Complicating Antioxidants Some More

We'll start off today's post with a quick refresher on the present state of knowledge regarding antioxidants and life span in laboratory animals. Antioxidants are compounds that neutralize oxidants, such as the reactive oxygen species produced by your mitochondria that are implicated in the damage of aging. In theory, neutralizing those damaging oxidants before they can cause harm to your cellular machinery will lead to a lesser accumulation of cellular and tissue damage over time, and thus a slower rate of aging. Aging, after all, is no more than the accumulation of damage and the body's response to that damage.

Oxidant compounds also play important roles in the body's signaling mechanisms, however, so it's far from the case that we can declare all oxidants bad. What do researchers presently know?

At which point most people will throw up their hands and wait for the scientists to figure out what's going on here. You can't ignore the mice that are living 15-30% longer due to the targeted antioxidants, but equally you can't ignore the weight of other research in which boosting antioxidants doesn't increase life span. Personally, I still think it's down to the targeting, at least until some new work arrives to prove that thesis false.

In any case, the paper I wanted to point out today is another example of boosting natural antioxidants in a mammal and obtaining no benefit to life span.

Genetic manipulations of Mn superoxide dismutase (MnSOD), SOD2 expression have demonstrated that altering the level of MnSOD activity is critical for cellular function and life span in invertebrates. In mammals, Sod2 homozygous knockout mice die shortly after birth, and alterations of MnSOD levels are correlated with changes in oxidative damage and in the generation of mitochondrial reactive oxygen species.

In this study, we directly tested the effects of overexpressing MnSOD in young (4-6 months) and old (26-28 months) mice on mitochondrial function, levels of oxidative damage or stress, life span, and end-of-life pathology. Our data show that an approximately twofold overexpression of MnSOD throughout life in mice resulted in decreased lipid peroxidation, increased resistance against paraquat-induced oxidative stress, and decreased age-related decline in mitochondrial ATP production. However, this change in MnSOD expression did not alter either life span or age-related pathology.

Which muddies the water still further, given that we'd - perhaps naively - expect the biochemical changes listed above to be accompanied by at least some associated benefit to life span.

ResearchBlogging.orgJang, Y., Perez, V., Song, W., Lustgarten, M., Salmon, A., Mele, J., Qi, W., Liu, Y., Liang, H., Chaudhuri, A., Ikeno, Y., Epstein, C., Van Remmen, H., & Richardson, A. (2009). Overexpression of Mn Superoxide Dismutase Does Not Increase Life Span in Mice The Journals of Gerontology Series A: Biological Sciences and Medical Sciences DOI: 10.1093/gerona/glp100


Actually it is rather obvious why this line of research doesn't work. There is a system called the intracellular redox environment. Like in pH, a buffer system consisting of GSH/GSSG, ROS and antioxidants keeps the internal redox potential in a range where proteins and complex systems function best.

If the redox potential leaves this range, moieties get oxidised or reduced that are not supposed to be, and proteins and cellular structures may be harmed - or not. So it is really no wonder that punping antioxidants into this buffered systems just for the sake of it will produce contradictory results, depending on the situation.

In my opinion this kind of research is very popular because it sounds good to funding agencies and the food industry. But it will never yield useful results, because the whole concept is too simplicistic.

Posted by: Fischer at July 30th, 2009 2:01 AM
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