Metabolomics of Aging: Sub-study of the Healthy Elderly Active Longevity (HEAL) Study

Overview

This research is being done to learn more about healthy aging. We hope to learn which bodily processes or functions are important for the elderly to maintain good health. Metabolites (for example, glucose) are small molecules in our bodies that are used in all bodily reactions. Looking at their levels in healthy elderly people may help researchers find out which processes lead some people to get to disease and others to not. Metabolites are the basic building blocks for people. They are used to construct larger complexes(such as proteins), relay signals from one part of the body to another, and as a source of energy. While most people have essentially the same types of metabolites, the relative levels of these metabolites vary from one individual to another. These levels reflect the body's state of growth, development, and reproduction. An appropriate balance in metabolites is important to maintaining general health. Conditions like cancer and diabetes result in disrupted levels of metabolites that are associated with changes in bodily functions. Deviations from normal levels of metabolites can be used as a signature for disease. Researchers have discovered that a disruption in unique metabolite levels is associated with human aging. In this study we hope to learn which, if any, of these disruptions are associated with the onset of age-related disease.

The HEAL study criteria includes subjects who are 80 years of age and older who have not experienced a chronic condition. This sub-study will use plasma samples of up to 100 HEAL subjects to compare the metabolomic findings found within this group with existing young and elderly plasma samples that are currently under analysis at the Siuzdak lab. The aim of this sub-study is to determine if metabolites that are downregulated in elderly relative to young individuals are similarly downregulated in the Wellderly. Metabolomics is a rapidly emerging field focused on profiling small, naturally occurring (endogenous) molecules collectively known as the "metabolome." Metabolomics offers a significant advantage over other "omics" sciences (e.g., transcriptomics and proteomics) in that metabolites represent the most downstream end products of cellular reactions and therefore most closely correlate with the phenotype. Thus, by comparative untargeted profiling, metabolomics provides a powerful strategy for understanding changes associated with a unique phenotype at the molecular level. Untargeted metabolomics denotes the profiling of all low molecular weight biochemicals, including lipids, hormones, saccharides, nucleotides, organic acids, and amino acids that serve as substrates and products in metabolic pathways. The analytes are measured without specifically "targeting" distinct metabolites or molecules. Untargeted metabolomics has the capacity to implicate unanticipated metabolites or pathways associated with a unique phenotype (i.e., advanced age), and thereby provide great insight into cellular mechanisms and pathobiology. In the latter context, the Siuzdak Laboratory has pioneered a new approach for investigating disease known as therapeutic metabolomics in which cellular pathways associated with disease are identified and then perturbed.