Aging is a complex and multifactorial process influenced by both intrinsic and extrinsic factors at the cellular, tissue, and systemic levels. Two fundamental hallmarks of aging—cellular senescence and alterations in the immune microenvironment—have emerged as deeply interconnected processes that impact healthspan, increase vulnerability to disease, and drive age-associated pathologies.

Cellular senescence is characterized by an irreversible growth arrest in response to cellular damage or stress. Over time, senescent cells accumulate in various tissues and secrete a diverse array of pro-inflammatory cytokines, chemokines, proteases, and growth factors, collectively known as the senescence-associated secretory phenotype (SASP). These factors not only contribute to tissue dysfunction and chronic inflammation but also profoundly modulate the surrounding immune landscape.

The aging immune microenvironment undergoes substantial remodeling, often marked by declines in immune cell function, shifts in immune cell populations, and heightened chronic inflammation ("inflammaging"). Interactions between senescent cells and immune cells create feedback loops that can exacerbate tissue dysfunction, impair immune surveillance, and create a permissive environment for age-associated diseases, including cancer, metabolic disease, and neurodegeneration.

Despite significant advances, key questions remain regarding the precise molecular and cellular mechanisms underpinning these interactions, the tissue specificity of these processes, and the identification of new therapeutic targets to improve health outcomes in the elderly. State-of-the-art OMICS and single-cell technologies, as well as emerging senolytic and immunomodulatory strategies, are enabling unprecedented insights into this dynamic crosstalk.

This Research Topic aims to advance our understanding of how cellular senescence and immune microenvironmental changes co-contribute to aging and age-related diseases. We welcome studies on mechanistic insights into the bidirectional interactions between senescent cells and immune cells, the role of SASP factors in remodeling the immune microenvironment, the impact of immune dysfunction on the clearance of senescent cells, applications of OMICS technologies to dissect the senescence–immunity axis, tissue- and systemic-level consequences, contributions to inflammaging and disease susceptibility, therapeutic interventions targeting either senescent or immune cells, and translational or clinical perspectives on improving healthspan by addressing the crosstalk between senescence and immunity.

By gathering original research, reviews, and perspectives on this topic, we hope to foster a comprehensive understanding of this interconnectedness and promote novel therapeutic strategies for healthy aging

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The Interconnected Roles of Cellular Senescence and Immune Microenvironmental Changes in Aging