Twenty-five years of mTOR: Uncovering the link from nutrients to growth

Significance The mechanisms that regulate organismal growth and coordinate it with the availability of nutrients were unknown until a few decades ago. We now know that one pathway—the mechanistic target of rapamycin (mTOR) pathway—is the major nutrient-sensitive regulator of growth in animals and plays a central role in physiology, metabolism, the aging process, and common diseases. This work describes the development of the mTOR field, from its origins in studies into the mechanism of action of the drug rapamycin to our increasingly sophisticated understanding of how nutrients are sensed.