The ageing immune system as a driver of systemic ageing

Older individuals exhibit distinct biochemical and functional changes in their immune cells that can lead to chronic inflammation, reduced immunity to pathogens and organ dysfunction. Immune cells from older individuals acquire dysfunctional immunosenescent phenotypes that are classified as inflammatory, exhausted or senescent. Key molecular mechanisms, commonly described as hallmarks of ageing, drive the development of these phenotypes through both cell-autonomous and non-autonomous mechanisms. Importantly, the ageing immune system can drive multi-organ dysfunction and systemic ageing, suggesting that improving immune function in older individuals could have significant health benefits. Here, we review the effects of ageing on various immune cell subsets in mice and humans. We describe the molecular mechanisms that drive these functional changes and their effects on both lymphoid and non-lymphoid organs. We also discuss therapeutic approaches to improve the function of the ageing immune system to increase resilience and extend healthspan.