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Research Article

Molecular Networks of Human Muscle Adaptation to Exercise and Age

  • Bethan E. Phillips,

    Affiliation: Graduate Entry Medicine and Health, Royal Derby Hospital, Derbyshire, United Kingdom

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  • John P. Williams,

    Affiliation: Graduate Entry Medicine and Health, Royal Derby Hospital, Derbyshire, United Kingdom

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  • Thomas Gustafsson,

    Affiliation: Karolinska Institutet, Stockholm, Sweden

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  • Claude Bouchard,

    Affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States of America

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  • Tuomo Rankinen,

    Affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States of America

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  • Steen Knudsen,

    Affiliation: Medical Prognosis Institute, Hørsholm, Denmark

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  • Kenneth Smith,

    Affiliation: Graduate Entry Medicine and Health, Royal Derby Hospital, Derbyshire, United Kingdom

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  • James A. Timmons equal contributor mail,

    equal contributor Contributed equally to this work with: James A. Timmons, Philip J. Atherton

    Jamie.Timmons@gmail.com

    Affiliations: XRgenomics Ltd., Leicestershire, United Kingdom, Loughborough University, Loughborough, United Kingdom

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  • Philip J. Atherton equal contributor

    equal contributor Contributed equally to this work with: James A. Timmons, Philip J. Atherton

    Affiliation: Graduate Entry Medicine and Health, Royal Derby Hospital, Derbyshire, United Kingdom

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  • Published: March 21, 2013
  • DOI: 10.1371/journal.pgen.1003389

Reader Comments (2)

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Aging, Effects of Excercise, and Gene Activity may be Controlled by the Ratio of Testosterone and DHEA

Posted by jamesmhoward on 26 Mar 2013 at 14:21 GMT

Exercise can increase testosterone and dehydroepiansterone (DHEA). It is my hypothesis that testosterone and DHEA must interact to exert their effects ("DHEA, Estradiol, Testosterone, and the Relevance of Their Ratio …The Androgen Receptor …and the Secular Trend," at: http://anthropogeny.com/A... ) Basically, I suggest testosterone stimulates androgen receptors which DHEA uses to produce positive effects on cell growth. This may explain why treatment with testosterone or DHEA will produce positive effects sometimes. If the ratio of testosterone and DHEA is optimal, positive effects will be produced; if the ratio is not optimal, that is, if the individual does not produce the necessary part of this ratio upon treatment with either testosterone or DHEA, benefits do not occur. This could explain the variability in older individuals who exercise. Since both testosterone and DHEA decline with aging, only some will respond to exercise since individual reductions in testosterone or DHEA may not be optimal.

It is also part of my work that growth and differentiation rely on different levels of DHEA within cells. Genes of early growth and differentiation are exposed to higher levels of DHEA, therefore, they will not be expressed during subsequent differentiation. This may explain how early genes are activated, later reduced in activity, and replaced by subsequent gene activity as DHEA availability declines. (“DHEA, DNA, Multicellularity and Tissue Formation, Form and Segmentation,” at: http://anthropogeny.com/M... ) Therefore, I suggest that mTOR is a gene activated early in growth and development, that is, mTOR is active when DHEA is readily available. Since muscle growth and development rely on DHEA and, in older individuals, the DHEA and testosterone stimulated by exercise, if in the proper ratio, are used for increasing muscle mass, DHEA availability is reduced. Therefore, in those who gain lean muscle mass, they do so at the expense of genes that require readily available DHEA. They should exhibit reduced mTOR while they gain muscle mass. Suppression of mTOR is caused by low DHEA. In individuals who do not “suppress” mTOR, I suggest they do not produce DHEA, testosterone in sufficient amounts or in the proper ratio and should be common in aging individuals.

I suggest the findings of Phillips, et al., may be explained by the foregoing. I suggest aging exerts negative effects on muscle mass simply because of the natural decline of testosterone and DHEA of aging. Since some individuals can increase these androgens in an optimal ratio, some will increase muscle mass and, simultaneously, suppress mTOR. With this in mind, I suggest exercise may be beneficial for some individuals, possibly even disadvantageous for some, and that exercise and aging of muscle rely on an optimal ratio of testosterone and DHEA. Availability of testosterone and DHEA will be involved in positive and negative effects of exercise on muscle as well as aging within all tissues.

No competing interests declared.