Polyunsaturated fatty acids ameliorate aging via redox-telomere-antioncogene axis.
Polyunsaturated fatty acids ameliorate aging via redox-telomere-antioncogene axis.
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多不饱和脂肪酸通过氧化还原端粒抗癌基因轴改善衰老
DOI：
10.18632/oncotarget.14236
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发表时间：
2017-01-31
期刊：
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
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作者：
Chen J;Wei Y;Chen X;Jiao J;Zhang Y
多不饱和脂肪酸（PUFA）是一组营养和促进健康的营养素，可改善与年龄相关的慢性疾病。然而，PUFA尤其是n-3 PUFA如何发挥抗衰老作用的研究还不多。在这里，我们联系鱼油，二十二碳六烯酸（DHA）和花生四烯酸（AA）的衰老病因通过氧化还原端粒抗癌基因轴的基础上D-半乳糖诱导的衰老小鼠。鱼油和多不饱和脂肪酸分别使肝脏超氧化物歧化酶（SOD）、过氧化氢酶（CAT）活性和心脏SOD活性提高18%~ 46%、26%~ 65%和19%~ 58%，而使脑单胺氧化酶活性、血浆F2-异前列腺素水平和脑脂质过氧化水平分别降低56%~ 90%、20%~ 79%和16%~ 54%。因此，PUFA改善了体内氧化还原和氧化应激诱导的衰老过程，但不表现出剂量依赖性方式。值得注意的是，PUFA和鱼油都有效地灭活了睾丸端粒酶并抑制了c-Myc介导的端粒酶逆转录酶的表达，而n-3 PUFA而不是n-6 PUFA分别在13%-25%和25%-27%的范围内保护肝脏和睾丸免受端粒缩短。因此，n-3 PUFA可能更好地抑制DNA损伤诱导的衰老过程。令人惊讶的是，只有DHA显着抑制细胞衰老途径证明了睾丸抑癌基因p16和p53的表达。这项工作为PUFA尤其是n-3 PUFA与衰老过程之间的相互作用提供了明显的支持，通过维持体内氧化还原稳态、挽救与年龄相关的端粒磨损和下调抗癌基因表达。
Polyunsaturated fatty acids (PUFA), a group of nourishing and health-promoting nutrients, ameliorate age-related chronic diseases. However, how PUFA especially n-3 PUFA exert anti-aging functions remains poorly understood. Here we link fish oil, docosahexaenoic acid (DHA) and arachidonic acid (AA) to the aging etiology via a redox-telomere-antioncogene axis based on D-galactose-induced aging mice. Both fish oil and PUFA enhanced hepatic superoxide dismutase (SOD) and catalase activities and cardiac SOD activities within the range of 18%-46%, 26%-65% and 19%-58%, respectively, whereas reduced cerebral monoamine oxidase activity, plasma F2-isoprostane level and cerebral lipid peroxidation level by 56%-90%, 20%-79% and 16%-54%, respectively. Thus, PUFA improve the in vivo redox and oxidative stress induced aging process, which however does not exhibit a dose-dependent manner. Notably, both PUFA and fish oil effectively inactivated testicular telomerase and inhibited c-Myc-mediated telomerase reverse transcriptase expression, whereas n-3 PUFA rather than n-6 PUFA protected liver and testes against telomere shortening within the range of 13%-25% and 25%-27%, respectively. Therefore, n-3 PUFA may be better at inhibiting the DNA damage induced aging process. Surprisingly, only DHA significantly suppressed cellular senescence pathway evidenced by testicular antioncogene p16 and p53 expression. This work provides evident support for the crosstalk between PUFA especially n-3 PUFA and the aging process via maintaining the in vivo redox homeostasis, rescuing age-related telomere attrition and down-regulating the antioncogene expression.