Exploring the potential mechanisms underlying SASP-driven Atopic Dermatitis in the elderly comorbid with Alzheimer’s disease via the Immune-Aging Axis

The disease burden of Atopic Dermatitis in the elderly is increasing in tandem with global population aging, and epidemiological studies have revealed a significantly elevated risk of cognitive impairment and Alzheimer’s disease associated with this condition,, posing a serious threat to their quality of life. However, the specific mechanisms by which skin inflammation mediates central nervous system (CNS) neurodegeneration across organs remain unclear. Cellular senescence and immunosenescence may form a positive feedback loop through Senescence-Associated Secretory Phenotype (SASP): senescent cells release SASP that induce chronic low-grade inflammation, while chronic inflammation in turn accelerates cellular senescence and immunosenescence, creating a vicious immune-aging cycle. From the perspective of the Immune-Aging Axis, this study demonstrates that skin-derived SASP drive the comorbidity mechanism of Atopic Dermatitis and Alzheimer’s disease in the elderly through bidirectional skin-brain feedback loops—including disruption of the blood-brain barrier, induction CNS inflammation, and epigenetic remodeling, with the aim of providing theoretical strategies for targeted combined interventions against SASP. 1. Innovative Integration of Theoretical Frameworks: This study innovatively applies the concept of the “Immuno-Aging Axis” to elucidate the context of comorbidity between Atopic Dermatitis and Alzheimer’s disease. 2. In-Depth Mechanistic Elucidation: By synthesizing existing literature, this review explores how SASP may mediate bidirectional interactions between the skin and CNS, providing a molecular bridge for interventions targeting this comorbidity. 3. Translational Clinical Value: This study provides a theoretical basis for targeting SASP to treat the comorbidity of Atopic Dermatitis and Alzheimer’s disease and advances the development of precision treatment strategies for elderly patients with comorbidities.