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Updated: Jun 19, 2026
Measurement of Lifespan in Drosophila melanogaster
Published on: January 7, 2013
dSir2 and Dmp53 interact to mediate aspects of CR-dependent lifespan extension in D. melanogaster
Johannes H Bauer1, Siti Nur Sarah Morris, Chengyi Chang
1Department of Molecular Biology, Brown University Providence, RI 02912, USA.
Abstract:
Calorie Restriction (CR) is a well established method of extending life span in a variety of organisms. In the fruit fly D. melanogaster, CR is mediated at least in part by activation of dSir2. In mammalian systems, one of the critical targets of Sir2 is the tumor suppressor p53. This deacetylation of p53 by Sir2 leads to inhibition of p53's transcriptional activity. We have recently shown that inhibition of Dmp53 activity in the fly brain through the use of dominant-negative (DN) constructs that inhibit DNA-binding can extend life span. This life span extension appears to be related to CR, as CR and DN-Dmp53 donot display additive effects on life span. Here we report that life span extension by DN-Dmp53 expression is highly dynamic and can be achieved even when DN-Dmp53 is expressed later in life. In addition, we demonstrate that life span extension by activation of dSir2 and DN-Dmp53 expression are not additive. Furthermore, we show that dSir2 physically interacts with Dmp53 and can deacetylate Dmp53-derived peptides. Taken together, our data demonstrate that Dmp53 is a down stream target of dSir2 enzymatic activity and mediates some aspects of the life span extending effects of CR.
Insights
Calorie restriction extends life span by activating dSir2, which targets Dmp53. Inhibiting Dmp53 in flies also extends life, suggesting it mediates calorie restriction
Area of Science:
- Aging research
- Molecular biology
- Genetics
Background:
- Calorie Restriction (CR) is a proven life-extending intervention across species.
- In fruit flies, CR's effects involve the activation of dSir2.
- Mammalian Sir2 targets the tumor suppressor p53, inhibiting its activity via deacetylation.
Purpose of the Study:
- To investigate the role of Dmp53 in mediating CR's life-extending effects in fruit flies.
- To determine if dSir2 directly interacts with and modifies Dmp53.
- To explore the dynamic nature of life span extension induced by Dmp53 inhibition.
Main Methods:
- Utilizing dominant-negative (DN) constructs to inhibit Dmp53 DNA-binding activity in Drosophila melanogaster.
- Assessing the additive effects of CR and DN-Dmp53 on life span.
- Investigating the physical interaction between dSir2 and Dmp53.
- Performing in vitro deacetylation assays on Dmp53-derived peptides using dSir2.
Main Results:
- Inhibition of Dmp53 activity in the fly brain extends life span, an effect not additive with CR.
- Life span extension by DN-Dmp53 is dynamic and can be induced later in life.
- dSir2 physically interacts with Dmp53 and deacetylates its peptides, indicating Dmp53 is a downstream target.
Conclusions:
- Dmp53 acts as a downstream target of dSir2 enzymatic activity.
- Dmp53 mediates some of the life-extending benefits of Calorie Restriction.
- The findings elucidate a molecular pathway linking CR, dSir2, and Dmp53 in life span regulation.
