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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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The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
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Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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mTORC2: A neglected player in aging regulation.

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|July 10, 2024
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Mammalian target of rapamycin complex 2 (mTORC2) is increasingly linked to aging. Genetic elimination of mTORC2 subunits, like RICTOR, may slow aging, unlike mTOR complex 1 (mTORC1) inhibition.

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Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Gerontology

Background:

  • Mammalian target of rapamycin (mTOR) is a kinase regulating cell growth, metabolism, and survival.
  • mTOR functions in two complexes: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2).
  • mTORC1 is known for its role in proliferation and aging, while mTORC2's role in aging is less understood.

Purpose of the Study:

  • To review the characteristics and signaling network of mTORC2.
  • To explore the molecular regulation of mTORC2 in cellular senescence and organismal aging.
  • To discuss the potential of mTOR inhibitors in anti-aging strategies.

Main Methods:

  • Literature review of studies on mTORC2.
  • Analysis of genetic manipulation studies involving mTORC2 subunits (e.g., RICTOR).
  • Synthesis of current research on mTORC2 signaling in aging and senescence.

Main Results:

  • mTORC2 exhibits multifaceted regulatory roles in both senescent and non-senescent cellular contexts.
  • Evidence suggests mTORC2, particularly through subunits like RICTOR, is implicated in aging processes.
  • Genetic inactivation of mTORC2 components shows potential for alleviating aging progression.

Conclusions:

  • mTORC2 is a significant, yet understudied, regulator of aging.
  • Targeting mTORC2 may offer novel anti-aging therapeutic strategies.
  • Further research is needed to fully elucidate mTORC2's role and therapeutic potential in aging.