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Targeting Immune Dysfunction in Aging and Age-Related Diseases

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 10 September 2026 | Viewed by 1628

Special Issue Editors


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Guest Editor
Laboratory of Immunopathology and Immunosenescence, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90133 Palermo, Italy
Interests: immunosenescence; longevity; nutraceuticals in healthy and longevity; aging; immunopathology; immunogenetics
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Laboratory of Immunopathology and Immunosenescence, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90133 Palermo, Italy
Interests: immunopathology; immunosenescence; aging; role of nutraceuticals in health and longevity

Special Issue Information

Dear Colleagues,

A progressive decline in immune function, known as immunosenescence, accompanies aging and is often linked to chronic, low-grade inflammation, termed inflammaging. These changes increase susceptibility to infections, reduce vaccine efficacy, and contribute to numerous age-related diseases (ARDs), including cancer, neurodegeneration, and cardiovascular as well as metabolic disorders.

Despite the growing recognition of immune dysfunction as a key driver of aging and its associated pathologies, effective strategies to modulate immune aging remain limited.

This Special Issue aims to highlight recent advances in the understanding of the mechanisms of immune dysfunction in aging and its role in the pathophysiology of ARDs, including the impaired resolution and regeneration phases of inflammation. In aging, immune dysfunction often disrupts these critical phases, leading to the defective clearance of inflammatory cells, the reduced production of pro-resolving mediators, and a sustained inflammatory milieu. These processes contribute to chronic inflammation, tissue damage, fibrosis, and a diminished capacity for regeneration, ultimately driving the progression of ARDs.

We invite original research and review articles that explore emerging therapeutic interventions, such as immunomodulators, immunoceutical-based strategies, senotherapeutics, and lifestyle approaches, with a focus on innovative drug and delivery systems (e.g., plant-derived extracellular vesicles, nanoparticles) aimed at targeting the molecular and cellular mechanisms of immunosenescence. We also welcome studies on the effects of chronic inflammation and immune–metabolic interactions on immune function. By integrating insights from basic science and clinical research, this Special Issue seeks to foster translational strategies to restore immune homeostasis and improve the healthspan in aging populations.

Dr. Anna Aiello
Dr. Anna Calabrò
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • immunosenescence
  • inflammaging
  • immune dysfunction
  • aging
  • age-related diseases (ARDs)
  • immune–metabolic interactions
  • immunomodulators
  • immunoceuticals
  • senotherapeutics
  • lifestyle interventions

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Published Papers (2 papers)

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Review

31 pages, 4565 KB  
Review
Network Rewiring in the Aging Immune System: From Chronic Inflammation to Age-Related Pathologies
by Ludmila Müller and Svetlana Di Benedetto
Cells 2026, 15(5), 414; https://doi.org/10.3390/cells15050414 - 27 Feb 2026
Viewed by 604
Abstract
Aging is accompanied by profound alterations in immune function that collectively drive increased susceptibility to infection, reduced vaccine efficacy, impaired tissue repair, and heightened risk of age-related diseases (ARDs). These alterations are characterized by the coexistence of immunosenescence and inflammaging. Rather than reflecting [...] Read more.
Aging is accompanied by profound alterations in immune function that collectively drive increased susceptibility to infection, reduced vaccine efficacy, impaired tissue repair, and heightened risk of age-related diseases (ARDs). These alterations are characterized by the coexistence of immunosenescence and inflammaging. Rather than reflecting isolated cellular defects, immune aging emerges as a systems-level reprogramming of immune networks that disrupts the initiation, resolution, and regenerative phases of inflammatory responses. In particular, aging is associated with impaired resolution of inflammation, defective efferocytosis, reduced responsiveness to pro-resolving signals, and diminished regenerative capacity, leading to persistent inflammatory milieus and tissue damage. This review summarizes recent advances in the mechanisms underlying immune dysfunction in aging, with a focus on how chronic inflammation, failed resolution, and defective repair reinforce one another. We discuss how alterations in innate and adaptive immunity, immunometabolism, cellular senescence, and immune–tissue interactions drive inflammaging and contribute to major ARDs, including cancer, neurodegenerative, and cardiometabolic diseases. Finally, we highlight emerging therapeutic strategies aimed at restoring immune balance and resolution. By adopting a systems-level and network-based perspective, this review underscores immune aging as a modifiable driver of ARDs and identifies key knowledge gaps and future directions toward interventions that promote healthy aging and extended healthspan. Full article
(This article belongs to the Special Issue Targeting Immune Dysfunction in Aging and Age-Related Diseases)
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31 pages, 926 KB  
Review
CD57-Expressing Lymphocytes: From Chronic Viral Response to Age-Related Inflammation
by Isabel María Vallejo-Bermúdez, Mabel Rocio Miranda-Echagüe, Silvia Fernández-Álvarez, Irene Reina-Alfonso, Laura Blanca-Pariente, Alexander Batista-Duharte and Alejandra Pera
Cells 2026, 15(5), 403; https://doi.org/10.3390/cells15050403 - 26 Feb 2026
Viewed by 620
Abstract
CD57-expressing lymphocytes constitute a distinct subset of immune cells with enhanced cytotoxic and pro-inflammatory functions. Initially described in the context of chronic viral infections, most notably cytomegalovirus (CMV), these cells are now recognized as central contributors to immunosenescence and age-related immune dysregulation. Their [...] Read more.
CD57-expressing lymphocytes constitute a distinct subset of immune cells with enhanced cytotoxic and pro-inflammatory functions. Initially described in the context of chronic viral infections, most notably cytomegalovirus (CMV), these cells are now recognized as central contributors to immunosenescence and age-related immune dysregulation. Their progressive accumulation reflects prolonged antigenic exposure and sustained immune activation, thereby linking persistent viral infections with long-term disruptions of immune homeostasis. Emerging evidence indicates that CD57 expression denotes a state of terminal differentiation in both T and natural killer (NK) cell compartments, and is associated with cytotoxicity, altered cytokine secretion, and a pro-inflammatory phenotype. This review summarizes the phenotypic and functional characteristics of CD57+ lymphocytes, examines their association with CMV and other chronic viral infections, and explores their potential role in ageing and age-related diseases. Elucidating the biology of CD57+ lymphocytes in the context of chronic viral infections may provide novel insights into immune ageing and help identify potential targets for therapeutic strategies aimed at restoring immune balance in older adults. Full article
(This article belongs to the Special Issue Targeting Immune Dysfunction in Aging and Age-Related Diseases)
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