Reducing signs of aging and increasing lifespan by drug synergy

Aging Cell

Xinhe Huang²  Jun Liu²  Bradley R. Withers²  Aaron J. Samide²  Markos Leggas¹ 

[1] Department of Pharmaceutical Sciences and the Lucille Markey Cancer Center, College of Pharmacy, University of Kentucky, Lexington, KY, USA;Department of Molecular and Cellular Biochemistry and the Lucille Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY, USA

关键词: aging;    autophagy;    genomic stability;    longevity;    S6 Kinase;    TORC1;   

DOI  :  10.1111/acel.12090

来源: Wiley

【 摘 要 】

Summary

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.

【 授权许可】

Unknown   
© 2013 John Wiley & Sons Ltd and the Anatomical Society