miR-34a and miR-9 are overexpressed and SIRT genes are downregulated in peripheral blood mononuclear cells of aging humans
miR-34a and miR-9 are overexpressed and SIRT genes are downregulated in peripheral blood mononuclear cells of aging humans
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DOI：
10.1177/1535370217720884
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发表时间：
2017-08-01
影响因子：
3.2
通讯作者：
Puzianowska-Kuznicka, Monika
中科院分区：
文献类型：
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作者：
Owczarz, Magdalena;Budzinska, Monika;Puzianowska-Kuznicka, Monika
sirtuins的增加表达降低了与年龄有关的疾病的风险，但它们在调节寿命方面的作用尚未得到确定。由于衰老与免疫衰老相关，我们测试了外周血单核细胞（PBMC）中sirtuin的表达是否以年龄相关的方式改变，以及这是否可能是由所选mirna表达改变引起的。实时荧光定量PCR检测了7个SIRT基因以及SIRT1 mrna相互作用的miR-9、miR-34a、miR-132和miR-199a-5p在年轻（Y, n = 57，平均年龄274.3岁）、老年（E, n = 52, 65 +/- 3.4岁）和长寿（L, n = 56, 94 +/- 3.5岁）PBMC个体中的表达。年龄越大，大多数SIRT基因的表达就越低。受影响最严重的是SIRT1的中位表达（整个研究组P = 0.000001， Y比E: P < 0.000001， Y比L: P < 0.000001）和SIRT3 （P = 0.000001， Y比E: P = 0.000004， Y比L: P = 0.000028）。年龄的增长也与miR-34a （P = 0.000001, Y vs. E: P = 0.001, Y vs. L: P = 0.000004）和miR-9 （P = 0.05, Y vs. L: P = 0.054）的中位表达增加有关。在功能研究中，miR-9与SIRT1 mRNA的3UTR相互作用。SIRT1 mRNA水平与miR-34a表达呈负相关（r = -0.234, P = 0.003）。总之，PBMC中与年龄相关的SIRT1表达下降可能部分是由于miR-34a和miR-9的过表达。此外，PBMC中SIRT基因的持续表达并不是人类长寿的先决条件，但可能是老年人免疫系统功能障碍的原因之一。
Increased expression of sirtuins lowers the risk of age-related diseases, while their role in the regulation of longevity is not firmly established. Since aging is associated with immunosenescence, we tested whether sirtuin expression was modified in peripheral blood mononuclear cells (PBMC) in an age-related manner and whether this might result from altered expression of the selected miRNAs. The expression of seven SIRT genes and of SIRT1 mRNA-interacting miR-9, miR-34a, miR-132, and miR-199a-5p was evaluated by real-time PCR in PBMC originating from young (Y, n = 57, mean age 274.3 years), elderly (E, n = 52, 65 +/- 3.4 years), and long-lived (L, n = 56, 94 +/- 3.5 years) individuals. Older age was associated with a decreased expression of the majority of the SIRT genes. Most severely affected were median expressions of SIRT1 (P = 0.000001 for the whole studied group, Y vs. E: P < 0.000001, Y vs. L: P < 0.000001), and of SIRT3 (P = 0.000001, Y vs. E: P = 0.000004, Y vs. L: P = 0.000028). Older age was also associated with the increased median expression of miR-34a (P = 0.000001, Y vs. E: P = 0.001, Y vs. L: P = 0.000004) and of miR-9 (P = 0.05, Y vs. L: P = 0.054). In functional studies, miR-9 interacted with the 3UTR of SIRT1 mRNA. The SIRT1 mRNA level negatively correlated with the expression of miR-34a (r = -0.234, P = 0.003). In conclusion, age-related decrease of SIRT1 expression in PBMC might in part result from overexpression of miR-34a and miR-9. In addition, the sustained expression of the SIRT genes in PBMC is not a prerequisite to longevity in humans but might be one of the reasons for the immune system dysfunction in the elderly.