Does mTOR Inhibition Negatively Diminish Muscle Growth?

Q You’ve published some articles talking about the benefits of suppressing or inhibiting mTOR. But as I understand it, mTOR is critical to building muscle, so suppressing it would presumably make it harder to maintain a healthy body composition and prevent catabolism, which is often a problem associated with aging. How does one find balance here?

WAYNE, Ellwood City, PA

A It is still believed by some that that inhibition of the mammalian target of rapamycin (mTOR) by rapamycin suppresses myocardial hypertrophy, and that’s good. However, the opposite may be true.1 Nevertheless, at this point the question to ask (facetiously) is whether you want to look good in the casket or not be in one, or at least too soon! Seriously, this is a complex subject and I understand your concern.

In the study cited, mTOR overexpression suppressed secretion of IL-6 (IL-6 is an interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine), and the mTOR inhibitors rapamycin and PP242 abolished this inhibitory effect of mTOR. Furthermore, mTOR overexpression reduced NF-κB-regulated transcription in HL-1 cells, a cardiac muscle cell line. These data suggest that mTOR lessens adverse outcomes of pressure overload and that this cardioprotective effect of mTOR is mediated by regulation of the inflammatory reaction. It’s complicated.

However, remember that decreased mTOR activity has been found to slow aging in S. cerevisiae (yeast), C. elegans (roundworms), D. melanogaster (fruit flies), and most recently the mTOR inhibitor rapamycin has been confirmed to increase lifespan in mice by independent groups at the Jackson Laboratory, University of Texas Health Science Center, and the University of Michigan.

Furthermore, it’s been hypothesized that some dietary regimes, like caloric restriction and methionine restriction, cause lifespan extension by decreasing mTOR activity. Then again, infusion of the amino acid leucine into the rat brain has been shown to decrease food intake and body weight via activation of the mTOR pathway. More answers are needed.


  1. Song X, Kusakari Y, Xiao CY, Kinsella SD, Rosenberg MA, Scherrer-Crosbie M, Hara K, Rosenzweig A, Matsui T. mTOR attenuates the inflammatory response in cardiomyocytes and prevents cardiac dysfunction in pathological hypertrophy. Am J Physiol Cell Physiol 2010 Dec;299(6):C1256-66.

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