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
    STE12 STErile 12 Deletion of STE12 has no effect on replicative lifespan in strain PSY142 or BKY1-14c [7859289]. STE12 null mutants are sterile [6993497]. Budding yeast
    PUF4 PUmilio-homology domain Family 4 Deletion of PUF4 has no effect on replicative lifespan in either uth4-14c (C-terminal truncation) or UTH4 background. However, PUF4 is required for lifespan extension by the semi-dominant Sir4-42 allele in the uth4-14c background [9150138]. PUF4 is required for nucleolar relocalization of Sir3 in a Sir4-42 background [9150138]. puf4;mpt5 double deletion strain has increased telomere silencing relative to the mpt5 single mutant [9651685]. Budding yeast
    CIT2 CITrate synthase 2 Deletion or overexpression of CIT2 has no effect on replicative lifespan. CIT2 is not required for the strain specific lifespan extension in petite cells [10224252], although it is transcribed up to 30-fold higher in petite cells relative to grande cells [1986232]. Budding yeast
    VPS36 Vacuolar Protein Sortin 36 VPS36 deletion mutants have a chronological lifespan as long as wild type BY4741. Thus, Vps36 is not necessary for the starvation/extreme DR-dependent lifespan extension [20657825]. Budding yeast
    IMD2 IMP Dehydrogenase 2 Deletion of IMD2 does non-significantly decrease mean replicative lifespan by 1% and non-significantly increased maximum replicative lifespan by 21% [20550517]. 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
    HDA1 Histone DeAcetylase 1 Deletion of HDA1 has no effect on longevity under AL, but acts synergistically with 0.1% glucose restriction to increase replicative lifespan [12213553]. Deletion of HDA1 leads to a slightly increased chronological lifespan [19801973]. Deletion of HDA1 has no effect on the wild-type lifespan in the short-lifespan of YSK771 strain, but suppresses the short-lifespan of SIR3 mutants [10512855]. Budding yeast
    rrf-1 RNA-dependent RNA polymerase Family Although rrf-1(pk1417) mutants seem to have elevated DAF-16 activity (as sod-3 transcript level is increased) the mean and maximum lifespan or ability to withstand elevated temperature is not different from wild-type [22574120]. Nematode
    (-)-epidcatechin Treatment with (-)-epidcatechin do no extend C. elegans lifespan [20717869]. Nematode
    ced-3 CEll Death abnormality RNA interference of ced-3 in adulthood results in a 19% increase in mean lifespan [17411345]. The ced-3(n1286) allele has no effect on lifespan, although the transgenic animals are defective in apoptosis [12136014]. 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-1 abnormal DAuer Formation daf-1(mk40) mutation increases mean lifespan by 18-46% and maximum lifespan by 29% [17900898]. The daf-1(m40) allele has no effect on lifespan and fails to prevent lifespan extension by sir-2.1 overexpression, but it results in a temperautre-sensitive, dauer-constitutive phenotype in larvae [11242085]. Nematode
    dod-19 Downstream Of DAF-16 (regulated by DAF-16) RNA interference of dod-19 extends lifespan by 28%. dod-19 is differentially transcribed in daf-16 and daf-2 RNAi animals [12845331]. Nematode
    fem-3 FEMinization of XX and XO animals fem-3(e1996) mutants do not produce sperm or self-progeny, therefore develop as females, but have a normal lifespan (See also ref 10) [8247153]. Nematode
    fog-1 Feminization Of Germline The fog-1(q180) allele has no effect on lifespan [11799246]. fog-1 mutants are sterile and make oocytes but not sperm [2341035]. Nematode
    fog-2 Feminization Of Germline 2 fog-2(q71) allele has no effect on lifespan [10747056]. fog-2 mutant display hermaphrodite specific germ line feminization [11076749]. Nematode
    fog-3 Feminization Of Germline 3 The fog-3(q470) allele has no effect on lifespan [11799246]. In fog-3 mutant animals cells that would normally become sperm differentiate into oocytes [7713418]. Nematode
    ins-22 INSulin related 22 RNAi of ins-22 has no effect on lifespan. ins-22 is differentially transcribed in daf-16 and daf-2 RNAi animals [12845331]. Nematode
    lars-2 Leucyl Amino-acyl tRNA Synthetase A mutation that impairs mitochondrial function was associated with a longer lifespan. Mutation of lrs-2/lars-2(mg312) extends lifespan and is associated with impaired mitochondrial function. The recessive allele mg312 of lars-2 extends lifespan by 200% at 20 degree Celsius and 30% at 25 degree Celsius. Lifespan extension by mg312 was not dependent on daf-16(mgDf47). Homozygous lars-2(mg312) worms had multiple pleotropies like lower rates of growth, pumping and defecation as well as remain the size of early L4 worms and are sterile, with an arrested gonad that exhibited no germ-cell differentiation lars-2 is ubiquitously express, with prominent expression in body-wall muscle and neurons, with a mitochondrial subcellular localisation. Mitochondria of lars-2 are noticeably disorganized, swollen and sometimes fused. lars-2 animals have lower ATP content and oxygen consumption [12447374]. Nematode
    mec-1 MEChanosensory abnormality 1 Loss of function mutations in mec-1 do not effect lifespan [2428682]. mec-1 mutants are touch insenstive, lethargic, and have displacement of some microtubule cells and amphidial neurons as well as defective fasciculation [2428682]. Nematode
    sip-1 Stress Induced Protein 1 RNAi of sip-1 has no effect on wild-type adult lifespan, but slightly shortens the long lifespan of age-1(hx546) mutant animals [14668486]. Nematode
    unc-1 UNCoordinated 1 Mutation in unc-1 has no effect on lifespan [9789046]. Nematode
    unc-15 UNCoordinated 15 Mutation of unc-15 has no effect on lifespan [9789046]. Some alleles of un-15 display severe paralysis [4366476; 2051482]. Nematode
    unc-2 UNCoordinated 2 Loss of function in unc-2 has no effect on lifespan [9789046]. unc-2 mutant is uncoordinated [4366476] and its rate of pharyngeal pumping is reduced [8325482]. Nematode
    unc-24 UNCordinated 24 Mutations in unc-24 have no significant effect on lifespan [9789046] and unc-24(e138) fails to extend male lifespan [10747056]. unc-24 mutant is uncoordinated and displays irregular movement [4366476; 8667025]. Nematode
    Factors are an extension of GenAge and GenDR.

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