<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,...

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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