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Gene Review

mth  -  methuselah

Drosophila melanogaster

Synonyms: CG6936, Dmel\CG6936, G-protein coupled receptor Mth, MTH, Mth, ...
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Psychiatry related information on mth

  • The hypotheses tested here were: (i) that the extension of life span by mth might be temperature-dependent, and (ii) that it might be associated with depression of reproductive output, physical activity, or the rate of metabolism [1].

High impact information on mth


Biological context of mth

  • In ten surveyed populations, the most common mth haplotype exhibited a 40% cline in frequency that coincided with population level differences in multiple life-history traits including lifespan [5].
  • Here we report the identification and characterization of two endogenous peptide ligands of Methuselah, designated Stunted A and B. Flies with mutations in the gene encoding these ligands show an increase in lifespan and resistance to oxidative stress [3].

Anatomical context of mth

  • As Sun has been identified as the ligand for the Methuselah receptor that regulates aging, Sun may function both within and outside mitochondria [6].
  • Interestingly, slowing of stem cell division rate was not observed in long-lived methuselah mutant flies [7].

Other interactions of mth

  • However, Ka : Ks ratios indicate a difference in levels of functional constraint at the two methuselah, loci with mth2 exhibiting a five- to six-fold reduction in levels of amino acid divergence relative to mth [8].
  • The N-terminal Rel homology domain (RHD) of Dl was not sufficient for repression of mth [9].

Analytical, diagnostic and therapeutic context of mth

  • Unexpectedly, semi-quantitative RT-PCR analysis revealed that the level of mth transcripts was reduced in dl flies [9].


  1. Temperature-dependent trade-offs between longevity and fertility in the Drosophila mutant, methuselah. Mockett, R.J., Sohal, R.S. Exp. Gerontol. (2006) [Pubmed]
  2. Extended life-span and stress resistance in the Drosophila mutant methuselah. Lin, Y.J., Seroude, L., Benzer, S. Science (1998) [Pubmed]
  3. The endogenous ligand Stunted of the GPCR Methuselah extends lifespan in Drosophila. Cvejic, S., Zhu, Z., Felice, S.J., Berman, Y., Huang, X.Y. Nat. Cell Biol. (2004) [Pubmed]
  4. Crystal structure of the ectodomain of Methuselah, a Drosophila G protein-coupled receptor associated with extended lifespan. West, A.P., Llamas, L.L., Snow, P.M., Benzer, S., Bjorkman, P.J. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  5. Adaptive evolution of a candidate gene for aging in Drosophila. Schmidt, P.S., Duvernell, D.D., Eanes, W.F. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  6. The epsilon-subunit of mitochondrial ATP synthase is required for normal spindle orientation during the Drosophila embryonic divisions. Kidd, T., Abu-Shumays, R., Katzen, A., Sisson, J.C., Jiménez, G., Pinchin, S., Sullivan, W., Ish-Horowicz, D. Genetics (2005) [Pubmed]
  7. Dynamics of the male germline stem cell population during aging of Drosophila melanogaster. Wallenfang, M.R., Nayak, R., DiNardo, S. Aging Cell (2006) [Pubmed]
  8. Clines and adaptive evolution in the methuselah gene region in Drosophila melanogaster. Duvernell, D.D., Schmidt, P.S., Eanes, W.F. Mol. Ecol. (2003) [Pubmed]
  9. Transcriptional regulation of the methuselah gene by dorsal protein in Drosophila melanogaster. Kim, H., Kim, J., Lee, Y., Yang, J., Han, K. Mol. Cells (2006) [Pubmed]
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