The Tight Bond Between Fanconi Anemia and Aging

Marco Antonio Mejía-Barrera¹Enya Enara Martínez-Torres¹Ulises Juárez¹Leda Torres²Moisés Ó Fiesco-Roa³Benilde García de Teresa³Juan Carlos Gómez-Verjan⁴Jorge Melendez-Zajgla⁵Alfredo Rodríguez⁶Silvia Sánchez³Bertha Molina¹Sara Frias^7*

• ¹Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Instituto Nacional de Pediatría, Laboratorio de Citogenética, Mexico City, Mexico
• ²Laboratorio de Citogenética., Instituto Nacional de Pediatria, Mexico City, Mexico
• ³Instituto Nacional de Pediatría, Laboratorio de Citogenética, Mexico City, Mexico
• ⁴Dirección de Investigación, Instituto Nacional de Geriatria, Mexico City, Mexico
• ⁵Laboratorio de Genómica Funcional del Cáncer, Instituto Nacional de Medicina Genomica, Mexico City, Mexico
• ⁶Laboratorio de Falla Medular, Instituto Nacional de Pediatría, Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
• ⁷Laboratorio de Citogenética, Instituto Nacional de Pediatría, Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico

Fanconi anemia (FA) is a rare genetic disorder characterized by genomic instability, bone marrow failure, physical abnormalities, and increased cancer susceptibility. Growing evidence suggests that FA may represent a progeroid syndrome, displaying features of accelerated aging at the cellular and molecular levels. This review examines the cellular and molecular characteristics of FA in the context of the established hallmarks of aging, supporting the hypothesis that FA constitutes a premature aging disorder. The hallmarks of aging, classified as primary, antagonistic, and integrative, are highly interconnected and mutually influential. FA cells exhibit primary hallmarks such as genomic instability, telomere attrition, epigenetic alterations, and dysregulated autophagy. Antagonistic hallmarks, including cellular senescence, mitochondrial dysfunction, and altered nutrient sensing, are also evident. Integrative hallmarks, such as stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis, arise as downstream consequences of the accumulated primary and antagonistic damage. The presence of these hallmarks, together with the early onset of clinical manifestations such as bone marrow failure, cancer, and premature menopause, strongly supports the notion that FA involves accelerated aging. Although patients with FA lacks the overt physical features typical of other progeroid syndromes, its clinical, cellular, and molecular abnormalities demonstrate a strong association with age-related decline, making FA a valuable model of premature aging. Despite limited experimental evidence directly demonstrating accelerated aging, this review highlights the molecular mechanisms linking FA and aging and identifies understudied areas that warrant further investigation.