Ferroptosis and Ferro-Aging in Obesity: Bibliometric Mapping, Shared Mechanisms, and Translational Perspectives.

Background: Obesity is a chronic metabolic disease characterized by lipid overload, low-grade inflammation, oxidative stress, and progressive organ dysfunction. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has been increasingly implicated in obesity-related complications. However, an acute cell death-centered model does not fully explain the chronic senescence-like decline observed in metabolic tissues. The recently proposed concept of ferro-aging provides a potential framework for linking iron-dependent lipid peroxidation to cellular senescence and metabolic aging. Methods: In this review, we combined bibliometric mapping with mechanistic synthesis to characterize the evolving research landscape of ferroptosis in obesity and integrate the emerging concept of ferro-aging into this field. Bibliometric analysis was performed to screen qualified literature, and keyword co-occurrence and co-citation analyses were conducted to extract mainstream research hotspots. We further systematically summarized the pathological microenvironment constructed by obesity and the core molecular mediator connecting ferroptosis and ferro-aging, and proposed a pathological continuum hypothesis for obesity-mediated lipid peroxidation injury. Results: A total of 564 eligible publications were identified, including 455 original articles and 109 reviews, with a marked increase in publication output after 2020. Keyword and co-citation analyses highlighted oxidative stress, lipid peroxidation, iron metabolism, GPX4/Nrf2-mediated antioxidant defense, mitochondrial dysfunction, gut microbiota, NAFLD, and DCM as major research themes. Mechanistically, obesity creates a pro-ferroperoxidative microenvironment through iron dysregulation, polyunsaturated fatty acid enrichment, chronic inflammation, mitochondrial stress, and impaired antioxidant capacity. Within this context, ACSL4 is proposed as a candidate molecular hub that may link acute ferroptotic injury with chronic iron-lipid peroxidation-driven cellular senescence. We proposed a hypothesis-generating framework. In this framework, acute lipid peroxidation may promote ferroptotic cell death. Persistent sublethal iron-lipid peroxidation stress may contribute to ferro-aging-like senescence. Conclusions: To our knowledge, this is the first review to place ferro-aging within the obesity-ferroptosis framework. Targeting the ACSL4-lipid peroxidation axis and restoring antioxidant defense, particularly through Nrf2-GPX4-related pathways, may provide new translational opportunities for stratifying and managing obesity-related complications. However, clinical validation of ferro-aging biomarkers and intervention strategies remains urgently needed.