kin-29 encodes the C. elegans homolog of mammalian Salt-Inducible Kinases (SIKs).
kin-29 mutants are small, have increased propensity to develop into non-reproductive dauer larvae, have reduced chemoreceptor gene expression (Lanjuin and Sengupta, 2002; van der Linden et al.., 2007), have reduced cellular ATP despite increased fat stores, and show reduced sleep (Grubbs et al., 2020). KIN-29 phosphorylates and inhibits the class II histone deacetylase 4 homolog HDA-4 to regulate gene expression in sensory neurons (van der Linden et al., 2007). The longevity phenotype of
kin-29 mutants is suppressed by mutations in
daf-16 (Lanjuin and Sengupta, 2002), which encodes a forkhead box protein O (FOXO) transcription factor (Kenyon et al., 1993). These results indicated that the increased lifespan of
kin-29 mutants may be due to reduced insulin signaling.
To determine whether HDA-4 is required for the KIN-29 regulation of lifespan, we performed a survival analysis. As previously reported (Lanjuin and Sengupta, 2002),
kin-29(
oy38) mutants are long-lived. In contrast,
hda-4(
oy57) mutants are short lived (Fig. 1). The
kin-29hda-4 double mutant longevity phenotype was similar to the phenotype of
hda-4 single mutants (Fig. 1), suggesting that
hda-4 acts downstream of
kin-29 to regulate lifespan. Together with our previous findings (van der Linden et al., 2007), these genetic results suggest that KIN-29 may regulate lifespan via the action of HDA-4. Since SIKs can inhibit FOXO activity via HDAC4 to regulate gene expression (Mihaylova et al., 2011; Wang et al., 2011), it would be interesting in future studies to test the model that KIN-29/HDA-4 signaling converges on DAF-16/FOXO to modulate gene expression associated with longevity.