| ztf-12 | Zinc finger Transcription Factor family | RNA interference of ztf-12 results in a shortened lifespan. ztf-12 is a target of daf-16 [16380712]. | Nematode |
| Y47D3A | — | RNAi against Y47D3A.29 decreases mean and maximum lifespan by 19-26% and 34% [18059442]. | Nematode |
| wwp-1 | WW domain Protein (E3 ubiquitin ligase) 1 | RNA interference of wwp-1 decreases median lifespan by 9% in wild-type animals and 24% in daf-2 mutants [18006689]. Loss of wwp-1 function by RNAi or mutation reduces lifespan at 25 degree Celsius, but not 20 degree Celsius. wwp-1 overexpression extends lifespan by up to 20%. Reduced levels of wwp-1 completely suppress the extended longevity of eat-2 mutants. Lifespan of wwp-1 mutants across entire food concentration range by bacterial dilution in liquid culture or on solid plates does not noticeable change. There is no difference in wwp-1 mRNA levels under AL and DR. RNAi reduction of pha-4, but not of daf-16 suppresses increased longevity by wwp-1 overexpression. Mutations in iron sulphur component of complex III, isp-1, increases longevity by reducing mitochondrial function. wwp-1 RNAi does not suppress the extended lifespan of isp-1 mutants and has only minor suppressive effects on lifespan of another mitochondrial mutant, clk-1, and in cyc-1 RNAi treated worms. RNAi depletion of wwp-1 has no effect on long lifespan of daf-2 mutants [19553937]. | Nematode |
| wrn-1 | human WRN (Werner's syndrome) related | RNAi kockdown of wrn-1 shortens the lifespan, increases sensitivity to DNA damage, and accelerates aging phenoypes [15115755].
A nonfunctional wrn-1 DNA helicase decreases the lifespan. The expression of miR-124 in whole wrn-1 mutant worms is significantly reduced. Supplementation with vitamin C normalizes the median lifespan of wnr-1 and mir-124 mutants [23075628]. | Nematode |
| wnk-1 | mammalian WNK-type protein kinase homolog 1 | RNA interference of wnk-1 decreases lifespan by 9% and suppresses lifespan extension by eat-2 mutation [22829775]. | Nematode |
| W09C5.8 | — | RNAi against W09C5.8 increases mean and maximum lifespan by 62% and 50%, respectively [12447374]. Lifespan extension by RNAi of W09C5.8 is not suppressed by daf-16. Loss of W09C5.8 activity via RNAi can also result in a shortened lifespan, reduced fertility and defects in mitochondrial respiratory chain function [19074434].
W09C5.8 RNAi animals have lower ATP content and oxygen consumption [12447374]. | Nematode |
| vps-33.1 | Vacuolar sorting protein | RNA interference of vps-33.1 decreased median lifespan 30% in daf-2 mutants and 15% in a wild-type background [18006689]. | Nematode |
| vps-22 | related to yeast Vacuolar Protein Sorting factor 22 | RNA interference of vps-22 decreases median lifespan by 43% in wild type animals, 33% in a daf-2 background and 9% in daf-2/daf-16 double mutants [18006689]. | Nematode |
| unc-31 | UNCoordinated | Mutation in unc-31 increases hermaphrodite lifespan by approximately 70% and male lifespan by 150% [10377425; 11063684; 10747056]. unc-31 also cause constitutive dauer formation. Both phenotypes, enhanced longevity and constitutive dauer formation are suppressed by mutations in daf-16. unc-31 site of action is neuronal [10377425].
unc-31 mutants are uncoordinated [4366476] and exhibit dauer constitutive phenotype [10377425], are lethargic, feed constitutively, are defective in egg-laying, and produce dauer larvae that fail to recover [8462849]. | Nematode |
| unc-10 | UNCoordinated | Mutation in unc-10 reduces maximum lifespan 35% [17592521]. | Nematode |
| ubc-18 | UBiquitin Conjugating enzyme 18 | ubc-18 overexpression is unable to extend lifespan (possibly, UBC-18 is not limiting for WWP-1 function in lifespan). Loss of ubc-18 function by mutation or RNAi reduces lifespan at 25 degree Celsius, but only slightly at 20 degree Celsius. RNAi depletion of ubc-18 completely suppresses increased longevity of eat-2 mutants. RNAi depletion of ubc-18 has no effect on long lifespan of isp-1 or daf-2 mutants. Combined knockdown of wwp-1 and ubc-18 by RNAi does not shorten lifespan any further than RNAi of either single gene. Knockdown of ubc-18 suppresses extended lifespan of wwp-1 overexpression [19553937]. | Nematode |
| trx-1 | ThioRedoXin 1 | Thioredoxins regulate many cellular redox processes. trx-1 is mainly associated with neurons and is expressed in ASJ ciliated sensory neurons and to some extent also on the posterior-most internal cells. trx-1 reduces protein disulfides in the presence of a heterologous thioredoxin reductase. trx-1 null mutant display reduced mean and maximum lifespan [16387300]. Mutants with a deletion in the trx-1 gene display a decrease in lifespan and are sensitive to oxidative stress [16324156]. trx-1 overexpression extends lifespan in wild-type but not in eat-2 mutants. trx-1 deletion completely suppresses the lifespan extension caused by eat-2 mutation, but only partially suppresses that by daf-2 or osm-5 mutations. Ectopic expression of trx-1 in ASJ neurons (but not in the intestine) in trx-1 mutants rescues the lifespan-extension conferred by eat-2 mutation. trx-1 overexpression extends lifespan of wild-type but not in eat-2 mutants. trx-1 deletion almost completely suppresses lifespan extension induced by dietary deprivation (DD). DD upregulates trx-1 expression in ASJ neurons. DR activates trx-1 in ASJ neurons which in turn triggers a trx-1-dependent non-cell autonomous mechanism to extend adult lifespan [21334311].
| Nematode |
| tbp-1 | TATA-Binding Protein | RNAi against tbp-1 decreases mean and maximum lifespan by 15-27% and 21%, respectively [18059442]. | Nematode |
| sptf-3 | Specificity Protein Transcription Factor 3 | RNAi against sptf-3 decreases mean and maximum lifespan by 20 - 28% and 28%, respectively. sptf-3 RNAi in the adulthood decreases the mean and maximum lifespan by 23 and 37% [23144747]. sptf-3 overexpression extends lifespan [18059442]. | Nematode |
| sod-1 | SOD (superoxide dismutase) | sod-1 overexpression increases mean, median, and maximum lifespan by 32, 25, and 35% [22737090]. | Nematode |
| snap-29 | SNAP (Soluble NSF Attachment Protein) homolog 29 | RNAi against snap-29 starting in the adulthood decreases mean and maximum lifespan by 49 and 72%, respectively [23144747]. | Nematode |
| snap-1 | SNAP (Soluble NSF Attachment Protein) 1 | snap-1 RNAi in the adulthood reduces mean and maximum lifespan by 34 and 50%, respectively [23144747]. | Nematode |
| skn-1 | SKiNhead 1 | RNA interference of or mutations in skn-1 prevent the life-extension effects of dietary restriction [17538612]. skn-1 transgenes that overexpress a constitutive nuclear form of SKN-1 in the intestine extend the mean lifespan by 5-21%, independently of DAF-16 [18358814]. skn-1 mutation does not alter lifespan under AL, but cancels out the lifespan extension effect of lDR or food variation at all. Response to lDR in skn-1 mutant is restored by ectopic expression of skn-1 in ASI neurons and gut. Ectopic expression of skn-1b in ASI neurons rescued lDR longevity defects of skn-1. Ablation of ASI neurons completely suppresses the response to DR in wild-type or daf-16 mutants and cause a small increase in basal longevity of wild-type but not daf-16 mutants. lDR significantly increases SKN-1 expression in ASI neurons. lDR worms exhibit elevated respiration, which is absent in skn-1 mutants. skn-1 is necessary for increased respiration and the increase in respiration is necessary for lDR longevity effect, because two different inhibitors of mitochondrial electron transport chain complex III, myxothiazol and antimycin, suppress lDR longevity without shortening lifespan under AL. In contrast, the long life of a daf-2 mutant is not affected by antimycin. Some isoforms of SKN-1 are expressed from an operon downstream of bec-1. Beclin-1 mediates autophagy induced by nutrient deprivation. Therefore, skn-1 might be regulated by nutritional stress [17538612]. IF significantly extends lifespan of skn-1 mutants [19079239]. sDR extends lifespan of a skn-1 loss-of-function mutant (which displays a premature stop codon in all three isoforms) and wild-type to a similar extent [19239417].
skn-1(zu67) mutation decreases mean, median, and maximum lifespan by 11-23, 13-28 and 12-23%, respectively, and totally cancels out lifespan extension by ragc-1 RNAi [22560223].
| Nematode |
| sir-2.1 | Yeast SIR related 1 | sir-2.1 deletion slightly reduces lifespan of wild-type [16860373]. sir-2.1 overexpression extends lifespan by about 50% and this lifespan extension depends on DAF-16 activity as it is suppressed by mutation in daf-16 and it does not synergize with daf-2 [11242085]. sir-2.1 suppresses longevity of unc-13 and eat-2, but not daf-2 or unc-64 mutants. sir-2.1 is therefore partially required for lifespan extension from mutation of eat-2 [16860373], but is completely independent for lifespan extension from DR using a reduced feeding protocol [Kaeberlein et al. in press]. sDR increases lifespan of wild-type and sir-2.1 mutants to the same extent [19239417].
Overrexpression of sir-2.1 synergizes with TGF-beta mutation (daf-4 and daf-1) for dauer formation [11242085]. | Nematode |
| scl-20 | SCP-Like extracellular protein 20 | scl-20 appears to inhibit the growth of gld-1 tumours. RNA interference of scl-20 reduces mean lifespan up to 18% in wild-type animals, 15% in daf-2 mutants and 28% in daf-2/gld-1 mutants [17934462]. | Nematode |
| scl-1 | SCP-Like extracellular protein | Downregulation of scl-1 by RNAi reduces slightly but reproducibly lifespan as well as stress resistance, similar to the effect of mutation in daf-16. scl-1 RNAi prevents lifespan extension associated with mutation of daf-2 or age-1. scl-1 contains several DAF-16 consensus binding elements within its predicted regulatory region and is a direct target for transcriptional activation by DAF-16. scl-1 mRNA levels increase highly in daf-2 and age-1 mutation, lowly in wild-type N2 and undetectable in daf-16 mutants. [12620193].
RNAi of scl-1 causes hat shock and UV sensitivity [12620193]. | Nematode |
| rpt-1 | proteasome Regulatory Particle, ATPase-like 1 | rpt-1 RNAi in the adulthood decreases the mean and maximum lifespan by 28 and 50%, respectively [23144747]. | Nematode |
| rpn-11 | proteasome Regulatory Particle, Non-ATPase-like 11 | rpn-11 RNAi in the adulthood decreases mean and maximum lifespan by 19 and 25%, respectively [23144747]. | Nematode |
| rab-5 | RAB family 5 | rab-5 RNAi in the adulthood reduces mean and maximum lifespan by 38 and 50% [23144747]. | Nematode |
| pyk-1 | PYruvate Kinase 1 | RNA interference of pyk-1 during adulthood significantly shortens the lifespan of both wild-type and eat-2 mutants. RNAi knockdown of pyk-1 from hatching causes larval lethality. PYK-1 is downregulated in eat-2 mutants [22810224].
pyk-1(ok1754) mutation extends the lifespan and this effect is non-additive with the lifespan extension mediated by DDS treatment [20974969]. | Nematode |
