TOR, A Key Mediator of the effects of Dietary Restriction and its Impact on Aging
 

Newswise, June 2010 — The slogan “With TOR, less is more” may someday be part of the scientific lexicon – when it comes to acknowledging one of the key molecular players involved in increasing the healthy years of life via the process of dietary restriction.

Why all the attention on TOR? TOR (target of rapamycin) is a key nutrient-sensing catalytic enzyme that evolution has conserved among every plant and animal species that has cells containing a nucleus.

TOR mediates the connection between nutrients in the environment to the growth and metabolism of the organism. Studies in flies, worms, yeast and mice support the notion that the TOR signaling network also plays a pivotal role in regulating the aging process.

When TOR signaling is reduced, either through genetic manipulation or via the use of drugs, the organism presumes there are reduced nutrients in its environment and goes into a ‘survival’ mode similar to that seen in dietary restriction, which has been shown to extend lifespan and slow the onset of certain age-related diseases.

In a review article (“With TOR less is more: a key role for the conserved nutrient sensing pathway in aging”) in the June 8, 2010 edition of Cell Metabolism, Buck Institute faculty member Pankaj Kapahi, PhD, synthesizes work from various labs to discusses how reduction in activity in the TOR signaling network slows aging by affecting a number of downstream molecular processes including mRNA translation, autophagy, endoplasmic reticulum stress signaling, stress responses and metabolism.

“Identifying the mechanisms by which the TOR signaling network works as a pacemaker of aging is a major challenge and opportunity in the field,” said Kapahi. “This body of work provides an array of excellent potential drug targets for extending lifespan and slowing age-related disease.”

Kapahi says future work in this area needs to focus on understanding the impact that different types of nutrients have on the TOR signaling pathway in various species in order to examine the particulars of dietary restriction and resulting lifespan extension.

He also says it remains to be seen which downstream effectors of TOR are key drivers of longevity and which ones elicit only minor effects. In addition to simply extending lifespan, research on the protective effects of TOR is likely to identify which age-related diseases can be slowed by inhibition of the TOR pathway.

 “Further analysis of the conserved nutrient sensing TOR pathway will shed important light on the link between diet and various age-related conditions such as cancer, neurodegeneration and diabetes,” said Kapahi.

Contributors to this work:
Other Buck Institute researchers involved in the review include Di Chen, Subhash D. Katewa, Patrick Li and Emma L. Thomas, along with Lutz Kockel of the University of California, San Francisco, Diabetes Center, Department of Medicine. The work was funded by grants from the Ellison Medical Foundation, American Federation for Aging Research, the Larry L. Hillblom Foundation, a Nathan Shock Startup award and the National Institutes of Health/National Institute of Aging and REAC Award.

About the Buck Institute for Age Research:
The Buck Institute is the only freestanding institute in the United States that is devoted solely to basic research on aging and age-associated disease.

The Institute is an independent nonprofit organization dedicated to extending the healthspan, the healthy years of each individual’s life.

Buck Institute scientists work in an innovative, interdisciplinary setting to understand the mechanisms of aging and to discover new ways of detecting, preventing and treating conditions such as Alzheimer’s and Parkinson’s disease, cancer and stroke. Collaborative research at the Institute is supported by new developments in genomics, proteomics and bioinformatics technology.