title: Cystathionine beta synthase modulates senescence of human endothelial cells.
abstract: Availability of methionine is known to modulate the rate of aging in model organisms, best illustrated by the observation that dietary methionine restriction extends the lifespan of rodents. However, the underlying mechanisms are incompletely understood. In eukaryotic cells, methionine can be converted to cysteine through the reverse transsulfuration pathway thereby modulating intracellular methionine availability. Whereas previous results obtained in yeast and fruit flies suggest that alterations in the reverse transsulfuration pathway modulate the rate of aging, it is not known whether this function is conserved in evolution. Here we show that depletion of cystathionine beta synthase (CBS), a rate limiting enzyme in the reverse transsulfuration pathway, induces premature senescence in human endothelial cells. We found that CBS depletion induces mild mitochondrial dysfunction and increases the sensitivity of endothelial cells to homocysteine, a known inducer of endothelial cell senescence and an established risk factor for vascular disease. Our finding that CBS deficiency induces endothelial cell senescencein vitro, involving both mitochondrial dysfunction and increased susceptibility of the cells to homocysteine, suggests a new mechanism linking CBS deficiency to vascular aging and disease.
authors.affiliation: Institute for Biomedical Aging Research (IBA), University of Innsbruck, Innsbruck, Austria.
authors.forename: Eva
authors.initials: E
authors.lastname: Albertini
authors.forename: Rafal
authors.initials: R
authors.lastname: Kozieł
authors.forename: Angela
authors.initials: A
authors.lastname: Dürr
authors.forename: Michael
authors.initials: M
authors.lastname: Neuhaus
authors.forename: Pidder
authors.initials: P
authors.lastname: Jansen-Dürr
mesh_terms: D000375:Aging / Q000378:metabolism; D016922:Cellular Senescence; D003541:Cystathionine beta-Synthase / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000201:enzymology*; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans
chemical_list: D003541:Cystathionine beta-Synthase