Across eukaryotes, ribosomal DNA (rDNA) loci are characterized by intrinsic genomic instability due to their repetitive nature and their base composition that facilitate DNA double strand breaks and RNA:DNA hybrids formation. In the yeast, ribosomal DNA instability affects lifespan via the formation of extrachromosomal rDNA circles (ERC) that accrue into aged cells. In humans, rDNA instability has long been reported in a variety of progeric syndromes caused by the dysfunction of DNA helicases, but its role in physiological aging and longevity still needs to be clarified. Here we propose that rDNA instability leads to the activation of innate immunity and inflammation via the interaction with the cytoplasmic DNA sensing machinery. Owing to the recent clarified role of cytoplasmic DNA in the pro-inflammatory phenotype of senescent cells, we hypothesize that the accrual of rDNA derived molecules (i.e. ERC and RNA:DNA hybrids) may have a role in aging by contributing to inflammaging i.e. the systemic pro-inflammatory drift that associates with the onset of geriatric syndromes and age related dysfunctions in humans.

在整个真核生物中，核糖体DNA（rDNA）基因座的特征是固有的基因组不稳定性，这是由于它们的重复性质和促进DNA双链断裂和RNA：DNA杂种形成的碱基组成。在酵母中，核糖体DNA的不稳定性会通过形成老化细胞中的染色体外rDNA环（ERC）来影响寿命。在人类中，长期以来一直有报道说，DNA解旋酶功能障碍导致的各种早衰综合征中，rDNA不稳定，但其在生理衰老和长寿中的作用仍需要弄清。在这里，我们提出rDNA不稳定性通过与细胞质DNA传感机制的相互作用导致先天免疫和炎症的激活。由于最近澄清了胞质DNA在衰老细胞促炎表型中的作用，例如ERC和RNA：DNA杂种）可能通过导致发炎（即与人类老年人衰老和年龄相关的功能障碍有关的全身性促炎性漂移）而在衰老中起作用。