Variation in longevity of rats: Evidence for a systematic increase in lifespan over time

Abstract

Male Sprague-Dawley rats (CrL:CD(SD)BR) were maintained under barrier conditions at Charles River Breeding Laboratories (Wilmington MA) from August, 1975, to July, 1983. Animals were provided food and water ad libitum. Survival data from 8 completed cohorts of 100 animals each and one continuing cohort reveal a highly significant linear increase in median lifespan, yielding a 26% increase in this parameter for cohorts born over a period of less than six years. The biological factors responsible for this increase are not clear at present. Nevertheless, these results in outbred rats, taken in conjunction with previous observations of a trend towards increased longevity in inbred mice, indicate that the assumption of cohort equivalence underlying many cross-sectional studies of biological aging may not be valid.     

Nimodipine ameliorates aging-related changes in open-field behaviors of the rabbit

Abstract

The open-field behavior of old rabbits (32-50 months) was compared to that of young-controls (3 months). Old rabbits engaged in less grooming and rearing behaviors and were more active than young controls. The old rabbits demonstrated a pattern of ambulation which did not indicate a preference for any particular area of the open-field. In contrast, young rabbits exhibited a very stereotypic pattern of exploration in the open-field, engaging in relatively low levels of ambulation confined to the area near the sides of the open-field. Old rabbits fed a diet which included 860 ppm nimodipine showed behaviors in the open-field which closely approximated those of the young-controls. Nimodipine-treated rabbits made fewer crossings and more rears and grooms than the old controls. These results indicate that very specific aging-related changes occur in the open-field behaviors of rabbits, and that nimodipine effectively reverses these aging-associated changes. These data are consistent with previous studies that have shown improvements in open-field behaviors by old rats receiving nimodipine.     

The risk of maternal obesity to the long‐term health of the offspring

The prevalence of maternal obesity has risen dramatically in recent years, with approximately one in five pregnant women in the UK now classed as obese (body mass index ≥ 30 kg/m²) at antenatal booking. Obesity during pregnancy has been hypothesized to exert long‐term health effects on the developing child through ‘early life programming’. While this phenomenon has been well studied in a maternal undernutrition paradigm, the processes by which the programming effects of maternal obesity are mediated are less well understood. In humans, maternal obesity has been associated with a number of long‐term adverse health outcomes in the offspring, including lifelong risk of obesity and metabolic dysregulation with increased insulin resistance, hypertension and dyslipidaemia, as well as behavioural problems and risk of asthma. The complex relationships between the maternal metabolic milieu and the developing foetus, as well as the potential influence of postnatal lifestyle and environment, have complicated efforts to study the programming effects of maternal overnutrition in humans. This review will examine the emerging evidence from human studies linking maternal obesity to adverse offspring outcomes.     

Rate of environmental change determines stress response specificity

Cells use general stress response pathways to activate diverse target genes in response to a variety of stresses. However, general stress responses coexist with more specific pathways that are activated by individual stresses, provoking the fundamental question of whether and how cells control the generality or specificity of their response to a particular stress. Here we address this issue using quantitative time-lapse microscopy of the Bacillus subtilis environmental stress response, mediated by σ^B. We analyzed σ^B activation in response to stresses such as salt and ethanol imposed at varying rates of increase. Dynamically, σ^B responded to these stresses with a single adaptive activity pulse, whose amplitude depended on the rate at which the stress increased. This rate-responsive behavior can be understood from mathematical modeling of a key negative feedback loop in the underlying regulatory circuit. Using RNAseq we analyzed the effects of both rapid and gradual increases of ethanol and salt stress across the genome. Because of the rate responsiveness of σ^B activation, salt and ethanol regulons overlap under rapid, but not gradual, increases in stress. Thus, the cell responds specifically to individual stresses that appear gradually, while using σ^B to broaden the cellular response under more rapidly deteriorating conditions. Such dynamic control of specificity could be a critical function of other general stress response pathways.