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

prometheus--2.jpg

  • symbol name observation species
    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
    phi-50 RNA interference of phi-50 decreases mean lifespan by 29% and suppresses lifespan extension by isp-1 and eat-2 mutation but does not significantly affect lifespan extension by daf-2 [22829775]. Nematode
    nekl-2 NEK (NEver in mitosis Kinase) Like 2 RNA intereference of nekl-2 decreases lifespan by 24% and suppresses lifespan extension by eat-2 mutation [22829775]. Nematode
    wnk-1 mammalian WNK-type protein kinase homolog 1 RNA interference of wnk-1 decreases lifespan by 9% and suppresses lifespan extension by eat-2 mutation [22829775]. Nematode
    cpf-2 Cleavage and Polyadenylation Factor 2 RNA interference of cpf-2 decreases mean lifespan by 6% and suppresses lifespan extension by eat-2 mutation [22829775]. Nematode
    NNT1 Nicotinamide N-methylTransferase 1 Deletion of NNT1 decreases mean and maximum lifespan by 9 and 19%. 0.5% glucose DR extends the mean and maximum lifespan of NNT1 deletion mutants by 35 and 40%. Overexpression of NNT1 by 5-fold extends mean and maximum replicative lifespan by 18 and 23%, which is approximately of the same magnitude as the lifespan extension obtained from DR. DR in NNT1 overexpression mutant fails to significantly affect the lifespan and only results in extended mean lifespan by 12% and reduced maximum lifespan by 11%. NNT1 overexpression increases rDNA silincing, whereas deletion decreases rDNA silencing. Overexpression of human nicotinamide N-methyltransferase also increases rDNA silencing [12736687]. Budding yeast
    ERG3 ERGosterol biosynthesis Deletion of ERG3 decreases replicative lifespan under AL, cancels out replicative lifespan extension of 0.5% glucose DR and results under DR also into a shorter replicative lifespan than under AL [18690010]. Budding yeast
    ATG16 AuTophaGy related 16 Under AL atg16 mutation shortens chronological, but not replicative lifespan. 0.5% glucose DR extends chronological lifespan of atg16 mutants, but amino-acid DR does not extend the short chronological lifespan of atg16 mutants (similar to several other autophagy mutants). ADE4 deletion in atg16 mutants results only in a partial extension of chronological lifespan by 0.5% glucose DR. The long chronological lifespan of tor1 mutants requires ATG16 [20421943]. Budding yeast
    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
    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
    Thor Null mutation in Thor (alias d4E-BP) causes a significant decrease in longevity (-25% median lifespan in males). Thor is strongly upregulated during starvation. foxo and Thor null mutants are compromised in stress resistant. Stress resistance of foxo null mutants is rescued by Thor overexpression [16055649]. Thor is upregulated on the protein level in a foxo-independent manner upon DR, while it is transcriptional induced in a foxo-dependent fashion by starvation. Thor null mutants cancel out DR-induced lifespan extension, because mutants exhibit a diminished change in lifespan when nutrient conditions were varied. Ubiquitously expression of Thor rescued DR response in females and males. Thor null mutants have a wild-type similar reduction in egg production upon DR. Ubiquitously overexpression of wild-type Thor causes no change under AL, but an activated allele (with more than 3-fold increased binding activity to delF4E) significantly extends lifespan of females (weak allele) and females as well as males (strong allele). Mean lifespan is extended by 11 to 40%. Median lifespan of males and females is enhanced by by 11 and 22%, respectively. Maximum lifespan is extended by 16 and 18% for males and females, respectively. Under DR (0.25% YE) there is no lifespan extension, beyond the effect of DR alone, in all (wild-type, weak and strong) Thor alleles [19804760]. Lifespan of animals with increased Pten and 4E-BP activity in muscle exhibit and extended mean and maximum lifespan by 20% and 15.8% [21111239]. Fruit fly
    VPS20 Vacuolar Protein Sorting 20 VPS20 deletion decreases mean and maximum replicative lifespan by 16% and 19%, respectively, and additionally cancels out the DR-induced replicative lifespan extension [22912585]. Budding yeast
    GTR1 GTp binding protein Resemblance 1 GTR1 deletion decreases mean and maximum replicative lifespan under AL by 36 and 51%, respectively, and cancels out the lifespan extending effect of DR [22912585]. Budding yeast
    DAP2 Dipeptidyl AminoPeptidase 2 DAP2 deletion decreases mean and maximum replicative lifespan under AL by 19 and 36%, respectively, and cancels out the lifespan extending effect of moderate DR [22912585]. Budding yeast
    TSA1 Thiol-Specific Antioxidant 1 A gain-of-function allele of peroxiredoxin (thioredoxin peroxidase, Tsa1) causes a dominant oxidative stress-resistance and robust premature aging phenotype with reduced mean lifespan. These effect is not provoked by altered Tsa1 levels, nor can it be stimulated by deletion, haploinssufficiency or overexpression of wild-type allele [20729566]. Disruption of TSA1 shortens chronological lifespan [15129730]. Replicative lifespan extension by DR in sir2;fob1 double mutant is reduced by TSA1 deletion mutant. Wild-type cells require TSA1 to fully extend lifespan. Mutation in CDC35 (adenylate cyclase), a genetic mimetic of DR, is dependent on TSA1 to extend lifespan [21884982]. Budding yeast
    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
    YPT7 Yeast Protein Two 7 YPT7 deletion decreases replicative lifespan by 15% in the alpha strain [18340043]. Deletion of YPT7 cancels out replicative lifespan extension of 0.5% glucose restriction and results under DR also into a shorter replicative lifespan than under AL [18690010]. Budding yeast
    VMA2 Vacuolar Membrane Atpase 2 VMA2 deletion mutants have a reduced ΔΨ and mitochondrial morphology similar to aged cells. The restoration of the vacuolar acidity in daughter cells requires V-ATPase activity as it is eliminated in VMA2 deletion mutant cells [23172144]. VMA2 deletion mutation decreases the mean replicative lifespan by 80% in the alpha strain [18340043]. Deletion of VMA2 decreases mean, median and maximum replicative lifespan by 84%, 84% and 70%, respectively. DR (0.5% glucose restriction) does not extend the replicative lifespan of VMA2 and shortens it even more [23172144]. Budding yeast
    VAM7 VAcuolar Morphogenesis 7 VAM7 deletion decreases replicative lifespan under AL and blocked DR-mediated lifespan extension. Replicative lifespan decreases by 70% on DR in VAM7 deletion mutant [18690010]. Budding yeast
    SIR2 Silent Information Regulator 2 Deletion of SIR2 shortens replicative lifespan by approximately 30%. Integration of a second copy of SIR2 into the wild-type strain leads to an extension of replicative lifespan by around 35% in W303R strain [10521401]. Deletion of SIR2 causes genomic instability at rDNA array [2647300] and shortens replicative lifespan by 50% [11000115]. 0.5% glucose restriction fails to increase the short lifespan of sir2Delta [11000115] probably duo to hyperaccumulations of extrachromosomal rDNA circles (ERCs) [16311627]. 0.1% glucose restriction extends replicative lifespan of sir2 mutants [12213553]. 0.5, 0.1 and 0.05% glucose restriction are able to increase lifespan of sir2;fob1 double mutant to a greater extent than in wild-type [15328540]. 0.05% glucose restriction further extends replicative lifespan of SIR2 overexpression mutant [15328540]. Sir2 blocks extreme chronological lifespan extension as the lack of Sir2 along with DR and/or mutations in the yeast AKT homolog, Sch9, or Ras pathways causes a dramatic chronological lifespan extension (6-fold) [16286010]. Sir2 inhibits formation of ERCs and acts on histones as well metabolic enzymes among others. Overexpression extends replicative lifespan in several strains, but not in PSY316 [15684413]. Chronological lifespan of sir2 deletion mutant is significantly extended compared with wild-type in water (extreme DR) but not in saturated cultures containing 2% glucose (ad libitum). SIR2 mutants are defective for telomere [1913809] and HM silencing [6098447; 3297920]. have increased rDNA recombination [2647300] and a loss of rDNA silencing [9009207; 9009206]. Budding yeast
    PNC1 Pyrazinamidase/NiCotinamidase 1 Cells with 5 copies of PNC1 have a 70% longer replicative lifespan which is cancelled out by SIR2 deletion. PNC1 is upregulated under glucose DR [12736687]. Pnc1 reduces cellular nicotinamide levels, a product and noncompetitive inhibitor of Sir2 deacetylation reaction. Overexpression of PNC1 suppresses the effect of exogenously added nicotinamide on Sir2-dependent silencing at HM loci, telomeres and rDNA loci [12736687; 14729974]. Pnc1 catalyses the breakdown of nicotinamide to nicotinate and ammonia [12736687]. Deletion of PNC1 shortens replicative lifespan approximately by 10% [12736687] and largely prevents replicative lifespan extension of 0.5% glucose restriction. 0.5% glucose restriction slightly extends median replicative lifespan (by 10 - 15%) but not maximum replicative lifespan in pnc1Delta [14724176]. PNC1 overexpression suppresses the inhibitory effect of exogenously added NAM on silencing, lifespan, and Hst1-mediated transcriptional repression [14729974]. Increased expression of PNC1 is both necessary and sufficient for replicative lifespan extension by DR and low-intensity stress. Under non-stressing conditions (2% glucose, 30 degree Celsius), a strain with additional copies of PNC1 (5XPNC1) has 70% longer replicative lifespan than the wild-type and some cells live for more than 70 divisions. Neither DR nor heat stress further increase the lifespan of the 5XPNC1 strain [12736687]. PNC1 deletion decreases chronological lifespan [17110466]. Budding yeast
    • Page 1 of 2
    • 25 of 39 factors
    Factors are an extension of GenAge and GenDR.

    Comment on This Data Unit