Open AccessReducing signs of aging and increasing lifespan by drug synergy
Author(s) -
Huang Xinhe,
Liu Jun,
Withers Bradley R.,
Samide Aaron J.,
Leggas Markos,
Dickson Robert C.
Publication year - 2013
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12090
Subject(s) - biology , autophagy , signal transduction , longevity , saccharomyces cerevisiae , disease , kinase , drug discovery , senescence , bioinformatics , microbiology and biotechnology , yeast , genetics , medicine , apoptosis
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 S accharomyces 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 ( TORC 1) 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.