Serum Thiols as a Surrogate Estimate of DNA Repair Correlates to Mammalian Life Span

Summary: Mammalian species with higher thiol fractions in their protein live longer

Interestingness: 2

Paper by Ronald W Pero, Catharina Hoppe and Yezhou Sheng in the Journal of Anti-Aging Medicine, Volume 3, Issue 3, Spring 2000.


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These people grabbed blood samples from mostly one or two specimens of 17 different mammalian species (mouse, rat, wolf, dog, goat, sheep, rabbit, bear, cat, lynx, musk ox, fallow deer, cow, gorilla, chimpanzee, horse and human) and precipitated the proteins in those samples. They found a correlation (r=0.819) between the proportion of thiol in the precipitate and the lifespan of the species (not the specimen, they didn't measure how long the actual specimen they took blood from lived), and a stronger correlation (r=0.841) between the proportion of thiols in the thiol-rich fraction of the proteins and the lifespan of the species.

The plots don't look as good as the r-numbers would indicate because they are heavily influenced by the human specimens since they were many more of them (25 vs 1 or 2 of each of the others), and they are out there way on the right in the lifespan axis (they were assigned a lifespan of 95 years). The graphs don't look horrible either.

Their theoretical explanation confuses me. They are saying that this shows that creatures with higher lifespan have lower oxidation levels. I don't know if they are saying that this is being shown directly, that is oxidation would get rid of the thiol (this assumes that their measuring of the thiols wouldn't count oxidised thiols in them), or that this is being shown indirectly, that is if high lifespan animals didn't have lower oxidisation levels their higher thiol-fractioned proteins would be more affected by oxidation, their enzymes would not work, and so these animals wouldn't have high lifespans. I think they mean the second explanation, but I'm not sure. Backing this second interpretation, is them pointing at the unoxidised thiol-dependence of poly adenosine diphosphate-ribose polymerase (PARP), a DNA-repair enzyme, and from there making other claims about the link between mutation, DNA repair and oxidative stress.
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Abstract follows:

Biologically occurring thiols are a sensitive estimate of the reduction/oxidation balance of cells, being easily and reversibly converted from sulfhydryl to disulfide structures in proteins and amino acids. Thiols are also known to regulate DNA repair, especially via the influence on poly (adenosine diphosphate-ribose) polymerase activity. Here the thiol content of saturated ammonium sulphate-precipitated proteins from sera was correlated to a mammalian life span of 17 species. A close correlation was established between the thiol-rich proteins and the life span of the mammals (r = 0.841, p < 0.001). These data provide a strong scientific connection between mechanisms of DNA repair and oxidative stress leading to DNA damage accumulation and mutation, which may be important to the aging process.