A Cell Metabolism review framing mTOR as the 'grand conductor' that coordinates whole-body metabolism, tissue by tissue. Especially valuable for its clear-eyed section on WHY rapamycin causes metabolic side effects (the mTORC2 problem) - which is the main barrier to using it against aging. Pairs perfectly with Lamming's own 2012 mechanism paper.
| Evidence tier | D Mechanistic / in vitro / review |
| Study type | Narrative Review |
| Model system | Review (metabolism/aging) |
| Journal | Cell Metabolism |
| Year | 2016 |
| Peer reviewed | Yes |
| Source | DOI 10.1016/j.cmet.2016.05.009 · PMID 27304501 · Free full text (PMC4910876) |
Since the discovery that rapamycin, a small molecule inhibitor of the protein kinase mTOR (mechanistic target of rapamycin), can extend the lifespan of model organisms including mice, interest in understanding the physiological role and molecular targets of this pathway has surged. While mTOR was already well known as a regulator of growth and protein translation, it is now clear that mTOR functions as a central coordinator of organismal metabolism in response to both environmental and hormonal signals. This review discusses recent developments in our understanding of how mTOR signaling is regulated by nutrients and the role of the mTOR signaling pathway in key metabolic tissues. Finally, we discuss the molecular basis for the negative metabolic side effects associated with rapamycin treatment, which may serve as barriers to the adoption of rapamycin or similar compounds for the treatment of diseases of aging and metabolism.
| Intervention | Not applicable (review) |
| Target | mTOR |
| Model | Review |
| Effect | Reviews mTOR as a central coordinator of organismal metabolism and aging |