Credit: Courtesy of Thomas von Zglinicki and PLoS Biology The paper: J. F. Passos et al., "Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence," PLoS Biology, 5:1138, 2007. (Cited in 31 papers) The study: To investigate why cells senesce at different rates, Thomas von Zglinicki of" /> Credit: Courtesy of Thomas von Zglinicki and PLoS Biology The paper: J. F. Passos et al., "Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence," PLoS Biology, 5:1138, 2007. (Cited in 31 papers) The study: To investigate why cells senesce at different rates, Thomas von Zglinicki of" />
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Energetic senescence

Credit: Courtesy of Thomas von Zglinicki and PLoS Biology" /> Credit: Courtesy of Thomas von Zglinicki and PLoS Biology The paper: J. F. Passos et al., "Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence," PLoS Biology, 5:1138, 2007. (Cited in 31 papers) The study: To investigate why cells senesce at different rates, Thomas von Zglinicki of

By | January 1, 2009

<figcaption> Credit: Courtesy of Thomas von Zglinicki and PLoS Biology</figcaption>
Credit: Courtesy of Thomas von Zglinicki and PLoS Biology

The paper:

J. F. Passos et al., "Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence," PLoS Biology, 5:1138, 2007. (Cited in 31 papers)

The study:

To investigate why cells senesce at different rates, Thomas von Zglinicki of the University of Newcastle and colleagues examined mitochondrial dysfunction in cultured fibroblasts. They found that reactive oxygen species (ROS) were produced by mitochondria in senescent cells. This ROS boost caused telomere shortening, a hallmark of cellular senescence; conversely, reducing ROS production delayed the cells' senescence.

The impact:

Von Zglinicki's "was one of the first labs to show the effects of oxidative stress on telomere length," says Gordon Lithgow of the Buck Institute for Age Research in Novato, Calif. This was thought to be a cell-autonomous mechanism, but this paper "adds another dimension to what might drive telomere shortening," says Judy Campisi, also of the Buck Institute, by showing that "that ROS can also come from within the cell."

The debate:

"There's a big controversy about how significant loss of telomere length is in aging phenotypes," says Lithgow. By suggesting that telomere shortening "is a random mechanism that reacts to the environment," Von Zglinicki says his findings argue against the idea that the process is a molecular clock controlling aging.

The future:

Can senescence be postponed by reducing ROS production? "There is a very elaborate interaction going both ways," Von Zglinicki says. Meanwhile, notes Lithgow, others have gone on to pinpoint surprising interactions between metabolic signaling and senescence in diseases such as Parkinson's and cancer.

Telomere shortening rate (per population doubling)
Normal mitochondrial ROS production 80 +/- 14 base pairs
Halved mitochondrial ROS production (by treatment with 2,4-Dinitrophenol) 9 +/- 29 base pairs
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Posts: 16

January 5, 2009

DNP, the uncouplor of mitochondial ox-phos used in this experiment, was once extensively used as a weight-reduction drug in humans. By report, it was pretty effective too. The main side-effect seems to have been hyperthermia. However, DNP was forced off the market due to an alleged association with cataracts, never really verified. \n\nMore recently, DNP has been shown to protect in brain injury secondary to experimental acute ischemic stroke. It may be time to revaluate this old agent.

January 13, 2009

Am I missing something? Isn't this a possible mechanism by which antioxidants produce their reported effects on chronic disease? More antioxidants - fewer ROS?

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