Ageing and the oxidative stress conundrum

ageing may be caused by mitochondria
Image by By OpenStax College via Wikimedia Commons

One of the top candidates for ‘THE cause of ageing’ is oxidative stress caused by reactive oxygen species (also called free radicals) inside our cells. Organelles called mitochondria make the energy required to keep each cell alive. Free radicals are one of the byproducts of the chemical reactions that occur inside mitochondria. They are also produced by cellular damage from things like pollution and smoking. Free radical molecules have been oxidised and so have an unpaired electron floating around. Electrons don’t like to be alone, so a lone electron is looking to hook up with a friend. This makes free radicals unstable and reactive, and likely to damage cellular proteins, membranes, and DNA. This damage is termed oxidative stress and has long been thought to be directly responsible for the ageing of cells and tissues. However, 20 years of intensive study on the oxidative stress theory of ageing has produced very confusing results.

On the pro side, calorie restriction, which increases lifespan in animals from yeast to monkeys, is associated with increased activity of antioxidant enzymes and less oxidative damage. Also very old humans (100 years or older) show less oxidative damage in their cells than 70-99 year olds. When scientists increase antioxidant enzymes in yeast, they live longer. The reverse is also true: yeast with less antioxidants have a shorter life span.

Once we go a bit higher up the evolutionary chain, the story gets muddier. Increasing antioxidant enzymes in worms does not increase life span. Flies with more antioxidant activity sometimes live longer, but sometimes have a shorter life span than control flies. Likewise with mice: a few studies have shown that mice with more antioxidants can live longer, but most studies show no affect on lifespan.

But there’s a silver lining. While mice with more antioxidants don’t live longer, they do have less heart, brain and metabolic disease. And mice with less antioxidants seem to have more of these diseases. Also, in the majority of studies, increasing antioxidant enzyme expression can ameliorate symptoms in animal models of age-related diseases including Alzheimer’s, Parkinson’s and cardiomyopathy. So antioxidants can increase ‘health span’. Being healthy for longer may be more important than living longer.

So should we all buy into the media hype and start guzzling antioxidants by the bucketload? No. No studies have proven that eating more anti-oxidants can prevent ageing. When over consumed, common antioxidants Vitamin A, Vitamin C, Vitamin E and beta-carotene have nasty side effects like nausea, vomiting, diarrhoea and bleeding.

So, after countless studies on oxidative stress, we are no closer to finding the elixir of youth.

The Scientific Review:
Edrey and Salmon. Revisiting an age-old question regarding oxidative stress. Free Radical Biology and Medicine. 2014.

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