Metabolic regulation of immunological aging

All biological activities require energy through the intake and generation of metabolites. After reproductive age, altered metabolism, together with cellular and molecular perturbations in the immune system, are linked to organismal functional decline. Unresolved chronic inflammation originating from innate immune cells and loss of naive T cells with restriction of T cell receptor repertoire diversity emanating from age-related thymic involution are some of the mechanisms that limit healthspan and even lifespan. Here, we provide an overview of the hallmarks of immunological aging and synthesize how the immune system, coupled to cellular and organismal metabolism, controls disease susceptibility. Furthermore, we highlight the potential unifying immunometabolic mechanisms of various genetic, pharmacological and dietary interventions that may underlie lifespan-healthspan extension. Given that immune and metabolic systems are modifiable and targetable, understanding the role of myriads of organ-resident immune cells and the underlying metabolic mechanisms that cause dysfunction can have transformational potential for the health of older adults.