Evolutionary conservation of regulated longevity assurance mechanisms

Table 4 Gene-level conservation of IIS-regulated transcriptional responses, and effects of RNAi on lifespan in C. elegans

Gene ID	Gene description	Percentage of vector control	p value	Microarray fold change	p value
R13H8.1/daf-16	FOXO transcription factor, acts downstream of daf-2	43	<0.0001	-	-
C10G11.5/pnk-1	Pantothenate kinase	26	<0.0001	3.81	0
T25G3.4	Glycerol-3-phosphate dehydrogenase	101	0.64	1.96	0.004
F57C2.5	Contains similarity to strictosidine synthase	100	0.34	1.65	0.001
C41C4.7	Ortholog of the human cystinosin gene	100	0.17	1.63	0.0001
F19H8.1/tps-2	Trehalose-6-phosphate synthase	100	0.90	2.28	0.007
F56D1.6/cex-1	Calexcitin, involved in serotonin-mediated responses	91	0.37	2.11	0.004
Y105C5B.28/ *gln-3*	Glutamine synthetase	92	0.25	2.00	0.006
F55D10.1	Orthologous to mannosidase, α, class 2B, member 1	103	0.046	2.96	0.0007
H03A11.1	Ortholog of a protein expressed in hematopoietic cells	83	0.012	1.59	0.0009

This table shows the nine worm-fly orthologous genes that show increased expression in response to reduced IIS (fold change in expression in daf-2 relative to daf-16; daf-2 shown). In bold: genes also differentially expressed in the Little mouse; a paralog of pnk-1 is also up-regulated in the Little mouse (additional Table 2 in Additional data file 3). For simplicity, only the gene name for the worm ortholog of the gene pair is shown. Only ortholog pairs (or triplets) that showed the same direction of change were considered, and at the level of significance used (q < 0.1), only up-regulated ortholog pairs were identified. To test for a possible role in longevity, expression of each individual gene was knocked down in C. elegans using RNAi; lifespans were compared to those of animals treated with control vector RNAi and calculated as a percentage of vector control (full lifespan data are available in Additional data file 5). The p value is the result of the log rank test comparing experimental lifespans to vector control. RNAi of R13H8.1/daf-16 was used as a positive control, but is not a differentially expressed orthologous gene.

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