Alberro Ainhoa, Bravo-Miana Rocío Del Carmen, Gs Iñiguez Saioa, Iribarren-López Andrea, Arroyo-Izaga Marta, Matheu Ander, Muñoz-Culla Maider, Otaegui David
Neuroimmunology Group, Neuroscience Area, Biogipuzkoa Health Research Institute, 20014 San Sebastián, Spain.
Neurodegenerative Diseases Research Area of CIBER (CIBERNED), Carlos III Health Institute (ISCIII), 28029 Madrid, Spain.
Int J Mol Sci. 2024 Nov 29;25(23):12872. doi: 10.3390/ijms252312872.
Small non-coding RNAs (sncRNAs), particularly microRNAs (miRNAs), play an important role in transcriptome regulation by binding to mRNAs and post-transcriptionally inhibiting protein production. This regulation occurs in both physiological and pathological conditions, where the expression of many miRNAs is altered. Previous reports by our group and others have demonstrated that miRNA expression is also altered during aging. However, most studies have analyzed human peripheral blood samples or brain samples from animal models, leaving a gap in knowledge regarding miRNA expression in the human brain. In this work, we analyzed the expression of sncRNAs from coronal sections of human hippocampal samples, a tissue with a high vulnerability to deleterious conditions such as aging. Samples from young (n = 5, 27-49 years old), old (n = 8, 58-88 years old), and centenarian (n = 3, 97, 99, and 100 years old) individuals were included. Our results reveal that sncRNAs, particularly miRNAs, are differentially expressed (DE) in the human hippocampus with aging. Besides, miRNA-mediated regulatory networks revealed significant interactions with mRNAs deregulated in the same hippocampal samples. Surprisingly, 80% of DE mRNA in the centenarian vs. old comparison are regulated by hsa-miR-192-5p and hsa-miR-3135b. Additionally, validated hsa-miR-6826-5p, hsa-let-7b-3p, hsa-miR-7846, and hsa-miR-451a emerged as promising miRNAs that are deregulated with aging and should be further investigated.
小非编码RNA（sncRNAs），特别是微小RNA（miRNAs），通过与mRNA结合并在转录后抑制蛋白质产生，在转录组调控中发挥重要作用。这种调控发生在生理和病理条件下，许多miRNA的表达都会发生改变。我们小组和其他研究小组之前的报告表明，miRNA表达在衰老过程中也会发生改变。然而，大多数研究分析的是人类外周血样本或动物模型的脑样本，在人类大脑中miRNA表达方面存在知识空白。在这项工作中，我们分析了人类海马体样本冠状切片中sncRNAs的表达，海马体是一种对衰老等有害条件高度敏感的组织。纳入了年轻个体（n = 5，27 - 49岁）、老年个体（n = 8，58 - 88岁）和百岁老人个体（n = 3，97、99和100岁）的样本。我们的结果表明，随着衰老，sncRNAs，特别是miRNAs，在人类海马体中差异表达（DE）。此外，miRNA介导的调控网络显示与同一海马体样本中失调的mRNA有显著相互作用。令人惊讶地是，在百岁老人与老年人的比较中，80%的DE mRNA受hsa-miR-192-5p和hsa-miR-3135b调控。此外，经验证的hsa-miR-6826-5p、hsa-let-7b-3p、hsa-miR-7846和hsa-miR-451a成为有前景的miRNAs，它们随着衰老而失调，应进一步研究。
