Abstract
Aging is a universal and complex process that affects all tissues and cells types, including immune cells, in a process known as immunosenescence. However, many aspects of immunosenescence are not completely understood, as the characteristics of the immune cells of nonagenarians and centenarians or the features and implications of extracellular vesicles (EVs). In this study, we analyzed blood samples from 51 individuals aged 20-49 and 70-104 years. We found that senescent CD8 cells accumulate with age, while there is a partial reduction of senescent CD4 cells in nonagenarians and centenarians. Moreover, plasma EVs carry T cell specific markers, but no accumulation of “senescent-like EVs” was found within any of analyzed age groups. Our functional studies of cocultures of peripheral blood mononuclear cells and EVs showed that EVs enhance T cell viability and, under phytohemagglutinin stimulation, they influence cytokine secretion and cell activation in an age-dependent manner. These results underline the importance of EVs on the immune system functioning, and open new perspectives to further study their implication in human aging.
Highlights
Human aging is a complex and heterogenic process, in which several cellular mechanisms are affected and modulated, leading to functional decline [1]
The lymphocyte subsets were compared and an increased T cell and decreased B cell and NK cell proportions were found with age
Several works have studied the lymphocyte subsets with aging, both at the total number and percentage level
Summary
Human aging is a complex and heterogenic process, in which several cellular mechanisms are affected and modulated, leading to functional decline [1]. Differentiated T cells exhibit features of replicative senescence and lose the expression of the costimulatory molecule CD28 from their membrane [4,5,6,7,8]. T lymphocytes have a reduced capacity to react against new stimuli, contributing to the aforementioned immune dysfunction. Another feature found in immunosenescent T cells is the enhanced cytotoxicity. Expression of NK cell characteristic receptors such as CD56 and CD57 membrane molecules have been widely reported in these cells, which promote their cytotoxic capacity [12,13,14,15]. Many authors have found a higher prevalence of an inverted CD4/CD8 ratio in the elderly, a feature known as immune risk phenotype, that predicts shorter survival [16,17,18]
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