Metabolism and Translational Science Core

Summary The University of Florida (UF) Older Americans Independence Center (OAIC) supports the overall theme of “promotion of mobility and independence.” The Metabolism and Translational Science Core (RC2), in collaboration with our other UF OAIC cores, supports biochemical analyses for preclinical, human interventional, or observational clinical studies. By measuring a selected set of biomarkers, we can determine how targeted interventions influence the rate of aging, as well as loss of mobility and independence. This core thereby provides the support for the Research Education Core (REC) Scholars and pilot study investigators. Aging and disease feature progressive deterioration of various physiological and metabolic processes. This is associated with altered functions or contents of protein, RNA, and DNA, which provide biomarkers to monitor aging. Multiple pathways and domains have been associated with aging, such as genomic instability (including telomere attrition, mutations, and deletions); epigenetic alterations; loss of proteostasis (including dysfunctional autophagy); deregulated nutrient sensing; mitochondrial (Mt) dysfunction; inflammation and cellular senescence; stem cell exhaustion, disrupted circadian clock rhythms; and dysfunctional nicotinamide adenine dinucleotide (NAD+) homeostasis. The specific analyses of protein, RNA, and DNA biomarkers that this core will provide are related to major biological and metabolic pathways known to regulate aging and focus on: (i) Mt function; (ii) inflammation and senescence; (iii) autophagy; (iv) circadian clock biology; and (v) NAD+ homeostasis. We use innovative analytical tools and standard high-throughput analysis to determine the fundamental biological mechanisms of aging. The Metabolism and Translational Science Core (RC2) supports the overarching hypothesis that knowledge of specific protein, RNA, and DNA biomarkers, as well as measurements of metabolism of isolated mitochondria and white blood cells (WBCs), are critical for understanding the trajectory of healthy aging and the underlying biological causes of mobility loss. We will support extraction of proteins, RNA, and DNA; analysis of biomarkers; isolation of cells (WBCs) and organelles (mitochondria); and assessments of Mt function. RC2 will provide investigators across the OAIC Cores and REC Scholars with established methodologies; scientific data; infrastructure; highly qualified personnel; and consultative and collaborative expertise. We have a rich history of completing studies for REC Scholars and senior investigators at UF, as well as scientists around the country. RC2 pursues the following aims: Aim 1: To support protein, RNA, and DNA isolation and analysis of specific biomarkers of aging. Aim 2: To support analysis of Mt respiration, Mt enzyme activities, and NAD coenzymes. Aim 3: To facilitate and provide consultation on analyses and sample storage, and collaborate synergistically with the other OAIC cores to pursue the common OAIC theme of promotion of mobility and independence.