Cellular senescence, inflammation and immune regulation in healthy and pathological aging

Aging research increasingly highlights the interrelationship between chronic inflammation and cellular senescence—a persistent cellular phenotype with wide-ranging effects on tissue and immune system function. The concept of “inflammaging” describes the age-related increase in unresolved, low-grade inflammation. It is now recognized as a central feature that contributes to immunosenescence, impaired tissue repair, and increased susceptibility to age-related diseases, including cardiovascular, neurodegenerative, and metabolic disorders.

The accumulation of senescent cells, driven by stressors such as DNA damage, oxidative stress, and chronic immune activation, leads to increased secretion of pro-inflammatory factors collectively termed the senescence-associated secretory phenotype (SASP). This promotes an inflammatory milieu, further worsening immune dysfunction and perpetuating tissue deterioration. Recent methodologies—including single-cell transcriptomics, spatial profiling, and innovative senolytic and senomorphic therapeutics—have provided new insights into the complex, bidirectional communication between immune cells and senescent cells. Despite these advances, major gaps remain, particularly regarding tissue specificity, regulation of immune surveillance, senescent-cell clearance efficiency, and the development of effective therapies that selectively target maladaptive inflammation without compromising essential immune functions.

This Research Topic aims to advance understanding of the immunological mechanisms linking inflammation and cellular senescence during aging. The primary goal is to delineate how immune system components regulate the onset and maintenance of cellular senescence and, conversely, how senescent cells influence immune homeostasis and responsiveness. This Research Topic will bring together mechanistic, translational, and clinical studies to address key questions, such as identifying molecular drivers of inflammaging, elucidating immune checkpoints in senescent-cell clearance, and assessing the therapeutic potential of targeting the immune–senescence axis. By encouraging exploration of both fundamental biology and clinical interventions, this Research Topic seeks to catalyze multidisciplinary insights that support disease prevention and healthy aging.

The scope of this Research Topic centers on the immunological interactions governing inflammaging, with an emphasis on cellular and molecular mechanisms in both physiological and pathological contexts. Studies using integrative approaches in humans, animal models, and in vitro systems are invited. The scope excludes aspects of aging that are not directly linked to immunity or senescence.

To gather further insights, we welcome manuscripts addressing, but not limited to, the following themes:

- Immune regulation of cellular senescence and senescence-induced inflammation
- The senescence-associated secretory phenotype (SASP) and its impact on immune modulation
- Dysfunction of innate and adaptive immune cells in the context of inflammaging
- Mechanisms governing immune surveillance and clearance of senescent cells
- Tissue- or disease-specific processes underlying immune–senescence interactions
- Senolytic and senomorphic therapeutics targeting immune-mediated aging
- Epigenetic and metabolic regulation connecting inflammation and senescence
- Biomarkers and immune signatures relevant to inflammaging
- Advances in single-cell, spatial, and multi-omic profiling in inflammaging research
- Translational and clinical strategies aimed at mitigating inflammaging-driven immune dysfunction

We invite original research manuscripts, clinical studies, and comprehensive reviews.

Please note that manuscripts on aging that are not focused on immunological mechanisms or consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Community Case Study
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Community Case Study
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: cellular senescence, chronic inflammation, inflammaging, immunosenescence, senescence-associated secretory phenotype (SASP), immune surveillance, senescent cell clearance, senolytic therapeutics, senomorphic therapeutics, single-cell transcriptomics

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.