A gentler way to model deadly lung infections in old age

Respiratory infections are among the leading causes of illness and death in the elderly, driven by immune aging, chronic diseases, and reduced physiological resilience. Pseudomonas aeruginosa, an opportunistic pathogen known for antibiotic resistance and biofilm formation, frequently causes persistent and difficult-to-treat lung infections in older patients. While animal models have helped clarify infection mechanisms in young hosts, aged animals often fail to survive standard infection procedures, making chronic studies impossible. This gap has limited progress in understanding how aging alters immune responses and infection outcomes. Based on these challenges, there is a clear need to develop and optimize infection models specifically tailored for aged hosts.

Researchers from Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, report a refined mouse model that successfully mimics chronic Pseudomonas aeruginosa lung infection in old age. Published (DOI: 10.26599/AGR.2025.9340059) in Aging Research in 2025, the study introduces an agar bead-based delivery strategy that allows bacteria to persist in the lungs of aged mice without causing rapid death. This methodological advance enables sustained observation of infection dynamics, tissue damage, and immune responses in aging lungs, addressing a long-standing limitation in experimental respiratory infection research.

The researchers first confirmed that conventional intratracheal delivery of free-living P. aeruginosa is overwhelmingly lethal to aged mice, with all animals succumbing within 24 hours. This stark result underscored the extreme vulnerability of aging lungs and the unsuitability of standard approaches. To overcome this, the team encapsulated bacteria within agar beads before intratracheal administration.

This modification dramatically changed infection outcomes. Instead of acute death, aged mice survived while maintaining persistent bacterial colonization in the lungs for at least ten days. Quantitative analyses showed sustained bacterial loads, confirming the establishment of a chronic infection rather than a transient exposure. Histological examination revealed hallmark features of chronic lung disease, including disrupted alveolar structure, inflammatory cell infiltration, and tissue consolidation.

Crucially, the agar beads acted as a controlled-release system, allowing gradual bacterial exposure that better reflects real-world chronic infections in elderly patients. The model also proved reproducible, with consistent infection patterns across animals. Together, these results demonstrate that infection severity in aged hosts is not only pathogen-dependent but also strongly influenced by delivery dynamics—an insight with broad implications for aging research.

“This work solves a fundamental problem in aging-related infection research,” the authors note. “Aged organisms respond very differently to bacterial challenges, and models designed for young animals can produce misleading or unusable results.” By prioritizing host tolerance and infection persistence, the new approach allows researchers to study immune decline, bacterial adaptation, and tissue damage over time. The team emphasizes that this model provides a practical foundation for mechanistic studies that were previously impossible due to high mortality in aged animals.

This chronic infection model offers an essential tool for studying age-specific immune dysfunction, bacterial persistence, and treatment resistance. It can be used to test antibiotics, anti-biofilm strategies, and immune-modulating therapies under conditions that closely resemble elderly lung infections. Beyond P. aeruginosa, the approach may be adapted for other respiratory pathogens that disproportionately affect older populations. Ultimately, the model bridges experimental research and clinical reality, supporting the development of therapies tailored to aging patients rather than extrapolated from young, resilient hosts.

Funding information

This work was supported by the National Natural Science Foundation of China (Nos. 81872207 and 82102575) and the Sichuan Science and Technology Bureau (No. 2025YFHZ0123).

Aging Research

Aging Research is an Open Access publication addressing the biology and medicine issues of aging and aging-related diseases. Aging Research publishes original research results that are of unusual significance or broad conceptual or technical advances in all areas of aging, longevity and aging related health issues. The journal focuses on the following research: to explore the process, mechanism, biomarkers, anti-aging strategies or drugs at the population, individual, system, organ, tissue, cell and subcellular levels; to study the epidemiological characteristics, pathogenesis, pathophysiological processes, diagnostic criteria, clinical experiments and translational research of age-related diseases.