Persons with Down syndrome (DS) undergo a premature ageing with early onset of age-related diseases. The main endpoint of this study was the identification of blood circulating microRNAs (c-miRs) signatures characterizing DS ageing process. A discovery phase based on array was performed in plasma samples obtained from 3 young (31 ± 2 years-old) and 3 elderly DS persons (66 ± 2 years-old). Then, a validation phase was carried out for relevant miRs by RT-qPCR in an enlarged cohort of 43 DS individuals (from 19 up to 68 years-old). A group of 30 non-trisomic subjects, as representative of physiological ageing, was compared. In particular miR-628–5p, miR-152–3p, miR-28–5p, and let-7d-5p showed a lower level in younger DS persons (age ≤ 50 years) respect to the age-matched controls. Among those, miR-28–5p and let-7d-5p were found significantly decreased in physiological ageing ( oldest group ), thus they emerged as possible biomarkers of premature ageing in DS. Moreover, measuring blood levels of beta amyloid peptides, Aβ-42 was assessed at the lowest levels in physiological ageing and correlated with miR-28–5p and let-7d-5p in DS, while Aβ-40 correlated with miR-628–5p in the same cohort. New perspectives in terms of biomarkers are discussed.

患有唐氏综合症 (DS) 的人会过早衰老并出现与年龄相关的疾病。本研究的主要终点是鉴定表征 DS 衰老过程的血液循环 microRNA (c-miRs) 特征。在从 3 名年轻（​​31 ± 2 岁）和 3 名老年 DS 人（66 ± 2 岁）获得的血浆样本中进行基于阵列的发现阶段。然后，通过 RT-qPCR 在 43 名 DS 个体（从 19 至 68 岁）的扩大队列中对相关 miR 进行验证阶段。比较了一组 30 名非三体受试者，作为生理衰老的代表。特别是 miR-628-5p、miR-152-3p、miR-28-5p 和 let-7d-5p 在较年轻的 DS 人（年龄≤50 岁）中显示出低于年龄匹配对照的水平。在这些，发现 miR-28-5p 和 let-7d-5p 在生理衰老（最老组）中显着降低，因此它们成为 DS 中早衰的可能生物标志物。此外，通过测量血液中 β 淀粉样肽的水平，Aβ-42 在生理衰老中被评估为最低水平，并且与 DS 中的 miR-28-5p 和 let-7d-5p 相关，而 Aβ-40 与 miR-628-5p 相关在同一个队列中。讨论了生物标志物方面的新观点。