Senescent remodeling of the immune system and its contribution to the predisposition of the elderly to infections

Objective To review the senescent remodeling of the immune system with aging and its relevance to the increased susceptibility of the elderly to infectious diseases, along with an outlook on emerging immunological biomarkers. Data sources The data selected were from PubMed with relevant published articles in English or French from 1995 to the present. Searches were made using the terms immunosenescence and aging paired with the following： innate immunity, T-celr, B-cell, adaptive immunity and biomarkers. Articles were reviewed for additional citations and some information was gathered from web searches. Study selection Articles on aging of both the innate and adaptive immunity were reviewed, with special attention to the remodeling effect on the ability of the immune system to fight infectious diseases. Articles related to biomarkers of immunosenescence were selected with the goal of identifying immunological biomarkers predisposing the elderly to infections. Results Innate immunity is generally thought to be relatively well preserved or enhanced during aging compared with adaptive immunity which manifests more profound alterations. However, evidence, particularly in the last decade, reveals that both limbs of the immune system undergo profound remodeling with aging. Reported data on adaptive immunity is consistent and changes are well established but conflicting results about innate immunity were reported between in vivo and in vitro studies, as well as between murine and human studies. Epidemiological data suggests increased predisposition of the elderly to infections, but no compelling scientific evidence has directly linked senescent immune remodeling to this increased susceptibility. Recently, growing interest in identifying immunological biomarkers and defining immune risk phenotypes/profiles （IRP） has been expressed. Identification of biomarkers is in its early days and few potential biomarkers have been identified, with the Swedish having defined one IRP based on the adaptive immune response. Conclusions Aging does not necessarily lead to an unavoidable decline in immune functions. Instead, a complex remodeling occurs. Despite the lack of compelling scientific evidence, senescent immune remodeling surely is a significant contributing factor to the increased risk and severity of infections in the elderly. Although, no immunological biomarker has been formally linked to the increased risk of infections in the elderly, biomarkers remain a promising to