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

Award Number: R15AG078992
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/19/2024
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $428,397 )
2024	2024	UNIVERSITY OF PIKEVILLE, INC.	147 SYCAMORE ST	PIKEVILLE	KY	41501	PIKE	USA	Aging Research	000	1	9/18/2024	NEW	$428,397
														Subtotal = $428,397

Grand Total All Awards = $428,397

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

Award Number: R15AG078992

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/19/2024

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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