Aging Intervention Studies

National Institute On Aging

Investigators

Linked publications & trials

Abstract

Within this program several studies are on-going 1. 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. 2. 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. 3. 17alpha-estradiol as a therapeutic in male monkeys The compound 17alpha-estradiol, a naturally occurring enantiomer of 17beta-estradiol, is emerging as a candidate for improving healthspan and has been shown to increase lifespan in male mice. Because it minimally activates estrogen receptors, it is presumably non-feminizing and therefore a potential candidate compound for translational interventions. The Core had conducted trials to determine the appropriate dosing and followed with two short-term trials testing the metabolic effects. 4. 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. 5. 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. 6. Impact of age on the host response to SARS-CoV-2 infection in broncho-alveolar lavage samples In the human population, aging is associated with a higher incidence and severity of pulmonary infections and disease. Contributing factors for this phenomenon include reduced pulmonary function, decreased muco-ciliary clearance, microbial imbalance, and changes in immune composition. The COVID pandemic has highlighted this age disparity and the increased risk of death in elderly populations. In a collaboration project, we assessed the effect of age on the loss of compartmentalization between the oral and lung microbiome and increased immune activation. Following collection and processing, samples will be sent to our collaborator where BAL cells will be infected with SARS-CoV-2 to measure activation of immune cells, bioactivity of chemokines, and identify cell recruitment. Immune cells will be profiled with RNA-Seq. Ultimately, this study will help identify the response within immune and epithelial cells and determine the impact of age on viral infection and host response.