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Figure 19.2. Conserved regulation of longevity. In yeast, worms, flies, and mice the down-regulation of partially conserved glucose or insulin/ insulin-like growth factor 1 (IGF-1) pathways promotes the expression of antioxidant enzymes and heat-shock proteins, induces the accumulation of glycogen or fat, and extends life span. In yeast and worms the induction of stress resistance is required for longevity extension. In flies and mice a conclusive role for stress resistance induction in promoting life span has not been established yet. Sch9 and Pkhl are functional homologs of Aktl and PDK1, respectively.

Figure 19.3. Wild-type (left) and long-lived ''dwarf'' (right) yeast, flies and mice with mutations that decrease glucose or insulin/IGF-I-like signaling. Yeast sch9 null mutants form smaller colonies (left panel). sch9 mutants are also smaller in size, grow at a slower rate, and survive three times longer than wild-type yeast. Chico homozygous mutant female flies are dwarfs and exhibit an increase in life span of up to 50% (center panel) (figure provided by D. Gems). Chico functions in the fly insulin/IGF-I-like signaling pathway. The GHR/BP mice are dwarfs deficient in IGF-I and exhibit a 50% increase in life span (right panel) (figure provided by A. Bartke). Other yeast and worm mutants exhibit life-span extension of more than 100% but do not have detectable growth defects. (Figure reproduced from Science, Vol. 299, pp. 1342-1346, 2003.)

Figure 19.3. Wild-type (left) and long-lived ''dwarf'' (right) yeast, flies and mice with mutations that decrease glucose or insulin/IGF-I-like signaling. Yeast sch9 null mutants form smaller colonies (left panel). sch9 mutants are also smaller in size, grow at a slower rate, and survive three times longer than wild-type yeast. Chico homozygous mutant female flies are dwarfs and exhibit an increase in life span of up to 50% (center panel) (figure provided by D. Gems). Chico functions in the fly insulin/IGF-I-like signaling pathway. The GHR/BP mice are dwarfs deficient in IGF-I and exhibit a 50% increase in life span (right panel) (figure provided by A. Bartke). Other yeast and worm mutants exhibit life-span extension of more than 100% but do not have detectable growth defects. (Figure reproduced from Science, Vol. 299, pp. 1342-1346, 2003.)

separate PCR reactions. The UPTAG amplification uses primers B-U1 (5'biotin-GATGTCCACGAGGTCTCT) and B-U2- comp (50biotin-GTCGACCTGCAGCG TACG); the DNTAG amplification uses B-D1 (50biotin-CGGTGTCGGTCTCGTAG) and B-D2-comp (50biotin-CGAGCTCGAATTCATCG). Biotinylated amplicons are combined and used to probe high-density oligo-nucleotide arrays. The arrays are stained with phycoery-thrin-streptavidin and scanned at an emission wavelength of 560 nm. The enrichment or depletion of any specific deletion over time is determined by monitoring the changes in TAG intensities after normalizing using day 3 arrays. Based on the relative abundance of each strain on a time course, it is possible to identify genes whose expression is required for long-term survival (the corresponding deletion mutants disappear early in the experiment), and genes whose activity reduces the life span (the corresponding deletion mutants are found in the pool after the death of the majority of the population). We expect that most deletions will have either no effect or a negative effect on life span and that only a few deletions will cause major increases in life span. However, this method should allow an accurate classification of each deletion based on its negative, positive or neutral effect on survival. After identifying the potential long-lived deletion mutants, we will test each of them individually to confirm their life-span extension phenotype. We predict that this system will allow us to identify novel long-lived deletion mutants we previously missed because of the limitations of the mutagenesis method used.

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How To Add Ten Years To Your Life

How To Add Ten Years To Your Life

When over eighty years of age, the poet Bryant said that he had added more than ten years to his life by taking a simple exercise while dressing in the morning. Those who knew Bryant and the facts of his life never doubted the truth of this statement.

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