Reducing signs of aging and increasing lifespan by drug synergy.
Reducing signs of aging and increasing lifespan by drug synergy.
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DOI：
10.1111/acel.12090
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发表时间：
2013-08
期刊：
影响因子：
7.8
通讯作者：
Dickson RC
中科院分区：
文献类型：
--
作者：
Huang X;Liu J;Withers BR;Samide AJ;Leggas M;Dickson RC
疾病发病率随着年龄的增长而迅速上升，增加了人类的痛苦和经济困难，同时缩短了寿命。在了解影响衰老的信号通路和细胞过程方面的进展，支持通过药物干预减少年龄相关疾病的发病率和延长寿命的可能性。在这里，我们展示了一种新的药理学策略，既可以减少出芽酵母酿酒酵母的衰老迹象，又可以协同增加寿命。通过联合使用低剂量的雷帕霉素来降低雷帕霉素复合物1 （TORC1）蛋白激酶靶点的活性，以及豆蔻素来降低鞘脂合成，我们发现自噬、基因组稳定性、线粒体功能和AMP激酶途径活性都得到了增强。这些过程是由进化保守的信号转导途径控制的，这对于维持健康状态和促进长寿至关重要。因此，我们的数据表明，应该有可能找到药理学方法来协同减少人类年龄相关疾病的发病率，以改善老年人的健康质量并延长寿命。
Disease incidence rises rapidly with age and increases both human suffering and economic hardship while shortening life. Advances in understanding the signaling pathways and cellular processes that influence aging, support the possibility of reducing the incidence of age-related diseases and increasing lifespan by pharmacological intervention. Here, we demonstrate a novel pharmacological strategy that both reduces signs of aging in the budding yeast Saccharomyces cerevisiae and generates a synergistic increase in lifespan. By combining a low dose of rapamycin, to reduce activity of the target of rapamycin complex 1 (TORC1) protein kinase, and myriocin, to reduce sphingolipid synthesis, we show enhancement of autophagy, genomic stability, mitochondrial function, and AMP kinase pathway activity. These processes are controlled by evolutionarily conserved signal transduction pathways that are vital for maintaining a healthy state and promoting a long life. Thus, our data show that it ought to be possible to find pharmacological approaches to generate a synergistic reduction in the incidence of human age-related diseases to improve health quality in the elderly and enhance lifespan.
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DOI：
10.1083/jcb.200707154
发表时间：
2008-01-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Madia F;Gattazzo C;Wei M;Fabrizio P;Burhans WC;Weinberger M;Galbani A;Smith JR;Nguyen C;Huey S;Comai L;Longo VD
通讯作者：
Longo VD
影响因子：
7.8
作者：
Alvers AL;Fishwick LK;Wood MS;Hu D;Chung HS;Dunn WA Jr;Aris JP
通讯作者：
Aris JP
影响因子：
29
作者：
Longo VD;Shadel GS;Kaeberlein M;Kennedy B
通讯作者：
Kennedy B
DOI：
10.1126/science.1201940
发表时间：
2011-08-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Green DR;Galluzzi L;Kroemer G
通讯作者：
Kroemer G
影响因子：
9.2
作者：
Casamayor, A;Torrance, PD;Alessi, DR
通讯作者：
Alessi, DR