Anne Brunet: Gracefully studying how we age

Why do we age? Is it inevitable? Lifespans vary across species as much as 150,000-fold, yet all sexually reproducing species eventually experience loss of function, sometimes sliding into senescence before succumbing to death. Research has pointed to genetic, epigenetic, metabolic, and environmental factors that figure in the aging process. However, the reasons behind organismal aging remain an enduring and somewhat terrifying mystery. Anne Brunet is not afraid to tackle this mystery, even if it means venturing into the unknown. Her postdoctoral work on the " pro-longevity " FOXO transcription factors (1, 2), and more recent studies on epigenetic (3) and metabolic (4) determinants of aging, have helped frame the kinds of questions we should be asking if we want to solve this mystery. Now, Brunet's lab at Stanford University is leveraging new technologies—and even a new model animal (5)—to probe these questions in more depth. We called her to learn more. When did you first become interested in science? I grew up in the French Alps, and as a child I loved music and the arts. Music is still very important to me today. But in high school I had great teachers who made me realize that science was beautiful too, just like the arts. In college I had a wonderful mentor, Philippe Ascher, who suggested I go to graduate school in Nice, to work in the lab of Jacques Pouysségur. Jacques is someone who is really passionate about science, so I had an amazing experience in graduate school. At the time, little was known about signaling pathways. MAP kinase had been cloned and discovered, but how it connected to environmental stimuli was unknown. I worked on MAP kinase then, and it was neat going into the unknown to try to puzzle out how the pathway functions. How did you first encounter FOXOs? I was interested in the brain and wanted to study neuroscience. I saw one of Michael Greenberg's postdocs give a talk at a meeting and thought, " This is perfect! I can study signaling in the brain. " That was a good choice because Mike is an awesome scientist and a very supportive mentor. His lab had recently made the intriguing observation that the PI 3-kinase/ Akt signaling pathway is important to prevent cell death and regulate neuronal survival. We were hunting for potential Akt substrates that could mediate this effect. At the same time, when I …