| Partial uncoupling of oxidative phosphorylation induces premature senescence in human fibroblasts and yeast mother cells. | |
| | |
MedLine Citation:
|
PMID: 17697939 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The mitochondrial theory of aging predicts that functional alterations in mitochondria leading to reactive oxygen species (ROS) production contribute to the aging process in most if not all species. Using cellular senescence as a model for human aging, we have recently reported partial uncoupling of the respiratory chain in senescent human fibroblasts. In the present communication, we address a potential cause-effect relationship between impaired mitochondrial coupling and premature senescence. Chronic exposure of human fibroblasts to the chemical uncoupler carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) led to a temporary, reversible uncoupling of oxidative phosphorylation. FCCP inhibited cell proliferation in a dose-dependent manner, and a significant proportion of the cells entered premature senescence within 12 days. Unexpectedly, chronic exposure of cells to FCCP led to a significant increase in ROS production, and the inhibitory effect of FCCP on cell proliferation was eliminated by the antioxidant N-acetyl-cysteine. However, antioxidant treatment did not prevent premature senescence, suggesting that a reduction in the level of oxidative phosphorylation contributes to phenotypical changes characteristic of senescent human fibroblasts. To assess whether this mechanism might be conserved in evolution, the influence of mitochondrial uncoupling on replicative life span of yeast cells was also addressed. Similar to our findings in human fibroblasts, partial uncoupling of oxidative phsophorylation in yeast cells led to a substantial decrease in the mother-cell-specific life span and a concomitant incrase in ROS, indicating that life span shortening by mild mitochondrial uncoupling may represent a "public" mechanism of aging. |
| | |
Authors:
|
Petra Stöckl; Christina Zankl; Eveline Hütter; Hermann Unterluggauer; Peter Laun; Gino Heeren; Edith Bogengruber; Dietmar Herndler-Brandstetter; Michael Breitenbach; Pidder Jansen-Dürr |
Related Documents
:
|
11857449 - Termination of lifespan of sv40-transformed human fibroblasts in crisis is due to apopt... 12496279 - Evidence that high telomerase activity may induce a senescent-like growth arrest in hum... 2632279 - The relationship between cell size, the activity of dna polymerase alpha and proliferat... 8300279 - Are somatic cells inherently deficient in methylation metabolism? a proposed mechanism ... 10787419 - Telomere shortening is proportional to the size of the g-rich telomeric 3'-overhang. 12100489 - Molecular regulation of melanocyte senescence. 1311629 - Insulin like growth factor i is an autocrine regulator of human colon cancer cell diffe... 11401689 - Pathogenicity island-dependent activation of rho gtpases rac1 and cdc42 in helicobacter... 18420049 - Label-free cell-based assay using localized surface plasmon resonance biosensor. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-06-13 |
Journal Detail:
|
Title: Free radical biology & medicine Volume: 43 ISSN: 0891-5849 ISO Abbreviation: Free Radic. Biol. Med. Publication Date: 2007 Sep |
Date Detail:
|
Created Date: 2007-08-16 Completed Date: 2007-10-31 Revised Date: 2011-04-06 |
Medline Journal Info:
|
Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: United States |
Other Details:
|
Languages: eng Pagination: 947-58 Citation Subset: IM |
Affiliation:
|
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, A-6020 Innsbruck, Austria. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acetylcysteine
/
metabolism Aging, Premature / chemically induced, etiology*, metabolism Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / pharmacology Cell Aging* Cell Proliferation Cell Respiration Cells, Cultured Fibroblasts / drug effects, metabolism Humans Oxidative Phosphorylation* / drug effects Reactive Oxygen Species / metabolism Saccharomyces cerevisiae / drug effects, metabolism Uncoupling Agents / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
|
S 9302-B18//Austrian Science Fund FWF |
| Chemical | |
Reg. No./Substance:
|
0/Reactive Oxygen Species; 0/Uncoupling Agents; 370-86-5/Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; 616-91-1/Acetylcysteine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Dietary antioxidants as inhibitors of the heme-induced peroxidation of linoleic acid: mechanism of a...
Next Document: Cellular prion protein protects against reactive-oxygen-species-induced DNA damage.