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Table 4 C. elegans candidate genes

From: 3D Network exploration and visualisation for lifespan data

Gene symbol NCBI gene ID Ageing relevance evidence
acdh-7, acdh-8 181758 173979 Expression of human homologous gene ACADM decreases over age in skin [45].
aco-1 181324 Mutant animals lacking genes aco-1 and ftn-1 show significant reduced lifespan upon iron stress, while N2 and ftn-2 animals show no difference. The results suggest that ftn-1 and aco-1 are transcriptionally regulated by iron and are important for iron homeostasis affecting lifespan upon iron stress conditions in C. elegans [42].
alh-4 179026 Gene alh-4 is involved in determination of adult lifespan [46].
acs-3 178677 acs-3 mutants exhibited a significantly shorter lifespan on E. coli OP50 (12.8 days), as compared to WT animals (17.9 days) [52].
acs-4 176005 RNAi of acs-4 resulted in a 6.1% increase in lifespan compared to wildtype [53].
acs-17 180859 Many “dod” genes are responsible for the longevity of daf-2 mutants. The “dod” genes that could previously be identified as life span regulating genes include among others dod-9/acs-17 [54, 55].
alh-5 alh-12 sodh-1 sodh-2 178680 176056 179627 179628 Metabolic fingerprint studies with long-lived mutants daf-2 and eat-2 showed strong upregulation of enzymes involved in alcohol fermentation including alh-5, alh-12, sodh-1 and sodh-2 [56].
dbl-1 179068 C. elegans mutants with a loss-of-function in dbl-1 showed reduced lifespan [57].
ech-6 176376 Metabolism of short-chain organic acids (e.g. gene ech-6) is upregulated in states of impaired IGF-1 signalling in a daf-2 mutant strain with extended lifespan [47].
ech-9 184065 The top five overrepresented categories yielded by the comparative expression analysis in three ets-4 deletion strains with increased lifespan include fatty acid metabolic process genes (acdh-2, ech-9, and C48B4.1) [48].
enol-1 174423 Compared to wild type strain N2 the RNAi knockdown of gene enol-1 reduced the mean lifespan by 11-14%. Compared to eat-2 knockout strains it reduced the mean lifespan by 15-19% in strain eat-2(ad1116) and by 28% in strain eat-2(ad465) [41].
F08F8.7 176043 F08F8.7 was found to be upregulated in long-living mutant daf-2 in comparison to N2 [56].
F54C8.1 186222 Concerning branched-chain amino acid metabolism, F54C8.1 was upregulated in the long-lived mutant daf-2 [56]
F59F4.1 181668 Gene F59F4.1 was linked to Parkinson’s disease by screens involving alpha-synuclein. In alpha-synuclein expressing nematode lines age dependent degeneration of dopaminergic neurons was observed [49].
hacd-1 178638 Gene hacd-1 was linked to lifespan effects of germline mutants by transcriptome analysis [50].
idhg-2 172430 Energy metabolism seems to be differentially regulated in long-lived mutants compared to N2. Particularly idhg-2 was upregulated in daf-2 mutants [56].
mek-1 181004 The lifespan extending effect of intermittent feeding (IF) of 74.9% in wiltype strain N2 is reduced to 21.7% in the mek-1 loss-of-function strain ks54 [58].
pfk-1.2 179335 Long-living mutants show upregulation of pfk-1.2 a gene encoding for one of the key enzymes of glycolysis [56].
pkc-2 181166 Knockout of gene pkc-2 decreased the mean lifespan significantly by 3–5% at 15°C and compensated for the short-lived phenotype of trpa-1 mutant worms at 20°C. Overexpression of gene pkc-2 increased the mean lifespan significantly by 3–6% at 20°C [43].
plc-3 174586 The youthful swimming phenotype of let-23 (gf) mutant was suppressed by RNAi knockdown of plc-3 and itr-1 [59].
pyk-1 172744 Compared to wildtype strain N2 the RNAi knockdown of gene pyk-1 reduced the mean lifespan by 19–21%. And compared to eat-2 knockout strain eat-2(ad1116) it reduced the mean lifespan by 19–29% [41].
R04A9.7 3565956 The traditional Chinese medicine Gengnianchun (GNC) prolongs the lifespan of C. elegans. Comparison of genome-wide transcriptional profiling of untreated and GNC treated worms at day 22 showed that GNC downregulated the expression of R04A9.7 [60].
Gene symbol NCBI gene ID Ageing relevance evidence
rbx-1 179358 RNAi of rbx-1 results terminal stage arrest during embryogenesis[61].
sdhd-1 174692 Extension of lifespan in gas-1 (fc21) was observed after sdhc-1 and sdhd-1 knockdown [62].
skr-9 skr-14 sma-4 178494 178839 175815 Wnt signaling is highly involved in the aging process of C. elegans with a shifting dynamic. From L4 to D6 Wnt signalling is upregulated and from D6 to D15 it is down-regulated. Eight genes including skr-9, skr-14, and sma-4, which are involved in the Wnt signalling, were significantly up-regulated from L4 to D6 and down-regulated from D6 to D15 [63].
sucg-1, sucl-2 177555 175252 The decrease of female reproductive senescence is a hallmark of ageing. The inactivation of sucg-1 or sucl-2 by RNAi extends the reproductive lifespan [64].
T02G5.7 3565206 The gene kat-1, a parolog of gene T02G5.7, is included as AF AF_006931 in AgeFactDB [51].
tpi-1 174844 RNAi knockdown of gene tpi-1 reduced the the mean lifespan by 8% and the maximum lifespan by 10% [44].
  1. Candidate genes obtained by the candidate gene selection strategy summarised in Fig. 7. Results of the literature search for ageing relevance evidence. No specific ageing relevance evidence was found for the following genes: acox-1, acox-3, acox-5, acs-2, acs-13, acs-15, acs-16, acs-18, acs-19, acs-23, agxt-1, aldo-2, alh-8, alh-9, B0272.3, C30H6.7, C44H4.6, C50D2.7, D2063.1, dlst-1, ech-8, F08A8.4, F11F1.1, F44E5.4, F44E5.5, got-1.3, got-2.1, got-2.2, gstk-1, hsp-70, hxk-1, idhg-1, ist-1, pdhb-1, pfk-1.1, pgk-1, R03D7.5, R05F9.6, rpia-1, skr-4, skr-6, skr-10, skr-16, skr-17, skr-18, skr-21, suca-1, sucl-1, tpi-1, ugt-23, ugt-46, ugt-48, ugt-50, ugt-55, ugt-56, ugt-58, ugt-61, ugt-62, Y105E8B.9, Y43F4B.5, Y71G12B.10