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

  • Types: + -
  • symbol name observation species
    VPH2 Vacuolar pH 2 Overexpression of VPH2 increases the levels of assembled V-ATPase at the vacuolar membrane, increases vacuolar acidity and suppresses age-induced mitochondrial dysfunction of aged cells (17 or 18 cell divisions) which requires the V-ATPase activity. VPH2 overexpression significantly increases mean, median and maximum replicative lifespan by 23, 25 and 34%, respectively [23172144]. Budding yeast
    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
    VMA1 Vacuolar Membrane Atpase 1 Overexpression of VMA1 increases vacuolar acidity and suppresses age-induced mitochondrial dysfunction of aged cells (17 or 18 cell divisions) which requires the V-ATPase activity. VMA1 overexpression significantly increases mean, median and maximum lifespan by 39 - 45%, 39 - 48% and 50 - 60%, respectively. DR (0.5% glucose restriction) does not further increase the lifespan of VMA1 overexpression strain [23172144]. Budding yeast
    PEP4 carboxyPEPtidase Y-deficient 4 Overexpression of vacuolar aspartyl protease (PEP4) extends chronological lifespan by increasing cytosolic polyamine and S-adenosylmethionine (SAM) levels. Deletion of PEP4 results in both apoptotic and necrotic cell death during chronological aging [21593793]. PEP4 is not DR-essential [18690010]. Budding yeast
    NDT80 Non-DiTyrosine 80 Transient overexpression of NDT80 rejuvenates old cells [21700873]. Budding yeast
    IME1 Inducer of MEiosis 1 Transient overexpression of IME1 resets the replicative lifespan of old cells back to that of young cells [21700873]. Budding yeast
    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
    HPR1 HyPerRecombination 1 Deletion of HPR1 decreases replicative lifespan [11756539] Budding yeast
    OSH7 OxySterol binding protein Homolog 7 Overexpression of OSH7 extends mean replicative lifespan. PERG6-OSH7 does not extend the maximum lifespan significantly [Xia et al., unpublished]. Deletion of the CC domain of Osh7 (Perg6-OSH7-ORD) greatly shortens the lifespan. Deletion of the Osh7's CC domain decreases lifespan (Perg6-OSH7-ORD) shortens the lifespan [Tang et al., personal communication]. Osh7 interacts with the late endosome ATPase Vps4 by their C-terminal coiled-coil (CC) domain. Budding yeast
    ERG2 ERGosterol biosynthesis 2 Overexpression of ERG2 with the promoter of ERG6 (Perg6-ERG2) extends replicative lifespan and this effect was overlapping with moderate DR, because DR can not extend the lifespan of this mutant [Tang et al., unpublished]. Perg6-ERG2 does not extend the lifespan significantly on normal medium, but it reverses the effect of DR. DR greatly shortens the lifespan of Perg6-ERG2 mutants. Perg6-ERG2 shortens the lifespan of nyv1 deletion mutations [Xia et al. unpublished]. Deletion of OSH5 greatly shortens the lifespan of Perg6-ERG2. SIR2 overxpression extends the lifespan of Perg6-ERG2 [Xia et al. unpublished]. Budding yeast
    RPL6A Ribosomal Protein of the Large subunit 6A Deletion of RPL6A decrease mean replicative lifespan by 25% in the alpha strain [18340043; 18423200], but increases mean replicative lifespan by 40% in the remade strain. Its deletion non-significantly increases mean replicative lifespan in the ORF collection [22377630]. Budding yeast
    BMH2 Brain Modulosignalin Homologue 2 Overexpressing 14-3-3 protein, Bmh2, significantly extends median chronological lifespan by activating stress response [19805817]. Budding yeast
    OSH6 OxySterol binding protein Homolog 6 Elevation of OSH6 levels by an ERG6 promoter extends mean, median and maximum replicative lifespan by 39, 52 and 18% which is non-additive with 0.5% glucose restriction. It also extends the lifespan of NYV1 mutant [Geber et al., unpublished]. The long lifespan of Perg6-OSH6 is not further extended by deletion of TOR1 [22622083]. OSH6 overexpression decreases total cellular sterol content and reduces Lst8 protein levels. The CC domain of Osh6 is dispensable for longevity. Deletion of the CC domain leads Osh6 to the late endosome. [Fusheng Tang, personal communication]. OSH6 deletion does not affect lifespan under normal conditions, but it abrogates the lifespan extension by 0.5% glucose restriction [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
    SRX1 SulfiRedoXin 1 Extra copy of SRX1 counteracts age-related hyperoxidation of Tsa1 and extends replicative lifespan by 15 - 20% in a TSA1-dependent manner. Replicative lifespan extension in sir2;fob1 double mutant by DR is reduced by SRX1 deletion. Wild-type cells require SRX1 to fully extend lifespan. DR fails to further extend replicative lifespan of cells carrying an extra copy of SRX1. Mutation in CDC35 (adenylate cyclase), a genetic mimetic of DR, is dependent on SRX1 to extend replicative lifespan [21884982]. Budding yeast
    YMR018W Deletion of YMR018W increases replicative lifespan by 35% in the alpha strain [18340043]. Budding yeast
    SIR4 Silent information regulator 4 Deletion of SIR4 results in 20-25% reduction of lifespan [10521401]. SIR4 deletion mutants exhibit loss of silencing at the silent mating type loci [3297920] and telomeres [1913809] and have slightly elevated level of rDNA marker loss [10521401]. The short lifespan of a SIR4 mutant is probably due to the simultaneous expression of a and alpha mating-type information, which indirectly causes an increase in rDNA recombination and likely increases the production of extrachromosomal rDNA circles. Lifespan reduction by SIR4 deletion is suppressed by preventing mating type heterozygosity (co-expression of MATa and MATalpha). The sir4-42 mutation extends lifespan of by more than 30% and is semidominant in Bx1-14c strain which carrys a C-terminal truncation of MPT5/UTH4. sir4-42 extends lifespan by preventing recruitment of the SIR proteins to HM loci and telomeres, thereby increasing their concentration at other chromosomal regions. Expression of only the carboxyl terminus of SIR4 interferes with silencing at HM loci and telomere, which also extends lifespan [7859289]. Both Sir3 and Sir4 relocate to the nucleolus in the sir4-42 mutant background, dependent upon MPT5 and YGL023. sir4-42 has no effect on lifespan in a UTH4 wild-type strain background [9150138]. sir-4-42 results in constitutive localization of SIR3 to the rDNA. Lifespan extension by sir4-42 is likely due to increased dosage of SIR2 at the rDNA [10521401]. 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
    PMR1 High affinity Ca2+/Mn2+ P-type ATPase required for Ca2+ and Mn2+ transport into Golgi; involved in Ca2+ dependent protein sorting and processing; mutations in human homolog ATP2C1 cause acantholytic skin condition Hailey-Hailey disease Deletion of PMR1 increses the replicative lifespan by 40% in the alpha strain and by 15% in the a strain. Overexpression of PMR1 extends the lifespan [21918615]. Budding yeast
    PGA3 Processing of Gas1p and ALP Low glucose condition induces expression and activity of plasma membrane NADH coenzyme Q reductase (PGA3). Overexpression of PGA3 extends replicative and chronological lifespan by 20-30% [19239415]. Budding yeast
    NPT1 Nicotinate PhosphoribosylTransferase 1 Increased dosage of NPT1 increases SIR2-dependent silencing, stabilizes the rDNA locus and extends replicative lifespan by up to 60%. 0.5% glucose restriction does not significantly further increase replicative lifespan of NPT1 overexpression [11884393]. NPT1 deletion decreases replicative lifespan by 50% [17482543] as well as chronological lifespan [17110466]. Deletion of NPT1 shortens the lifespan in W303R. Replicative lifespan extension of cdc25-10 mutation (assumed to act as a genetic DR-mimetic) is cancelled out by NPT1 deletion [11000115]. NPT1 mutation results in loss of telomere and rDNA silencing [10841563], an effect that is likely caused by a loss of SIR2 activty due to decreased NAD levels. Mutation of NPT1 is synthetical lethal with mutation of QPT1 [11000115]. Budding yeast
    NDE2 NADH Dehydrogenase, External 2 Overexpression of NDE1 and NDE2 increases intracellular NAD/NADH ratio by lowering NADH concentration and increases replicative lifespan by 20-25%. This lifespan extension is non-additive with 0.5% glucose restriction [14724176]. Budding yeast
    NDE1 NADH Dehydrogenase, External 1 Overexpression of NDE1 and NDE2 increases intracellular NAD/NADH ratio by lowering NADH concentration and increases replicative lifespan by 20-25%. This lifespan extension is non-additive 0.5% glucose restriction [14724176]. Deletion of NDE1 extends chronological lifespan [16436509]. Budding yeast
    MDH1 Malate DeHydrogenase 1 Overexpression of MDH1 extends replicative lifespan by 25% and does not synergize with 0.5% glucose restriction [18381895]. Budding yeast
    LAT1 LAT1 is suggested to play a role in lifespan extension of DR. Deleting LAT1 abolishes replicative lifespan extension induced by 0.5% and 0.05% glucose restriction. In contrast, overexpressing Lat1 extends replicative lifespan, and this lifespan extension was not further increased by 0.5% glucose restriction. Similar to DR, replicative lifespan extension by LAT1 overexpression largely requires mitochondrial respiration [17200108]. Overexpressing LAT1 extends lifespan (20% mean lifespan increase) and this lifespan extension is not further increased by DR. Similar to DR, lifespan extension by Lat1 overexpression largely requires mitochondrial respiration indicating mitochondrial metabolism plays an important role in DR. Interestingly, LAT1 overexpression does not require the Sir2 family to extend lifespan. Lat1 is also a limiting longevity factor in non-dividing cells in that overexpressing LAT1 extends cell survival during prolonged culture at stationary phase. Budding yeast
    • Page 1 of 2
    • 25 of 37 factors
    Factors are an extension of GenAge and GenDR.

    Comment on This Data Unit