Gero-Immunology: The critical role of aging when defining immune phenotypes

The immune system is complex, dynamic, and essential for organismal health. As organisms age, immune cells undergo numerous changes that often limit their ability to fight infections, eradicate diseases, and tolerate foreign entities. Although many studies have advanced our understanding of key immune functions, many overlook the effects of age, which can potentially limit the generalizability of their findings. In this review, we argue that age should be critically considered when designing in vitro models of the immune system. We begin by outlining some practical and conceptual challenges that limit the inclusion of age in immune models. We then propose practical strategies that researchers can use to account for age effects and summarize recent findings that demonstrate how aging alters cellular immune functions to drive immune dysfunction. Lastly, pose open questions that could benefit from bioengineering solutions and look ahead to how considering age can improve model fidelity, increase translational value, and accelerate discoveries that are both relevant and generalizable across the lifespan.