Project description:Aging is a major risk factor for various forms of disease. An enhanced understanding of the physiological mechanisms related to aging is urgently needed. Nonhuman primates (NHPs) have the closest genetic relationship to humans, making them an ideal model to explore the complicated aging process. Multiomics analysis of NHP peripheral blood offers a promising approach to evaluate new therapies and biomarkers. Here, we explored the mechanisms of aging using proteomics (serum and serum-derived exosomes [SDEs]) in rhesus monkey (Macaca mulatta) blood.
Project description:Cardiovascular (CV) disease is a leading cause of morbidity and mortality in Western societies. Even after accounting for traditional CV risk factors (e.g. obesity, smoking and hypertension), the inflammation-driven thickening and stiffening of central arteries is a strong predictor of adverse outcomes. Arterial wall changes are universally associated with advancing age and show unparalleled worsening in metabolic syndrome. In mice, resveratrol ameliorates a high-fat diet induced arterial wall inflammation and slows age-associated physiologic deteriorations within the arterial wall. Here we tested resveratrol in adult male rhesus monkeys, an experimental model relevant to humans. A diet rich in fat and sucrose (HFS) led to an increase in body weight as well as thickening and stiffening of the aortic wall, marked by diffuse inflammation, fibrosis and fat infiltration. Dietary resveratrol supplementation prevented diet-induced structural and functional alterations within the aortic wall, and abrogated the deleterious vascular endothelial and smooth muscle responses. Integrative genomic and proteomic analyses of aortic tissues revealed molecular signatures consistent with improved vascular functions. Thus, resveratrol conferred protection against the initiation of diet-induced inflammatory events that progress to pathological thickening and stiffening of large arteries. Dietary resveratrol may therefore hold promise as a novel therapy to ameliorate metabolic stress-induced CV disease. After baseline assessment, four male rhesus monkeys remained on the healthy standard diet (SD), 10 male rhesus monkeys were begun on a high fat/high sucrose (HFS) diet and 10 male rhesus monkeys were begun on a high fat/high sucrose (HFS) diet plus Resveratrol, 80mg/day. After one year of dietary intervention, the amount of resveratrol was increased to 240mg/day for one additional year. Tissues were then harvested for the array experiments.
Project description:Aging is a major risk factor for various forms of disease. An enhanced understanding of the physiological mechanisms related to aging is urgently needed. Nonhuman primates (NHPs) have the closest genetic relationship to humans, making them an ideal model to explore the complicated aging process. Multiomics analysis of NHP peripheral blood offers a promising approach to evaluate new therapies and biomarkers. Here, we explored the mechanisms of aging using proteomics (serum) in rhesus monkey (Macaca mulatta) blood.
Project description:Cardiovascular (CV) disease is a leading cause of morbidity and mortality in Western societies. Even after accounting for traditional CV risk factors (e.g. obesity, smoking and hypertension), the inflammation-driven thickening and stiffening of central arteries is a strong predictor of adverse outcomes. Arterial wall changes are universally associated with advancing age and show unparalleled worsening in metabolic syndrome. In mice, resveratrol ameliorates a high-fat diet induced arterial wall inflammation and slows age-associated physiologic deteriorations within the arterial wall. Here we tested resveratrol in adult male rhesus monkeys, an experimental model relevant to humans. A diet rich in fat and sucrose (HFS) led to an increase in body weight as well as thickening and stiffening of the aortic wall, marked by diffuse inflammation, fibrosis and fat infiltration. Dietary resveratrol supplementation prevented diet-induced structural and functional alterations within the aortic wall, and abrogated the deleterious vascular endothelial and smooth muscle responses. Integrative genomic and proteomic analyses of aortic tissues revealed molecular signatures consistent with improved vascular functions. Thus, resveratrol conferred protection against the initiation of diet-induced inflammatory events that progress to pathological thickening and stiffening of large arteries. Dietary resveratrol may therefore hold promise as a novel therapy to ameliorate metabolic stress-induced CV disease.
Project description:Resveratrol improves adipose insulin signaling and reduces the inflammatory response in adipose tissue of rhesus monkeys on a high-fat, high-sugar diet.
Project description:Chronic high-fat/high-sugar (HFS) feeding is linked to the development of insulin resistance as well as arterial wall and adipose tissue inflammation in nonhuman primates. These changes are significantly reduced when the animals are fed a HFS diet supplemented with resveratrol (RSV) for two years. Herein, we evaluated the occurrence of cerebral cortex injury in these HFS-fed middle-aged male rhesus monkeys and investigated the possibility of brain protection by RSV treatment. HFS caused a reduction in capillary density in the cerebral cortex that was preempted by RSV supplementation. The patterns of cDNA microarray analysis revealed upregulation of markers of oxidative stress, inflammation and apoptosis in the cortical cortex of HFS-fed monkeys, which was reversed by RSV. The underlying mechanism of RSV action included its ability to prevent the HFS-mediated NF-kappa-B activation and loss in mitochondrial aldehyde dehydrogenase 2 expression. We conclude that RSV may confer neuroprotection against HFS-mediated cerebral vascular dysfunction and activation of inflammatory pathways.