Fanconi anaemia as a human model of accelerated epigenetic and immune ageing

IF 15.5 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews Pub Date : 2026-03-01 Epub Date: 2026-01-29 DOI:10.1016/j.arr.2026.103038

Eunike Velleuer , Carsten Carlberg

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引用次数: 0

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.

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范可尼贫血作为加速表观遗传和免疫衰老的人类模型

范可尼贫血（FA）是一种dna修复障碍，它将多种衰老特征压缩到童年和成年早期。FA持续的基因组不稳定沉淀了氧化应激、炎症重塑和代谢重编程，这些因素共同侵蚀表观遗传完整性和免疫能力。在这里，我们提供证据表明，fa特异性dna修复失败与线粒体代谢、营养传感网络和免疫功能障碍有关。在这种情况下，我们讨论这些相互作用如何加速表观遗传漂变和癌症易感性。我们建议将FA作为一种人类“延时”模型，以分离选定的衰老标志的序列和相互依赖性，如基因组不稳定、表观遗传失调、干细胞衰竭和免疫衰老，这些特征共同导致早期癌症发展的风险显著增加。我们进一步强调营养基因组机制，包括维生素d依赖性染色质重塑和氧化还原敏感辅助因子，它们调节表观遗传状态和免疫弹性。在更广泛的衰老生物学框架内构建FA，可以提出可测试的生物标志物和精确预防策略，旨在稳定表观基因组，延缓致癌作用，延长健康寿命。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Ageing Research Reviews 医学-老年医学

CiteScore

19.80

自引率

2.30%

发文量

216

审稿时长

55 days

期刊介绍： With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.