Switching On Reactive Oxygen Species To Increase Lifespan

Posted on 16 January 2017

Credit: ZEISS Microscopy

Credit: ZEISS Microscopy

Transient, specific bursts of reactive oxygen species can extend lifespan in C. elegans

To many people it may sound counter-intuitive to use reactive oxygen species (ROS) as a way to increase lifespan. After all, high levels of ROS have been associated with many age-dependent diseases, due to the fact that ROS are highly reactive and can damage proteins and DNA leading to tissue injury.  Surprisingly, however, ROS are normally employed intracellularly as a modulator of signaling pathways and as an intercellular signal.  Cells are filled with antioxidants, such as glutathione, which neutralize the toxic effects of ROS, thereby allowing small amounts of ROS to only act transiently in specific locations.  Now researchers at ETH Zurich, in a collaboration with the FMI Basel and the Joslin Diabetes Center in Boston, have found a new way to manipulate a specific class of proteins that produce ROS locally.

“Tweaking these proteins, the NADPH oxidases (NOX), in the appropriate manner produces transient bursts of ROS that alter intracellular signaling to promote protection and long life of the nematode C. elegans”, explains shared first and co-corresponding author Collin Ewald at ETH Zurich.

Credit: Wikimedia Commons

Credit: Wikimedia Commons

Nancy Hynes from the FMI Basel, the last and co-corresponding author, continued explaining:

“We were originally interested in the role of a protein called Memo1 that functions downstream of the EGF-related family of receptor tyrosine kinases in mammalian cells and is known to be important for metastatic spread of breast tumors. Eleven years ago when we started the work in C.elegans, we asked the simple question of whether or not Memo1 might also function downstream of the C.elegans EGFR homologue. The answer was clearly “no”, but at that point we had no good ideas on how to proceed in the worm work.”

The answer to what Memo1 was doing came through collaborative efforts with John Hourihan and Keith Blackwell at Joslin Diabetes Center and Harvard Medical School. The shared first author John Hourihan explains: “Deciphering the mechanisms by which Memo1 regulates NOX-derived ROS facilitates the observed lifespan extension revealed a key role for the antioxidant factor SKN-1 which I think confirms how C. elegans can act as a lynchpin between Biochemistry and Genetics to further unravel the complex relationships between redox biology and lifespan extension.”  And co-corresponding author Keith Blackwell elaborates further:

“The idea that ROS have physiological functions as signals is a very exciting emerging area that has many implications for normal, disease-related, and aging biology.  We are very excited about understanding these functions and how they can be leveraged in ways that are beneficial for health.”

Source: NADPH oxidase-mediated redox signaling promotes oxidative stress resistance and longevity through memo-1 in C. elegans. eLife 2017;6:e19493 DOI: http://dx.doi.org/10.7554/eLife.19493 Collin Yvès Ewald, John M Hourihan, Monet S Bland, Carolin Obieglo, Iskra Katic, Lorenza E Moronetti Mazzeo, Joy Alcedo, T Keith Blackwell, Nancy E Hynes https://elifesciences.org/content/6/e19493

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