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The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
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mTOR as a senescence manipulation target: A forked road.

Sarah Saoudaoui1, Monique Bernard1, Guillaume B Cardin1

  • 1Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada; Institut du cancer de Montréal, Montreal, QC, Canada.

Advances in Cancer Research
|April 16, 2021
PubMed
Summary

Mechanistic target of rapamycin (mTOR) signaling is key to cellular senescence, aging, and cancer. Inhibiting mTOR with rapamycin may offer therapeutic benefits for age-associated diseases and cancer by manipulating senescence.

Keywords:
AgingApoptosisAutophagyLifespanMetabolismSenescenceSenolyticsmTOR

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Area of Science:

  • Molecular Biology
  • Gerontology
  • Oncology

Background:

  • Cellular senescence, cancer, and aging are interconnected biological processes.
  • Mechanistic target of rapamycin (mTOR) signaling regulates cell metabolism, proliferation, survival, and homeostasis.
  • Dysregulation of mTOR is linked to age-associated diseases and cancer progression.

Purpose of the Study:

  • To review the role of mTOR in cellular senescence.
  • To explore the interplay between senescence, autophagy, and mTOR.
  • To discuss therapeutic strategies targeting mTOR in senescence for age-associated diseases and cancer.

Main Methods:

  • Literature review focusing on mTOR signaling pathways.
  • Analysis of the connection between mTOR, cellular senescence, and autophagy.
  • Discussion of pharmacological interventions targeting mTOR.

Main Results:

  • mTOR is a central regulator at the intersection of senescence, aging, and cancer.
  • Rapamycin and rapalogs demonstrate therapeutic potential in various diseases, including cancer.
  • Rapamycin is a known lifespan-extending drug across species.

Conclusions:

  • Targeting mTOR offers a promising avenue for manipulating senescence phenotypes.
  • Exploiting senescence-associated mTOR functions could lead to novel treatments for age-associated diseases and cancer.
  • Further research into mTOR's role in senescence is crucial for therapeutic development.