| icl-1 | IsoCitrate Lyase homolog 1 | RNAi knockdown of icl-1 (alias gei-7) 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 |
| fat-2 | FATty acid desaturase 2 | RNAi knockdown of fat-2 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. FAT-2 is downregulated in eat-2 [22810224].
| Nematode |
| shk-1 | SHaKer family of potassium channels 1 | shk-1 encodes a shaker family of potassium channel which functions in muscle [21059759], is expressed in sensory neurons [16899454], and downregulated in space. Mutation or RNA interference of shk-1 extends lifespan on NGM agar covered with killed or live bacteria as well as in liquid culture medium. shk-1 RNAi extends mean, 75%ile, and maximum lifespan by 16, 15, and 22%. shk-1(RB1392) mutation extends mean, 75%ile, and maximum lifespan by 19-22, 19-21, and 20-24%. Lifespan extension by unc-17 mutation is totally abolished by RNAi inactivation of either daf-16 or skn-1. eat-2 RNAi shortens the lifespan of shk-1 mutants. RNAi inactivation of shk-1 reduces Q35 aggregation [22768380].
Mutation and RNAi of shk-1 enhance pheromone-induced dauer formation [22768380].
| Nematode |
| F57A8.4 | Protein F57A8.4 | F57A8.4 encodes a rhodopsin-like G-protein coupled receptor that is known to sense light [11493519] and is downregulated in space.
Mutation or RNA interference of F57A8.4 extends lifespan on NGM agar covered with killed or live bacteria as well as in liquid culture medium. F57A8.4 RNAi extends the mean, 75%ile and maximum lifespan by 34, 39, and 61%. F57A8.4(tm4341) mutation extends the mean, 75%ile, and maximum lifespan by 18-38, 21-25, and 42-68%. Lifespan extension by gar-3 mutation is not abolished by RNAi inactivation of either daf-16 nor skn-1. eat-2 RNAi shortens the lifespan of F57A8.4 mutants [22768380].
Mutation and RNAi of F57A8.4 suppresses pheromone-induced dauer formation [22768380].
| Nematode |
| cha-1 | abnormal CHoline Acetyltransferase 1 | cha-1 encodes a choline acetyltransferase which is expressed in motor [18041778] neurons and downregulated in space. Mutation or RNA interference of cha-1 extends lifespan on NGM agar covered with killed or live bacteria as well as in liquid culture medium [22768380]. cha-1(TY1652) mutation extends mean, 75%ile, and maximum lifespan by 23, 29, and 38%. The cha-1(PR1152) allele extends mean, 75%ile, and maximum lifespan by 22-49, 18-25, and 11-21%. Lifespan extension by cha-1 mutation is not abolished by daf-16 RNAi inactivation. eat-2 RNAi shortens the lifespan of cha-1 mutants. RNAi inactivation of cha-1 reduces Q35 aggregation [22768380].
cha-1 participates in determining pharyngeal pumping rate to affect food intake [6698395]. | Nematode |
| rab-10 | RAB family | rab-10 RNA interference significantly extends lifespan of wild-type by 14 - 16%, of daf-16 mutants by 47%, and of daf-2 by 46%, but fails to significantly further extend lifespan of eat-2 mutants. rab-10 RNAi does not affect pumping, but similar to DR reduces and delays reproduction as well as cause a slender appearance. rab-10 mRNA is 2-fold downregulated in response to DR [16103914]. rab-10 RNAi significantly reduces paralysis in Q35YFP transgenic animals [18331616]. | Nematode |
| let-363 | LEThal 363 | let-363 RNAi significantly extends the lifespan of wild-type, but does not further extend the long lifespan of eat-2 mutant [17266679]. let-363 RNAi led to an average increase in lifespan of 8% in wild-type and 3% in eat-2 background. let-363 works synergistically with eat-2 mutation. Inhibition of let-363 leads to a phenotype similar to starved animals and modest increase in lifespan [16720740]. DR fails to significantly extend lifespan of let-363 RNAi-treated animals [19079239]. RNAi or mutation of let-363 results in a doubling of lifespan. RNAi of let-363 begun at hatching extends lifespan to the same extent as RNAi begun at the first day of adulthood. RNAi of let-363 fails to further extend the lifespan of daf-2(e1370) mutants [14668850]. Lifespan extension of let-363 RNAi does not require daf-16, as mutations in daf-16 do not suppress the long-lived phenotype of let-363 RNAi animals [14668850]. let-363 RNAi slightly extends lifespan of daf-16 mutation [16720740]. RNAi of let-363 causes many phenotypes similiar to daf-2 mutation: lipid accumulation in intestinal cells, reduced fertility, and reduced viability due to embryonic/larval arrest [14668850]. The let-363(h111) allele has no significant effect on lifespan [15253933]. Disruption of let-363 by RNAi appears to incomplete as lifespan is not extended as much asin let-363 mutants [14668850]. The let-363(h114) allele at 25.5 degree Celsius extends mean lifespan by 150% [14668850].
The absence of LET-363 activity causes developmental arrest at the L3 stage [12225660]. | Nematode |
| rheb-1 | RHEB (Ras Homolog Enriched in Brain) hom | rheb-1 RNAi extends lifespan by mimicking the DR effect. Under AL condition, rheb-1 RNAi extends lifespan by 19.1% and the longevity-promoting effects of two DR regimens sDR and intermittent fasting are abolished [19079239]. Knockdown of rheb-1 by RNAi only during the adulthood increases mean, median and 75th %ile lifespan by 18-25, 25 and 23-24%, respectively, but failed so in skn-1 or daf-16 mutant (with and without FUdR). Knockdown of rheb-1 dramatically enhances stress tolerance in an skn-1, but not daf-16-dependent manner [22560223]. | Nematode |
| hsp-12.6 | Heat Shock Protein | hsp-12.6 loss-of-function mutation significantly extends lifespan under AL and significantly suppresses intermittent fasting (IF)-induced increase in lifespan, to a similar extend to that of daf-16 mutation. HSP-12.6 expression is induced by fasting in various tissues, including body wall muscle and neuronal systems. hsp-16.2 is one of downstream targets of DAF-16 in IF-induced longevity. The extent of IF-induced longevity in daf-16 hsp-12.6 double mutant is similar to that of single hsp-12.6 or daf-16 mutants. hsp-12.6 and daf-16 function in same signaling pathway. Low insulin/IGF-like signaling in daf-2 results in constitutive activation of DAF-16 and higher expression of hsp-12.6 [19079239]. Expression of hsp-16.2 predicts longevity [13-18 in 22829775]. | Nematode |
| hif-1 | HIF (hypoxia inducible factor) homolog 1 | hif-1 mutation does not suppress lifespan extension of bDR or eat-2 mutation [19372390]. hif-1 deletion extends lifespan by 24% and inhibition of hif-1 by RNAi also extends adult lifespan. hif-1 mutation extends lifespan under AL, but does not further extend lifespan extension under modified sDR. Activation of hif-1 by egl-9 deletion diminishes lifespan extension by modified sDR. hif-1 acts independent of insulin-like signaling: Lifespan extension by hif-1 suppression does not require DAF-16, because inhibition of hif-1 by RNAi extends lifespan of wild-type and daf-16 null mutant to a similar level. hif-1 RNAi further extends the lifespan of daf-2 mutants. hif-1 is in the TOR pathway, downstream of S6K/rsks-1: Inhibition of hif-1 by RNAi does not further extend lifespan of daf-15 heterozygous mutants. Lifespan extension by deletion mutant of rsks-1 is fully suppressed by egl-9 mutation. hif-1 mutation does not further extend rsks-1 lifespan. pha-4 RNAi slightly reduces lifespan in wild-type and hif-1 mutants, but hif-1 mutation extends lifespan of animals treated with control or pha-4 RNAi to a similar level [19461873]. | 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| eat-2 | EATing: abnormal pharyngeal pumping EAT-2 | eat-2 mutations result in partial starvation by disrupting the function of the pharynx and an approximately 50% extension of lifespan. eat-2 mutants life significant longer by up to 57% [9789046]. eat-2(ad1116) mutants have an extended mean, 75%ile and maximum lifespan by 30, 35, and 24% [22810224]. eat-2 RNAi significantly reduces paralysis in Q35YFP or ABeta42 transgenic animals [18331616]. sDR further increases the long lifespan of eat-2 mutants [19239417]. eat-2 mutants live longer than wild-type at high food concentration but are short lived at lower concentrations (via bacterial dilution) [19229346]. eat-2(ad1113) mutation increases mean lifespan by 56% and is non-additive with SCNA overexpression [16782295]. Combining eat-2 mutation with bacterial deprivation DR does not result in an additive increase in lifespan [17081160;17096674]. Loss of function of eat-2 extends lifespan by 20-30%. Lifespan extension is proposed to be similar to DR. eat-2;daf-2 double mutant live longer than daf-2 single mutants [9789046]. Therefore, eat-2 mutants can synergize with daf-2 mutants, but not with clk-1 mutants, for lifespan extension. Lifespan extension conferred by eat-2 is not suppressed by daf-16 mutation [9789046]. | Nematode |
| drr-2 | Dietary Restriction Response (WT but not eat-2 lifespan increased) 2 | RNA interference of drr-2 extends lifespan [15998808]. drr-2 RNAi extends lifespan of wild-type by 10-16%, but fails to significantly extend lifespan of daf-2 mutants or eat-2 mutants. drr-2 RNAi keeps a normal, well-fed appearance and normal reproduction. drr-2 mRNA expression is 2-fold reduced in eat-2 mutants [16103914]. drr-2 RNAi significantly reduces paralysis in Q35YFP transgenic animals [18331616]. drr-2 overexpression suppresses lifespan extension by eat-2 mutation and solid plate-based DR [20456299]. | Nematode |
| drr-1 | Dietary Restriction Response (WT but not eat-2 lifespan increased) 1 | RNAi of drr-1 starting at L1 extends mean, 25%ile and median lifespan by 3, 8 and 8% [15998808]. drr-1 RNAi significantly extends mean lifespan of wild-type by 37 - 44%, of daf-16 mutants by 18%, and of daf-2 mutants by 14%, but does not extend significantly the lifespan of eat-2 mutants. drr-1 RNAi does not affect pumping, but similar to DR reduces and delays reproduction as well as causes a slender appearance. drr-1 mRNA is 2-fold downregulated in response to DR [16103914]. | Nematode |
| daf-2 | abnormal DAuer Formation 2 | daf-2 mutants live more than twice as long as controls. daf-2(sa189) mutation extends mean and maximum lifespan by 133 and 129%, respectively, when shifted to 20 degree Celsius. The daf-2(e1370) mutation extends mean and maximum lifespan by 32 and 119%, respectively, when shifted to 25 degree Celsius and by 110 and 145%, respectively, at 20 degree Celsius. daf-2(sa189) mutation extends mean lifespan by 67% as well as maximum lifespan [8247153]. This lifespan extension requires the activity of daf-16 [8247153]. The lifespan extension of daf-2(e1370) mutants is cancelled out by daf-16(m26) mutation. daf-2 mutants still exhibit a long lifespan after ablation of the gonad and germ cells. [8247153]. daf-2(e1370) increases mean (95-118%) and maximum (165%) lifespan [18828672]. RNAi against daf-2 extends mean and maximum lifespan by 47 and 65% [12471266]. daf-2 mutation extends lifespan of wild-type and eat-2 mutants [9789046]. Long lifespan of daf-2 insulin receptor mutation is further extended by sDR. However, daf-2 mutation is not a null mutation, therefore it is still possible that part of sDR-induced increase in lifespan might depend on insulin receptor pathway [17900900]. DR by bacterial dilution extends lifespan of daf-2 mutants [17538612]. IF does not markedly extend lifespan of daf-2 mutants [19079239]. 2% glucose reduce fractions of animals that become dauers at 22.5 degree Celsius in daf-2 mutants. Glucose almost completely suppresses lifespan extension of daf-2 ligand binding domain and tyrosine kinase mutants back to wild-type levels [19883616]. daf-2 mutation increases average lifespan by 157%. Under AL daf-2 mutation increases lifespan by 30%. bDR increases lifespan by 65%. daf-2 mutation further increases lifespan under bDR by 40%. Resistance to oxidative stress is reduced daf-2 mutation [19924292]. daf-2 RNAi increases mean lifesapn by 89% [18828672]. daf-2(m577) mutation increases mean and maximum lifespan by 33 and 29%, respectively, while daf-2(e1370) mutation increases mean and maximum lifespan by 101 and 181%, respectively [16782295]. DR from eat-2(ad465) mutation has an addative effect on lifespan of daf-2(e1370) adults, but not on lifespan of daf-2(e1368) adults [18043747]. Mutation in daf-2 in combination with mutation of daf-12 results in nearly 300% increase in lifespan [7789761]. daf-2 mutants are dauer constitutive [7219552] and exhibit reduced brood size [9504918; 9725835]. daf-2 mutants synergize with germ line ablation for lifespan extension [10360574] and also exhibit synergy with clk-1 mutation for lifespan prolongation [8638122]. All the phenotypes of daf-2 mutants are suppressed by mutation of daf-16 [8247153; 8601482; 7789761; 9725835; 9504918]. Mutation of daf-2 increases expression of sod-3 [10428762]. daf-2(e1370) increases mean lifespan by 146% [23097426].
Reducing expression of daf-2 in the adult stage alone extends lifespan [12399591]. | Nematode |
| clk-1 | CLocK (biological timing) abnormality 1 | Mutations in clk-1 slow down development and extend lifespan by 30%. Mutation of both clk-1 and daf-2 results in nearly 5-fold (500%) increase in lifespan [8638122]. Food restriction by eat-2 mutation does not further extend the long lifespan of clk-1 mutant [9789046]. DR and clk-1 mutations may extend lifespan by a similar process. DR by intermittent fasting (IF) significantly extends lifespan of clk-1 mutants, but to a lesser extent than that of wild-type [19079239]. clk-1 mutants do not respond to sDR-induced lifespan extension [19239417]. Overexpression of clk-1 shortens lifespan and is associated with increased mitochondrial activity [10202142].
Transgenic overexpression of mouse Coq7 reverts the extended lifespan of clk-1 mutants [11511092].
clk-1 encodes a enzyme participating in coenzyme Q synthesis [9020081; 11136229]. clk-1 mutants have a decreased pharyngeal pumping and may provoke volunteering DR [9789046]. Mutations in clk-1 are highly pleiotropic resulting in an average lengthing of embryonic development, post-embryonic development, and adult rhythmic behaviours such as defecation, swimming and pharyngeal pumping [7768437]. clk-1 mutants require coeznyme Q [11136229]. clk-1 protein binds the mitochondrial O(L) region and may regulate replication of mitochondrial DNA [11959146]. | Nematode |
| age-1 | AGEing alteration 1 | Recessive knockout mutants of age-1 have a 40-65% increase in mean lifespan and a 65-110% increase in maximum lifespan [8608934; 8700226]. age-1(mg44) zygotic null mutants have a mean (99%) and maximum (117%) lifespan extension [18828672]. Even in axenic culture lifespan of age-1 is extended up to 100%. age-1 mutation significantly extends lifespan under AL, but only slightly under sDR [16720740].
RNAi against age-1 extends lifespan by 30% [8700226; 8608934]. age-1 RNAi increases mean and maximum lifespan by 36-46% and 48-50% [12447374]. RNAi against age-1 increases mean lifespan by 83% [18828672].
age-1 mutants are dauer constitutive [8056303] and display lower brood size as well as increased embryonic lethality [9504918]. Additionally, age-1 mutants have elevated levels of superoxidase dismutase and catalase activities [8389142]. age-1 RNAi and mutation extend lifespan by 30% and 100%, respectively [8700226; 8608934]. | Nematode |
