mTOR activation is a biomarker and a central pathway to autoimmune disorders, cancer, obesity, and aging

Ann N Y Acad Sci. 2015 Jun;1346(1):33-44. doi: 10.1111/nyas.12756. Epub 2015 Apr 23.


The mechanistic target of rapamycin (mTOR) is a ubiquitous serine/threonine kinase, which plays pivotal roles in integrating growth signals on a cellular level. To support proliferation and survival under stress, two interacting complexes that harbor mTOR, mTORC1 and mTORC2, promote the transcription of genes involved in carbohydrate metabolism and lipogenesis, enhance protein translation, and inhibit autophagy. Although rapamycin was originally developed as an inhibitor of T cell proliferation for preventing organ transplant rejection, its molecular target, mTOR, has been subsequently identified as a central regulator of metabolic cues that drive lineage specification in the immune system. Owing to oxidative stress, the activation of mTORC1 has emerged as a central pathway for the pathogenesis of systemic lupus erythematosus and other autoimmune diseases. Paradoxically, mTORC1 has also been identified as a mediator of the Warburg effect that allows cell survival under hypoxia. Rapamycin and new classes of mTOR inhibitors are being developed to block not only transplant rejection and autoimmunity but also to treat obesity and various forms of cancer. Through preventing these diseases, personalized mTOR blockade holds promise to extend life span.

Keywords: T cell activation; autoimmunity; autophagy; biomarker; glutathione; glycolysis; hypoxia; inflammation; keloid disease; kynurenine; mTOR; metabolism; mitochondria; oxidative stress; pathogenesis; pentose phosphate pathway; rapamycin; sirolimus; systemic lupus erythematosus; treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / drug effects
  • Aging / metabolism*
  • Animals
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / metabolism*
  • Biomarkers / metabolism*
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Obesity / drug therapy
  • Obesity / metabolism*
  • Precision Medicine / methods
  • Signal Transduction / drug effects
  • Sirolimus / analogs & derivatives
  • Sirolimus / therapeutic use
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism*


  • Biomarkers
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus