The untwining of immunosenescence and aging

From a holistic point of view, aging results from the cumulative erosion of the various systems. Among these, the immune system is interconnected to the rest as immune cells are present in all organs and recirculate through bloodstream. Immunosenescence is the term used to define the remodelling of immune changes during aging. Because immune cells-and particularly lymphocytes-can further differentiate after their maturation in response to pathogen recognition, it is therefore unclear when senescence is induced in these cells. Additionally, it is also unclear which signals triggers senescence in immune cells (i) aging per se, (ii) specific response to pathogens, (iii) underlying conditions, or (iv) inflammaging. In this review, we will cover the current knowledge and concepts linked to immunosenescence and we focus this review on lymphocytes and T cells, which represent the typical model for replicative senescence. With the evidence presented, we propose to disentangle the senescence of immune cells from chronological aging.