| RIF1 | RAP1-Interacting Factor 1 | Deletion of RIF1 decrease replicative lifespan by 40% [9275199]. RIF1 deletion increases telomere silencing and length [8319907; 1577274], and therefore likely recruits SIR2 from rDNA to the telomeres which result in lifespan shortening. The sir4-42 allele suppresses the short lifespan of a RIF1 mutant [9275199]. | Budding yeast |
| Sirt6 | sirtuin 6 (silent mating type information regulation 2, homolog) 6 (S. cerevisiae) | Sirt6 knockout mice develop signs of premature ageing including a short lifespan [16439206].
Overexpression of Sirt6 in male mice lengthens the median lifespan by 9.9-14.5% and maximum lifespan by 13.1-15.8% [22367546].
Mice without Sirt6 have a higher risk of gastrointestinal cancers. SIRT6 dampens cancer growth by repressing aerobic glycolysis (i.e. conversion of glucose to lactate; a major feature of cancer cells). Loss of Sirt6 increases the number, size and aggressiveness of tumors. Sirt6 loss leads to tumor formation even without activation of oncogenes. Transformed SIRT6-deficient cells exhibit increased glycolysis and tumor growth. Sirt6 inhibits the transcriptional activity of the oncogene Myc via corepression [23217706]. Sirt6 also protects against diet-induced obesity [http://www.biocompare.com/Life-Science-News/127206-Anti-Aging-Gene-Identified-As-Tumor-Suppressor-In-Mice-Research-Finds/].
| House mouse |
| htr1b | 5-hydroxytryptamine (serotonin) receptor 1B | Knockout mice displayed a decreased lifespan and early age-related motor decline. | House mouse |
| 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 |
| lin-40 | abnormal cell LINeage 40 | RNA interference decreases median lifespan by 24% in wild-type animals, 38% in a daf-2 background and 24% in daf-2/daf-16 double mutants [18006689]. | Nematode |
| daf-5 | abnormal DAuer Formation | daf-5(e1386) mutation reduces mean lifespan by 19% and maximum lifespan by 21% [17900898]. | Nematode |
| daf-3 | abnormal DAuer Formation | daf-3(mgDf90) mutation decreases mean lifespan by 0-16% and maximum lifespan by up to 9-21%. daf-3(mgDf90) decreases mean lifespan even by 19% [17900898]. Mutation of daf-3 results in a wild-type lifespan, but greatly extends the lifespan of the long-lived daf-9 mutant [11782415]. daf-3 mutations are dauer defective. | 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 |
| glp-1 | abnormal Germ Line Proliferation | glp-1(qu158) mutations result in defects in germ-line proliferation and extension of lifespan by about 30%, which requires daf-16 [11799246]. glp-1(bn18) mutation increases mean, median, 75th %ile and maximum lifespan by 27-37, 26-33, 24-29 and 35%, respectively [22560223]. glp-1(e2141) mutation increases mean (32%) and maximum (53%) lifespan [18828672]. Two alleles of glp-1 that cause overproliferation of gemrline cells, glp-1(oz112gf) and glp-1(q485), result in a shortened lifespan [11799246]. In glp-1 mutants, Z2 and Z3 generate only a few germ cells, which enter meiosis and differentiate as sperm [3677168]. | Nematode |
| mev-1 | Abnormal MEthyl Viologen sensitivity | Loss of function in mev-1 shortens lifespan to 66% of wild-type (i.e. by 34%) and accelerates accumulation of aging-associated biomarkers such as protein carboynls and fluorescent materials. mev-1 mutants are hypersensitive to raised oxygen concentrations and their lifespan decreases dramatically as oxygen concentrations increase [9716135]. Mutation of mev-1 results in paraquat sensitivity, slow grows, and low fecundity. mev-1 mutants have a 50% reduction in superoxide dismutase activt relatively to wild-type [2233820]. | Nematode |
| ACH1 | Acetyl CoA Hydrolase 1 | ACH1 deletion cells accumulate a high amount of extracellular acetic acid and display a reduced mean and maximum chronological lifespan. Maximum lifespan is reduced by 32%. Lifespan shortening is completely abrogated by alleviating the acid stress either by a DR regimen that prevents acetic acid production or by transferring chronologically aging mutant cells to water. Deletion of ACH1 is accompanied by reactive oxygen species accumulation, severe mitochondrial damage, and an early insurgence of apoptosis [22754872]. | Budding yeast |
| ACO1 | ACOnitase 1 | Deletion of ACO1 decreases mean chronological lifespan by 42 - 56% in diploid cells [21447998]. | Budding yeast |
| ARP1 | Actin-Related Protein 1 | Deletion of ARP1 decreases replicative lifespan by 40% in the alpha strain [18340043; 19030232]. | Budding yeast |
| ain-1 | ALG-1 INteracting protein 1 | RNA interference of ain-1 decreases median lifespan by 10% in wild type animals, 20% in a daf-2 background and 44% in daf-2/daf-16 double mutants [18006689]. | Nematode |
| agmo-1 | AlkylGlycerol MonoOxygenase 1 | RNA interference of agmo-1 decreases median lifespan by 30% in wild type animals and 60% in daf-2 mutants [18006689]. | Nematode |
| AVT1 | Amino acid Vacuolar Transport 1 | Overexpressing or deleting AVT1 is sufficient to extend or shorten replicative lifespan, respectively [23172144].
Overexpression of AVT1 prevents mitochondrial dysfunction, prevents alterations in mitochondrial structure and ΔΨ of aged cells even through the vacuolar acidity is reduced in these cells. AVT1 overexpression extends the mean, median and maximum replicative lifespan by 28, 28, and 22%, respectively [23172144].
Deletion of AVT1 accelerates the development of age-induced mitochondrial dysfunction without effecting the kinetics of vacuolar acidity decline and prevents the suppression of mitochondrial dysfunction by VMA1 and VPH2 overexpression without affecting vacuolar acidity. AVT1 deletion decreases mean, median and maximum replicative lifespan by 21, 22, and 12%, respectively [23172144]. | Budding yeast |
| 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 |
| aakb-1 | AMP-Activated Kinase Beta subunit 1 | RNA interference of aakb-1 results in decreased lifespan and earlier accumulation of lipofuscin [16673436]. | Nematode |
| aakb-2 | AMP-Activated Kinase Beta subunit 2 | RNA interference of aakb-2 results in decreased lifespan and earlier accumulation of lipofuscin [16673436]. | Nematode |
| AKR1 | AnKyrin Repeat-containing protein 1 | Deletion of AKR1 decreases replicative lifespan by 40% in the alpha strain [18340043]. Replicative lifespan decreased by 50% in the alpha strain [19030232]. | Budding yeast |
| 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 |
| arl-8 | ARF-Like 8 | RNA interference of arl-8 decreases median lifespan by 35% in a daf-2 background and 9% in daf-2/daf-16 double mutants [18006689]. | Nematode |
| alg-1 | Argonaute (plant)-Like Gene | Adult-specific knockdown of the C. elegans argonaute-like gene 1 alg-1 results in shortened lifespan with a reduction in the mean and maximum lifespan by 9 - 16% and 14%, respectively [21810936]. | Nematode |
| alg-2 | Argonaute (plant)-Like Gene 2 | RNA interference of alg-2 decreases median lifespan by 24% in wild type animals and 50% in a daf-2 background [18006689]. | Nematode |
| arx-4 | ARp2/3 compleX component 4 | RNA interference of arx-4 decreases median lifespan by 61% in a daf-2 background and 51% in daf-2/daf-16 double mutants [18006689]. | Nematode |
