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RESEARCH PAPER / 2025-06-24

Molecular mechanisms of immune cell death in immunosenescence.

Joost Verduijn, Kelly Coutant, Mitchell E Fane, Lorenzo Galluzzi

Cancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, PA, USA.Cancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, PA, USA. · pubmed

Abstract

Along with organismal aging, multiple compartments of the immune system undergo a progressive functional degeneration that may contribute to - or at least allow for - disease, a scenario that is commonly known as "immunosenescence". While not all immune cell populations suffer from organismal aging through similar mechanisms, immunosenescence appears to involve numerical alterations in specific immune cell types that - at least in some settings - result from the unscheduled activation of regulated cell death (RCD), often along with unbalanced hematopoietic output downstream of thymic involution and bone marrow defects. Here, we critically discuss core RCD mechanisms including apoptosis, necroptosis, ferroptosis, pyroptosis and NETosis as key regulators of global immune homeostasis in the context of immunosenescence.

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Research summary

The paper discusses the role of regulated cell death mechanisms in the context of immunosenescence and their impact on immune system degeneration with aging. This research is relevant as it addresses underlying mechanisms of aging that contribute to immune dysfunction, which is a critical aspect of longevity and age-related diseases.

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