| Title: |
Transcriptional profiling of MnSOD-mediated lifespan extension in Drosophilareveals a species-general network of aging and metabolic genes |
| Authors: |
Curtis, Christina; Landis, Gary N; Folk, Donna; Wehr, Nancy B; Hoe, Nicholas; Waskar, Morris; Abdueva, Diana; Skvortsov, Dmitriy; Ford, Daniel; Luu, Allan; Badrinath, Ananth; Levine, Rodney L; Bradley, Timothy J; Tavaré, Simon; Tower, John |
| Source: |
Genome Biology ; volume 8, issue 12 ; ISSN 1474-760X |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2007 |
| Description: |
Background Several interventions increase lifespan in model organisms, including reduced insulin/insulin-like growth factor-like signaling (IIS), FOXO transcription factor activation, dietary restriction, and superoxide dismutase (SOD) over-expression. One question is whether these manipulations function through different mechanisms, or whether they intersect on common processes affecting aging. Results A doxycycline-regulated system was used to over-express manganese-SOD (MnSOD) in adult Drosophila , yielding increases in mean and maximal lifespan of 20%. Increased lifespan resulted from lowered initial mortality rate and required MnSOD over-expression in the adult. Transcriptional profiling indicated that the expression of specific genes was altered by MnSOD in a manner opposite to their pattern during normal aging, revealing a set of candidate biomarkers of aging enriched for carbohydrate metabolism and electron transport genes and suggesting a true delay in physiological aging, rather than a novel phenotype. Strikingly, cross-dataset comparisons indicated that the pattern of gene expression caused by MnSOD was similar to that observed in long-lived Caenorhabditis elegans insulin-like signaling mutants and to the xenobiotic stress response, thus exposing potential conserved longevity promoting genes and implicating detoxification in Drosophila longevity. Conclusion The data suggest that MnSOD up-regulation and a retrograde signal of reactive oxygen species from the mitochondria normally function as an intermediate step in the extension of lifespan caused by reduced insulin-like signaling in various species. The results implicate a species-conserved net of coordinated genes that affect the rate of senescence by modulating energetic efficiency, purine biosynthesis, apoptotic pathways, endocrine signals, and the detoxification and excretion of metabolites. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1186/gb-2007-8-12-r262 |
| DOI: |
10.1186/gb-2007-8-12-r262.pdf |
| DOI: |
10.1186/gb-2007-8-12-r262/fulltext.html |
| Availability: |
https://doi.org/10.1186/gb-2007-8-12-r262; https://link.springer.com/content/pdf/10.1186/gb-2007-8-12-r262.pdf; https://link.springer.com/article/10.1186/gb-2007-8-12-r262/fulltext.html |
| Rights: |
http://creativecommons.org/licenses/by/2.0/ ; http://creativecommons.org/licenses/by/2.0/ |
| Accession Number: |
edsbas.2890D73F |
| Database: |
BASE |