Adult-specific over-expression of the Drosophila genes magu and hebe increases life span and modulates late-age female fecundity

Abstract

During Drosophila aging mortality rate increases exponentially and progeny production per animal declines dramatically, correlating with decreased number and division of somatic and germ-line stem cells in the gonads. To search for genes that might promote both longevity and fecundity, a P element transposon (PdL), containing an outwardly directed, doxycycline-inducible promoter was used to generate conditional mutations. Mutant females were screened for increased fecundity at late ages in the presence of doxycycline. Two genes were identified, named hebe (CG1623) and magu (CG2264), that when over-expressed in adult flies could increase life span by ~5–30% in both sexes and increase female fecundity at late ages. Transcripts for magu are enriched in the Drosophila stem cell niche region, and magu encodes a protein related to the human SMOC2 regulator of angiogenesis. While moderate over-expression of magu in adult females increased fecundity at late ages, high-level over-expression of magu was maternal-effect lethal. The data demonstrate that adult-specific over-expression of hebe and magu can increase life span and modulate female fecundity, and provide further evidence against obligatory trade-offs between reproduction and longevity.

Mechanisms of scaling in pattern formation

“…pent is the name used for gene CG2264 in the primary literature describing scale invariance of developing wing primordia referenced herein (Vuilleumier, et al, 2010;Ben-Zvi et al, 2011;Hamaratoglu et al, 2011). It is now known as magu (Li and Tower, 2009). Ltl, together with the intracellular inhibitory smad protein Dad, is upregulated by BMP signaling, whereas pent, dally and the BMP receptor gene thickveins (tkv) are downregulated in response to BMP signaling (Fig.…”

Dissecting the genetics of longevity inDrosophila melanogaster

“…42 Generation of a P-type transposable element with a doxycycline-inducible promoter has permitted, in genome-wide screens, the identification of genes that extend lifespan by overexpression; aging genes identified by this method include CTP:phosphocholine cytidylyltransferase-I (Cctl), filamin, four wheel drive (fwd), Sugar baby (Sug), VhaSFD, 43 hebe and magu. 44 Forced misexpression via a genome-wide P-element gene search has also identified 23 genic elements, out of a total of 646 inserts, that are correlated with relatively longer lifespan; 45 this method may also prove useful in the characterization of specific genes that mediate longevity.…”

“…In fact, the ability to identify aging genes by extended longevity mutant phenotypes underscores the existence of antagonistic pleiotropy at these loci: gene disruption that extends life must also compromise fitness, or else functional copies would not persist in populations. Despite some evidence that lifespan and reproduction can be decoupled, 44,61,81 multiple analyses have revealed previously undetected tradeoffs under specific conditions. 82,83 Furthermore, the close association between stress tolerance and longevity has permitted the use of this trait as a proxy for long-lived phenotypes in studies that examine the genetic basis of lifespan.…”

The song of the old mother: Reproductive senescence in female drosophila

“…A conditional screen for genes promoting longevity and late-life fertility identified 2 additional promising candidates; hebe and magu. 149 Overexpression of hebe and magu resulted in 6-23% and 2-28%, respectively, increases in median lifespan and varying levels of increased fecundity later in life (30-40 d pe) and occasionally reduced fecundity earlier in life (1-20 d pe). 149 In both cases, expression in female motorneurons was sufficient for the longevity effects.…”

“…149 Overexpression of hebe and magu resulted in 6-23% and 2-28%, respectively, increases in median lifespan and varying levels of increased fecundity later in life (30-40 d pe) and occasionally reduced fecundity earlier in life (1-20 d pe). 149 In both cases, expression in female motorneurons was sufficient for the longevity effects. These results also suggest that there is not necessarily a trade-off between longevity and reproduction.…”