Anti-aging and anti-oxidant activities of murine short interspersed nuclear element antisense RNA.
Anti-aging and anti-oxidant activities of murine short interspersed nuclear element antisense RNA.
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DOI：
10.1016/j.ejphar.2021.174577
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发表时间：
2021-10
影响因子：
5
通讯作者：
Zhi-gang Song;S. Shah;Baixue Lv;N. Ji;Xin Liu;Lifang Yan;Murad Khan;Yufang Zhao;Pei-Chen Wu;Shufeng Liu;Longpo Zheng;Libo Su;Xiufang Wang;Z. Lv
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作者：
Zhi-gang Song;S. Shah;Baixue Lv;N. Ji;Xin Liu;Lifang Yan;Murad Khan;Yufang Zhao;Pei-Chen Wu;Shufeng Liu;Longpo Zheng;Libo Su;Xiufang Wang;Z. Lv
短散布核元件（西内斯）在调节基因表达中起关键作用，SINE RNA参与年龄相关疾病。本研究观察了基因工程鼠SINE B1反义RNA（B1 as RNA）对自然衰老BALB/c（≥14月龄）和中度衰老C57 BL/6 N（≥9月龄）小鼠的抗衰老作用，并探讨了其作用机制。尾静脉注射后，B1 as RNA在小鼠血液中可持续约30分钟，在大多数检测到的组织中持续约2-4小时，在肺中持续约48小时。我们发现，B1 as RNA治疗改善了老年小鼠的耐力，促进了毛发的再生。用B1 as RNA治疗也部分挽救了在老年和中度衰老小鼠中观察到的肝和脾组织中线粒体DNA拷贝数的增加。最后，B1 as RNA治疗增加了老年和中度衰老小鼠的超氧化物歧化酶和谷胱甘肽过氧化物酶的活性，降低了这些动物的丙二醛和活性氧水平，并调节了几个衰老相关基因的表达，包括Sirtuin 1，p21，p16 Ink 4a，p15 Ink 4 band p19 Arf和抗氧化基因（Sesn 1和Sesn 2）。这些数据表明，B1 as RNA通过增强抗氧化活性，促进自由基的清除，以及调节衰老相关基因的表达来抑制衰老过程。这是首次报道SINE反义RNA的抗衰老活性，它可能作为一种有效的核酸药物用于治疗与年龄相关的疾病。
Short interspersed nuclear elements (SINEs) play a key role in regulating gene expression, and SINE RNAs are involved in age-related diseases. We investigated the anti-aging effects of a genetically engineered murine SINE B1 antisense RNA (B1as RNA) and explored its mechanism of action in naturally senescent BALB/c (≥14 months) and moderately senscent C57BL/6N (≥9 months) mice. After tail vein injection, B1as RNA was available in the blood of mice for approximately 30 min, persisted for approximately 2–4 h in most detected tissues and persisted approximately 48 h in lungs. We found that treatment with B1as RNA improved stamina and promoted hair re-growth in aged mice. Treatment with B1as RNA also partially rescued the increase in mitochondrial DNA copy number in liver and spleen tissues observed in aged and moderately senescent mice. Finally, treatment with B1as RNA increased the activities of superoxide dismutase and glutathione peroxidase in aged and moderately senescent mice, reduced these animals’ malondialdehyde and reactive oxygen species levels, and modulated the expression of several aging-associated genes, including Sirtuin 1, p21, p16Ink4a, p15Ink4band p19Arf, and anti-oxidant genes (Sesn1 and Sesn 2). These data suggest that B1as RNA inhibits the aging process by enhancing antioxidant activity, promoting the scavenging of free radicals, and modulating the expression of aging-associated genes. This is the first report describing the anti-aging activity of SINE antisense RNA, which may serve as an effective nucleic acid drug for the treatment of age-related diseases.