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Extended Life-Span Conferred by Cotransporter Gene Mutations in Drosophila
Abstract
Aging is genetically determined and environmentally modulated. In a study of longevity in the adult fruit fly, Drosophila melanogaster , we found that five independent P-element insertional mutations in a single gene resulted in a near doubling of the average adult life-span without a decline in fertility or physical activity. Sequence analysis revealed that the product of this gene, named Indy (for I'm not dead yet ), is most closely related to a mammalian sodium dicarboxylate cotransporter—a membrane protein that transports Krebs cycle intermediates. Indy was most abundantly expressed in the fat body, midgut, and oenocytes: the principal sites of intermediary metabolism in the fly. Excision of the P element resulted in a reversion to normal life-span. These mutations may create a metabolic state that mimics caloric restriction, which has been shown to extend life-span.
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Citations
Cited by
Mitochondria, Oxidants, and Aging
Balaban, R. S., Nemoto, S., & Finkel, T. (2005) · Cell · doi:10.1016/j.cell.2005.02.001 · Cited by 4,388
Wallace, D. C. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.110304.095751 · Cited by 3,185
Sir2 mediates longevity in the fly through a pathway related to calorie restriction
Rogina, B., & Helfand, S. L. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404184101 · Cited by 1,361
Self-citationThe plasticity of aging: insights from long-lived mutants
Kenyon, C. (2005) · Cell · doi:10.1016/j.cell.2005.02.002 · Cited by 1,338
Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue
Blüher, M., Kahn, B. B., & Kahn, C. R. (2003) · Science · doi:10.1126/science.1078223 · Cited by 1,155
Metadata
- Authors
- Rogina, B., Reenan, R. A., Nilsen, S. P., & Helfand, S. L.
- Venue
- Science
- Published
- 2000-12-15
- Volume
- 290
- Issue
- 5499
- Pages
- 2137-2140
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1990276200
- Cited by
- 505
- References
- 0
- FWCI
- 8.78
- Type
- journal article
- Language
- en
- Open access
- closed
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- Rogina, B., Reenan, R. A., Nilsen, S. P., & Helfand, S. L. (2000). Extended Life-Span Conferred by Cotransporter Gene Mutations in Drosophila. Science. https://doi.org/10.1126/science.290.5499.2137
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