4.7 Article

Anti-aging and anti-oxidant activities of murine short interspersed nuclear element antisense RNA

期刊

EUROPEAN JOURNAL OF PHARMACOLOGY
卷 912, 期 -, 页码 -

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ELSEVIER
DOI: 10.1016/j.ejphar.2021.174577

关键词

Genetically engineered murine B1 antisense; RNA; Naturally senescent mice; Anti-aging; Anti-oxidative; Short interspersed nuclear element

资金

  1. National Natural Science Foundation of China [81771499]
  2. Natural Science Foundation of Hebei Province, China [H2018206099]
  3. Construction Program of Scientific Fundamental Conditions, and a Resource Sharing Special Project of the Science and Technology Department of Hebei Province [18964802D]
  4. Youth Fund of National Natural Science Foundation of China [31702076]

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Research shows that SINE antisense RNA inhibits the aging process by enhancing antioxidant activity and modulating the expression of aging-associated genes, demonstrating anti-aging effects.
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 regrowth 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, p15Ink4b and p19Arf, and antioxidant 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 agingassociated 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.

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