Biology Reference
In-Depth Information
downregulating
nhr
-
25
to bring about a cessation of molting (
Hayes,
Frand, & Ruvkun, 2006
). Further exploring the relationship between the
molting clock and the heterochronic timer should help us understand
how iterative cyclical timing devices interface with switches to promote
the proper succession of temporal fates.
4. HORMONAL CONTROL OF LONGEVITY
Pioneering studies in the worm have illuminated conserved signaling
pathways that regulate longevity. Several pathways have emerged that regulate
longevity across taxa including reduced IIS, mitochondrial function, dietary-
restriction-mediated longevity, and signaling from the gonad (
Kenyon, 2010
).
Below, we highlight recent discoveries linking heterochronic functions and
hormonal signaling to the gonadal longevity pathway.
4.1. Gonadal longevity pathway
Reproductive tissues are not only involved in propagation of the species but
can also affect the life span. Removal of the gonad or parts thereof can extend
life span in a variety of species (
Hansen, Flatt, & Aguilaniu, 2013
). Kenyon
and coworkers originally showed that removal of
C
.
elegans
germline precur-
sor cells by laser microsurgery or genetic mutation in germlineless
glp
-
1
mutants extends life span by 60% (
Arantes-Oliveira, Apfeld, Dillin, &
Kenyon, 2002; Hsin & Kenyon, 1999
). This longevity depends upon the
presence of the somatic gonad, since removal of somatic gonadoblasts abro-
gates the longevity. That the reproductive system controls the life span of the
whole organism implies that hormonal mechanisms might be involved.
An analysis of genes required for life span extension of germlineless ani-
mals revealed that a number of transcription factors including
daf
-
12
, the
FOXO homolog
daf
-
16
(
Hsin & Kenyon, 1999
), the HNF4
a
-like nuclear
hormone receptor
nhr
-
80
(
Goudeau et al., 2011
), and the FOXA homolog
pha
-
4
are required (
Lapierre, Gelino, Melendez, & Hansen, 2011
). These
transcription factors stimulate proteasomal activity, lipolysis, fatty acid
desaturation, and autophagy, demonstrating that germline removal entails
a remodeling of the regulatory and metabolic state of the whole organism
to somehow promote longevity (
Vilchez et al., 2012; Hansen et al.,
2013
). For example, the liberation of fatty acids is central to the longevity
phenotype in the gonadal pathway (
Wang, O'Rourke, & Ruvkun,
2008
). One way in which fatty acids contribute to the longevity is through
stimulation of autophagy (
Lapierre et al., 2011
), which is important for
