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
    VPS27 Under starvation conditions VPS27 deletion mutants have a dramatically reduced lifespan [20953148]. Budding yeast
    VPS25 Under starvation conditions VPS25 deletion mutations have dramatically reduced lifespan [20953148]. 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
    unc-76 UNCoordinated unc-76(e911) allele extends male lifespan by about 50%, but has no effect on hermaphrodite lifespan [10747056]. unc-76 mutants are uncoordinated [4366476]. Nematode
    unc-51 UNCoordinated-51 unc-51(e369) mutation reduces mean but extends maximum lifespan. unc-51(e369) mutation reduces lifespan of eat-2(ad1116) mutants to that of wild-type [18219227]. Nematode
    unc-46 UNCoordinated 46 unc-46(e177) allele has no significant effect on lifespan [9789046]. unc-46 mutants are uncoordinated [4366476]. Nematode
    unc-32 UNCoordinated unc-32 mutation extends male lifespan by about 170%, but has no effect on hermaphrodite lifespan [10747056]. unc-31 mutants are uncoordinated [4366476]. Nematode
    unc-17 UNCoordinated 17 unc-17 encodes acteylcholine transporter which is expressed in motor [18041778] and inter-neurons and is downregulated in space. Mutation of unc-17 extends lifespan on NGM agar covered with killed or live bacteria. nc-17(CB933) extends mean, 75%ile, and maximum lifespan by 31-79%, 68-89%, and 68-79%. Lifespan extension by unc-17 mutation is totally abolished by RNAi inactivation of daf-16, but not skn-1. eat-2 RNAi further enhances the extension of lifespan by mutations of unc-17 [22768380]. Mutation and RNAi of unc-17 suppresses pheromone-induced dauer formation [22768380]. Nematode
    UCP3 uncoupling protein 3 (mitochondrial, proton carrier) UCP3 was found to be associated with longevity [22743239]. UCP3 was found to be associated with longevity [22743239]. UCP3 was found to be associated with longevity [22743239]. UCP3 was found to be associated with longevity [22743239]. UCP3 was found to be associated with longevity [22743239]. UCP3 was found to be associated with longevity [22743239]. Human
    UCP1 uncoupling protein 1 (mitochondrial, proton carrier) UCP1 was found to be associated with longevity [21827845]. Human
    UCK2 uridine-cytidine kinase 2 UCK2 was found to be associated with longevity [22445811]. Human
    UCHL1 ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) UCHL1 is assoicated with Parkinson's disease [9774100]. UCHL1 belongs to a family of de-ubiquitinating enzymes responsible for the hydrolysis of bonds between ubiquitin molecules and small adducts [11084366]. Decreased activity due to mutation may result in decreased labeling of abnormal proteins for clearance. Human
    Tsc1 CG6147-PA Tuberous sclerosis complex genes 1 Ubiquitously overexpression of UAS constructs (via the daughterless (da)-GAL-4 driver) containing dTSC1 extends mean lifespan at 29°C by 14% [15186745]. Fruit fly
    SOD1 superoxide dismutase 1, soluble Ubiquitous overexpression of SOD1 does not extend lifespan in mice. Homozyous transgenic mice with two- to five-fold overexpression of SOD1 in various tissues exhibit a light reduction in lifespan. Hemizygous transgenic mice, with 1.5- to 3-fold overexpression of SOD1 display no difference in lifespan compared with nontransgenic litermate controls [10719757]. Transgenic mice with a mutant SOD1 transgene develop neuronal cytoskeletal lesions resembling the human amytrophic lateral sclerosis (ALS) phenotype [8610185]. Transgenic mice overexpressing SOD1 (and having 3.1-fold higher cellular Cu,Zn SOD activity in the brain) have reduced infarct size following experimental cerebral ischemia [1763030].SOD1 was not found to be associated with longevity [24163049]. Human
    S6k RPS6-p70-protein kinase Ubiquitous overexpression of a dominant-negative form of S6k (alias dS6K) increases mean lifespan by 22% and overexpression of a constitutively active form of S6k decreases mean lifespan by 34% at 29°C. Overexpression of a dominant-negative form of S6k protects mutants from deleterious effects of rich food, as if mimicking the effect of DR [15186745]. Fruit fly
    Cbs Ubiquitous or neuron-specific transgenic overexpression of Cbs enhances longevity in fully-fed animals. Cbs RNAi partially abrogates increased lifespan by DR, but has no effect on fully fed animals. Cbs upregulation is required for increased lifespan under low-nutrient conditions. Response of male flies to DR is muted in comparison with females. Adult-specific ubiquitous expression of Cbs is sufficient to increase female mean and maximum lifespan by 12 - 43% and 10%, respectively. Males, whose lifespan is relatively less affected by DR, exhibite a smaller, but still significant increase in lifespan by 7% upon Cbs overexpression. Neuronal overexpression also increases lifespan, albeit modestly (approximately 12% mean and 15% maximum lifespan extension), whereas overexpression in the fat body and in the gut has no effect [21930912]. Fruit fly
    UBE2H ubiquitin-conjugating enzyme E2H (UBC8 homolog, yeast) UBE2H was found to be associated with longevity [22279548]. Human
    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
    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
    U4 U4 spliceosomal RNA U4 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
    TXNRD1 thioredoxin reductase 1 TXNRD1 was found to be associated with longevity [22406557]. Human
    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
    SST Somastatin Two with age-related differential methylation markers lay within Somastatin (SST) [23177740] which declines with age and is linked to Alzheimer's disease [15778722]. Human
    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
    rut rutabaga Two rutabaga mutants, rut1 and rut2080, have significantly shortened lifespans [17369827]. Fruit fly
    Factors are an extension of GenAge and GenDR.

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