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Review
. 2024 Oct 16:5:1490302.
doi: 10.3389/fragi.2024.1490302. eCollection 2024.

The 3 I's of immunity and aging: immunosenescence, inflammaging, and immune resilience

Marianna V Wrona  1 , Rituparna Ghosh  2   3   4 , Kaitlyn Coll  5 , Connor Chun  6 , Matthew J Yousefzadeh  1   2   3   4
Affiliations
Review

The 3 I's of immunity and aging: immunosenescence, inflammaging, and immune resilience

Marianna V Wrona et al. Front Aging. .

Abstract

As we age, our immune system's ability to effectively respond to pathogens declines, a phenomenon known as immunosenescence. This age-related deterioration affects both innate and adaptive immunity, compromising immune function and leading to chronic inflammation that accelerates aging. Immunosenescence is characterized by alterations in immune cell populations and impaired functionality, resulting in increased susceptibility to infections, diminished vaccine efficacy, and higher prevalence of age-related diseases. Chronic low-grade inflammation further exacerbates these issues, contributing to a decline in overall health and resilience. This review delves into the characteristics of immunosenescence and examines the various intrinsic and extrinsic factors contributing to immune aging and how the hallmarks of aging and cell fates can play a crucial role in this process. Additionally, it discusses the impact of sex, age, social determinants, and gut microbiota health on immune aging, illustrating the complex interplay of these factors in altering immune function. Furthermore, the concept of immune resilience is explored, focusing on the metrics for assessing immune health and identifying strategies to enhance immune function. These strategies include lifestyle interventions such as diet, regular physical activity, stress management, and the use of gerotherapeutics and other approaches. Understanding and mitigating the effects of immunosenescence are crucial for developing interventions that support robust immune responses in aged individuals.

Keywords: cellular senescence; immune resilience; immunosenescence; inflammaging; inflammation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

FIGURE 1
FIGURE 1
Cellular senescence and inflammaging as drivers of age-related dysfunction. Cells undergoing stress can undergo various cell fates including transformation, apoptosis, or cellular senescence. Senescent cells can exhibit diverse features such as morphological and molecular changes that result in stable cell cycle arrest and resistance to apoptosis, ensuring their continued survival. Senescent cells can also develop a secretory phenotype known as the senescence-associated secretory phenotype (SASP). The inflammatory factors that constitute SASP can induce secondary senescence and disrupt tissue, contributing to an overall state of inflammaging that accelerates the aging process.
FIGURE 2
FIGURE 2
Immunological characteristics of exhausted and senescent cells. Functional, molecular, and enzymatic features as characterized through standard immunological methods.
FIGURE 3
FIGURE 3
Hallmarks of immunosenescence. Cellular, molecular, and phenotypic changes occur in multiple immune cell types with the onset and progression of immunosenescence. HSC: Hematopoietic Stem Cell; IFN: Interferon; IL: Interleukin; ROS: Reactive Oxygen Species; SASP: Senescence-Associated Secretory Phenotype; TCR (T Cell Receptor).
FIGURE 4
FIGURE 4
Strategies to rejuvenate an aged immune system and restore immune resilience. Interventions including biologics, cell-based therapies, and pharmacological approaches that have been demonstrated to restore immune function in mice and humans. CAR-T: Chimeric Antigen Receptor T Cell; CTLA-4: Cytotoxic T Lymphocyte Associated Protein-4; iPSC: Induced Pluripotent Stem Cells; PD-1: Programmed Cell Death Protein 1.
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