Abstract
Although advances in preventive medicine have greatly improved prognosis, cardiovascular disease (CVD) remains the leading cause of death worldwide. This clearly indicates that there remain residual cardiovascular risks that have not been targeted by conventional therapies. The results of multiple animal studies and clinical trials clearly indicate that inflammation is the most important residual risk and a potential target for CVD prevention. The immune cell network is intricately regulated to maintain homeostasis. Ageing associated changes to the immune system occurs in both innate and adaptive immune cells, however T cells are most susceptible to this process. T-cell changes due to thymic degeneration and homeostatic proliferation, metabolic abnormalities, telomere length shortening, and epigenetic changes associated with aging and obesity may not only reduce normal immune function, but also induce inflammatory tendencies, a process referred to as immunosenescence. Since the disruption of biological homeostasis by T cell immunosenescence is closely related to the development and progression of CVD via inflammation, senescent T cells are attracting attention as a new therapeutic target. In this review, we discuss the relationship between CVD and T cell immunosenescence associated with aging and obesity.
Highlights
Immune function shows characteristic changes, including progressive decline in acquired immune response to foreign pathogens and a tendency to produce excessive inflammatory responses [17,18]. This phenomenon is referred to as immune senescence or immunosenescence [17,18] and is thought to be closely related to the development of cardiovascular disease (CVD) because the senescence-associated secretory phenotype (SASP) factor secreted by senescent immune cells causes progressive organ remodeling [15,16]
Since naïve T cells in the periphery are primarily maintained by homeostatic proliferation after thymic involution, there is no doubt that T cells are strongly affected by aging, unlike other immune cell types that depend on the production of hematopoietic stem cells (HSCs) [31,32]
We discovered that diet-induced obesity reduced the frequency of CD44lo CD62Lhi naïve CD4+ T cells and increased the frequency of both CD44hi CD62Llo memory phenotype CD4+ T cells in visceral adipose tissue (VAT) and a unique population of CD44hi CD62Llo CD4+ T cells that constitutively express programmed cell death 1 (PD-1) and CD153 exhibit cellular senescence [25]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Cellular senescence has been implicated as a major cause in age-related functional decline and chronic low-grade inflammation observed during aging [9,10] It has several triggers, including DNA damage, telomere length shortening, metabolic dysfunction, and organelle stress, which occur in multiple cell types [11,12]. Immune function shows characteristic changes, including progressive decline in acquired immune response to foreign pathogens (e.g., decreased vaccine efficiency) and a tendency to produce excessive inflammatory responses [17,18] This phenomenon is referred to as immune senescence or immunosenescence [17,18] and is thought to be closely related to the development of CVD because the SASP factor secreted by senescent immune cells causes progressive organ remodeling [15,16]. We summarize the current understanding of immune senescence and explore the evidence linking aging, obesity, and T cell immunosenescence with CVD
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