Indy

Symbol: Indy
Name: I'm not dead yet
Alias: CG3979
Entrez gene ID: 40049
Ensembl gene ID: FBgn0036816
Species: Fly (Taxid: 7227)

Functional description:
Cation-independent electroneutral transporter (not associated with membrane depolarization) of a variety of tricarboxylic and dicarboxylic acid-cycle intermediates. There is also small, but detectable, transport of monocarboxylics. Transport is through the epithelium of the gut and across the plasma membranes of organs involved in intermediary metabolism and storage. Affinity for substrates is citrate > succinate > pyruvate. Fumarate, a-ketoglutarate, and glutarate are also transported, but not lactate. Transport mechanism that is not coupled to Na(+), K(+), or Cl(-). Function is shown in Xenopus oocytes and human retinal pigment epithelial (HRPE) cell lines. [UniProt]

Observation:

Flies heterozygotic for a disruption in Indy gene have extended mean (87-92%) and maximum (45%) lifespan. Homozygotes for the disruption show only a 10 - 20% increase in mean lifespan [11118146]. Heterozygous insertion of a p-element in the non-coding region of Indy locus leads to a reduction in Indy mRNA expression and causes a significant median lifespan extension in male and female by about 29% and 34%, respectively. At normal or high calorie conditions Indy heterozygote mutants have a significant lifespan extension, but under low calorie conditions, Indy heterozygous mutants have minimal median lifespan extension. Reduction of calorie content from high to normal calorie condition results in 19% decline in Indy mRNA and from normal to low calorie condition results in additional 9% decrease in Indy mRNA. Reduction of calorie content from high to normal calorie conditions in heterozygous Indy mutants leads to 20% reduction in Indy mRNA expression without any additional decrease upon further reduction to low calorie food. Maximum lifespan extension is associated with Indy mRNA levels between 25 - 75% of normal. Long-lived heterozygous Indy mutants on high-calorie food and normal wild-type on low-calorie food have several phenotypes in common: 50 - 60 % reduced mRNA expression levels of Ilp2, Ilp3 and Ilp 5; similar high percentage of anti-FOXO-positive nuclei in fat body cells; higher sensitivity to starvation; do not gain weight; similar decrease in triglycerides and fat storage; normal food intake [19470468].

Mutations in Indy dramatically extend lifespan without a loss in fertility, physical activity, flight velocity or metabolic rate [11118146; 12626742]. Indy encodes a high-affinity dicarboxylate/citrate plasma membrane transporter found most abundantly in adult fat body, oenocytes and midgut cells, the primary sites of intermediary metabolism [12391301]. Indy mutation alters metabolism in a manner similiar to DR and mutants have several phenotypes with long-lived DR files in common, including decreases insulin-like signaling, lipid storage, weight gain, and resistance to starvation, and an increase in spontaneous physical activity [19470468].

Of the Indy206 and Indy302 mutation only one of the two has lower mRNA levels and both do not extend lifespan of female flies in any genetic background. In original genetic background only Indy mutation associated with altered RNA expression extends the lifespan of males. This effect is abolished by back-crossing into standard out-bred genetic backgrounds and is associated with an unidentified locus on the X chromosome. Original Indy line with long-lived males is infected by the cytoplasmic Wolbachia. Longevity of Indy males disappear after tetracycline clearance of this endosymbiont [17571923].



Interventions:
  • Indy mutation +10 to +92% +45%

  • Assays: Organismal Lifespan
    Mean: +87 to 92
    Median: +29 to 34
    Maximum: +45

    Classification:
  • Gerontogene
  • Positive Gerontogene
  • DR-Essential


  • References:
  • 21937764: Indy knockdown in mice mimics elements of dietary restriction.
  • 19470468: Long-lived Indy and calorie restriction interact to extend life span.
  • 11118146: Extended life-span conferred by cotransporter gene mutations in Drosophila.
  • 12626742: Conditional tradeoffs between aging and organismal performance of Indy long-lived mutant flies.
  • 17571923: No influence of Indy on lifespan in Drosophila after correction for genetic and cytoplasmic background effects.
  • 12391301: Functional characterization and immunolocalization of the transporter encoded by the life-extending gene Indy.


  • Aging Relevance Analysis/Source:
  • GenAge
  • GenDR

  • Homologs
  • SLC13A2 (9606)
  • SLC13A2 (9598)
  • SLC13A2 (9615)
  • SLC13A2 (9913)
  • Slc13a2 (10090)
  • Slc13a2 (10116)
  • SLC13A2 (9031)
  • slc13a2 (7955)
  • Indy (7227)
  • AgaP_AGAP007055 (7165)
  • AgaP_AGAP007054 (7165)
  • TDT (3702)
  • Os09g0484900 (4530)
  • Os08g0503700 (4530)

  • Orthologs
  • SLC13A4 (9544)
  • Slc13a5 (10090)
  • Slc13a4 (10116)
  • Slc13a2 (10090)
  • SLC13A3 (9544)
  • Slc13a1 (10090)
  • SLC13A4 (9606)
  • SLC13A1 (9606)
  • Slc13a4 (10090)
  • nac-3 (6239)
  • Slc13a2 (10116)
  • Slc13a5 (10116)
  • SLC13A1 (9544)
  • PHO91 (4932)
  • B0285.6 (6239)
  • Slc13a3 (10116)
  • SLC13A5 (9606)
  • nac-1 (6239)
  • Slc13a3 (10090)
  • SLC13A2 (9606)
  • PHO87 (4932)
  • Slc13a1 (10116)
  • SLC13A3 (9606)
  • PHO90 (4932)
  • nac-2 (6239)
  • SLC13A4 (9544)
  • Slc13a5 (10090)
  • Slc13a4 (10116)
  • Slc13a2 (10090)
  • SLC13A3 (9544)
  • Slc13a1 (10090)
  • SLC13A4 (9606)
  • SLC13A1 (9606)
  • Indy-2 (7227)
  • Slc13a4 (10090)
  • nac-3 (6239)
  • Slc13a2 (10116)
  • Slc13a5 (10116)
  • SLC13A1 (9544)
  • PHO91 (4932)
  • B0285.6 (6239)
  • CG7309 (7227)
  • Slc13a3 (10116)
  • SLC13A5 (9606)
  • nac-1 (6239)
  • Slc13a3 (10090)
  • SLC13A2 (9606)
  • PHO87 (4932)
  • Slc13a1 (10116)
  • SLC13A3 (9606)
  • PHO90 (4932)
  • nac-2 (6239)
  • CG33934 (7227)

  • Inparanoids
  • FBpp0074848 (7227)
  • ENSMUSP00000001122 (10090)
  • ENSRNOP00000038185 (10116)
  • ENSMMUP00000028937 (9544)
  • ENSP00000316202 (9606)

  • Note: A specfic level of Indy expression, something less than normal, is optimal for lifespan extension.

    Edit \ Update (Admin) | Delete

    Comment on This Data Unit