The anatomical and functional study of the thymus - defining the milestones of the thymic aging in the elderly human population

The concept of this program derives from our observations that the involution of the human thymus does not follow linear kinetics and is tailored to each individual. In most humans, the involution process gradually shuts down the thymic T cell output until about the age of fifty. Still, in some cases, the structure

and function of this primary lymphatic organ are preserved in elderly subjects until they are about 100-years old. Our research plan asks how often we can find a functional thymus in the elderly, and we propose a qualitative and quantitative study of the thymic structure using cadavers in the Gross Anatomy

course at KYCOM. Applying immunohistochemistry techniques, we will determine the degree of thymic involution and rank it by preserving the thymic epithelial space, the symmetry of the involution in both thymic lobes, and the presence of the T cells. To determine whether the thymus was functional at the

time of death, we will apply molecular biology techniques to amplify the FoxN1 mRNA in thymic tissue and TREC (T cell receptor rearrangement excision circles) DNA in the splenocytes. Based on preliminary data, we expect to find four stages of thymic involution in elderly: (i) functional thymus with active

thymopoiesis [TEC+/CD3+/FoxN1+/TREC+], (ii) functional thymus with no thymopoiesis [TEC+/CD3- /FoxN1+/TREC-], (iii) structural thymic support with no thymopoiesis and no FoxN1 activity [TEC+/CD3- /FoxN1-/TREC-], and, (iv) silent, involuted thymus [TEC-/CD3-/FoxN1-/TREC-]. We shall apply descriptive statistics to find the central tendency or a typical element of the preserved thymic function in our sample

in the context of the donor’s age and COD. We will apply inferential statistics to establish relationships between characteristics within the data sample. If we detect the functional thymus, we will correlate it with the degree of the structural preservation of the organ and the cause of death (COD). In the long-

term plan, we will apply the results generated from this application to predict the longevity of the immune system based on markers of the thymic function established in this study. This research proposal serves two functions: (1) to meet the research goals, and (2) through this REAP funding mechanism, to provide

the Kentucky College of Osteopathic Medicine students much-needed exposure to basic biomedical research. To ensure the feasibility of the proposed work, we formed an interdisciplinary team of experts in immunology, molecular biology, gross anatomy, and statistics. Over three years, we will offer sixteen

research Fellowships to Osteopathic Medical students to provide much-needed exposure to basic biomedical research.