TY - JOUR
T1 - Sex-specific regulation of aging in Caenorhabditis elegans
AU - Hotzi, Bernadette
AU - Kosztelnik, Mónika
AU - Hargitai, Balázs
AU - Takács-Vellai, Krisztina
AU - Barna, János
AU - Bördén, Kincső
AU - Málnási-Csizmadia, András
AU - Lippai, Mónika
AU - Ortutay, Csaba
AU - Bacquet, Caroline
AU - Pasparaki, Angela
AU - Arányi, Tamás
AU - Tavernarakis, Nektarios
AU - Vellai, Tibor
N1 - Publisher Copyright:
© 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
PY - 2018/6
Y1 - 2018/6
N2 - 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.
AB - 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.
KW - aging
KW - Caenorhabditis elegans
KW - daf-16/FOXO
KW - dauer development
KW - insulin/IGF-1 signaling
KW - sex determination
KW - TRA-1/GLI
UR - http://www.scopus.com/inward/record.url?scp=85042563139&partnerID=8YFLogxK
U2 - 10.1111/acel.12724
DO - 10.1111/acel.12724
M3 - Artículo
C2 - 29493066
AN - SCOPUS:85042563139
SN - 1474-9718
VL - 17
JO - Aging Cell
JF - Aging Cell
IS - 3
M1 - e12724
ER -
