Potential therapeutic effects of the MTOR inhibitors for preventing ageing and progeria-related disorders

Br J Clin Pharmacol. 2016 Nov;82(5):1229-1244. doi: 10.1111/bcp.12928. Epub 2016 May 18.

Abstract

The mammalian target of rapamycin (mTOR) pathway is an highly conserved signal transduction axis involved in many cellular processes, such as cell growth, survival, transcription, translation, apoptosis, metabolism, motility and autophagy. Recently, this signalling pathway has come to the attention of the scientific community owing to the unexpected finding that inhibition of mTOR by rapamycin, an antibiotic with immunosuppressant and chemotherapeutic properties, extends lifespan in diverse animal models. Moreover, rapamycin has been reported to rescue the cellular phenotype in a progeroid syndrome [Hutchinson-Gilford Progeria syndrome (HGPS)] that recapitulates most of the traits of physiological ageing. The promising perspectives raised by these results warrant a better understanding of mTOR signalling and the potential applications of mTOR inhibitors to counteract ageing-associated diseases and increase longevity. This review is focused on these issues.

Keywords: Hutchinson-Gilford Progeria syndrome (HGPS); ageing; lamin A; mTOR inhibitors; progeria-related diseases; rapamycin.

Publication types

  • Review

MeSH terms

  • Aging / drug effects*
  • Animals
  • Humans
  • Models, Biological
  • Progeria / drug therapy*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*

Substances

  • Protein Kinase Inhibitors
  • MTOR protein, human
  • TOR Serine-Threonine Kinases