| ire-1 | IRE1 kinase related 1 | ire-1 mutation reduces slightly the lifespan under AL, but reduces significantly the lifespan extension by DR. ire-1 mutant has a significantly reduced slope in mean lifespan versus food concentrations relative to wild-type. ire-1 mutation fully suppresses lifespan extension by hif-1 mutation under AL and DR conditions [19461873]. | Nematode |
| egl-9 | EGg Laying defective 9 | egl-9 deletion does not affect lifespan under AL. Lifespan extension under modified sDR regimen is diminished by egl-9 mutation. egl-9 mutation significantly suppresses the lifespan extension by a strong loss-of-function allele of eat-2. Lifespan extension by deletion mutants of rsks-1 is fully suppressed by egl-9 mutation [19461873]. | 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 |
| aqp-1 | AQuaPorin or aquaglyceroporin related 1 | aqp-1 expression changes in response to glucose or glycerol. Similar to daf-16 and hsf-1 mutants, aqp-1 mutants were short-lived, and their short lifespan was not further decreased by glucose. Overexpression of aqp-1::GFP rescues short lifespan of aqp-1 deletion mutants and partially prevented glucose from shortening lifespan. Glucose or glycerol feeding downregulates aqp-1 in wild-type. In daf-16 and/or hsf-1 mutants aqp-1 is repressed and glucose feeding does not significantly affect its expression. aqp-1 mutation does not further decrease the short lifespan of daf-16 and/or hsf-1 mutants. aqp-1 transgene is expressed in pharynx and intestine (which behaves as entire endoderm of animal, including adipose tissues). Dietary glucose does not cause significant differences in levels of glucose or glycerol in wild-type vs. aqp-1 mutants [19883616]. | Nematode |
| nlp-7 | Neuropeptide-Like Protein | nlp-7 RNAi or overexpression reduces oxidative stress resistance and shortens lifespan of wild-type under AL. nlp-7 RNAi significantly reduces extended lifespan of eat-2 mutants, but failed to block lifespan extension of age-1 or clk-1 mutants. Lifespan of nlp-7 mutants increases only moderately by sDR [19783783]. nlp-7 expression is induced under DR via the use of a chemically defined axenic medium [17023606] and by sDR [19783783]. | Nematode |
| cup-4 | Coelomocyte UPtake defective 4 | cup-4 RNAi or overexpession reduces oxidative stress resistance and shortens lifespan of wild-type under AL. cup-4 RNAi significantly reduces the extended lifespan of eat-2 mutants, but failed to block lifespan extension of age-1 or clk-1 mutants. Lifespan of cup-4 mutants increases only moderately by sDR [19783783]. | Nematode |
| lgc-26 | Ligand-Gated ion Channel 26 | lgc-26 RNAi significantly decreases lifespan of eat-2 mutants specifically, whereas lifespan of age-1 or clk-1 mutants are not affected [19783783]. | Nematode |
| cup-5 | Coelomocyte UPtake defective 5 | cup-5 RNAi significantly decreases lifespan of eat-2 specifically, whereas lifespan of age-1 or clk-1 mutants are not affected [19783783]. | Nematode |
| ckr-2 | CholecystoKinin Receptor homolog 2 | ckr-2 RNAi significantly reduces the lifespan of eat-2 but not that of age-1 nor clk-1 mutants [19783783]. | Nematode |
| cbp-1 | CBP/p300 homolog 1 | bDR and daf-2 mutation induce cbp-1 expression. There is no decrease in cbp-1 expression in whole C. elegans during aging. Overexpression of cbp-1 does not significantly affect lifespan. daf-16 RNAi and cbp-1 RNAi reduce average lifespan under AL to about the same extent. Inhibiting cbp-1 via RNAi by 50%, specifically in adult phase and completely blocks lifespan extension of DD, bDR as well as eat-2, glp-1 and clk-1 mutation, but only partially that of daf-2 mutation and not at all that of cold. cbp-1 RNAi completely blocks the lifespan increase by daf-2 mutation under bDR. cbp-1 RNAi blocks the delay of other age-related pathologies by bDR. cbp-1 RNAi prevents protective effects of bDR and accelerates ABeta42-related pathology. bDR significantly delays onset of paralysis even in presence of cbp-1 RNAi. cbp-1 RNAi specifically in adults completely blocks lifespan extension by three distinct protocols of DR (mutation of eat-2), partly by daf-2 mutation but not of cold and blocks the delay of other age-related pathologies by bDR. cbp-1 RNAi has no effect on lifespan in daf-16 hypomorphic mutants. Combining cbp-1 and daf-16 RNAi in wild-type produces similar lifespan as either alone. Resistance to oxidative stress is strikingly reduced by cbp-1 RNAi and cbp-1 RNAi attenuates the protection against oxidative stress by bDR. cbp-1 RNAi accelerates accumulation of autofluorescence, but has no effect on activity, egg laying, or pharyngeal pumping. cbp-1 RNAi does not block induction of daf-16 or hsf-1 by bDR, but does block the induction of DAF-16 target gene, sod-3, and HSF-1 target gene, sip-1 by bDR. cbp-1 RNAi blocks induction of sod-3 expression by daf-2 RNAi. cbp-1 RNAi does not block the increased Nile Red staining produced by daf-2 mutation, but enhanced Nile Red staining. cbp-1 RNAi blocks the effect of bDR on metabolic gene expression from glycolysis towards beta-oxidation. Drugs that enhance histone acetylation increase lifespan and reduce ABeta42-related pathologies, but these protective effects are completely blocked by cbp-1 RNAi. cbp-1 RNAi decreases H4 Lys 5 acetylation and blocks the extension of lifespan as well as delays the onset of paralysis by ABeta1-42 transgene under AL and bDR by sodium butyrate (NaB) and trichostatin (TSA). cbp-1 RNAi does produce dye-filling defects in all C. elegans amphid neurons (ASI, ADL, ASK, AWB, ASH, and ASJ) [19924292]. | Nematode |
| dve-1 | DVE (Defective proVEntriculus in Drosophila) homolog) 1 | dve-1 RNAi attenuates lifespan extension by bDR, but only partially that of daf-2 mutation. dve-1 RNAi attenuates protection against oxidative stress by bDR. dve-1 expression is not induced by bDR [19924292].
| Nematode |
| faah-1 | Fatty Acid Amide Hydrolase 1 | faah-1 overexpression reduces eicosapentaenoyl ethanolamide (EPEA), palmitoleyol ethanolamide, linoleyol ethanolamide, as well as arachidonoyl ethanolamide (AEA) levels, delays development, increases thermal stress resistance, and was associated with mean and maximum adult lifespan extension by 19 and 35%, respectively, in presence of abundant food but not under (two different protocols of) DR. Overexpression in pharynx was largely sufficient for this lifespan extension [21562563]. | Nematode |
| elt-3 | Erythroid-Like Transcription factor 3 | Expression of elt-3 decreases with development and aging. elt-3 RNAi extends maximum lifespan and totally cancels out the daf-2 or DR-induced (eat-2) lifespan extension [18662544]. | 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 |
| slcf-1 | SoLute Carrier Family 1 | slcf-1 RNAi or mutation extends the lifespan. slcf-1 mutation increases average lifespan by 40%. DR (by dilution of bacteria on solid medium or by bacterial deprivation) failes to extend slcf-1 mutant's long lifespan and lifespan is even reduced by lowering bacteria concentration (i.e. higher strength of DR) [21040400]. | 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 |
| sbds-1 | Shwachman-Bodian-Diamond Syndrome protein homolog 1 | RNA interference of sbds-1 decreases median lifespan by 24% in daf-2 mutants [18006689]. RNAi knockdown of sbds-1 starting at hatching or only during the adulthood significantly decreases lifespan of eat-2 without affecting wild-type lifespan. SBDS-1 are elevated in eat-2 mutants. Increased content of SBDS-1 is, at least partially, required for lifespan-extension by DR [22810224]. | Nematode |
| vit-5 | VITellogenin structural genes (yolk protein genes) 5 | RNA interference against vit-5 extends mean lifespan by 10-22%. vit-5 is differentially transcribed in daf-16 and daf-2 RNAi animals [12845331]. RNAi knockdown of vit-5 starting at hatching or only during the adulthood significantly extends lifespan of wild-type, but does not alter, or even shortens the lifespan of eat-2 mutants [22810224]. | Nematode |
| unc-52 | UNCoordinated 52 | RNA interference of unc-52 in adulthood extends mean lifespan by 11% [17411345]. RNAi knockdown of unc-52 starting at hatching or only during the adulthood significantly decreases lifespan of eat-2 without affecting wild-type lifespan. UNC-52 levels are elevated in eat-2 mutants. Increased content of UNC-52 is, at least partially, required for lifespan-extension by DR [22810224]. | Nematode |
| smk-1 | SMEK (Dictyostelium Suppressor of MEK null) homolog 1 | RNA interference of smk-1 completely suppresses the extended longevity of daf-2 mutations and partly the life-extension of clk-1 mutants. smk-1 RNAi decreases mean and maximum lifespan of similar level than daf-16 knockdown [16530049]. smk-1 RNAi only slightly shortens the lifespan of wild-type worms, but abolishes the extended lifespan of eat-2 mutants [17476212]. Loss of smk-1 by temperature sensitive allele suppresses the extended lifespan under optimal bDR, but not the response to DR itself [17476212]. | 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 |
| sams-1 | S-Adenosyl Methionine Synthetase 1 | sams-1 RNAi significantly extends lifespan of wild-type by 14 - 15%, of daf-16 mutant by 30% and daf-2 by 55%, but fails to significantly further extend lifespan of eat-2 mutants. mRNA level of sams-1 is 2-fold reduced in eat-2 mutants. Like DR, sams-1 RNAi reduces brood size and slightly reproductive timing as well as causes a slender phenotype [16103914]. sams-1 RNAi significantly reduces paralysis in Q35YFP transgenic animals [18331616]. | Nematode |
| pha-4 | defective PHArynx development 4 | pha-4 is required for multiple forms of DR. RNAi of pha-4 completely cancels out the lifespan extension of eat-2 mutation. Mutants of pha-4 do not respond to bacterial DR. Therefore, loss of pha-4 completely blocks the response to varying food concentration. Moreover, pha-4 expression is increased in response to DR in wild-type. pha-4 overexpression increases longevity of wild-type only slightly, but significant that of daf-16 mutants. The response to DR involves the PHA-4-dependent expression of sod-1, sod-2 and sod-5. Reduction of pha-4 does not suppress the long lifespan of daf-2 mutants or animals with defective electron transport chain [17476212]. IF significantly extends lifespan of pha-4 [19079239]. sDR extends lifespan of mutants with a temperature sensitive allele of pha-4 or pha-4 RNAi knockdown, but not daf-16 RNAi [19239417]. PHA-4 may play a role in the life-extending effects of dietary restriction. RNAi of pha-4 decreases lifespan of wild-type worms, but not of daf-2 mutants or of animals with defective electron transport chains. | Nematode |
| ins-7 | INSulin related 7 | RNA interference of ins-7 extends the mean lifespan by 55% at 20 degree Celsius in N2 rrf-3(pk1426) [12845331]. ins-7 RNAi significantly extends lifespan under AL. Treating wild-type with 2% glucose produced pattern of gene expression that overlaps significantly with that produced by genetic inhibition of daf-16 activity in daf-2 mutants. This results in changes in expression of several insulin-like genes, including DAF-16 target gene ins-7. Addition of glucose triggers an increased ins-7:GFP expression. Glucose suppresses the extended lifespan by ins-7 RNAi [19883616]. RNAi of ins-7 does not further extend the lifespan in daf-2 mutants [12845331]. ins-7 is repressed in animals with reduced daf-2 activity and elevuated in animals with reduced daf-16 activity. | Nematode |
