T and B Cell Metabolism in Older Adults

Abstract Immunosenescence, a process that describes age-related declines in immune responses, renders the elderly more susceptible to infections and malignancies. Many changes that accumulate during aging contribute to immunosenescence and one of them is a decline in metabolic fitness. Here we discuss how aging affects functions and metabolism of cells of the adaptive immune system. Both T and B cells once they become activated have to rapidly adjust their metabolism to allow for cell proliferation and effector functions. In younger adults most T cell subsets switch to glycolysis upon activation, while B cells, in addition, increase mitochondrial energy production. Once lymphocytes transition towards memory, they again must adjust their metabolism. These metabolic switches, which are prompted by a number of signaling pathways that concomitantly regulate mitochondrial biogenesis, protein translation, and glycosylation pathways, as well as protein transport and autophagy, become impaired in the aged. As a result, invasion of a pathogen commonly triggers low quality effector T and B cell responses that, compared to those in younger individuals, are less potent, less functional, and less broad. Formation of memory also becomes impaired, reducing the benefits of vaccines in the elderly.