Researchers here review the landscape of immune aging with a particular focus on vulnerability to respiratory infections, such as influenza. As we age the immune system becomes ever less capable, the outcome of impaired manufacture of new immune cells, as well as issues that affect the internal workings of cells throughout the body, such as mitochondrial dysfunction and cellular senescence. At the same time the immune system becomes ever more active and inflammatory, a maladaptive reaction to forms of damage in cells and tissues. This creates a landscape in which infectious pathogens find it easier to overwhelm immune defenses, and in which inflammatory reactions to infection can readily become life-threatening, amplified by a dysfunctional immune system.
Every country around the globe is facing continuous growth in both the size and the proportion of older people; by 2050, the global population aged 60 years and above is projected to double, reaching approximately 2.1 billion people. As the population shifts towards older ages, new challenges are emerging, including increased healthcare demands. Among these challenges is "the destruction and remodelling of immune organ structure as well as innate and adaptive immune dysfunction with ageing", so-called immunosenescence, alongside inflammageing, a characteristic inflammatory state in which high levels of pro-inflammatory molecules are expressed. Both states predispose older adults to dysregulated immune responses and, inadvertently, to increased proportions of adverse outcomes, especially in the context of infections such as respiratory viral infections.
In this review, we examine the molecular and cellular pathophysiological mechanisms of immunosenescence and inflammageing that predispose older adults to increased morbidity and mortality from respiratory viral infections. We also outline the clinical implications of the ageing immune system, along with the most up-to-date evidence on possible biomarkers, preventative measures and treatment options aimed at mitigating the effects of immunosenescence on the vulnerability of older adults in respiratory viral infections.
Link: https://doi.org/10.1183/16000617.0248-2025
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