Prof. Bernard C. Rossier

Ms Marie-Madeleine
+41 22 704 36 41


Chemin Rieu 17
P.O. Box 270
1211 Geneva 17
+41 22 704 36 36
+41 22 704 36 37



Perelman School of Medicine,

University of Pennsylvania (USA)

Wednesday, October 24, 11:00 - 11:30

TOR signalling, insulin and ageing

Rapamycin, an inhibitor of mTOR (mechanistic target of rapamycin), extends lifespan in lower organisms and has the strongest experimental support to date as a potential anti-aging therapeutic in mammals.  Unlike many other compounds that have been claimed to influence longevity, rapamycin has been repeatedly tested in long-lived, genetically heterogeneous mice, where it extends both mean and maximum lifespan. However, the mechanism that accounts for these effects is far from clear, and a growing list of side effects, including insulin resistance, make it doubtful that rapamycin would ultimately be beneficial in humans. We have shown that rapamycin disrupts both mTOR complexes in vivo, and that mTORC2 is required for the insulin-mediated suppression of hepatic gluconeogenesis. Further, inhibition of mTORC1 signalling alone appears to be sufficient to extend lifespan, as female mice heterozygous for both mTOR and mLST8 exhibit a selective decrease in mTORC1 activity and extended lifespan, but have normal glucose tolerance. Understanding the downstream pathways that influence mammalian ageing may offer insights into how we can live longer, healthier lives.


Joseph A. Baur is an Assistant Professor in the Institute for Diabetes, Obesity, and Metabolism and the Department of Physiology at the Perelman School of Medicine of the University of Pennsylvania (USA).

He received his PhD from the University of Texas Southwestern Medical Center, and was a postdoctoral fellow at Harvard Medical School. He was the first to show that a sirtuin activator, resveratrol, is able to improve insulin sensitivity and extend lifespan in obese mice.

Current work in Joseph A. Baur's laboratory is focused on the use of small molecules to understand and mimic effects of caloric restriction in rodents.