Complex interaction between innate immune memory and aging: a narrative review

Aging is associated with immune dysfunction, and many age-associated pathologies and aged immune cell phenotypes resemble those found in innate immune memory, which includes two distinct phenotypes: endotoxin tolerance and trained immunity. This review discusses the similarities and differences between innate immune memory and an aged immune system, underscoring a probable interconnection between them. For example, both aging and innate immune memory share (i) an increased myelopoiesis over lymphopoiesis; and (ii) epigenetic changes in immune cells. The review also explores the interaction between innate immune memory and aging, as well as the underlying mechanisms, with a focus on the roles of mitochondrial biogenesis and macroautophagy—both of which are reduced in aged immune cells. Finally, the role of sirtuins as anti-aging and anti-endotoxin tolerance is underscored.