Transcription of Senescence: A Focus on the Immune System

Research Topic Highlights

This collection of articles explores the interplay between aging, cellular senescence, immune dysregulation, mitochondrial dysfunction, and their collective impact on human diseases and conditions, particularly highlighting infections such as COVID-19. The articles discuss how aging leads to alterations in immune cell metabolism, mitochondrial impairment, accumulation of senescent cells with inflammatory phenotypes, and exacerbated susceptibility to severe infections. Notably, cellular senescence, characterized by altered cell cycle regulation and inflammatory senescence-associated secretory phenotype (SASP), significantly contributes to age-related pathology and infection severity. Additionally, mitochondrial dysfunction exacerbates clinical outcomes in aging and obesity-related conditions, particularly COVID-19 and its prolonged effects (long COVID), underlining mitochondrial health as a possible therapeutic target. Collectively, the studies underscore senescence markers' variability, metabolic immunological shifts in aging, and long-lasting cellular responses following oxidative stress and infections, enhancing our understanding of aging mechanisms and potential therapeutic pathways for age-related vulnerabilities.

Context and Scope

Aging is a significant and progressive physiological process that starts as soon as a child is born. Scientific evidence shows that aging and cellular senescence are intertwined phenomena. There is also a reciprocal relationship between immune cells and aging, i.e. senescent immune cells are potent producers of Senescene-Associated-Secretory-Phenotype (SASP) and thereby can accelerate cellular senescence in non-immune cells. On the other hand, immunosenescence refers to the alterations of immune cells due to aging which is also affected by the history of antigenic encounters and viral/bacterial infections.

So far, several hundred human senescence genes in the cell cycle, DNA repair system, apoptosis, and metabolic pathways are characterized. Modifications in the transcription profile and epigenetic regulation of these genes induce and regulate the process of cellular senescence. Transcription factors, micro RNAs, long noncoding RNAs (LncRNAs), epigenetic modifications, heterochromatin re-organization, and architecture-associated gene expression are parts of senescence regulome.

Transcriptional deregulation of genes plays a major role in the initiation or progression of many diseases. Deregulation of several genes in the immune cells has been associated with metabolic changes and SASP production during aging and aging-related inflammatory diseases. Transcriptional changes during viral/bacterial infections may accelerate immunosenescence and immunosenescence genes may aggravate infections. Investigation of immunosenescence regulome in physiological and pathological conditions may therefore reveal ways to prevent premature aging in infectious and inflammatory settings.

In this Research Topic, we intend to bring transcriptional regulatory factors of immunosenescence and their related cellular pathways to the spotlight and highlight their potential in drug discovery. Recognizing the transcription factors and their specific cofactors in the senescence of immune cells will provide more specific molecules/pathways to target. Also, even though the broad regulatory function of miRNAs may hamper their direct targeting in drug development, understanding their function in the senescence will pave the way to design other RNA-based therapeutics (such as siRNA) for specific genes. Similarly, the characterization of LncRNAs which affect senescence pathways through chromatin modifications or gene transcriptional and/or post-transcriptional interference would shed some light on the future opportunities in drug development against senescence of the immune system and premature aging.

The aim of the current Research Topic is to collect recent data on the transcriptional regulation of senescence genes of the immune system and unravel the potential molecules for therapeutic targeting. Research articles may include, but are not limited to:

•Senescence genes in the immune cells and their regulation in physiological and pathological conditions

•Transcriptional factors involved in immunosenescence and its related pathways

•LncRNA, miRNAs, and siRNAs in immune cell senescence and/or drug design

•Epigenetic modifications, heterochromatin re-organization, and architecture-associated gene expression in immunosenescence

•Transcriptome, regulome, and epigenome in immune cell senescence in physiological and pathological conditions

The submissions to this research topic can be Original Research articles, Review articles (narrative, systematic, etc.), Perspectives, and methods.

Keywords: Aging, Cellular Senescence, Immunosenescence, Metabolism, Mitochondrial Dysfunction, Senescence-associated Secretory Phenotype (SASP), Oxidative Stress, Immune Response, COVID-19, Chronic Inflammation, Biomarkers, Infectious Diseases, Long COVID, Adaptive Immunity, Senotherapy

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.