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

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        General outpatient and community population
      
Biospecimen description: 
      Blood sample will be collected from each subject after informed consent is obtained

      Blood collection

      Approximately 10mL of blood will be collected. The blood will be collected for the purpose of
      isolating plasma, as follows:

      1 X 10mls Sodium (Na) Heparin tube

      Blood will be drawn by hospital/clinic phlebotomy services, a nurse or a medical assistant.
      Blood will be collected from each subject one time.

      Once aliquoted, the plasma will be catalogued in a central registry (LIMS database) and then
      stored. Metabolite extraction and protein precipitation will be performed to remove proteins
      and extract the maximum number of metabolites. The samples will be maintained at 4 degrees
      Celcius in the autosampler and then analyzed.