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mTOR Signaling and Cancer Progression03:03

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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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Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
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Updated: Apr 7, 2026

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Dual mTORC1/C2 inhibitors suppress cellular geroconversion (a senescence program).

Olga V Leontieva1, Zoya N Demidenko1, Mikhail V Blagosklonny1

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|July 16, 2015
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Summary

Dual mTOR inhibitors, like Torin1 and PP242, prevent cell cycle arrest from becoming permanent senescence. These compounds preserve cells' ability to proliferate, suggesting potential anti-aging applications.

Keywords:
GerotargetPathology Sectionagingpan-mTOR inhibitorsrapalogsrapamycinsenescence

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Area of Science:

  • Cellular senescence
  • Molecular biology
  • Aging research

Background:

  • Mammalian target of rapamycin (mTOR) pathway regulates cell growth and proliferation.
  • Cellular senescence is a state of irreversible cell cycle arrest.
  • mTOR activity drives the conversion of reversible cell cycle arrest into senescence (geroconversion).

Purpose of the Study:

  • To investigate the effect of ATP-competitive mTOR kinase inhibitors on geroconversion.
  • To determine if these inhibitors can preserve re-proliferative potential in arrested cells.
  • To explore the potential of dual mTOR inhibitors as anti-aging therapeutics.

Main Methods:

  • Utilized p21-arrested cells to study geroconversion.
  • Administered ATP-competitive mTOR inhibitors Torin1 and PP242 at varying concentrations.
  • Assessed geroconversion suppression, re-proliferative potential (RP), senescent morphology, hypertrophy, and phosphorylation of S6 kinase (S6K) and S6.
  • Investigated inhibition of both mTOR complex 1 (mTORC1) and mTOR complex 2 (TORC2).

Main Results:

  • Torin1 and PP242 significantly suppressed geroconversion in a dose-dependent manner.
  • Near-maximal gerosuppression correlated with inhibition of p-S6K(T389) and p-S6(S235/236).
  • Dual mTOR inhibitors prevented the development of senescent morphology and cellular hypertrophy, preserving re-proliferative potential.

Conclusions:

  • ATP-competitive mTOR inhibitors effectively suppress geroconversion, offering an alternative to rapalogs.
  • These inhibitors maintain re-proliferative potential in arrested cells, counteracting senescence.
  • Low-dose dual mTOR inhibitors represent a promising new class of drugs for anti-aging strategies and delaying age-related diseases.