It has long been observed that mild or nonlethal stress often has the apparently paradoxical effect of benefiting the organism by increasing its longevity (Minois, 2000). Conversely, it has also been suggested that all long-lived strains and mutants exhibit some form of stress resistance (Parsons, 1995; Johnson et al., 1996). This relationship is thought to reflect the fact that their natural environment usually exerts substantial, albeit variable, stresses on organisms. Evolutionary considerations of Darwinian fitness will thus impose a premium on genotypes conferring metabolic efficiency and stress resistance (Parsons, 1997, 2003). The magnitude of the effects of stress resistance on longevity are summarized in Table 25.3.
We will examine four complementary lines of evidence bearing on the relationship of stress resistance and extended longevity in Drosophila. The first involves the use of strains selected for extended longevity, followed by an analysis of the mechanisms responsible for the altered phenotype. The second involves standard mutational techniques in which candidate genes thought to play an important role in longevity are inactivated, and the life span of the experimental animals is assayed to see if the original hypothesis was correct or not. The third approach involves ''genetic engineering'' or transgenic work in which extra copies of candidate genes are inserted into experimental animals and their longevity is then assayed to determine if the added gene has a significant effect on the life span. The fourth approach involves the environmental induction of stress response genes and the analysis of their effect on the longevity of the tested animals.
As a result of our studies on the biochemistry and stress resistance properties of the long-lived La strains, we knew that the only predictive factor clearly and significantly associated with extended longevity in our strains was an enhanced resistance to oxidative stress (Arking et al., 1991; Force et al., 1995). Thus it seemed logical to conclude that the long-lived La animals probably live long because of higher-than-normal activity of the antioxidant defense system genes early in life. Quantitative trait loci (QTL) mapping is a genetic method of identifying small chromosome regions which have a significant statistical effect on longevity, and may be viewed as a genome-wide scan that allows one to identify interesting genes for further investigation. Curtsinger and Khazaeli (2002) did such a procedure on recombinant inbred strains derived from the La and Ra strains discussed above. They found four QTLs located on chromosomes 2 and 3 of the (La x Ra) recombinant inbred strains that accounted for almost all of the selection response. The major QTLs for both paraquat resistance and longevity are coincident with each other and are centered over a small region of chromosome 3L which contains the loci of the CuZnSOD
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For centuries, ever since the legendary Ponce de Leon went searching for the elusive Fountain of Youth, people have been looking for ways to slow down the aging process. Medical science has made great strides in keeping people alive longer by preventing and curing disease, and helping people to live healthier lives. Average life expectancy keeps increasing, and most of us can look forward to the chance to live much longer lives than our ancestors.