Worm Breeder's Gazette 13(5): 82 (February 1, 1995)
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
Institute for Behavioral Genetics, Campus Box 447, University of Colorado, Boulder, Colorado, 80309.
There are five published accounts of single-gene mutations leading to an extended metazoan life span (Age). Four or these were discovered in C. elegans (1-4), and the fifth study (5), in drosophila, has neverbeen replicated. age-1(1), daf-2(2) and spe-26(3) all extend lifespan at 20¡C anywhere from 45percent to 100percent. rad-8 life-extension is curious as it is limited to a 42percent increase at 1 6¡C (4). C. elegans also happens to be the only system in which a single gene mutation has been shown to confer increased thermotolerance (survial at 35¡C) or Itt (6). That gene is also age-1. We proposed that Itt may be mechanistically related to Age in the following fashion; aging is the result of the accumulation of conformationally altered protein (CAP) which is produced by the action of reactive oxygen species (ROS), a by-product of oxidative metabolism. The accumulation of CAP can be prevented by the conversion of ROS to non-ROS by antioxidant enzymes such as superoxide dismutase and catalase or by refolding of CAP by molecular chaperones or targeting of CAP for degradation. age-1 over-expresses SOD and catalase (7,8) and also over-expresses hsp16 under stress conditions (see accompanying article). We propose that age-1-associated Itt is a consequence of hsp over-expression. We questioned whether any of the other published Age mutants were consistent with this view. Itt was assayed by shifting 2 agar plates of 25 four-day-old adult hermaphrodites from 20¡C to 35¡C and assessing provoked movement and pharyngeal pumping at various time intervals. Animals lacking both of these characteristics were scored as dead. We assayed two alleles of daf-2 and two alleles of spe-26 and found that all were thermotolerant. daf-2(e 1370), daf-2(el368) and spe-26(hcl38) were significantly different from N2 at the p < .0001 level and spe-26(it118) at the p < .01 Ievel. A number of other daf-c mutations also confer thermotolerance including daf-4 and daf-7. Although we have not yet shown a causal relationship between the thermotolerance phenotype and life span our results are consistent with the notion that increased thermotolerance is essential for life-span extension but, perhaps not surprisingly, not sufficient. The figure shows a compilation of life span data from different labs [age-1 and daf-2 are from TEJ spe-26 from(2)j] and observed increases in themmotolerance. (1) Friedman and Johnson, J. Geront. B.S. 4, B102. 1988. (2) Van Voorheis, Nature. 360, 456. 1992. (3) Kenyon et al. Nature, 366, 461, 1993. (4) Ishii et al. J. Geront. B. S. 49, B117, 1994. (5) Maynard Smith, Nature, 181, 496,1958 (6) Lithgow et al. J. Geront. B.S. 49, B270, 1994. (7) Larsen, PNAS, 90, 8905, 1993. (8) Vanfleteren, Biochem. J. 292, 605, 1993.