A role for p16 High immune cells in disease tolerance as a crucial defence strategy

In the context of infectious diseases, it is well established that older individuals are more susceptible to pathogens. However, an organism's survival does not rely solely on its ability to eliminate pathogens, a process collectively referred to as resistance. An additional protective strategy, known as disease tolerance, has evolved in multiple species. In response to severe inflammation and tissue damage, disease tolerance allows the host to limit the negative impact of infection without directly reducing pathogen burden. It relies on mechanisms that control tissue damage and stress response to preserve host health and physiological fitness. In recent years, the concept of disease tolerance has gained attention, as it offers a complementary approach to traditional resistance-based strategies in managing inflammation, tissue damage and infection, ultimately improving survival outcomes. However, the full spectrum of disease tolerance mechanisms and the therapeutic opportunities to enhance them remain incompletely understood. In this context, we will discuss recent insights into disease tolerance and propose a role for immune cells exhibiting senescence-like features-specifically, the activation of the p16 gene-in the positive regulation of disease tolerance, with implications for treating various pathological conditions and potentially extending healthspan. This article is part of the theme issue 'Developmental circuits in ageing'.