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.

journal_name

Aging (Albany NY)

journal_title

Aging

authors

Albertini E,Kozieł R,Dürr A,Neuhaus M,Jansen-Dürr P

doi

10.18632/aging.100491

subject

Has Abstract

pub_date

2012-10-01 00:00:00

pages

664-73

issue

10

issn

1945-4589

pii

100491

journal_volume

4

pub_type

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