[Infringement of the seasonal rhythm of fluctuations of the oxidized and methylated guanine's contents in urine of mice after the irradiation].

The lifetime research of the oxidized and methilated guanine's contents in urine of intact and radiated mice was carried out. For statistical processing of results we used the method of the trial periods. This method has been created by A.A. Konradov, but has not been published during a life of the author. It has allowed finding out oscillatory part of age-related dependences. For intact animals the most probable (p = 0.001) is the period of 7 months. The infringement of a seasonal rhythm of fluctuations of oxidized and methilated guanine's concentration in urine is marked for the radiated mice. It is specific feature of the radiation-accelerated ageing.

Correlations of life-span variation parameters in 128 successive generations of Drosophila melanogaster with changes in atmospheric pressure and geomagnetic activity.

Correlations between the parameters of life-span (LS) distribution of Drosophila melanogaster, including mean LS (MLS) and the time of 10 and 90% population mortality, and some geophysical parameters that are usually beyond the control of researchers dealing with laboratory cultures, including atmospheric pressure, solar activity indices (Wolf's sunspot numbers and 2,800-MHz radio flux), and geomagnetic activity (planetary index, K(p)), were studied. Geophysical data were obtained from free-access official web sites of the National Oceanic & Atmospheric Administration of the US Department of Commerce and the Institute of Terrestrial Magnetism and Radiowave Propagation of the Russian Academy of Sciences. The geophysical parameters were calculated only for the period corresponding to 10 days of preimaginal development of the flies from egg to imago. Canonical correlation analysis, calculation of the non-parametric Spearman rank-order correlation coefficients, and graphical data analysis were used. Highly significant correlations between parameters of LS distribution in males and females and environmental factors, such as the atmospheric pressure on the 4th and 5th day of development and geomagnetic activity indices (K(p)) on the 6th and 10th day of development were found, with correlation coefficients varying from 0.31 to 0.37 (P<0.02). Assuming a causal relationship between geophysical factors and LS, it may be hypothesized that energetically weak environmental factors determine the formation of LS oscillatory dynamics in laboratory populations. The possible mechanisms underlying the contribution of these environmental factors to the LS variation in successive generations are discussed.

[Analysis of the life span distribution mode in 128 successive generations of D. melanogaster]. / Analiz vida raspredeleniia po prodolzhitel'nosti zhizni v riadu 128 pokolenii D. melanogaster.

A large body of experimental data consisting of 116 samples (sets) of individual life span (LS) values of D. melanogaster from the same laboratory strain Canton-S was analyzed. In total, 10180 Drosophila flies (5100 females and 5080 males) were studied. Each of 58 pairs of samples belonged to a definite generation in a continuous succession where every next generation was an offspring of the preceding one. Mathematical simulation made it possible to demonstrate that both the normal (Gaussian) and Gompertz distributions were equally good approximations of the experimental data. Both of them adequately described the LS distributions in laboratory populations of D. melanogaster. The confidence intervals for absolute deviations of the theoretical distributions from experimental ones were small (4-5%). In other words, the approximation error was no more than 5% in either case. The estimation of the dependence of approximation quality on the LS in the original (experimental) population showed that the normal distribution was preferable, because, in this case the absolute deviation from the experimental distribution was independent of the LS in the original population.

[Analysis of nonlinear dynamics of aging (experimental study)]. / Analiz nelineinoi dinamiki stareniia (éksperimental'noe issledovanie).

The research is devoted to the analysis of individual dependencies of weight of a body, rectal temperature and functional motor asymmetry of behavior of mice female CBA from age received in longitudinal research. Both individual, and the average age dependencies of the above named parameters have an extreme (nonlinear) kind. It is revealed, that by the age of achievement of the maximal weight (Tm) and greatest asymmetry of behavior (Tn) are connected with each other (r = 0.6, p < 0.001). The difference (Tm-Tn) is linearly connected to life expectancy (r = 0.62, p < 0.001), that is this parameter can be used for the forecast of individual life expectancy.

Life span variations in 128 successive generations of D. melanogaster. I. Evidence that the phenomenon exists and analysis of the variations mode.

Survival of Drosophila melanogaster was estimated in 128 successive generations for 5 years. The resultant 116 samples (58 for females and 58 for males) containing series of individual values of life span (LS; 50-90 values in each series) were analyzed. Each of 58 pairs of samples belonged to a definite generation in a continuous succession where every next generation was an offspring of the preceding one. In total, 10180 Drosophila flies (5100 females and 5080 males) were studied. The mean life span (MLS) was found to be considerably heterogeneous in the series of generations: in many pairs of consecutive generations, MLSs significantly differed within two errors of the mean (P<0.05), and the minimum and maximum MLSs in the series differed from each other almost twofold. The use of the nonparametric Kruskal-Wallis test made it possible to conclusively demonstrate highly significant (P<0.001) differences between LS distributions and their medians in the series of successive generations of D. melanogaster. Highly significant (P<0.0001) positive correlations (from 0.61 to 0.91) between the parameters characterizing the minimum (t(10)), mean, and maximum (t(90)) LSs were found. This indicates considerable consistency of the LS variations in successive generations of the same population, with the proportions of individuals with low and high LSs remaining about the same irrespective of the MLS. It was demonstrated with the use of mathematical simulation that the MLS changes in successive generations may be regarded as an oscillatory process and described as a sum of several (three to five) harmonic components. The calculated determination coefficients were high (93.51 and 88.93% for females and males, respectively). This indicates that the mathematical model used for simulation adequately described the observed variations in MLS. The results are discussed in terms of population gerontology and the problem of geroprotector effectiveness.

[The aging of the brain: relationship of difference between left and right cerebral hemisphere potential and motor asymmetry of mice]. / Starenie mozga: vzaimosviaz' mezhpolusharnoi raznosti postoiannykh potentsialov i funktsional'noi motornoi asimmetrii u myshei.

Difference between left and right cerebral hemisphere potential (mV) is biophysical reflection of brain asymmetry. Cymbate changes of constant potential run during the life in both hemisphere of brain of mice. Number turning on the right of 10 attempt in T maze is a quantitative criteria of functional motor asymmetry. Manifest right asymmetry of behavior of mice observe only from 12 to 17 month old. Ambylateral behavior is character to animals younger and older this period. Thus, as difference between left and right cerebral hemisphere potential both motor asymmetry have nonlinear change with age. Coefficient of correlation between this parameters equal -0.42 for young (3-7 month) mice, +0.53 for old (21-28 month) mice. But this coefficient is near zero for mice from 11 to 19 month old. Results of our research show, that quality change in brain run in middle age.

Effect of epitalon on the lifespan increase in Drosophila melanogaster.

The geroprotector activity of epitalon, a synthetic tetrapeptide Ala-Glu-Asp-Gly, was studied on the Drosophila melanogaster wild strain Canton-S. The substance was added to the culture medium only at the developmental stage (from egg to larva). Epitalon significantly increased the lifespan (LS) of imagoes by 11-16% when applied at unprecedented low concentrations-from 0.001 x 10(-6) to 5 x 10(-6) wt.% of culture medium for males and from 0.01 x 10(-6) to 0.1 x 10(-6) wt.% of culture medium for females. The increase in LS did not depend on the substance dose. Effective concentrations of epitalon were 16,000-80,000,000 times lower than those of melatonin. The possible mechanisms of the antioxidant and regulatory effects of epitalon are discussed.

Geroprotector effectiveness of melatonin: investigation of lifespan of Drosophila melanogaster.

The lifespan (LS) of Drosophila melanogaster was studied under the effect of melatonin at a concentration of 0.08% selected in preliminary experiments. The compound was introduced into a culture medium only at the stage of development. An inverse relationship was observed between the change in LS after the impact of the preparation and the value of LS in the corresponding control group (Spearman's rank correlation coefficient R = -0.83, P < 0.02). For a relatively low LS in a population from which the control and experimental groups were formed, the geroprotector effect of melatonin is the most distinct; for a relatively high LS, the effect of the hormone is either not detected or appears as a toxic reduction in LS (up to 10%) in the experimental group. Such nonuniform effects of melatonin are connected with fluctuating changes in viability in successive generations of D. melanogaster. The antioxidant mechanism of the geroprotector effect is also discussed.

[Inhibition of endogenous oxidation of DNA by spin traps]. / Ingibirovanie éndogennogo okisleniia DNK spinovymi lovushkami.

It was shown that spin trap feeding resulted in a decrease of oxidation of rat DNA. This is an evidence of free radical mechanism of endogenous DNA oxidation.

[Comparative study of of natural and radiation-induced aging in mice]. / Sravnitel'noe izucheniie protsessov estestvennogo i radiatsionnogo stareniia myshei.

Aging of female CBA mice was accelerated by irradiation of the head at 10 and 12 Gy. The mean life span was shortened by 10.5 and 21%, respectively. The distribution by life span was similar in the control and experimental groups. The level of DNA oxidation products in the urine was normalized within 28 days after irradiation. At the age of more than 7.5 months, the irradiated mice had a lower body weight. Age-related changes of body temperature in irradiated (10 Gy) and control mice mostly coincided; the differences were evident after 18 months. It was concluded that physiological and radiation-induced aging are significantly similar.

[Changes in functional motor asymmetry during aging and after irradiation]. / Izmenenie funktsional'noi motornoi asimmetrii pri starenii i posle oblucheniia.

We studied the changes in functional motor asymmetry in female CBA mice during the course of natural aging and after irradiation of the head with 10 Gy. The functional motor asymmetry was assessed by the behavior of the animal in a T-shaped maze. The proportion of right turns in ten attempts was recorded for each mouse and the asymmetry index was calculated for the population. The asymmetry-age relationship in irradiated and intact mice has a similar shape with a distinct peak at the age of 13-17 months. The control population features a predominance of right turns, while left turns are specific for the irradiated one. This behavioral inversion is due to radiation-induced brain disturbance: the dominant left hemisphere proved to be more sensitive. Possible different rates of hemisphere aging is discussed.

Geroprotector efficiency depends on viability of control population: life span investigation in D. melanogaster.

Ability of the radical spin trap 4-hydroxy-2,2,6,6,-tetramethyl-l-piperidine-N-oxyl (4-hydroxy-TemPO, (4HT)), to delay senescence in D. melanogaster has been studied. The spin trap, at a concentration of 0.2%, was added to the culture medium at the flies development stage. Reliable correlation (r = 0.76, P < 0.05) has been found between the viability of a control population, assessed by the mean life span (LS) value, and the level of LS alteration after geroprotector treatment in a corresponding experimental population. Thereby the local minimum values and local decreases in the mean LS in successive generations of the control line are associated most likely with LS extension effects in the corresponding experimental groups after 4HT treatment, and on the contrary, the local maximum values and local increases in the mean LS of the control line are associated more probably either with LS decreasing effects in the corresponding experimental groups or with the lack of significant differences between the control and experimental groups. A possible mechanism of the discovered phenomenon is discussed, based on the concept about free-radical activity variations. A probability approach to the evaluation of geroprotector efficiency in serial studies is proposed.

[Radiation-protective effectiveness of lycopene]. / Radiozashchitnaia éffektivnost' likopina.

Radioprotective action of natural carotenoid Lycopene in mice during exposure to lethal dose of 6.5 Gy has been shown. Lycopene was found to be two-fold more effective radioprotector than beta-carotene at the same conditions. This correlates with the difference in their antioxidant activity. Lycopene also exhibits antimutagenic effect resulting in increased survival of Drosophila melanogaster chrysalis under exposure to 40 Gy gamma-radiation.

Phenomenon of life span instability in Drosophila melanogaster: II. Change in rhythm of natural variations of life span after single exposure to gamma-irradiation.

The dynamics of life span (LS) have been studied in successive generations of postirradiation and control groups of Drosophila melanogaster, strain D-32, after a single exposure to Co60 gamma-quantum irradiation. It has been shown using mathematical procedures that in all postirradiation generations, with one exception, survival curves retain their canonical shape. This is indicative of the unchangeable nature of LS distribution. The mean LS of the progeny of irradiated parents either coincides with control values or can be higher or lower. Moreover, single irradiation results in an altered time-scanning of LS variations in successive generations as compared with controls. The possible origin of LS instability is discussed.

Phenomenon of life span instability in Drosophila melanogaster: I. Nonrandom origin of life span variations in successive generations.

The dynamics of life span (LS) and fecundity in Drosophila melanogaster, strain D-32, were analyzed in a series of successive generations. Highly reliable variations in both fitness components were found. On initial inspection the variations would be characterized as random or irregular wherein mean values differed up to threefold. The variance in longevity is greater in females than in males. By use of mathematical procedures we have shown a scale regularity in LS distributions for all generations. Such regularity, in spite of considerable differences in absolute values (mean and maximum LS), suggested that the origin of LS instability is nonrandom.