Alpha-ketoglutarate stabilizes redox homeostasis and improves arterial elasticity in aged mice.

The objective of this study was to evaluate the effect of α-ketoglutarate on redox state parameters and arterial elasticity in elderly mice. Mice in the control group were fed with standard diet, while the experimental animals received the diet supplemented either with calcium (Ca-AKG) or sodium salt of α-ketoglutarate (Na-AKG). The experimental animals were divided into 4 groups with 10 individuals in each: control I (12 months old), control II (2 months old), experimental group I fed with Ca-AKG (12 months old) and experimental group II fed with Na-AKG (12 months old). Mice treated with Ca-AKG as well as the control II animals demonstrated significantly higher level of total antioxidant status (TAS), comparing to the control I animals and those treated with Ca-AKG. Thiobarbituric acid reactive substances (TBARS) level in blood plasma was found significantly lower in young and Ca-AKG treated mice. TBARS liver concentration was significantly different in each examined group. The study also demonstrates the decrease in TBARS level in Ca-AKG treated animals. Treatment with Na-AKG significantly increased glutathione peroxidase activity and decreased the activity of superoxide dismutase. The presented results suggest that Ca-AKG protects the organism against the free radicals related elderly processes. The study presents also the effect of Ca-AKG treatment on arterial elastic characteristics in elderly mice. The beneficial effect of Ca-AKG on ageing organisms was confirmed via redox state stabilization and blood vessel elasticity improvement.

Loss of heterozygosity on chromosome 5 in vicinity of the telomere in gamma-radiation-induced thymic lymphomas in mice.

Analysis of the loss of heterozygosity at the D5Mit143 locus was done for thymic lymphlomas induced by gamma-irradiation of mice from two reciprocal backcrosses (BALB/c x CcS-13)F1 x BALB/c and (BALB/c x CcS-13)F1 x CcS-13. BALB/c mice are susceptible to gamma-ray induction of lymphomas. The CcS-13 strain is one of 20 CcS/Dcm (CcS) series of recombinant congenic strains, and the CcS-13 mice are resistant to gamma-radiation-induced lymphomas [1, 8]. Our preliminary tests show 50% (6/12) frequency of allelic loss at the D5Mit143 locus in thymic lymphomas induced by gamma-irradiation of the mice from (BALB/c x CcS-13)F1 x BALB/c backcross. Yet, in gamma-radiation-induced lymphomas from the backcross made in opposite direction, namely, (BALB/c x CcS-13)F1 x CcS-13, the analysis with the DSMit143 marker revealed low incidence of the loss of heterozygosity, 6.7% (15). The D5Mit143 locus resides in the distal part of chromosome 5, close to the telomere. Allelic loss of heterozygosity at the D5Mit143 locus showed strain specificity. In each case, the lost allele derived from the CcS-13 resistant strain. Our current results and previously done) linkage analysis [8] let us to suspect existence of a putative tumor suppressor gene for gamma-radiation-induced lymphoma at the region of murine chromosome 5.

Longevity and aging of mice from lines divergently selected for body weight for over 90 generations.

We have analysed the differences between longevity and aging process in two lines of mice selected divergently for body weight. As a result of long-term selection, the mice from two lines varied significantly in body weight during their life span. The differences regarded maturation rate, the length of the life time, reproduction performance, and fertility. Females from the light line (L) were fertile for a longer period of time than those from the heavy line (C), while the process of spermatogenesis disappearance started earlier in the light males than in the heavy ones. There were also differences in the relative weight of adrenal glands and histopathological changes connected with the hyperplasia of their spindle cells. The adrenal glands in females from both lines were heavier than in males. A significantly higher percentage of the cortex cell hyperplasia was observed in adrenals of mice from the C line than the L line. The differences were also scored between mice from the selection lines in relation to the length of their life. On average, the L mice lived 30 days longer than the heavy ones. Body weight loss was observed earlier in the old heavy males than the L ones and this was correlated with the earlier mortality in this group of animals.

An attempt at comparing external changes taking place during maturation of male mice with the development of the process of spermatogenesis.

Evaluation of the degree of sexual maturation was performed in male mice of two selected lines differing in respect of body weight. Four developmental stages were distinguished: (1) loosening of the skin between the urinary papilla and the anus, (2) projection of the scrotum, (3) descent of the testes to the scrotum, (4) demonstration of sexual drive. Histological examination of the testes revealed that at the first developmental stage the animals had clearly immature gonads. In a few, not numerous, seminiferous tubules spermatogenesis had reached the phase of primary spermatocytes. At the second stage of development the male gonads reached the phase of secondary spermatocytes and sporadically of early spermatids. At the third stage of the animals development, the spermatogenesis observed in numerous cross-sections of the seminiferous tubules reached the spermatid phase and in males at the fourth stage some sperm cells appeared in the lumen of the tubules. A greater diameter of the sperminiferous tubules was demonstrated in the heavy line males than in the light line animals. In males of the heavy line the diameter of the Leydig cells increased between the third and fourth stage. The investigation results suggest that the accepted criteria of determination of sexual maturation stages correspond to various phases of changes taking place in the process of spermatogenesis.