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

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.