BPB Reports

Paper Details

BPB Reports
Vol. 8 No. 6 p.208-215 2025
Regular Article
Disruption of Thymic Microenvironment with Age: Remodeling of Blood Vessels and Extracellular Matrix
  • Hiroshi Hasegawa (Laboratory of Hygienic Sciences, Kobe Pharmaceutical University / h-hase@kobepharma-u.ac.jp)
Hiroshi Hasegawa , Mari Kondo , Takumi Hikida , Kei Nakayama
Laboratory of Hygienic Sciences, Kobe Pharmaceutical University
Received: October 28, 2025;   Accepted: December 03, 2025;   Released: December 16, 2025
Keywords: thymus, aging, blood vessel, extracellular matrix, matrix metalloproteinase
Abstracts

Thymic involution is a hallmark of aging characterized by reduced thymic size and function, leading to impaired T lymphocyte development and increased susceptibility to infection and cancer. While previous studies have described histological and cellular changes during thymic aging, the impact on vasculature and extracellular matrix (ECM) organization remains incompletely understood. In this study, we analyzed thymic tissue from young (8–10 weeks) and aged (18–27 weeks) mice to investigate age-associated changes in blood vessels and ECM components. Immunohistochemical analysis revealed that CD34-positive blood vessels in the cortex were abundant, elongated, and oriented toward the medulla in young thymus, but were significantly reduced and structurally disorganized in aged thymus. In contrast, CD31-positive vessels were localized mainly in the medulla and remained largely unaffected. ECM proteins laminin and tenascin-C displayed well-aligned vascular structures in young mice, but became more dispersed and mesh-like in aged thymus. Collagen type I, prominently detected in large blood vessels and some microvessels in young thymus, was nearly absent in aged samples. These structural changes were accompanied by a specific upregulation of Mmp3 mRNA, encoding matrix metalloproteinase-3, which is known to degrade ECM proteins and disrupt vascular integrity. The remodeling of blood vessels and ECM in the aged thymus may weaken the blood-thymus barrier, impair T lymphocyte development, and contribute to inflammaging. Our findings provide new insights into the microenvironmental deterioration of the thymus with age and identify vascular and ECM remodeling as potential therapeutic targets to mitigate age-related immune decline.