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当抗衰老研究遇上癌症化学预防:抗衰老剂能否一举两得?

When Anti-Aging Studies Meet Cancer Chemoprevention: Can Anti-Aging Agent Kill Two Birds with One Blow?

作者信息

Yokoyama Noriko N, Denmon Andria, Uchio Edward M, Jordan Mark, Mercola Dan, Zi Xiaolin

机构信息

Department of Urology, University of California, Irvine, Orange, CA 92868, USA.

Department of Pathology and Laboratory Medicine, University of California, Irvine, Orange, CA 92868, USA.

出版信息

Curr Pharmacol Rep. 2015 Dec 1;1(6):420-433. doi: 10.1007/s40495-015-0039-5. Epub 2015 Apr 14.

Abstract

Recent evidence has strongly supported that the rate of aging is controlled, at least to some extent, by evolutionarily conserved nutrient sensing pathways (e.g. the insulin/IGF-1-signaling, mTOR, AMPK, and sirtuins) from worms to humans. These pathways are also commonly involved in carcinogenesis and cancer metabolism. Agents (e.g. metformin, resveratrol, and Rhodiola) that target these nutrient sensing pathways often have both anti-aging and anti-cancer efficacy. These agents not only reprogram energy metabolism of malignant cells, but also target normal postmitotic cells by suppressing their conversion into senescent cells, which confers systematic metabolism benefits. These agents are fundamentally different from chemotherapy (e.g. paclitaxel and doxorubicin) or radiation therapy that causes molecular damage (e.g. DNA and protein damages) and thereby no selection resistance may be expected. By reviewing molecular mechanisms of action, epidemiological evidence, experimental data in tumor models, and early clinical study results, this review provides information supporting the promising use of agents with both anti-aging and anti-cancer efficacy for cancer chemoprevention.

摘要

最近的证据有力地支持了衰老速率至少在一定程度上是由从蠕虫到人类进化上保守的营养感知通路(如胰岛素/胰岛素样生长因子-1信号通路、mTOR、AMPK和沉默调节蛋白)所控制的。这些通路也通常参与致癌作用和癌症代谢。靶向这些营养感知通路的药物(如二甲双胍、白藜芦醇和红景天)往往具有抗衰老和抗癌功效。这些药物不仅能重新编程恶性细胞的能量代谢,还能通过抑制正常的有丝分裂后细胞转化为衰老细胞来靶向这些细胞,从而带来系统性的代谢益处。这些药物与导致分子损伤(如DNA和蛋白质损伤)的化疗药物(如紫杉醇和阿霉素)或放射治疗有着根本的不同,因此预计不会产生选择抗性。通过综述作用的分子机制、流行病学证据、肿瘤模型中的实验数据以及早期临床研究结果,本综述提供了支持具有抗衰老和抗癌功效的药物有望用于癌症化学预防的信息。

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