AP2A1 AS A NOVEL REGULATOR OF CELLULAR AGING: ROLE IN ADHESION, CYTOSKELETAL REMODELING, AND PROSPECTS FOR CELL REJUVENATION

Relevance. Cellular aging is a major contributor to age-related diseases, and understanding its mechanisms opens avenues for anti-aging strategies.

The aim of this review is to systematically analyze the literature data on the role of the AP2A1 protein in the processes of cellular aging and rejuvenation.

Results. Recent studies have identified AP2A1 (Adaptor Protein 2 Alpha 1 subunit), previously known for its role in endocytosis, as a crucial regulator of the senescent cell phenotype. In aged cells, AP2A1 localizes along actin stress fibers, interacts with integrin β1, and promotes strong adhesion to the extracellular matrix. These changes allow senescent cells to maintain their enlarged size and sustain cell cycle arrest. Experimental data show that AP2A1 knockdown leads to partial rejuvenation, characterized by reduced cell size, decreased senescence markers (p53, p21, SA-β-gal), and weakened adhesion. Conversely, AP2A1 overexpression in young cells accelerates senescence. These findings suggest that AP2A1 is not merely a biomarker of aging but an active regulator of cellular state. Targeting AP2A1 could offer a novel anti-aging therapeutic approach, aiming to modify senescent cell adhesion properties, mitigate their impact on tissues, and potentially induce partial rejuvenation.

Conclusion: This review provides a systematic analysis of AP2A1’s role in cellular aging, its link to integrin pathways, and the therapeutic potential of its modulation in biomedicine.

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