Heat shock protein 70 (HSP70) protects cells from accumulating damaged proteins and age-related functional decline. We studied plasma and skeletal muscle (SkM) HSP70 levels in adult vervet monkeys (life span ≈ 25 years) at baseline and after 4 years (≈10 human years). Insulin, glucose, homeostasis model assessment scores, triglycerides, high-density lipoprotein and total plasma cholesterol, body weight, body mass index, and waist circumference were measured repeatedly, with change over time estimated by individual regression slopes. Low baseline SkM HSP70 was a proximal marker for developing insulin resistance and was seen in monkeys whose insulin and homeostasis model assessment increased more rapidly over time. Changes in SkM HSP70 inversely correlated with insulin and homeostasis model assessment trajectories such that a positive change in SkM level was beneficial. The strength of the relationship between changes in SkM HSP70 and insulin remained unchanged after adjustment for all covariates. Younger monkeys drove these relationships, with HSP70 alone being predictive of insulin changes with aging. Plasma and SkM HSP70 were unrelated and HSP70 release from peripheral blood mononuclear cells was positively associated with insulin concentrations in contrast to SkM. Results from aged humans confirmed this positive association of plasma HSP70 and insulin. In conclusion, higher levels of SkM HSP70 protect against insulin resistance development during healthy aging.
The ideal animal model would contribute no confounding variables in experimental science. Variables affect experimental design resulting in increased animal use or repeated studies. We demonstrated a simple refinement which may reduce the number of animals used experimentally while simultaneously improving animal welfare. The objective of this study was to determine if the presence of a hut was an impact on physiological stress levels, as determined by faecal cortisol concentration, during a routine four-day acclimatization period of newly received male Hartley-Outbred guineapigs. We hypothesized that those animals provided with huts would have decreased physiological stress compared with animals not provided with huts. We examined this effect within both paired and single-housed animals. A between-subjects one-way analysis of variance revealed that pair-housed animals with a hut had significantly lower faecal cortisol concentration than pair-housed animals without a hut and the presence and absence of a hut had no significant impact on faecal cortisol concentration in single-housed animals. These findings show that presence of a hut is beneficial in reducing physiological stress when pair housing male guineapigs and does not appear to have an impact when single housing male guineapigs. In addition, we have shown that faecal cortisol, and therefore physiological stress, is still increasing on study day 4 suggesting a longer acclimatization period is necessary. A simple refinement in housing environment and acclimatization time can both reduce the number of animals used experimentally and improve animal welfare. The guineapig has been used as a research model for decades.1 The physiological response of this species makes it an ideal animal model for multiple research applications such as anaphylaxis, delayed hypersensitivity and pharmacology, to name a few. In experimental design we minimize as many of these variables as possible by using, for example, controlled breeding practices, health surveillance and sentinel monitoring programmes. Another method of maintaining uniformity in our animal models is consistency in animal husbandry practices. One of these practices is the quarantine and stabilization 2 period provided to animals upon receipt into research facilities, the objective of which is to provide time for recovery from transport and identify animals which are unwell or less than ideal. Once complete it is commonly accepted, that unless grossly apparent otherwise, these animals are physiologically, behaviourally and nutritionally recovered from transport and therefore in model animal condition. Since we generally only employ observational signs of wellbeing such as water and food consumption, faeces and urine output along with physical appearance (i.e. posture, body condition, behaviour), we may be unaware of other subclinical factors that are still present. These unrecognized, and as such uncorrected, variables may result in profound consequences on research objectives 3 leading to repeated studie...
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