ausblenden:
Schlagwörter:
Adenosine Triphosphatases/genetics/metabolism
Adolescent
Adult
Amino Acid Sequence
Animals
Caenorhabditis elegans/genetics/*metabolism
Caenorhabditis elegans Proteins/genetics/*metabolism
Carrier Proteins/genetics/metabolism
Cell Cycle Proteins/genetics/*metabolism
Cells, Cultured
Chromatin Assembly and Disassembly
Epistasis, Genetic
Fibroblasts/metabolism/radiography
Humans
*Longevity
Mice, Inbred C57BL
Mice, Inbred CBA
Molecular Sequence Data
Oxidative Stress
RNA Interference
Signal Transduction
Time Factors
Transfection
Ultraviolet Rays
Young Adult
Zusammenfassung:
Components or downstream targets of many signaling pathways such as Insulin/IGF-1 and TOR, as well as genes involved in cellular metabolism and bioenergetics can extend worm lifespan 20% or more. The C. elegans gene pch-2 and its homologs, including TRIP13 in humans, have been studied for their functions in cell mitosis and meiosis, but have never been implicated in lifespan regulation. Here we show that over-expression of TRIP13 in human fibroblasts confers resistance to environmental stressors such as UV radiation and oxidative stress. Furthermore, pch-2 overexpression in C. elegans extends worm lifespan, and enhances worm survival in response to various stressors. Conversely, reducing pch-2 expression with RNAi shortens worm lifespan. Additional genetic epistasis analysis indicates that the molecular mechanism of pch-2 in worm longevity is tied to functions of the sirtuin family, implying that pch-2 is another chromatin regulator for worm longevity. These findings suggest a novel function of the pch-2 gene involved in lifespan determination.
