Decline of Immunity with Aging in Humans

Life expectancy in the world has nearly doubled over the last century. However, aging is associated with the onset of multiple co-morbidities. Elderly people present increased susceptibility to infectious and malignant diseases, and impaired vaccine efficacy. This is most likely related to the decline of the immune system with age, or immunosenescence. A better understanding of the causes and consequences of immune aging is therefore a public health priority. In recent years, we have characterized immune cell compartments in the elderly, exploring putative causes of their decline in relation to elevated inflammation and chronic viral infections, and studying potential consequences on cellular immune competence with advanced age. Old individuals display an altered hematopoiesis and decreased lymphocyte replenishment associated with an exhaustion of primary immune resources (down to the level of hematopoietic progenitors). Using an original in vitro approach to examine T-cell priming efficacy in humans, we also show that old individuals consistently mount impaired de novo CD8+ T-cell responses against a melanoma antigen, which likely reflects reduced immuno-surveillance against cancer with advanced age. Overall, our work highlights the complexity of immune aging in humans, characterized by a combination of immune cell alterations, and the necessity to develop tailored immunotherapy and vaccine strategies in the elderly.