Factors

We need to know every factor which determines lifespan.

Lifespan factors often but not always originate from defined genetic elements. They are not just genes, by definition they can be anything for which a Classifications schema can be build for that is related to the regulation of lifespan, such entities may include Single-Nucleotide Polymorphism, transcript variants, proteins and their complexes, compounds (i.e. small molecules like metabolites and drugs), etc. A factor should be based on a defined molecular entity or genomic position and been classified. It shall be highly flexible and scalable Concept.

While individual lifespan factors within each species or precise defined molecular entities will be captured within the Lifespan App, Data Entries of the Data App may summarize for instance the relevance of each factor class (e.g. homologous group; chemical derivate of related structure and properties, etc.) as well as draw overall conclusions. o

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  • symbol name observation species
    ADE4 ADEnine requiring 4 ade4 mutation extends chronological lifespan, but not replicative lifespan, and is non-additive with 0.5% glucose or amino-acid DR on chronological lifespan extension. ADE4 deletion in atg16 mutants results only in a partial extension of the chronological lifespan by 0.5% glucose DR [20421943]. Budding yeast
    AIM4 Altered Inheritance rate of Mi 4 AIM4 (alias SOY1) deletion increases chronological and replication lifespan, which is non-additive with DR. On AL mean and maximum replicative lifespan are extended by 63 and 69%, respectively. DR appears to decrease aim4-induced replication lifespan extension, indicating a negative interaction. aim4 mutation does not change DR-induced chronological lifespan extension [21584246]. Budding yeast
    ATG11 AuTophaGy related 11 ATG11 deletion extends replicative lifespan under AL and abrogates DR-lifespan extension [18690010]. Budding yeast
    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
    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
    BMH1 Brain Modulosignalin Homologue 1 Deleting BMH1 extends chronological lifespan by 25% and is associated with activated stress response, decreased ROS levels and increased heat-shock-element-driven transcription activity. BMH1 deletion was non-additive with the genetic DR mimetic cdc25 and tor1. Water starvation (a form of extreme DR) extends chronological lifespan of BMH1 mutant even more as it does in wild-type. BMH1 genetically interacts with DR as well as TOR- and PKA-signaling pathways to regulate lifespan. Phosphorylation of Ser238 on Bmh1 increases during chronological aging, which is delayed by DR or reduced TOR activity [19805817]. Budding yeast
    ERG5 ERGosterol biosynthesis 5 Deletion of ERG5 decreases replicative lifespan by 35% in the a strain [18340043], but increases mean chronological lifespan by 26 - 116% (26, 40, 43, 62, 116) in diploid cells [21447998]. Deletion of ERG5 cancels out the replicative lifespan extension of 0.5% glucose restriction [18690010]. Budding yeast
    GIS1 GIg1-2 Suppressor 1 Deletion of GIS1 increases replicative lifespan by 25% in the alpha strain [19030232] and causes major although not complete reversion of chronological lifespan extension by 0.5% glucose restriction [18225956]. Budding yeast
    GPA2 G Protein Alpha subunit 2 Deletion of GPA2 increases mean and maximum replicative lifespan by 40% and 26%, respectively [11000115]. Deletion of GPA2 extends replicative lifespan by reducing cAMP-PKA activity and provides a genetic model for DR [11000115]. Budding yeast
    GPR1 G-Protein coupled Receptor 1 Deletion of GRP1 increases mean and maximum replicative lifespan by 41% and 26%, respectively. GRP1 deletion mutants have also longer chronological lifespan. Deletion of GPR1 extends replicative lifespan by reducing cAMP-PKA activity and provides a genetically model for DR [11000115]. Budding yeast
    HES1 Homologous to kES1 1 Deletion of HES1 (alias OSH5) extends replicative lifespan and is non-additive with moderate DR. Elevation of OSH5 levels by an ERG6 promoter reduces mean, median and maximum replicative lifespan by 25, 18 and 29%. HES1 is required for the longevity effect of DR, Perg6-OSH6, Perg6-ERG2 and Perg6-OSH7 (genetic mimetics of DR). Hes1 is upregulated in response to sterol down-regulation including DR. Deletion of OSH5 delays different steps of endocytosis, a sterol-requireing process [Xia et al., unpublished]. Perg6-OSH6 osh5 double mutant have a lifespan significantly shorter than that of Perg6-OSH6 [Xia et al. upublished]. Budding yeast
    HXK2 HeXoKinase 2 Deletion of HXK2 extends mean and maximum replicative lifespan by about 53% and 33%, respectively. Limiting glucose availability by mutating HXK2 significantly extends replicative lifespan and provides a genetically model of DR [11000115]. HXK2 deletion increases oxygene consumption. Changes in gene expression HXK2 mutation are quite similar to those of dietary-restricted cells. In fact, HXK2 mutants have a transcriptional profile that significantly resembles DR cells and cell overexpressing HAP4 [12124627]. Budding yeast
    IPK1 Inositol Polyphosphate Kinase 1 Deletion of IPK1 increases mean replicative lifespan by 41 - 40% in the alpha strain [16293764; 19030232]. IPK1 deletion extends mean and maximum replicative lifespan by 24 and 19%, respectively, and was non-synergistic with moderate DR [21584246]. Budding yeast
    LCB4 Long-Chain Base 4 Deletion of LCB4 increases replicative lifespan and cancels out replicative lifespan extension of 0.5% glucose DR [18690010]. Budding yeast
    MSN2 Multicopy suppressor of SNF1 mutation 2 Deletion of MSN2 and MSN4 extends replicative lifespan and is further extended by cyr1::mTn [14741356]. Deletion of MSN2 and MSN4 does not significantly decrease chronological lifespan under AL, but attenuates chronological lifespan extension by water starvation and 0.5% glucose restriction [18225956] as well as cancels out lifespan extension of cyr1::mTn [14741356] and decreases chronological lifespan extension of ras2 deletion mutant [12586694]. Simultaneous deletion of MSN2 and MSN4 has no effect on chronological lifespan, but prevents lifespan extension by RAS2 deletion [12586694]. msn2 msn4 has no effect on replicative lifespan in PSY316, and does not prevent lifespan extension by DR [11000115] or by high osmolarity [12391171]. Budding yeast
    MSN4 Multicopy suppressor of SNF1 mutation 4 Deletion of MSN2 and MSN4 extends replicative lifespan and is further extended by cyr1::mTn [14741356]. Deletion of MSN2 and MSN4 does not significantly decrease chronological lifespan under AL, but attenuates chronological lifespan extension by water starvation and 0.5% glucose restriction [18225956] as well as cancels out lifespan extension of cyr1::mTn [14741356] and decreases chronological lifespan extension of ras2 deletion mutant [12586694]. Simultaneous deletion of MSN2 and MSN4 has no effect on chronological lifespan, but prevents lifespan extension by RAS2 deletion [12586694]. msn2 msn4 has no effect on replicative lifespan in PSY316, and does not prevent lifespan extension by DR [11000115] or by high osmolarity [12391171]. Budding yeast
    RPL31A Ribosomal Protein of the Large subunit 31A Deletion of RPL31A increases mean replicative lifespan by 45% [16293764]. Mean replicative lifespan increases by 35% in the alpha strain and 50% in a strain [19030232; 18423200]. Mean replicative lifespan of the RPL31A deletion mutant increases by 35% in the ORF collection and by 29% in the remade strain [22377630]. RPL31A deletion increases significantly replicative lifespan [17174052]. Deletion of RPL31A extends replicative lifespan and is not further extended by 0.05% glucose restriction [18423200]. Budding yeast
    RPD3 Reduced Potassium Dependency 3 Deletion of the histone deacetylase gene RPD3 extends lifespan by 41%, independently of an intact Sir silencing complex (in the short lived YSK661 strain) [10512855]. Deletion of RPD3 extends replicative lifespan and there was no additive effect by neither 0.1% glucose nor amino acid restriction [12213553]. RPD3 deletion increases rDNA silencing in a partially SIR2-dependent manner [10082585]. Its effects on chromatin functional state were evidenced by enhanced silencing at the three known heterochromatic regions in the genome, the silent mating type (HM), subtelomeric, and rDNA loci, which occurred even in the absence of SIR3 [10512855]. Budding yeast
    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
    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
    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
    Indy I'm not dead yet Flies heterozygotic for a disruption in Indy gene have extended mean (87-92%) and maximum (45%) lifespan. Homozygotes for the disruption show only a 10 - 20% increase in mean lifespan [11118146]. Heterozygous insertion of a p-element in the non-coding region of Indy locus leads to a reduction in Indy mRNA expression and causes a significant median lifespan extension in male and female by about 29% and 34%, respectively. At normal or high calorie conditions Indy heterozygote mutants have a significant lifespan extension, but under low calorie conditions, Indy heterozygous mutants have minimal median lifespan extension. Reduction of calorie content from high to normal calorie condition results in 19% decline in Indy mRNA and from normal to low calorie condition results in additional 9% decrease in Indy mRNA. Reduction of calorie content from high to normal calorie conditions in heterozygous Indy mutants leads to 20% reduction in Indy mRNA expression without any additional decrease upon further reduction to low calorie food. Maximum lifespan extension is associated with Indy mRNA levels between 25 - 75% of normal. Long-lived heterozygous Indy mutants on high-calorie food and normal wild-type on low-calorie food have several phenotypes in common: 50 - 60 % reduced mRNA expression levels of Ilp2, Ilp3 and Ilp 5; similar high percentage of anti-FOXO-positive nuclei in fat body cells; higher sensitivity to starvation; do not gain weight; similar decrease in triglycerides and fat storage; normal food intake [19470468]. Mutations in Indy dramatically extend lifespan without a loss in fertility, physical activity, flight velocity or metabolic rate [11118146; 12626742]. Indy encodes a high-affinity dicarboxylate/citrate plasma membrane transporter found most abundantly in adult fat body, oenocytes and midgut cells, the primary sites of intermediary metabolism [12391301]. Indy mutation alters metabolism in a manner similiar to DR and mutants have several phenotypes with long-lived DR files in common, including decreases insulin-like signaling, lipid storage, weight gain, and resistance to starvation, and an increase in spontaneous physical activity [19470468]. Of the Indy206 and Indy302 mutation only one of the two has lower mRNA levels and both do not extend lifespan of female flies in any genetic background. In original genetic background only Indy mutation associated with altered RNA expression extends the lifespan of males. This effect is abolished by back-crossing into standard out-bred genetic backgrounds and is associated with an unidentified locus on the X chromosome. Original Indy line with long-lived males is infected by the cytoplasmic Wolbachia. Longevity of Indy males disappear after tetracycline clearance of this endosymbiont [17571923]. Fruit fly
    Ilp2 Insulin-like peptide 2 Flies with an ablation of median neurosecretary cells (which eliminates Ilp2 expression) exhibit a significant increase in mean and maximum lifespan over that of control flies and an increase to oxidative stress and starvation. The mutants also exhibit increased storage of lipid and carbohydrate, reduced fecundity, and reduced tolerance of heat and cold [15708981]. The median and maximum lifespan of females is increased by 33.5% and 40%, respectively. In males the median and maximum lifespan is increased by 10.5% and 27%, respectively [15708981]. Ilp2 RNA interference results in a 24% to 47% increase in median lifespan [19005568]. Ilp2 is transcriptional down-regulated in long-lived mutants. Ilp2 null mutants are significant longer-lived with a 8-13% longer median lifespan, but have a normal DR response. Ilp2 Ilp3 Ilp5 triple null mutants fail to have a normal response to DR. Their response is right shifted, with mutants shorter-lived compared to wild-type on low but longer-lived on high yeast concentrations [20195512]. Fruit fly
    FRE6 Ferric REductase 6 FRE6 deletion increases mean replicative lifespan by 14% and cancels out the lifespan extending effect of DR [22912585]. Budding yeast
    GUP1 Glycerol UPtake 1 GUP1 deletion extends mean and maximum replicative lifespan by 32 and 30%, respectively, as well as chronological lifespan. DR-induced maximal replicative lifespan extension is not further increased by GUP1 deletion, while gup1 mutant displayed longer chronological lifespan under DR [21584246]. Budding yeast
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    • 25 of 62 factors
    Factors are an extension of GenAge and GenDR.

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