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
    Zw Zwischenferment Mean lifespan of G6PD overexpressor flies is extended in comparison with driver and responder controls, armadillo-GAL4 (up to 38%), Tubulin-GAL4 (up to 29%), C23-GAL4 (up to 27%), da-GAL4 (up to 24%), D42-GAL4 (up to 18%) and Appl-GAL4 (up to 16%). The maximum lifespan is also increased [18809674]. G6PD enzymatic activity as well as levels of NADPH, NADH, and the GSH/GSSG ration are increased [18809674]. Fruit fly
    YTHDF2 YTH domain family, member 2 A locus associated with human longevity corresponds to (TG)n microsatellite is located in the YTHDF2 gene. 412 participants of different ages, including 137 centenarians, were genotyped. The increased homozygosity in centenarians at this locus was confirmed, and observed a concomitantly increased frequency of the most frequent allele and the corresponding homozygous genotype. The same genotype was associated with increased YTHDF2 messenger RNA levels in immortalized lymphocytes. [16799135].YTHDF2 was found to be associated with longevity [16799135]. Human
    yata yata mutation shortens the maximum lifespan by 68% and results in progressive deterioration of the nervous tissues and aberrant accumulation of Sec23 [19209226]. Fruit fly
    Yaf2 YY1 associated factor 2 Yaf2 is transcriptional upregulated in the cerebral cortex at the age 28 months under different longevity conditions such as under dietary restriction (DR) as well as in feeding switch regimens that result in extended lifespan, like early age switch to DR as well as the reverse switch under the influence of the DR-mimetic α-lipoic acid (i.e. DR switched to ad libitum+ lipoic acid) [Shona et al. 2013]. Norway rat
    XRCC6 X-ray repair complementing defective repair in Chinese hamster cells 6 The single-nucleotide polymorphism in rs132793 in XRCC6 has significant effect on telomere length, but it is not associated with longevity [21972126]. Human
    XRCC5 X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining) XRCC5 was found to be associated with longevity [22406557; 16518718]. Human
    XRCC4 X-ray repair complementing defective repair in Chinese hamster cells 4 XRCC4 was found to be associated with longevity [16518718]. Human
    XRCC3 X-ray repair complementing defective repair in Chinese hamster cells 3 XRCC3 was found to be associated with longevity [16518718]. Human
    XRCC1 X-ray repair complementing defective repair in Chinese hamster cells 1 XRCC1 was found to be associated with longevity [16518718]. Human
    XDH xanthine dehydrogenase XDH was found to be associated with longevity [22406557; 22279548]. Human
    WRN Werner syndrome, RecQ helicase-like Mutation in WRN causes Werner Syndrome which characteristics includes prematurely aged facies, scleroderma-like skin changes, cataracts, arteriosclerosis, subcutaneous calcification, and diabetes mellitus [McKusick et al. 1963; 5327241]. Inheritance is autosomal recessive and malignancy is frequent. THe frequency is 3 per million individuals in Japan [7460386]. Cells from a Werner heterozygote exit the cell cycle at a faster rate than do normal cells [8265666]. Loss of WRN promoter aberrant mitotic recombination [11316787]. The single nucleotide polymorphism rs1800392 in WRN has been associated with exceptional longevity in a plethora of genetic signatures [22279548]. WRN was found to be associated with longevity [10069711; 20855428; 20855428; 20855428 ;17903295; 22406557; 16405962; 16405962; 16405962; 20855428; 20855428; 20855428; 22279548]. WRN was found to be associated with longevity [24244950]. Human
    UCP2 uncoupling protein 2 (mitochondrial, proton carrier) Overexpression of human UCP2 in the fly nervous system extends lifespan by 10-30%. Ubiquitous overexpression is lethal [16054055]. Human
    Ubash3b ubiquitin-associated and SH3 domain-containing protein B Ubash3b is transcriptional downregulated in the cerebral cortex at the age 28 months under different longevity conditions such as under dietary restriction (DR) as well as in feeding switch regimens that result in extended lifespan, like early age switch to DR as well as the reverse switch under the influence of the DR-mimetic α-lipoic acid (i.e. DR switched to ad libitum+ lipoic acid) [Shona et al. 2013]. Norway rat
    Txnrd1 Thioredoxin reductase 1, cytoplasmic Txnrd1 is transcriptional upregulated in the cerebral cortex at the age 28 months under different longevity conditions such as under dietary restriction (DR) as well as in feeding switch regimens that result in extended lifespan, like early age switch to DR as well as the reverse switch under the influence of the DR-mimetic α-lipoic acid (i.e. DR switched to ad libitum+ lipoic acid) [Shona et al. 2013]. Norway rat
    ttll-9 Tubulin Tyrosine Ligase Like Knockdown of ttll-9 throughout the entire life increases the lifespan by 3% [23698443]. Nematode
    TSHR thyroid stimulating hormone receptor Two single nucleotide in the TSHR were associated with increased TSH in both centenarians and their offspring [19837933].TSHR was found to be associated with longevity [19837933]. TSHR was not found to be associated with longevity [19837933]. Human
    TrxT Thioredoxin T Overexpression of TrxT in neurons increases the level of locomotor activity in aged flies and extends the mean lifespan by 15% [17301052]. Fruit fly
    Trx-2 thioredoxin-2 Trx-2 mutants have a 25% reduction in maximum lifespan and exhibit lower tolerance to oxidative stress while animals carrying multiple copies of Trx-2 exhibit higher tolerance [17567437]. Fruit fly
    TOMM40 translocase of outer mitochondrial membrane 40 homolog (yeast) TOMM440 correlates substantial with longevity and has been associated with Alzheimer's disease [22279548]. rs4420638 at TOMM40 gene locus exhibits significant association with longevity p-value = 9.6x10^-8). Combined modeling of linkage and association shows that association of longevity with APOEepsilon4 and APOEepsilon2 alleles explain the linkage at 19q1.11-q13.32 with pvalue-0.02 and p-value=1.0x10^-5, respectively [23286790]. TOMM40 was found to be associated with longevity [21418511; 23040522; 22279548]. TOMM40 was not found to be associated with longevity [24924924]. TOMM40 was found to be associated with longevity [24924924]. Human
    to TakeOut Overexpression of to in adult neurons, pericerbral or abdonimal fat body increases male and female lifespan. to overexpression in the adult nervous system, head fat body and abdominal fat body results in 25, 20 and 12-18% increase of mean lifespan. On average the mean lifespan is extended for males and females by 18 and 26%, while maximum lifespan of male and female is increased by 13 and 25% [20519778]. Starvation, DR and many longevity mutants (like Rpd3, Sir2, chico, methusalem) all upregulate takeout (to). to is a secreted potential juvenile hormone binding protein and its induction by starvation is blocked by all arrhythmic central clock mutants [20519778; 20622267]. Fruit fly
    TNF tumor necrosis factor The frequency of the -308 polymorphism in the TNF gene was analyzed in 71 healthy elders, aged 80 to 96 years (mean 86.2 years). The control samples were obtained from 99 young (from 21 - 54 years; mean 35.2 years) healthy individuals unrelated to elders were studied, age ranged from 80 to 96 years (mean 86.2 years). The TNF2 allele was increased in the elder group when compared to young controls [16269080].TNF was found to be associated with longevity [20518833]. TNF was found to be associated with longevity [18511747]. TNF was found to be associated with longevity [12714268]. TNF was found to be associated with longevity [12714268]. TNF was found to be associated with longevity [12676903]. TNF was found to be associated with longevity [11640949]. TNF was found to be associated with longevity [21299522]. TNF was found to be associated with longevity [21299522]. TNF was not found to be associated with longevity [12676903]. TNF was found to be associated with longevity [16269080]. TNF was not found to be associated with longevity [11640949]. Human
    Tmem218 Transmembrane protein 218 Tmem218 is transcriptional upregulated in the cerebral cortex at the age 28 months under different longevity conditions such as under dietary restriction (DR) as well as in feeding switch regimens that result in extended lifespan, like early age switch to DR as well as the reverse switch under the influence of the DR-mimetic α-lipoic acid (i.e. DR switched to ad libitum+ lipoic acid) [Shona et al. 2013]. Norway rat
    Thrsp Thyroid hormone-inducible hepatic protein Thrsp is transcriptional upregulated in the cerebral cortex at the age 28 months under different longevity conditions such as under dietary restriction (DR) as well as in feeding switch regimens that result in extended lifespan, like early age switch to DR as well as the reverse switch under the influence of the DR-mimetic α-lipoic acid (i.e. DR switched to ad libitum+ lipoic acid) [Shona et al. 2013]. Norway rat
    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
    TH tyrosine hydroxylase Polymorphyc repeats in intron 1 (Short and Long alleles) of the TH gene were examined in 196 centenarians (143 females and 53 males) and 358 controls (196 females and 162 male; 10-85 years old). A significant loss of LL homozygous genotypes was found at the THO locus in male but not in female centenarians with respect to matched controls [9887369].TH was found to be associated with longevity [12297342]. TH was found to be associated with longevity [21407269]. TH was found to be associated with longevity [19367319]. TH was not found to be associated with longevity [19367319]. TH was found to be associated with longevity [11053670]. TH was found to be associated with longevity [17989723]. Human
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    • 25 of 223 factors
    Factors are an extension of GenAge and GenDR.

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