A mouse with the ability to mop up free radicals at the cellular level – and live longer as a result – has been created by scientists.
The research is a boost for the free radical theory of ageing. This proposes that reactive oxygen species damage cells and tissues, leading to declining health and, eventually, death.
“We hope that in future years, this knowledge can be applied to deliver similar benefits to humans,” says lead researcher Peter Rabinovitch, a pathologist working on ageing at the University of Washington, Seattle, US.
The results may also encourage those on the fringes of mainstream research who long for immortality.
The transgenic mice Rabinovitch’s team created produce higher-than-normal levels of the antioxidant enzyme catalase. Cells use catalase to convert damaging hydrogen peroxide to harmless water and molecular oxygen, but the enzyme is usually found only in the cytoplasm of cells.
His team made mice that produce high levels of catalase in their mitochondria, the powerhouses of cells. They found that cellular damage, as well as age-related damage in the heart, decreased in comparison to control mice that produced catalase in just cytoplasm or in cell nuclei. The lifespan of the mitochondria-catalase mice was extended by more than five months – an increase of around 20%.
Judith Campisi, who works on ageing at the Buck Institute in California, US, notes: “The theory is that inefficient mitochondria produce more reactive oxygen species, which in turn damage the mitochondria, making them more inefficient, and the cycle goes on,” she says.
However, Rabinovitch rules out genetically modifying humans to do the same thing. More likely are drugs to mimic or increase catalase activity in human mitochondria. “Eventually we hope that insights from this work can be used to help develop pharmacological interventions that will help extend the healthy life span of humans,” he says.
There is much evidence that a diet rich in green vegetables – high in antioxidants – is beneficial for health, but there is currently little data to support a beneficial effect of “antioxidant pills”. Rabinovitch says that the new work demonstrates the promise of an enzyme-based antioxidant, which could be given as a pill, if the enzymes can then find their way into the mitochondria.
Campisi is cautiously optimistic that the mouse work will lead to longer life-spans in humans, too. “But it is important to remember that, just as mice are more complicated than flies or nematodes, humans are more complicated than mice. So time will tell,” she says.
Howard Jacobs, a geneticist at the University of Tampere, Finland, also sounds a warning note. “Lifespan extension may carry other costs that are not immediately obvious, quite apart from considering ethical and societal issues,” he says. “Having said this, the finding is provocative, and certainly accords with our work showing that loss of mitochondrial genome integrity provokes an acceleration in mouse ageing.”