Alterations of Specific Lymphocytic Subsets with Aging and Age-Related Metabolic and Cardiovascular Diseases

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.

Growth Differentiation Factor-15 in Immunity and Aging

“…However, GDF-15 also suppressed T cell activation via promoting regulatory T cell activity, thereby limiting immune activation. Circulating GDF-15 levels were additionally recently shown to be correlated to accumulation of senescent T cells during aging ( Chen et al, 2020 ). GDF-15 may therefore be a regulatory SASP factor which limits inflammaging at the expense of suppressing immune function.…”

Diagnosis of Myelodysplastic Syndromes: From Immunological Observations to Clinical Applications

“…The incidence of MDS markedly increases in elderly people, making advanced age the greatest risk factor for developing MDS [14]. It is well known that during the process of aging, the hematopoietic system is characterized by (1) an increased number of myeloidbiased hematopoietic stem cells (HSCs), (2) a decreased number of B-cell progenitors and (3) an expansion of memory B and T cells [15]. Altogether, this leads to a spontaneously increased level of pro-inflammatory cytokines/chemokines and a functional decline of the immune system [16].…”

Immunosenescence profiles of lymphocyte compartments and multiple long-term conditions (multimorbidity) in very old adults: The Newcastle 85+ Study

“…Although a number of studies have investigated the role of T cell senescence in several age-related diseases that share similar pathological mechanisms such as inflammaging (Barbé-Tuana et al, 2020;Chen et al, 2020;Fülöp et al, 2016;Santoro et al, 2021), studies that link MLTC defined in terms of counts, indices, and patterns with multiple immune biomarkers are lacking. Understanding the role of age-associated decline in immune function in MLTC could help find solutions for their prevention and treatment (Aiello et al, 2019;Duggal et al, 2019;Weyand and Goronzy, 2016).…”

“…Current understanding of how immunosenescence in lymphocyte compartments may influence the development of MLTC is based on epidemiological and mechanistic studies investigating the role of immunity in individual age-related diseases (e.g., cardiovascular, rheumatoid arthritis, metabolic diseases, cancer), and in those with a common mechanism (e.g., inflammation) (Barbé-Tuana et al, 2020;Chen et al, 2020;Desdín-Micó et al, 2020;Fülöp et al, 2016;Santoro et al, 2021).…”

“…To our knowledge, only a few studies have investigated the association between multiple chronic diseases and immunosenescence of lymphocyte compartments (Chen et al, 2020;Nilsson et al, 2002), and these have reported mixed results. None used dimension reduction techniques to define immunosenescence profiles from multiple immune system markers to create summary variables of ageing immune system.…”