Immunology: Age shapes disease tolerance and survival in mice (Nature)
15 January 2026
Age may alter how animals respond to infection, according to a mouse study in Nature. The research reveals that immune processes that protect younger mice can harm older animals. Whether the same mechanisms occur in humans remains to be confirmed, but the findings potentially have implications for the tailoring of therapy to the age of an infected individual.
The immune system is the body’s first line of defence against infection and must regulate responses to fight infection with minimal costs to the body. However, strong inflammatory responses that are potentially beneficial early in life may later drive chronic inflammation, autoimmunity and tissue damage; this concept is called antagonistic pleiotropy. Janelle Ayres and colleagues provide evidence for that theory, showing how age reshapes mechanisms that once promoted survival.
To understand how age affects disease tolerance, the authors studied an animal model of polymicrobial sepsis, infecting young and old mice with two bacteria commonly responsible for human sepsis. Despite receiving the same infectious dose, the mice followed distinct disease paths. Young mice developed enlarged hearts and multi-organ congestion, whereas aged mice showed the opposite, often developing smaller hearts. Molecular analysis revealed that the proteins FoxO1 and MuRF1, which protect young hearts from sepsis-induced damage, instead worsened outcomes in older mice. Blocking these proteins improved survival in aged mice but harmed younger ones, demonstrating the complexity of age-specific responses.
Current sepsis treatments often aim to suppress immune activity. Although this may benefit older patients, the study warns it could harm younger ones. Further research is needed to pinpoint the processes that drive mortality across age groups. These findings underscore how age may influence the course of infection and the importance of developing therapies tailored to it.
- Article
- Open access
- Published: 14 January 2026
Sanchez, K.K., McCarville, J.L., Stengel, S.J. et al. Disease tolerance and infection pathogenesis age-related tradeoffs in mice. Nature (2026). https://doi.org/10.1038/s41586-025-09923-x
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