Within this program several studies are on-going 1. Muscle protein remodeling with exercise Muscle strength and function decline with age and lead to loss of mobility. Physical activity is known to attenuate the decline, but mechanisms are not clear. Muscle from sedentary older humans is associated with an imbalance in energetic metabolism, a pro-inflammatory profile, and a breakdown of protein. RNA functions to control synthesis of proteins and as it carries the message, it can be changed by a process of splicing, leading to changes in proteins. Studies in older sedentary humans shows that their muscles have more of this splicing while active age-matched subjects maintain a protein profile more consistent with younger subjects. The mechanisms for this activity induced preservation of muscle protein are unclear. Certainly, the inflammatory response may play a role and the gut microbiome provides a window into these changes. Rhesus monkeys, which are 95% genetically similar to humans, provide an excellent opportunity to more closely examine the time course of changes in RNA splicing, protein modifications and the role of the inflammatory pathways. Although largely sedentary, monkeys can be trained to run on treadmills and therefore, we can assess the effects of physical activity. 2. Multi-omics across the lifespan Omics-based assays can be used to study the complex interactions between multiple genetic and environmental factors that occur during aging and the pathogenesis of disease. These approaches can be used to develop diagnostic and therapeutic targets for treatment. The Core rhesus colony spans the average lifespan and provides a unique resource for a multi-omics approach to generate a multi-tissue profile associated with health status and biomarker development. This project will improve our understanding of the connectivity of the various omics components and will help identify important biological connections to disease and aging. 3. Treating pre-diabetes in NHPs Type II diabetes mellitus occurs spontaneously in aging rhesus monkey colonies at rates approximating those of the human population. An increasing incidence of diabetes among humans has led to rapid growth in the number of FDA approved treatments available for clinical use. However, managing diabetes in the research setting has not been expanded to include newer clinical treatments. We will evaluate outcome measures to compare some of the more commonly used human medications to improve long-term management for monkeys. 4. Immunogenicity of novel adjuvant to flu vaccine Seasonal influenza vaccines often provide suboptimal immune responses to current circulating influenza strains because of virus drift and the lack of adjuvants, added ingredients which boost the immune response. Aging populations are at high risk of death due to the seasonal flu; thus, more effective vaccine treatments are needed to protect this vulnerable population. The objective of this study is to test the antibody and T cell response to a novel computationally derived vaccine with and without an adjuvant. 5. Cardiovascular function in aging NHPs The objective of this project is to evaluate age-dependent changes in cardiac function (systolic and diastolic), the probability of developing cardiac rhythm abnormalities, and cardiac gene expression in nonhuman primates. These experiments will help to establish potential links between changes in gene expression and age-dependent cardiac dysfunction. 6. Epigenetic Clock DNA methylation is now widely used as an indicator of biological age and a marker of to evaluate the effectiveness of age-related interventions. Rhesus monkeys are an important translational model for aging studies with a 93% genetic homology with humans. Characterization of the epigenetic clock representing the lifespan will provide valuable information in an animal model that is widely used in translational aging research. In a cross-sectional approach, we have collected blood samples from of rhesus monkeys covering the adult lifespan to describe the DNA methylation pattern and generated rhesus specific clocks as well as comparisons to other nonhuman primates.