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肉碱促进. 从氧化应激中恢复并延长寿命。

Carnitine promotes recovery from oxidative stress and extends lifespan in .

机构信息

Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.

Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410008, China.

出版信息

Aging (Albany NY). 2020 Dec 3;13(1):813-830. doi: 10.18632/aging.202187.

Abstract

Carnitine is required for transporting fatty acids into the mitochondria for β-oxidation. Carnitine has been used as an energy supplement but the roles in improving health and delaying aging remain unclear. Here we show in that L-carnitine improves recovery from oxidative stress and extends lifespan. L-carnitine promotes recovery from oxidative stress induced by paraquat or juglone and improves mobility and survival in response to HO and human amyloid (Aβ) toxicity. L-carnitine also alleviates the oxidative stress during aging, resulting in moderate but significant lifespan extension, which was dependent on SKN-1 and DAF-16. Long-lived worms with germline loss () or reduced insulin receptor activity ( recover from aging-associated oxidative stress faster than wild-type controls and their long lifespans were not further increased by L-carnitine. A new gene, T08B1.1, aligned to a known carnitine transporter OCTN1 in humans, is required for L-carnitine uptake in . T08B1.1 expression is elevated in and mutants and its knockdown prevents L-carnitine from improving oxidative stress recovery and prolonging lifespan. Together, our study suggests an important role of L-carnitine in oxidative stress recovery that might be important for healthy aging in humans.

摘要

肉碱是将脂肪酸转运到线粒体进行β氧化所必需的。肉碱已被用作能量补充剂,但它在改善健康和延缓衰老方面的作用仍不清楚。在这里,我们表明 L-肉碱可改善氧化应激后的恢复并延长寿命。L-肉碱可促进百草枯或胡桃醌诱导的氧化应激后的恢复,并提高对 HO 和人淀粉样蛋白(Aβ)毒性的迁移率和存活率。L-肉碱还可减轻衰老过程中的氧化应激,从而适度但显著地延长寿命,这依赖于 SKN-1 和 DAF-16。生殖系缺失()或胰岛素受体活性降低()的长寿线虫比野生型对照更快地从与衰老相关的氧化应激中恢复,并且它们的长寿命不会因 L-肉碱而进一步延长。一个新的基因,T08B1.1,与人的已知肉碱转运蛋白 OCTN1 对齐,是在 中摄取 L-肉碱所必需的。T08B1.1 的表达在 和 突变体中升高,其敲低可阻止 L-肉碱改善氧化应激恢复和延长寿命。总之,我们的研究表明 L-肉碱在氧化应激恢复中起着重要作用,这可能对人类的健康衰老很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/115c/7835055/f3e9c61b3f9a/aging-13-202187-g001.jpg

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