A null mutation in SERPINE1 protects against biological aging in humans

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Science Advances  15 Nov 2017:
Vol. 3, no. 11, eaao1617
DOI: 10.1126/sciadv.aao1617

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  • RE: Mutated SERPINE1 Antagonizes the Natural Control of PAI-1 by Testosterone and DHEA

    I suggest the basis of these findings involves dehydroepiandrosterone (DHEA) and testosterone.

    DHEA reduces plasminogen activator inhibitor-1 (The American Journal of the Medical Sciences Volume 311, Issue 5, May 1996, Pages 205-210) and reduces insulin (Aging (Albany NY). 2011 May; 3(5): 533–542.) Reduced PAI-1 and reduced insulin are two characteristics found in the long lived Amish individuals.

    Physiological concentrations of testosterone also reduce PAI-1 levels (Biochem Cell Biol. 2007 Apr;85(2):246-51.). A case may be made that low testosterone is involved in diabetes type 2. I suggest the results of the increased testosterone to DHEA ratio is directly involved in the increased human life span compared to the great apes and that this ratio affects levels of PAI-1 ("Testosterone Controls Human and Great Ape Lifespans," on the internet).

    The foregoing may explain why "a rare loss-of-function mutation in SERPINE1 (c.699_700dupTA), which encodes PAI-1, could play a role in longevity and metabolism in humans."

    Competing Interests: None declared.

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