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.
