| Summary: | 碩士 === 國立清華大學 === 生物科技研究所 === 95 === The long-lived mutant strain EP1130 was screened from a multiple-stresses test. The P-element inserted in EP1130 down-regulating the expression of alpha-mannosidase-I (CG32684). Independent EP insertion alleles in the CG32684, EP1628 and 982 with reduced expression of alpha-mannosidase-I also showed increase of lifespan and stress resistances. EP1588 is another EP line screened from the multiple-stresses test associated with CG3810, which is a CG32684 paralogue, showed decreased expression and also displayed extended lifespan. We also found heterozygous mutants in these four mutant lines were sufficient for long-lived phenotype. Transheterozygotes among EP1130, 1628, and 982 do not show further enhancement of lifespan compared to homozygous strains. The treatments of alpha-mannosidase-I inhibitors, 1-deoxynojirimycin or kifunensine also showed beneficial effects on lifespan elongation in Drosophila melanogaster. Using molecular and genetic approaches, we found that longevity in EP1130 was independent from insulin/IGF-1, JNK pathway and ER stress. However, the genetics data suggested that it might be involved with ecdysone pathway. In conclusion, this study demonstrated that alpha-mannosidase-I plays a role in regulating lifespan in Drosophila melanogaster.
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