Pamela L. Larsen, Ph.D.Associate Professor
Vanderbilt University, Nashville, 1986
Currently, we are identifying genes regulated by reduction of cultivation temperature and/or by reduction of DAF-2 signaling. It is unknown whether the molecular and metabolic consequences of altering DAF-2 signaling and temperature are similar mechanistically. A molecular genetic approach will be used to sort candidate genes for life span effects. Importantly, we will gain insight into genes contributing to both the short-life of wild type and the long-life of daf-2 mutants. In addition, we are studying biochemical and physiological differences between the short-lived wild type and the long-lived mutants in adults and in dauer larvae. We are investigating the 39 insulin-like genes and fatty acid metabolism because dauer larvae and daf-2 mutant adults are obese compared to wild-type adults. The dysregulation of lipid metabolism may contribute to the longevity. Furthermore, changing the cultivation temperature alters lipid composition. Increased longevity by reduction of cultivation temperature and/or by reduction of DAF-2 signaling could be via increased triglyceride availability and utilization, since feeding declines dramatically in all genotypes upon cessation of reproduction and the rate of body size diminution correlates with longevity. Alternatively, changes in which polyunsaturated fatty acids are produced could alter the membrane phospholipids and increase survival. Finally, most of our studies include different genotypes at temperatures, with the goal being to define environmental and genetic interactions with regard to adult life span.
C. elegans culture and genetics
Transgenic strain construction
PCR and Real-time PCR
Jonassen T, Davis DE, Larsen PL, Clarke CF. Reproductive fitness and quinone content of Caenorhabditis elegans clk-1 mutants fed coenzyme Q isoforms of varying length. J Biol Chem. 2003 Dec 19;278(51):51735-42. Epub 2003 Oct 06.
Jonassen, T., B. N. Marbois, K. F. Faull, C. F. Clarke, and P. L. Larsen, 2002. Development and fertility in C. elegans clk-1 mutants depends upon transport of dietary coenzyme Q8 to mitochondria. JBC 2002, Nov 22; 277(47): 45020-7
Larsen, P. L. and C. F. Clarke, 2002. Extension of life span in C. elegans by a diet lacking coenzyme Q. Science 295, 120-123.
Jonassen, T., P. L. Larsen, and C. F. Clarke, 2001. A dietary source of coenzyme Q is essential for survival of long-lived C. elegans clk-1 mutants. Proc. Natl. Acad. Sci. USA 98, 421-426.
Yu, H. and P. L. Larsen, 2001. DAF-16- Dependent and -Independent Expression Targets of DAF-2 Insulin Receptor-like Pathway in Caenorhabditis elegans Include FKBPs. J. Mol. Biol. 314, 1017-1028.