| lin-4 | abnormal cell LINeage 4 | A loss-of-function mutation in lin-4 shortens lifespan and accelerated tissue ageing while overexpressing lin-4 extends lifespan by redarding aging [16373574].
lin-4 is regulated by DAF-16 in L1 arrest. | Nematode |
| aak-2 | AMP-Activated Kinase 2 | AAK-2 could be a sensor that couples energy levels and insulin-like signals to lifespan. aak-2(ok524) knockout mutants have a 12% and 18% shorter mean and maximum lifespan, respectively as well as faster age-dependent accumulation of a lipofuscin-like fluorescent pigment in the intestine [15574588]. sDR increases AMP:ATP ratio. aak-2 mutation suppresses lifespan extension and delay of the decline in locomotor activity resulting from sDR. A constitutive active mutation of aak-2 is sufficient to cause increase stress resistance as well as to significantly extend lifespan. Both increased stress resistance and extended lifespan is reverted in daf-16 knockdown by RNAi. sod-3 mRNA is increased by constitutive active form of aak-2 and decreased by aak-2 mutation. The increase in sod-3 mRNA is dependent on expression of DAF-16. Worm and human AMPK phosphorylate DAF-16 (greatly enhanced by presence of AMP) at least in six residues (T166, S202, S314, S321, T463 and S466) [17900900]. aak-2 mutation cancels out the lifespan extension effect of sDR and PD, regardless of the concentration of bacteria or peptones. bDR significantly extends lifespan of aak-2 mutants, but to lesser extent than that of wild-type. eat-2 mutation extends the lifespan of aak-2 mutants to the same extent than that of wild-type. Resveratrol does not increase lifespan of aak-2 mutants [19239417]. daf-2(m577);aak-2(ok524) double mutant has a lifespan that is indistinguishable from those of aak-2(ok524) single mutant. Transgenic animals with a higher aak-2 gene dose live on average 13% longer with a maximum lifespan extension on up to 25% [15574588]. | Nematode |
| aakg-2 | AMP-Activated protein Kinase Gamma subunit 2 | aakg-2 overexpression extends mean, median, and maximum lifespan by 47, 45, and 35%. Overexpression of aakg-2 toegther with D. rerio ucp2 was non-additive with sDR [22737090]. | Nematode |
| ctl-1 | CaTaLase 1 | ctl-1 loss of function shortens lifespan to 77% of wild-type animals. ctl-1 mutants accumulate fluorescent material faster than wild-type, indicating accelerated aging [12610632]. ctl-1 mutation prevents lifespan extension by daf-2 or clk-1. Mutation of ctl-1 reudces catalase activty by 50% [10335847].
All these results have been retracted. | Nematode |
| daf-18 | Abnormal DAuer Formation | daf-18 is required for complete dauer formation. Overexpression increases adult lifespan in individual tissues [16153634]. daf-18 mutation partially suppresses the lifespan extension of age-1 and daf-2 mutants. daf-18 mutants are defective for dauer formation and form some dauer-like larvae when starved [7789761; 8601482]. | 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 |
| hsb-1 | Heat Shock factor Binding protein | hsb-1(cg116) mutation at 20 degree Celsius extends mean, 75%ile, and maximum lifespan by 57-60%, 52-59%, and 37-69%. | Nematode |
| ins-1 | INSulin related | Increased dosage of ins-1 under its own promoter as well as a heat shock promoter increases lifespan by 25% and is also able to increase the lifespan of daf-2 mutants [11274053]. ins-1 RNAi increases lifespan by 20%. ins-1 is differentially transcribed in daf-16 and daf-2 animals [12845331]. Overexpression of ins-1 also causes an increase in dauer formation and can enhance the dauer formation of daf-2 mutants [11274053]. | Nematode |
| cst-1 | Caenorhabditis STE20-like kinase 1 | Knockdown of cst-1 shortens lifespan and accelerates tissue aging while its overexpression extends lifespan and delays aging in a daf-16-dependent manner [16751106]. | Nematode |
| ttll-9 | Tubulin Tyrosine Ligase Like | Knockdown of ttll-9 throughout the entire life increases the lifespan by 3% [23698443]. | Nematode |
| mir-71 | — | Loss and gain-of-function of mir-71 decreases and increases lifespan, respectively [21129974]. mir-71 mutants have a reduced lifespan with 40% decrease in mean lifespan, while extra copies of mir-71 extend the lifespan with an increase in lifespan by 15 - 25% [22482727],
Loss of mir-71 function suppresses the long lifespan of glp-1(e2141) mutants [22482727],
During adulthood mir-71 is strongly expressed in the intestine, body wall muscles and neurons. mir-71 is upregulated in aging adults [22482727], | Nematode |
| mir-246 | — | Mutating mir-246 decreases mean and maximum lifespan by 12%, while its overexpression increases mean and maximum lifespan by 6 and 5 - 14%, respectively [21129974]. | 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 |
| daf-16 | Abnormal DAuer Formation DAF-16, fork head-related transcription factor (daf-16) | Mutations in daf-16 suppresses life-extension caused by mutations in daf-2 [8247153]. daf-16 is required for lifespan extension by mutation of daf-2 or age-1 [8247153]. RNAi against daf-16 decreases lifespan of wild-type, daf-2 or glp-1 mutants [22509016; 16530050]. Loss of function alleles of daf-16 shorten lifespan, but some alleles have lifespan equal to wild-type [8247153]. daf-16 mutation significantly reduces lifespan under AL (-20%), but does not prevent lifespan extension by sDR. In another experiment daf-16 mutation totally suppresses lifespan extension by sDR [16720740]. sDR does not stimulate DAF-16 translocation to the nucleus, but daf-16 mutation cancels out the ability of sDR to extend lifespan and to delay the decline in locomotor activity [17900900]. DR by bacterial dilution extends lifespan of daf-16 mutants [17538612]. daf-16 mutation decreases lifespan under AL, but fails to prevent bDR to further extend lifespan [18331616]. IF-induced lifespan-extension by either 24h/48h/72h per 4 days is significantly diminished in null mutants of daf-16. All these regimens extend lifespan of daf-16 to a lesser extent than that of wild-type. daf-16 partially mediates IF-induced longevity [19079239]. Glucose or glycerol does not shorten lifespan of daf-16 mutants [19883616]. daf-16 mutation cancels out the lifespan extension effect of sDR and PD, regardless of the concentration of bacteria or peptones. bDR significantly extends lifespan of daf-16 mutants, but to a lesser extent than that of wild-type. eat-2 mutation extends the lifespan of daf-16 mutants to the same extent than that of wild-type. Resveratrol extends lifespan of daf-16 mutants [19239417]. daf-16 RNAi completely blocks the lifespan extension by daf-2 mutation, but only partially by bDR. daf-16 RNAi attenuates protection against oxidative stress by bDR. daf-16 expression is induced by bDR [19924292]. Knockdown of daf-16 decreases mean and maximum lifespan by 50% and 54%, respectively [22509016]. DAF-16 reduces expression of rsks-1 and daf-15 [15253933; 22560223]. daf-16(mgDf47) decreases mean (18-37%) and maximum (29%) lifespan [18828672]. Overexpression of wild-type DAF-16 modestly increases lifespan by 20% [11747825], while overexpression of constitutive nuclear forms of DAF-16 increases lifespan only slightly [11381260]. daf-16(mu86) mutation decreases mean (44%) and maximum (18%) lifespan [15905404]. daf-16(mgDf47) decreases mean (18-37%) and maximum (29%) lifespan [18828672]. daf-16 mutants are dauer defective [7219552] and completely suppress all the phenotypes of daf-2 and age-1 mutations, including lifespan extension, dauer arrest, reduced fertility, and viability defects [8247153; 7789761; 9504918; 7789761]. Mutations in daf-16 also suppress lifespan extension of animals that have a germ line ablation [10360574]. Sex-specific lifespan potential requires daf-16 [10747056].
daf-16 mutation suppresses enhanced UV resistance as well as increase longevity of daf-2, daf-23, spe-26, and clk-1 mutants. Mutation in daf-16 does not alter the reduced fertility in spe-26. daf-16 mutants are more fertile than wild-type [8807294]. | Nematode |
| nhr-62 | Nuclear Hormone Receptor family | NHR-62 is required for metabolic and physiologic responses associated with DR-induced longevity. *nhr-62* mediates the longevity response of *eat-2* mutants and blunts the longevity by bacterial food dilution [Heestand, et al. 2012].
Mutation in *nhr-62* suppresses the lifespan extension of eat-2(ad465) animals (p<0.001) [Heestand et al. 2013].
Wild-type (N2) worms with extrachromosomal array dhEx627 (carrying a wild-type nhr-62) exhibit a significant increase in lifespan compared to wild-type (p<0.001) [Heestand et al. 2013]. | Nematode |
| abu-11 | Activated in Blocked Unfolded protein response 11 | Overexpression of abu-11 extends mean lifespan by 9% to 28% [16256736]. | Nematode |
| hsp-6 | Heat shock 70kDa protein 9B (mortalin-2) | Overexpression of hsp-6 from a muscle-specific promoter extends lifespan mean and maximum lifespan by 43 and 45% relatively to animals expressing GFP from the same promoter [11959102]. | Nematode |
| jnk-1 | Jun N-terminal Kinase | Overexpression of jnk-1 increases lifespan by 40% [15767565; 23097426].
JNK-1 overexpression extends the lifespan in a daf-16-dependent manner. JNK-1 directly phosphorylates DAF-16. JNK-1 overexpression does not extend the lifespan of animals unable to synthesize miRNAs, i.e. pash-1(mj100) [23097426]. | Nematode |
| lmp-2 | LAMP (lysosome-associated membrane protein) homolog | Overexpression of lmp-2 increases mean, median and, maximum lifespan by 25, 35, and 48% [22737090]. | Nematode |
| old-1 | Overexpression Longevity Determinant | Overexpression of old-1 in transgenic animals increases mean and maximum lifespan by 40-100% (average 65%) and 97%, respectively. old-1 overexpression of increases stress resistance (to heat by 20% and ultraviolet irradiation by 33%) without altering development or fertility. Effects of old-1 on lifespan and stress resistance is under regulation of daf-16 [9768365].
old-1 mRNA levels are upregulated in response to stress and in daf-2 as well as age-1 mutant backgrounds [11591319]. old-1 expression is downregulated in daf-2 mutants [12845331]. old-1 RNAi in an rrf-3 mutant background slightly extends lifespan [12845331]. old-1 is expressed in the anterior region of the worm, in neuronal, hypodermal and pharyngeal tissues as well in the proximal region in the male gonad. Its expression is detectable in young adults and appears to increase as animals age and in response to heat, starvation, or UV irradiation. | Nematode |
| old-2 | Overexpression Longevity Determinant | Overexpression of old-2 increases slightly, although statistically significant mean and maximum lifespan by 19 and 44% [9768365]. | Nematode |
| hsp-16.1 | Heat Shock Protein | Overexpression of the hsp-16 loci enhances stress resistance and extends mean lifespan by 11% at 20 degree Celsius. Lifespan extension by hsp-16 overexpression requires daf-16 [12882326]. | Nematode |
| hsp-16.49 | Heat Shock Protein | Overexpression of the hsp-16 loci enhances stress resistance and extends mean lifespan by 11% at 20 degree Celsius. Lifespan extension by hsp-16 overexpression requires daf-16 [12882326]. | Nematode |
| hsp-16.48 | Heat Shock Protein | Overexpression of the hsp-16 loci enhances stress resistance and extends mean lifespan by 11% at 20 degree Celsius. Lifespan extension by hsp-16 overexpression requires daf-16 [12882326]. RNAi of hsp-16.48 has no effect on adult wild-type lifespan but slightly shortens the long lifespan of age-1(hx546) mutants [14668486]. | 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 |
