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The Double-Agent Theory of Ageing and Disease

The double-agent theory is a synthesis, rather than a new theory of ageing, but I think it helps resolve some of the glaring contradictions in ageing research. The idea is discussed in Chapter 14 of Oxygen, but it also cried out for a more formal scientific exposition, dignified by peer review.

The double-agent theory is framed around the simple question of whether or not antioxidant supplements, like vitamin C, protect against age-related diseases, and even the underlying process of ageing itself.

My own research on renal transplantation involved a lot of disappointing work on antioxidants. There are always many possible reasons why an experiment doesn't work -- the wrong antioxidant or combination of antioxidants, the wrong dose, the wrong route of administration, the wrong timing -- and it is disappointing enough to fail without then dedicating years to finding out exactly why. But I was far from alone. Nobody could make antioxidants work.

The optimism of the 1980s, when it seemed only a matter of time before the magical ingredient or right dose was found, has largely evaporated. The mainstream field has moved on and is now deeply embroiled in redox signalling and other such complexities. The general consensus is that, over and above being an essential part of a balanced diet, antioxidants just don't make much difference. They're a nice idea but the world is more complex.

Yet in writing Oxygen I became more and more convinced that oxygen free radicals really are largely responsible for ageing, and age-related diseases like cancer, heart disease, and dementia. They're not exclusively so -- nothing is exclusive in biology -- but I was left thinking that nothing else rivalled free radicals in importance as a cause of ageing.

So here's the dilemma. There's good evidence that free radicals are important in ageing, and there's also good evidence (of the irritatingly intangible, negative sort) that antioxidant supplements don't work. The consensus conclusion is that free radicals can only be partially responsible for ageing, so antioxidant supplements will at best make a trifling difference, even when taken at the right dose, etc etc.

But what if the evidence is no more complicated than meets the eye? What if free radicals cause ageing, but antioxidants cannot, for whatever reason, prevent or postpone the inevitable? Enter the double-agent....

If you want to read the article, addressed to a scientific audience (but I hope more widely accessible) here is the version that was accepted by the Jounal of Theoretical Biology. I can only show this for copyright reasons -- you'll have to check the journal for the final print version.


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