Graduate student Kristan Steffan and Assistant Professor of Biochemistry Brian Kennedy, together with Matt Kaeberlein and Stan Fields of the Department of Genome Sciences, have discovered a pathway linking nutrient response and aging in yeast. [Kaeberlein M, Powers RW 3rd, Steffen KK, Westman EA, Hu D, Dang N, Kerr EO, Kirkland KT, Fields S, Kennedy BK (2005) Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310, 1193-1196.]

Caloric restriction (a severe reduction in food intake) has been known for some time to extend the lifespan of laboratory animals such as mice, but the new results shed light on possible mechanisms by which caloric restriction affects aging. A genome-wide screen of budding yeast revealed 10 genes that regulate lifespan. Two of the genes encode proteins called Tor1 and Sch9, which are key players in signaling cascades linked to nutrient uptake in many different organisms.

Remarkably, caloric restriction did not further increase the lifespan of cells with a Tor1 mutation that reduces signaling through the TOR pathway. This suggests that caloric restriction works through the Tor1 pathway. The other protein, Sch9, is the yeast homolog of the mammalian protein Akt. Akt is involved in signaling through the insulin and insulin-like growth factor (IGF-1) pathways, and also affects lifespan in other model organisms.

For more information regarding genome-wide efforts to understand aging, visit the following websites:

A Consortium for the Determination of Public Pathways Regulating Longevity funded by the Ellison Medical Foundation http://www.pathology.washington.edu/research/bioage/ellison/

The Nathan Shock Center for Excellence in the Basic Biology of Aging http://www.pathology.washington.edu/research/bioage/

An interview with Matt Kaeberlein and Brian Kennedy
http://www.sagecrossroads.net/Default.aspx?tabid=171

Also see the following manuscripts:

Kaeberlein M, Hu D, Kerr EO, Tsuchiya M, Westman EA, Dang N, Fields S, Kennedy BK (2005) Increased Life Span due to Calorie Restriction in Respiratory-Deficient Yeast. PLoS Genet 1, e69 [Epub ahead of print].

Kennedy, B.K., Smith, E.D., and Kaeberlein, M. 2005. The enigmatic role of Sir2 in aging. Cell 123: 548-550.

Rine, J. (2005) Twists in the tale of the aging yeast. Science 310: 1124-1125.

Other news reports on these findings:

Howard Hughes Medical Institute
http://www.hhmi.org/news/fields20051118.html

University of Washington UWeek
http://admin.urel.washington.edu/uweek/archives/issue/uweek_story_small.asp?id=2641

University of Washington UW Medicine News
http://depts.washington.edu/hsnews/