PANoptosis in the Aging of the Heart
As the understanding of more recently discovered modes of programmed cell death are fleshed out, they receive greater attention from various groups focused on specific aspects of aging. In this review the programmed cell death mechanism is PANoptosis and the area of focus is the aging of the heart. Some means of preventing overly aggressive, maladaptive programmed cell death in the context of aging have performed fairly well in animal studies, but the details matter and progress towards useful therapies is ever slow and uncertain.
As the vital power organ of the human body, the health of the heart directly determines an individual's quality of life and longevity. With the accelerating global aging population, cardiac aging-related diseases have become a major public health threat. Although existing interventions (e.g., senolytics) can delay cardiac aging to some extent, their efficacy remains limited, necessitating the exploration of novel mechanisms to develop more effective therapeutic strategies.
lytic cell death modality, integrates core molecular mechanisms of pyroptosis, apoptosis, and necroptosis into a dynamically regulated "death signaling network". As a unique programmed cell death paradigm, it transcends classical boundaries of these pathways by forming the PANoptosome complex, which orchestrates caspase family members. It may contribute to cardiac functional decline by accelerating cardiomyocyte loss, fibrosis, and chronic inflammation. Targeting PANoptosis-based intervention strategies (e.g., gene editing, RNAi, combination therapy, and novel delivery systems) has demonstrated significant therapeutic potential, offering new preclinical avenues to delay or alleviate cardiac aging. This review summarizes the molecular mechanisms and roles of PANoptosis in cardiac aging, including its regulatory networks, key evidence driving cardiac aging, and targeted intervention strategies, thereby providing a theoretical foundation for developing PANoptosis-targeted therapies against cardiac aging.