The collaborative Interagency Agreement between the National Center for Toxicological Research (NCTR) and the National Institute on Aging (NIA) was aimed at identifying and validating a panel of biomarkers of aging in rodents in order to rapidly test the efficacy and safety of interventions designed to slow aging. Another aim was to provide a basis for developing biomarkers of aging in humans, using the assumption that biomarkers that were useful across different genotypes and species were sensitive to fundamental processes that would extrapolate to humans. Caloric restriction (CR), the only intervention that consistently extends both mean and maximal life span in a variety of species, was used to provide a model with extended life span. C57BI/6NNia, DBA/2JNia, B6D2F1, and B6C3F1 mice and Brown Norway (BN/RijNia), Fischer (F344/NNia) and Fischer x Brown Norway hybrid (F344 x BN F1) rats were bred and maintained on study. NCTR generated data from over 60,000 individually housed animals of the seven different genotypes and both sexes, approximately half ad libitum (AL) fed, the remainder CR. Approximately half the animals were shipped to offsite NIA investigators internationally, with the majority of the remainder maintained at NCTR until they died. The collaboration supplied a choice of healthy, long-lived rodent models to investigators, while allowing for the development of some of the most definitive information on life span, food consumption, and growth characteristics in these genotypes under diverse feeding paradigms.
The responses of immunocompetent cells to thymus-dependent antigen differ in mice of different strains. Immunization stimulated phagocytic activity of peritoneal macrophages in CBA/CaLac, DBA/2, and BALB/c mice and suppressed it in CC57W mice. By the formation of antibody-producing cells in the spleen in response to thymus-dependent antigen DBA/2 and CBA/CaLac mice can be classified as high responders, BALB/c mice as medium-responders, and C57Bl/6 and CC57W mice as low responders.
In mice, the plaque-forming cell response to sheep red blood cells was stimulated by a mixture of methoxy-substituted glycerol ethers isolated from Greenland shark liver oil and by synthetic 1-0-(2-methoxyhexadecyl)-glycerol, given in the diet. In preliminary experiments, this synthetic compound also increased the ability of parental spleen cells to induce graft-vs.-host reactions in F1 hybrid mice. Glycerol ethers occur in the bone marrow fat of mammals and in the membrane phospholipids. It is postulated that the methoxy-substituted glycerol ethers supplied in the diet may stimulate the bone marrow and/or may be incorporated into membrane lipids, thereby changing the structure and function of the membranes.
Crossbred CC57BR/Mv mice inherited tryptophan oxygenase gene and predisposition to alcohol consumption from parent BALB/c and C57BL mice, respectively. In CC57BR/Mv mice no relationships were found between alcohol consumption, tryptophan oxygenase activity, and single nucleotide substitutions in intron 6 of the TDO2 gene associated with predisposition to alcoholism in humans.
Examination of populations living in regions of fallout radiation revealed changes in the distribution of HLA genes not only in irradiated individuals, but also in their children and grandchildren. Combined irradiation of inbred mice in comparable doses showed that H-2 genes determine immune reactions in animals and their offspring to radiation. Our results indicate that the immune system in mammals is immunogenetically regulated by low-dose radiation.
Inherited predisposition of ASC mice with depressive behavior to catalepsy was accompanied by a significant decrease in the immune response to sheep erythrocytes (compared to parent strains CBA and AKR). The degree of immunosuppression was highest on day 5 after immunization.
The objective of the investigation was to study the influence of RNA isolated from the brains of immunized mice on the immune response in syngeneic recipients. (CBAxC57BL/6)F1 male mice immunized by SRBC and RRBC were used for isolation of experimental RNA. Mice injected with medium 199 were used for isolation of control RNA. Experimental and control RNA was injected into syngeneic mice recipients immunized by SRBC, RRBC or rat RBC preliminary. It was shown that experimental RNA stimulate the specific immune response only.
Voluntary ethanol (20% solution) consumption in mice of C57BL/6J (C57) and CBA/Lac (CBA) strains with consecutive experience of victories (winners) or defeats (losers) in daily intermale agonistic confrontations were studied. Winners and losers of the CBA strain maintained the ethanol consumption on the same level. Losers of the C57 strain increased the ethanol consumption most dramatically during the second week of testing, while winners of this strain did not change the ethanol intake. The aspiration to the social contact estimated by behavioral activity as a reaction to the other male significantly increased in "drinking" losers of the C57 strain. The influence of heredity and emotional state of animals formed by their social success on voluntary ethanol consumption are discussed.