Elsevier

Cellular Immunology

Volume 348, February 2020, 104024
Cellular Immunology

Aging, sex, inflammation, frailty, and CMV and HIV infections

https://doi.org/10.1016/j.cellimm.2019.104024Get rights and content

Highlights

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    Immunosenescence refers to immune system changes during aging.

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    Chronic low-grade inflammatory phenotype (CLIP) is a feature of immunosenescence (84).

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    Emerging data suggest sex as an important factor influencing immunosenescence.

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    Immunosenescence affects susceptibility to infection, chronic disease, and frailty (85).

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    Chronic CMV infection contributes to immunosenescence in aging and HIV infection (83).

Abstract

Aging is characterized by significant immune remodeling at both cellular and molecular levels, also known as immunosenescence. Older adults often manifest a chronic low-grade inflammatory phenotype. These age-related immune system changes have increasingly been recognized not only to lead to immune functional decline and increased vulnerability to infections, but also to play an important role in many chronic conditions such as frailty in older adults. In addition to sex as an important biological factor, chronic viral infections including that by human immunodeficiency virus (HIV) and cytomegalovirus (CMV) are all known to have major impact on the aging immune system. This article provides an overview of our current understanding of aging immunity, sex, inflammation, frailty, and HIV and CMV infections.

Introduction

The immune system undergoes significant changes with aging, collectively termed as immunosenescence by some. For example, aging is associated with thymus involution, contraction of the immune repertoire, decrease in the number and proportion of naïve lymphocytes, accumulation of memory and senescent lymphocytes, as well as T cell clonal expansion and loss of expression of costimulatory molecular CD28 [1], [2], [3]. Meanwhile, aging is associated with the development of a chronic low-grade inflammatory phenotype (CLIP) [4], [5] or inflammaging [6], [7]. Such complex immune remodeling constitutes a hallmark of aging [8]. The clinical impact of immunological aging is profound, particularly the immune functional decline leading to increased vulnerability to infections as well as CLIP that is believed to contribute to many chronic conditions in older adults. In this article, we will briefly review the relationships among aging immunity, sex, inflammation, frailty, and HIV and CMV infections, and what is known about how these relationships are affected by sex.

Section snippets

Impact of sex on aging immunity

Recently, sex has increasingly been recognized as an important biological factor with significant impact on the aging immune system. For instance, a number of studies have shown that older males have more accumulation of memory and senescent CD8+ T cells and lower CD4+:CD8+ T-cell ratio than their female aged peers (reviewed in [9], [10]). Brown and colleagues demonstrated the impact of sex on naïve and senescent T-cell redistribution in response to acute maximal exercise, with significant

Aging and chronic low-grade inflammatory phenotype (CLIP)

Aging is often accompanied by CLIP, which is characterized by low-grade, systemic, persistent, and smoldering chronic inflammation, marked by 2–4-fold higher circulating levels of multiple inflammatory mediators. The profound clinical implications of CLIP are best demonstrated by its association with the development of almost all age-related chronic conditions including frailty (see below), cardiovascular disease, neurodegenerative diseases, and metabolic dysfunctions [7]. Taking cardiovascular

Frailty, aging immunity, and HIV infection

Frailty is widely recognized as an important and common geriatric syndrome characterized by decreased physiological reserve and involving multiple physiologic systems and increased vulnerability to serious adverse health outcomes including falls, disability, and mortality [19], [20], [21], [22]. According to the most commonly utilized criteria, frailty as a phenotype is defined by the presence of three or more of the following clinical and functional characteristics: weakness (measured by grip

CMV, aging immunity, and HIV infection

It is possible that the additional immune activation associated with frailty, above that associated with treated HIV infection, is related to immune responsiveness to CMV infection. CMV, which is highly prevalent in the general HIV− geriatric population and almost universal among HIV+ aging persons, may cause clonal T-cell expansion, leading to immune activation and adverse health outcomes [48], [49], [50], [51]. The potentially important impact of CMV on aging immunity is further supported by

Concluding remarks

Substantial evidence indicates that a number of factors have major impact on aging immunity, including sex as a major intrinsic biological factor, and extrinsic and environment factors such as chronic CMV and HIV infections. It is generally established that aging immunity includes immune functional decline leading to increased susceptibility to infections in older adults, particularly those who are frail. Recent data support the notion that immunosenescence, particularly CLIP, contributes to

Acknowledgments

Work presented in this review was supported in part by NIH, the United States, grants R01AI108907 (SXL), U01AI35042 (MACS/WIHS, CCS) (JBM), U54AG062333-01 (SXL), and R21AG059742 (JBM and SXL), as well as funding from Irma and Paul Milstein Program for Senior Health, Milstein Medical Asian American Partnership (MMAAP) Foundation, the United States (www.mmaapf.org) (SXL).

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