The Dreaded PI3K-PTEN-Akt-TOR Pathway

Scientists are not in the business of assigning names that make life easy for the rest of us, as illustrated by the PI3K-PTEN-Akt-TOR pathway. But you should read about it anyway, for the same reasons you read about research into calorie restriction and other aspects of metabolism and aging. It's good to know how we work, and gain an appreciation of how close scientists are to safely manipulating the core mechanisms on which a mammal is built:

Cancer, diabetes, and aging are related by their use of the PI3K-PTEN-Akt-TOR signaling pathway. This pathway controls how cells grow when nutrients are available and plays a role in how caloric restriction is able to extend lifespan. If parts of the pathway malfunction due to somatic or genetic mutations, cancer or diabetes can result. Thus, the pathway presents an exciting new frontier in medicine as researchers discover how to treat diseases by stopping the propagation of harmful signals and promoting the transmission of beneficial ones.


When nutrients are plentiful, growth factors spur the pathway to direct the cell toward growth and proliferation. If the pathway becomes overactive, however, cancerous growth results. Persistent activation by excess nutrients can lead to insulin resistance and diabetes. The pathway also appears to be involved in cellular senescence and aging in flies and worms and quite possibly in humans as well. Designing therapies to treat cancer, diabetes, and the aging process will be a challenge given the ubiquitous nature of this signaling pathway.

A challenge if you're of the school that believes the only way to tackle aging is to slow it down somewhat by redesigning metabolism, a hugely complex task that produces results of very limited benefit to those who are already old.

There is an alternate way forward, however: learn to repair the metabolism we have, and that we have invested so much time in understanding. Reversing or fixing the known biochemical changes that are the root of aging is arguably no harder - and arguably very much easier - than changing our metabolism. Yet progress along this path would greatly benefit those already old by producing therapies capable of rejuvenation rather than just a slowing of aging.

Work that leads to a greater understanding of our biochemistry will never be a waste - but it is very possible for the research community to head down a path that will never produce rejuvenation therapies in time to help those of us reading this now. Our job is to do our best to avoid that outcome.


Understanding metabolism would be useful in stem cell therapies. One could engineer stem cells that are less prone to free radicals and enzymes to break down AGES and other unpleasantness intercellularly. Also, the DNA repair of such engineered stem cells would be enhanced so they would age slowly after they are differentiated.

The engineering approach would be better in the short term, though.

Posted by: HellKaiserRyo at October 24th, 2007 2:01 AM

"Designing therapies to treat cancer, diabetes, and the aging process will be a challenge given the ubiquitous nature of this signaling pathway."

It isn't mentioned in the diagram in the link though, although this is an example of how diabetes and cancer are involved in a related molecular pathway.

Treating diabetes and cancer would be difficult. DPP-4 inhibitors might increase the risk for cancer. Maybe such research provide some new drug targets. DPP-4 inhibitors, I dunno, maybe better targets would be found for diabetes. CEPT inhibition, the mechanism might be deterimental as torceptrapib increases death in clinic trials. However this might be due to the fact that it increases systolic blood pressure.

Posted by: HellKaiserRyo at October 24th, 2007 2:10 AM
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