Abstract

Background: Age-related thymic involution contributes to immunosenescence through progressive structural and cellular alterations. This study quantified changes in the corticomedullary (C:M) ratio, thymocyte distribution, tissue composition, proliferative activity, and Hassall's corpuscle morphology across different age groups. Methods: Fifty thymic autopsy specimens (five age groups; n = 10/group) underwent histological and immunohistochemical staining (H&E, Masson’s trichrome, pan-cytokeratin, CD3, and Ki-67). Digital morphometry quantified the C:M ratio, thymocyte density, tissue composition, Ki-67 index, and Hassall’s corpuscle morphology. Results: The C:M ratio declined significantly from 3.1 ± 0.4 in the youngest group to 0.7 ± 0.2 in the oldest (p < 0.001). Cortical and medullary thymocyte densities decreased by 75% and 54%, respectively, while Ki-67-positive cortical thymocytes declined from 18.6% to 3.1%. Thymic parenchyma decreased from 88.4% to 19.8%, accompanied by an increase in adipose tissue from 6.8% to 76.9%. Hassall’s corpuscles enlarged with age, although their density declined in older individuals. Age correlated negatively with the C:M ratio (r = –0.93) and positively with adipose tissue area (r = 0.94). Conclusion: Progressive thymic involution is characterized by cortical atrophy, reduced thymocyte proliferation, and adipose replacement, supporting the corticomedullary ratio as a reliable histomorphometric marker of thymic aging. 

Keywords: Thymus, Cortico-medullary ratio, Thymocytes, Hassall’s corpuscles, Histomorphometry