Sex-specific regulation of aging in Caenorhabditis elegans

Bernadette Hotzi, Mónika Kosztelnik, Balázs Hargitai, Krisztina Takács-Vellai, János Barna, Kincső Bördén, András Málnási-Csizmadia, Mónika Lippai, Csaba Ortutay, Caroline Bacquet, Angela Pasparaki, Tamás Arányi, Nektarios Tavernarakis, Tibor Vellai

Research output: Contribution to journalArticle

4 Citations (Scopus)


A fascinating aspect of sexual dimorphism in various animal species is that the two sexes differ substantially in lifespan. In humans, for example, women's life expectancy exceeds that of men by 3–7 years. Whether this trait can be attributed to dissimilar lifestyles or genetic (regulatory) factors remains to be elucidated. Herein, we demonstrate that in the nematode Caenorhabditis elegans, the significantly longer lifespan of hermaphrodites—which are essentially females capable of sperm production—over males is established by TRA-1, the terminal effector of the sex-determination pathway. This transcription factor directly controls the expression of daf-16/FOXO, which functions as a major target of insulin/IGF-1 signaling (IIS) and key modulator of aging across diverse animal phyla. TRA-1 extends hermaphrodite lifespan through promoting daf-16 activity. Furthermore, TRA-1 also influences reproductive growth in a DAF-16-dependent manner. Thus, the sex-determination machinery is an important regulator of IIS in this organism. These findings provide a mechanistic insight into how longevity and development are specified unequally in the two genders. As TRA-1 is orthologous to mammalian GLI (glioma-associated) proteins, a similar sex-specific mechanism may also operate in humans to determine lifespan.

Original languageEnglish
Article numbere12724
JournalAging cell
Issue number3
Publication statusPublished - Jun 2018



  • Caenorhabditis elegans
  • TRA-1/GLI
  • aging
  • daf-16/FOXO
  • dauer development
  • insulin/IGF-1 signaling
  • sex determination

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

Cite this

Hotzi, B., Kosztelnik, M., Hargitai, B., Takács-Vellai, K., Barna, J., Bördén, K., Málnási-Csizmadia, A., Lippai, M., Ortutay, C., Bacquet, C., Pasparaki, A., Arányi, T., Tavernarakis, N., & Vellai, T. (2018). Sex-specific regulation of aging in Caenorhabditis elegans. Aging cell, 17(3), [e12724].