Inside or newest release: Aging disrupts sympathetic innervation of the thymus

By Randall Carpenter and Mahamudun Bhuiyan

We are excited to share our latest work, now published in Cell Reports, examining how aging disrupts sympathetic innervation of the thymus!

Read it here

Highlights

• Sympathetic innervation controls thymopoiesis and aging of the thymus

• Aging causes sympathetic axon degeneration in the thymus

• Sympathectomy impairs thymic homeostasis

• Sympathomimetic treatment partially restores thymic function during aging

The thymus is essential for T cell development and life-long immune health, yet it undergoes profound functional decline with age. While it has long been known that the thymus is innervated, the organization and functional relevance of these neural inputs are poorly understood. In this study, we combined whole-thymus tissue clearing with high-resolution imaging to map sympathetic innervation across the mouse thymus.

We found that these nerves associated with vasculature and stromal niches, positioning them to directly influence thymic function. Importantly, we show that aging leads to a marked loss of thymic innervation, with clear hallmarks of axonal dystrophy and degeneration. These findings suggest that sympathetic degeneration may represent an underappreciated contributor to age-associated thymic involution and impaired thymopoiesis.

https://video.wixstatic.com/video/f58e07_bfca6fd98f26496cb3201a844a519913/1080p/mp4/file.mp4

To understand the potential roles of sympathetic nerves in the thymus, we performed complementary loss and gain of function experiments. Permanent chemical sympathectomy reduced thymus size, including a striking reduction of endothelial and early thymic progenitor cells. Conversely, just a two-week treatment with a sympathomimetic in aged mice increased thymus size by ~25%, with a rescue of endothelial and early thymic progenitor cells. Together, these findings suggest that loss of sympathetic signaling with age contributes directly to thymic dysfunction.

This work highlights the nervous system as a key regulator of the thymic microenvironment and raises the possibility that targeting neuro-immune interactions could help improve thymus function during aging. This project was a true team effort, and we are deeply grateful to our co-authors, mentors, and collaborators, as well as the outstanding support from the Analytical Imaging Facility, the Department of Cell Biology, the Gottesman Institute for Stem Cell and Regenerative Medicine, and the broader research community at Albert Einstein College of Medicine.