Abstract

To investigate the association of immunosenescence with aged-related morbidity in the elderly, a clinical study was conducted to analyze and compare the alterations in peripheral blood (PB) T-cell subsets among young healthy (YH) controls, elderly healthy (EH) controls, and age-matched elderly patients with metabolic diseases (E-MDs), with cardiovascular diseases (E-CVDs) or with both (E-MDs/E-CVDs). The frequencies of CD3T, CD8T and invariant natural killer T (iNKT) cells were decreased in the EH, E-MD and E-CVD cohorts, indicating a decline in defense function. Although CD4T and regulatory T (Treg) cell frequencies tended to increase with aging, they were lower in patients with E-MDs and E-CVDs. Subset analyses of T-cells consistently showed the accumulation of senescent T-cell in aging and in patients with E-MDs and E-CVDs, compared with YH volunteers. These accumulated senescent T-cells were undergoing apoptosis upon stimulation due to the replicative senescence stage of T-cells. In addition, serum levels of cytokines, including interferon (IF)-γ, transforming growth factor (TGF)-β and growth differentiation factor (GDF)-15, consistently reflected alterations in T-cell subsets. This study demonstrated that T-cell subset changes with paralleled alterations in cytokines were associated with aging and age-related pathogenesis. These altered T-cell subsets and/or cytokines can potentially serve as biomarkers for the prevention, diagnosis and treatment of age-related morbidities.

Highlights

  • With a global increase in aging populations, many societies are facing serious challenges due to age-related diseases [1]

  • We showed that alterations in T-lymphocyte subsets and the accumulation of terminally differentiated T-lymphocyte with a replicative senescence feature were significantly associated with aging and age-related metabolic diseases (MDs) and cardiovascular diseases (CVDs)

  • Flow cytometry was used to analyze the frequencies of different T-cell subsets, namely CD3T, CD4T, CD8T, invariant natural killer T (iNKT) and Treg cells, in the peripheral blood (PB) samples of healthy elderly (EH) subjects, and compared them to those of healthy young (YH) subjects and the three elderly diseased groups (E-MDs, elderly with cardiovascular diseases (E-CVDs), and elderly patients with metabolic diseases (E-MDs)/CVDs)

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Summary

Introduction

With a global increase in aging populations, many societies are facing serious challenges due to age-related diseases [1]. Aging of the immune system (known as immune aging or immunosenescence), characterized by decreased innate and adaptive immunity [2], likely contributes to this age-related morbidity [3]. The central T-cell-generating organ responsible for T-cell generation, involutes with age. The thymic generation of new T-cells cannot meet the replenishment demands required by the elderly [4]. T-cell receptor diversity [6,7], an increase in oligoclonal memory subsets, and the accumulation of senescent T-cells due to an insufficient homeostatic mechanism associated with aging [8]. Treg population, naturally occurring (n)Treg cells (a key immune regulator), accumulated with advancing age [9,10,11]

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