cycle.

The month of birth was significantly associated with the month of death in 102,265 individuals who died in Kiev during the period 1990-2000. A consistent trend in deaths was revealed, with an excess around the birthday. This excess on the actual anniversary of birth was 44.4% in men (chi2=11.48, P<0.001) and 36.2% in women (chi2=7.64, P<0.01) over the expected value. Significant variations in the mortality rate were obtained, according to the month of the individual annual cycle (IAC). The excess of mortality has been associated with the first and the last months of IAC in different age groups as well as for all major causes of death: circulatory (heart and cerebrovascular) diseases, malignant neoplasms and violent death. Neither the emotional stress nor the behavioral changes associated with the birthday can explain the results obtained. We hypothesize that 'birth stress' might be imprinted in a structure of the biological rhythms of the organism, thus resulting in periodic changes of vulnerability and survivability during the course of the IAC.

Early programming of adult longevity: demographic and experimental studies.

It is supposed that longevity might be programmed by early life exposures. We had carried out demographic and experimental researches for the examination of the possibility of longevity programming. In demographic study, the recorded deaths in Kiev (Ukraine) between 1990 and 2000 (51,503 men and 50,131 women) were used. Age at death was strongly associated with month of birth. Subjects born in the middle of year (April-July) had the lowest longevity. Increasing longevity was observed with each successive birth-month in the second half of the year, with a peak longevity for births in December. To research of the mechanisms responsible for longevity programming, study of adult D. melanogaster DNA repair capacity after irradiation at the egg stage was carried out, using marker such as DNA strand breaks. Insects irradiated in low doses (0.50 and 0.75 Gy) had extended life span and increased stability to S1 nuclease treatment. The probable explanation of observed postponed effects might be the long-term modulation of certain (possibly repair) genes activity. We hypothesize that life-extending effects of different anti-aging treatments might be a consequence of their unspecific (hormetic) action, rather then specific (geroprotector) action on the some aging-related processes, and induction an "transcriptional reprogramming" may be a key mechanism of the longevity programming and artificial life extension.

Effects of X-irradiation in early ontogenesis on the longevity and amount of the S1 nuclease-sensitive DNA sites in adult Drosophila melanogaster.

The long-term consequences of the X-irradiation of Drosophila melanogaster fruit fly one-hour eggs with doses of 0.25, 0.50, 0.75, 1, 2 and 4 Gy were investigated. Longevity hormesis was observed in males exposed to 0.5 Gy and 0.75 Gy, but no longevity increase was observed in females. The electrophoretic analysis has shown that the amount of the DNA segments resulting from cleavage in S1 nuclease-sensitive sites (<3 kb) reached 39.2% of the total DNA from control males. DNA from the irradiated males had a smaller amount of such fragments (10-30% in different experimental groups). These findings indicate that the longevity hormesis may be associated with irradiation-induced long-term structural and/or functional DNA modifications.