JNK signaling confers tolerance to oxidative stress and extends lifespan in Drosophila.
Changes in the genetic makeup of an organism can extend lifespan significantly if they promote tolerance to environmental insults and thus prevent the general deterioration of cellular function that is associated with aging. Here, we introduce the Jun N-terminal kinase (JNK) signaling pathway as a genetic determinant of aging in Drosophila melanogaster. Based on expression profiling experiments, we demonstrate that JNK functions at the center of a signal transduction network that coordinates the induction of protective genes in response to oxidative challenge. JNK signaling activity thus alleviates the toxic effects of reactive oxygen species (ROS). In addition, we show that flies with mutations that augment JNK signaling accumulate less oxidative damage and live dramatically longer than wild-type flies. Our work thus identifies the evolutionarily conserved JNK signaling pathway as a major genetic factor in the control of longevity.
Wang
Meng C
MC
Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Box 633, Rochester, NY 14642, USA.
Bohmann
Dirk
D
Jasper
Heinrich
H
D000375:Aging / Q000502:physiology*; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D048031:JNK Mitogen-Activated Protein Kinases; D008017:Life Expectancy; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018384:Oxidative Stress; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D019076:Transgenes
D029721:Drosophila Proteins; D017382:Reactive Oxygen Species; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C110854:puc protein, Drosophila; D010749:Phosphoprotein Phosphatases