Fanconi anaemia as a human model of accelerated epigenetic and immune ageing
Year: 2026
Type: review
Abstract: Fanconi anaemia (FA) is a DNA-repair disorder that compresses multiple hallmarks of ageing into childhood and early adulthood. Persistent genomic instability in FA precipitates oxidative stress, inflammatory remodelling, and metabolic reprogramming, which together erode epigenetic integrity and immune competence. Here we provide evidence FA-specific DNA-repair failure is linked to mitochondrial metabolism, nutrient-sensing networks, and immune dysfunction. In this context, we discuss how these interactions accelerate epigenetic drift and cancer susceptibility. We propose FA as a human “time-lapse” model to separate the sequence and interdependence of selected ageing hallmarks, such as genome instability, epigenetic deregulation, stem cell exhaustion, and immunosenescence, which together contribute to a markedly increased risk of early cancer development. We further highlight nutrigenomic mechanisms, including vitamin D-dependent chromatin remodelling and redox-sensitive cofactors, that modulate epigenetic states and immune resilience. Framing FA within the broader framework of ageing biology suggests testable biomarkers and precision-prevention strategies aimed at stabilising the epigenome, delaying carcinogenesis, and prolonging healthspan. • Compression of ageing hallmarks like genome instability, epigenetic drift and immunosenescence into early life. • Persistent DNA damage couples to metabolic/mitochondrial stress to reshape the epigenome and immune function. • Nutrient-sensing and redox-dependent cofactors (e.g., NAD⁺, α-ketoglutarate, vitamin D) modulate chromatin resilience. • Providing a “time-lapse” human model to benchmark biological-age biomarkers and test preventive strategies. • Extending conceptual and translational implications to therapy-induced ageing and population cancer risk.
Source: Ageing Research Reviews
Authors: Eunike Velleuer, Carsten Carlberg
Language: English
Subfield: Aging
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,520
Awards: G3359662964, Entwicklungsdynamik von Leukoplakien bei Patienten mit FanconiAnämie, G5145678602, Welcoming ERA Chair to Centre of excellence in nutrigenomics for optimising health and well-being in the Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, G578409985, G854206033
OpenAlex ID: W7126086524