Microbial translocation and skeletal muscle in young and old vervet monkeys.

Intestinal barrier dysfunction leads to microbial translocation (MT) and inflammation in vertebrate and invertebrate animal models. Age is recently recognized as a factor leading to MT, and in some human and animal model studies, MT was associated with physical function. We evaluated sarcopenia, inflammation, MT biomarkers, and muscle insulin sensitivity in healthy female vervet monkeys (6-27 years old). Monkeys were fed consistent diets and had large and varied environments to facilitate physical activity, and stable social conditions. Aging led to sarcopenia as indicated by reduced walking speeds and muscle mass, but general metabolic health was similar in older monkeys (n = 25) as compared to younger ones (n = 26). When older monkeys were physically active, their MT burden approximated that in young monkeys; however, when older monkeys were sedentary, MT burden was dramatically increased. MT levels were positively associated with inflammatory burden and negatively associated with skeletal muscle insulin sensitivity. Time spent being active was positively associated with insulin sensitivity as expected, but this relationship was specifically modified by the individual monkey's MT, not inflammatory burden. Our data supports clinical observations that MT interacts with physical function as a factor in healthy aging.

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.

Effects of bazedoxifene, conjugated equine estrogens, and a tissue-selective estrogen complex containing both bazedoxifene and conjugated equine estrogens on cerebral artery atherosclerosis in postmenopausal monkeys.

OBJECTIVE: This study aims to evaluate the effects of a new selective estrogen receptor modulator (bazedoxifene acetate [BZA]) and a tissue-specific estrogen complex (BZA combined with conjugated equine estrogens [CEE]) on the extent and severity of cerebral artery atherosclerosis. METHODS: Ninety-eight surgically postmenopausal monkeys (Macaca fascicularis) were fed a moderately atherogenic diet and randomized to receive no treatment or women's equivalent doses of BZA (20 mg/d), CEE (0.45 mg/d), or BZA + CEE. After an experimental period of 20 months (approximately equivalent to 5 years of participant experience), the extent and severity of atherosclerosis in the common carotid artery, carotid bifurcation, internal carotid artery, and basilar artery were determined. Lesion severity was determined using the American Heart Association grading system (grades 0-V). RESULTS: BZA had no consistent adverse effects on the extent and severity of atherosclerosis in the cerebral arteries and did not attenuate the beneficial effects of CEE on the severity of common carotid artery atherosclerosis. Although CEE had only modest beneficial effects on the extent of carotid bifurcation atherosclerosis, the severity of lesions and the number of affected cases in the common carotid artery were reduced with CEE treatment. As reported previously, plasma lipid profiles did not differ among the treatment groups. CONCLUSIONS: In this long-term (equivalent to 5 human patient-years) nonhuman primate trial, BZA shows no consistent adverse effect on cerebral artery atherosclerosis and does not attenuate the modest beneficial effect of CEE on the common carotid artery. Furthermore, CEE inhibits the development of complicated plaques in the common carotid artery.

Effects of bazedoxifene alone and with conjugated equine estrogens on coronary and peripheral artery atherosclerosis in postmenopausal monkeys.

OBJECTIVE: The objectives of this study were to evaluate the effects of bazedoxifene acetate (BZA), a new selective estrogen receptor modulator, on coronary and peripheral artery atheroscleroses and to determine if it would antagonize the atheroprotective effects of conjugated equine estrogens (CEE) on a monkey model. METHODS: Ninety-eight surgically postmenopausal monkeys (Macaca fascicularis) were fed a moderately atherogenic diet and randomized to receive no treatment or women's equivalent doses of BZA (20 mg/d), CEE (0.45 mg/d), or BZA + CEE. The experimental period lasted for 20 months (equivalent to approximately 5 y in humans) during which interim measures of cardiovascular risk factors were made. At the end of the experimental period, the extent and severity of coronary and iliac artery atheroscleroses were quantified. RESULTS: Body weight, adiposity, fasting glucose concentrations, and plasma lipid profiles were not different among treatment conditions. BZA had no adverse effects on the extent or severity of coronary or common iliac artery atherosclerosis when compared with no treatment. CEE, administered soon after inducing menopause, had robust atheroprotective effects on both the extent and the severity of iliac and coronary artery atheroscleroses. The addition of BZA to CEE treatment antagonized the atheroprotective effects of CEE. CONCLUSIONS: In this nonhuman primate trial, treatment with BZA alone, CEE alone, and combined BZA and CEE does not have significant effects on plasma lipid profiles. CEE markedly inhibits the progression and complications of both coronary and iliac artery atheroscleroses. BZA has no adverse effects on atherosclerosis but attenuates the atheroprotective effects of CEE.