Thymus function may hold the key to understanding immune ageing

As populations age worldwide, the decline of the immune system, a process known as immunosenescence, has become a critical biomedical challenge. This decline leads to increased susceptibility to infections, reduced vaccine effectiveness, and chronic low-grade inflammation in older individuals. In a new review published in the open-access journal Ageing and Cancer Research & Treatment, researchers Albert Mironenkov, Jian-Kang Zhu, and Yu-Xuan Lyu from the Southern University of Science and Technology highlight the thymus as the central driver of immune ageing.

The Engine of Immunity

The thymus is the primary organ responsible for generating naïve T cells, the "scouts" of the immune system that recognize new pathogens. However, the thymus is among the first organs to degenerate, undergoing a process called thymic involution. As it shrinks and loses functional tissue with age, its capacity to produce new immune cells drops sharply.

"While immune ageing affects multiple biological systems, the thymus plays a particularly critical role," the authors argue. This decline leads to a loss of T-cell diversity, leaving older adults with a "memory-heavy" immune system that struggles to recognize emerging threats, such as novel viruses or new vaccine antigens.

Quantifying the Decline

The review provides a comprehensive look at how thymic ageing manifests across different species. By examining common biological patterns in various animal models, the authors identify evolutionary mechanisms that may drive thymic decline and immune ageing.

To measure this decline, the authors highlight key quantitative indicators. Reduced levels of signal-joint T-cell receptor excision circles (sjTRECs) and diminished T-cell receptor diversity provide clear evidence that decreased thymic output is a central, measurable feature of immunosenescence. These biomarkers offer a vital roadmap for tracking the success of future thymic rejuvenation therapies.

Impact on Public Health and Medicine

The implications of thymic decline extend beyond simple infections. Immunosenescence is a major contributor to "inflammaging"—a state of chronic, low-grade inflammation that fuels age-related diseases and diminishes the success of modern immunotherapies.

Furthermore, the authors highlight that declining thymic activity may also undermine the effectiveness of modern therapies. A lack of fresh naïve T cells can limit the response to vaccines and weaken the performance of certain cancer immunotherapies, including CAR-T cell therapy and immune checkpoint inhibitors, which rely on a robust T-cell pool to be effective in older adults.

A Roadmap for Rejuvenation

To address these challenges, the review outlines several cutting-edge approaches to maintaining or restoring thymic function, including:

• genetic strategies to reprogram thymic cells
• pharmacological interventions to slow involution
• bioengineering-based approaches to regenerate thymic tissue

Rather than viewing immunosenescence as a diffuse, unstoppable systemic phenomenon, the authors propose that the thymus should be considered a primary, targetable driver of immune ageing. Understanding and intervening in thymic decline could be key to improving immune resilience, enhancing vaccine responses, and enhancing cancer immunotherapy in older populations.

Article information

Title: A thymus-centric perspective on immune ageing: Mechanisms, cross-species insights, and therapeutic directions
Journal: Ageing and Cancer Research & Treatment
Publisher: Science Exploration Press
DOI: 10.70401/acrt.2025.0008
Article link: https://www.sciexplor.com/articles/acrt.2025.0008