mTORC1, Nutrient Sensing and Age-Related Disease Processes

The cell’s ability to sense and respond to the availability of nutrients through growth and stasis is one of the hallmarks of aging and associated diseases. mTORC1 (mechanistic target of rapamycin complex 1) is the primary sensor and integrator of the cell’s response to nutrient availability, and dysregulation of mTORC1 activation is at the core of many age-related diseases.

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The mTORC1 pathway and fundamental cellular function and growth

The mTORC1 pathway plays a fundamental role in healthy cellular function and growth. mTORC1 integrates multiple signals that arise from dynamic changes in the extracellular environment, many of which are related to the availability of nutrients—particularly amino acids—that are used by the cell’s biosynthetic machinery to grow and function.

Within the mTORC1 pathway, amino acids play a specific and critical signaling role, serving as a fundamental cue that directs the cell either to:

  1. grow (when nutrient levels are abundant), or
  2. begin a well-controlled and systematic process of autophagy—i.e., recycling (during a scarcity of nutrients), whereby certain cellular components are broken down into basic building blocks, including amino acids, to maintain the biosynthetic integrity of the cell.

mTORC1 regulates both cell growth and autophagy through its kinase activity, primarily in response to the availability of amino acids and other nutrients which places it at the core of the cells metabolic control system.

mTORC1 and Nutrient Signaling

Nutrient signaling is the cell’s ability to sense and respond to the availability of amino acids, glucose, and other nutrients to enable normal cell function and survival. In particular, amino acids—the building blocks of proteins—are the nutrients that are most directly linked to cellular growth that is mediated by mTORC1.

Changes in supply of nutrients requires cells to sense and communicate with each other to enable normal cell function and survival.

When nutrients are abundant, cells respond by increasing their capacity for biosynthetic growth, including making proteins and other components required for normal cellular function and/or increasing their size or number.

When nutrients are scarce, cells respond by turning on their biosynthetic “recycling” process, known as autophagy—a process that degrades cellular structures such as proteins to generate the needed building blocks to maintain cellular survival and function.

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