Inducing Muscle Heat Shock Protein 70 Improves Insulin Sensitivity and Muscular Performance in Aged Mice.

Heat shock proteins (HSPs) are molecular chaperones with roles in longevity and muscular preservation. We aimed to show elevating HSP70 improves indices of health span. Aged C57/BL6 mice acclimated to a western diet were randomized into: geranylgeranylacetone (GGA)-treated (100 mg/kg/d), biweekly heat therapy (HT), or control. The GGA and HT are well-known pharmacological and environmental inducers of HSP70, respectively. Assessments before and after 8 weeks of treatment included glycemic endpoints, body composition, and muscular endurance, power, and perfusion. An HT mice had more than threefold, and GGA mice had a twofold greater HSP70 compared with control. Despite comparable body compositions, both treatment groups had significantly better insulin sensitivity and insulin signaling capacity. Compared with baseline, HT mice ran 23% longer than at study start, which was significantly more than GGA or control. Hanging ability (muscular endurance) also tended to be best preserved in HT mice. Muscle power, contractile force, capillary perfusion, and innervation were not different. Heat treatment has a clear benefit on muscular endurance, whereas HT and GGA both improved insulin sensitivity. Different effects may relate to muscle HSP70 levels. An HSP induction could be a promising approach for improving health span in the aged mice.

Selective serotonin reuptake inhibitor and bleeding in a cynomolgus macaque (Macaca fascicularis).

Selective serotonin reuptake inhibitors (SSRI) are associated with an increased bleeding risk in humans. This report describes a bleeding event in a cynomolgus macaque (Macaca fascicularis) treated with the SSRI sertraline HCl (Zoloft). During the treatment course, the subject presented with a maculopapular rash, cutaneous bleeding, epistaxis, bleeding from the eye, melena, and a severe thrombocytopenia. To our knowledge, this report is the first description of an SSRI-related adverse event in a nonhuman primate. This report demonstrates that the clinical presentation of SSRI-associated bleeding in cynomolgus macaques is consistent with that reported in humans and that complications from SSRI treatment should be considered as a differential diagnosis for maculopapular dermatitis or spontaneous bleeding in this species.

Effect of soy isoflavones on thyroid hormones in intact and ovariectomized cynomolgus monkeys (Macaca fascicularis).

OBJECTIVE: Soy isoflavones are commonly used to alleviate menopause-related symptoms. Postmenopausal women are at increased risk for hypothyroidism, and there are concerns that isoflavones may be detrimental to thyroid health. The aim of this study was to examine the effects of soy protein and isoflavones on thyroid function and the relationship between thyroid function and ovarian function. METHODS: Adult female cynomolgus monkeys (Macaca fascicularis) were randomized to consume two diets differing only in protein source: casein-lactalbumin (n = 44) or soy protein with isoflavones (n = 41). After 34 months, all animals were ovariectomized via laparotomy. Half of the monkeys from each diet treatment group continued to consume their preovariectomy treatment phase diet (either isolated soy protein [n = 19] or casein-lactalbumin [n = 21]) for an additional 34 months. The remaining animals did not continue their diets and thus were not considered further. Circulating progesterone, triiodothyronine, thyroxine, and thyroid-stimulating hormone were measured at baseline. Thyroid hormones were remeasured during each treatment phase. RESULTS: Dietary soy increased triiodothyronine in preovariectomized monkeys and prevented a decline in thyroxine after surgical menopause (both P's < 0.05). Mean progesterone concentrations were positively correlated with triiodothyronine at baseline in preovariectomized monkeys (P < 0.01). CONCLUSIONS: Progesterone levels and triiodothyronine are positively correlated in macaques. Dietary soy increases triiodothyronine in preovariectomized monkeys and prevents a decline in thyroxine after surgical menopause. The outcomes observed in this study suggest that soy protein and isoflavone consumption does not adversely affect-and may even preserve-thyroid function in postmenopausal women.

Characterization of ovarian aging and reproductive senescence in vervet monkeys (Chlorocebus aethiops sabaeus).

Female vervet monkeys (Chlorocebus aethiops sabaeus) are used as an experimental model for chronic diseases relevant to women's health. However, reproductive senescence (menopause) has not yet been characterized for vervet monkeys. Here we describe the histologic, hormonal, and menstrual markers of reproductive senescence in vervet monkeys from the Wake Forest Vervet Research Colony. Ovaries from monkeys (age, 0 to 27 y) were serially sectioned (5 µm), stained, and photographed. In every 100th section, the numbers of primordial, primary, and secondary follicles were determined, and triplicate measurements were used to calculate mean numbers of follicles per ovary. Antimüllerian hormone (AMH), follicle stimulating hormone, and menstrual cycle length were measured in additional monkeys. Primordial follicles and AMH decreased significantly with age, and significant correlations between numbers of primordial and primary follicles and between numbers of primary and secondary follicles were noted. Histologic evaluation revealed that ovaries from 4 aged monkeys (older than 23 y) were senescent. One aged monkey transitioned to menopause, experiencing cycle irregularity over 4 y, eventual cessation of menses, and plasma AMH below the level of detection. Finally, with increasing age, the percentage of female vervets with offspring declined significantly. The present study provides insight into ovarian aging and reproductive senescence in vervet monkeys. Results highlight the importance of considering this nonhuman primate as a model to investigate the relationships between ovarian aging and chronic disease risk.