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
    Aut1 Aut1 depletion form the first day of imaginal stage shortens lifespan by 28% on average in Drosophila and causes morphological behavioural features of premature aging [18219227]. Fruit fly
    bam bag of marbles Bam mutants have an extended lifespan due to germ cell loss. Lifespan of females is on average up to 50% higher and that of males on average s up to 27.8% higher [18434551]. Fruit fly
    CG17856 RNAi of CG17856 results in an increase in mean lifespan of 13-18% in females. In the case of males and post-developmental experiments the results are variable [19747824]. Fruit fly
    CG18809 RNAi of CG18809 results in a 7-19% increase in mean lifespan of females, while neural RNAi results in an increased mean lifespan of up to 12% in females. For males the results are variable [19747824]. Fruit fly
    CG5389 RNAi of complex V subunit CG5389 results in increased mean longevity under standard laboratory food conditions (3% yeast) in males. RNAi started from the development results in a mild lifespan increase in both sexes (3-11% in females and 3-8% in males). Post-developmental RNAi and silencing limited to neurons has variable effects with reduction in lifespan of up to 9% [19747824]. Under rich media conditions CG5389 knockdown throughout development and adulthood increases mean lifespan by 26% and abolished the lifespan extension by DR (started in the adulthood) in males. Suppression of CG5389 only during the adulthood either via RNAi by tub-GS or via oligomycin (a specific inhibitor of complex V) feeding prevents an increase in longevity under DR (started in the adulthood) in males [19968629]. Fruit fly
    CG9172 RNAi against CG9172 increases mean lifespan in females by up to 4-12% when applied in both development and adulthood, and up to 46% when applied in adult neurons only. For males the effect is variable [19747824]. Fruit fly
    DNApol-gamma35 DNA polymerase gamma 35kD Overexpression of DNApol-gamma35 (DNA polymerase gamma) in the nervous system results in a decrease in the median lifespan ranging from 39% to 52% [17999718]. Fruit fly
    Dys Dystroglycan Loss of dys function in the heart leads to an age-dependent disruption of the myofibrillar organization within the myocardium as well as to alterations in cardiac performance. dys RNAi-mediated knockdown in the mesoderm also shortens lifespan. Mesodermal dys knockout results in a morderate maximum lifespan reduction (13%), but not when exclusively targeted to the heart. In contrast, half of the transheteozygous DysExel618/Dyskx43 deficiency flies die at 29 days compared to 63 days in controls. This indicates that a moderate dye loss-of-function in all muscles, but not in just the heart, reduces the normal lifespan [18221418]. Fruit fly
    E(z) Enhancer of zeste Flies heterozygous for the protein null E(z)63 or the catalytically inactive E(z)731 mutation that are progeny of an out-cross to an Oregon-R (O-R) wild-type strain exhibit a substantially greater median lifespan than the O-R control (71% and 76%, respectively). When derived from an out-cross to a longer-lived Canton-S (C-S) wild-type strain, the median lifespan of E(z)63 heterozygous is 33% longer than the C-S control [20018689]. Fruit fly
    Edem1 The mean lifespan of Edem1 mutants of both male and female is increased by more than 30% [19302370]. Fruit fly
    elav embryonic lethal abnormal vision elav mutation significantly decreases the lifespan. Median lifespan in males is 66% lower [20589912]. Fruit fly
    esc extra sexcombs Males heterozygous for the null esc4 or the dominant negative esc9 mutation that are progeny of an out-cross to a O-R wild-type strain have median lifespan that is, respectively, 47% and 60% longer than the O-R control. When derived from an out-cross to a longer-lived C-S wild-type strain, heterozygous esc9 flies have a median lifespan that is 43% longer than the C-S control [20018689]. Fruit fly
    fh frataxin homolog Overexpression of fh in the mitochondria of female transgenic animals increases antioxidant capability, resistance to oxidative stress insults, and longevity [18258192]. Fruit fly
    Gadd45 growth arrest and DNA damage-inducible gene 45 Gadd45 overexpression in the nervous system leads to a significant increase of lifespan without a decrease in fecundity and locomotor activity. The lifespan extension effect is more pronounced in males than in females. Additional maximum lifespan is also extended. The maximum lifespan is increased by 50% and 59% for females and males, respectively. The median lifespan is extended by 46 and 77% for females and males, respectively [22661237]. Fruit fly
    Gr63a Gustatory receptor 63a Gr63a loss-of-function in female flies leads to 30% extended mean lifespan, increased fat deposition, and enhanced resistance to some (but not all) environmental stresses. Lifespan of males is not extended [20422037]. Overexpression of Gr63a has modest negative effect on lifespan [20422037]. Fruit fly
    GstS1 Glutathione S transferase S1 GstS1 overexpression increases the mean lifespan by 33% [18059160]. Fruit fly
    hebe Adult-specific overexpression of hebe increases the lifespan by 5-30% and modulates late-age female fecundity. Female and male mean lifespan is up to 11% and 24% higher [19011900]. Fruit fly
    Hsc70-3 Heat shock protein cognate 3 Overexpression of Hsc70-3 increases average female lifespan by 27% [18059160]. Fruit fly
    Hsp22 Heat shock protein 22 Overexpression of mitochondrial Hsp22 in all cells or specifically in motorneurons (using GAL4/UAS binary system) increases life lifespan by 32% and resistance to oxidative stress [19948727; 20036725]. Ubiquitous or a targeted expression of Hsp22 within motorneurons increases the mean lifespan by more than 30%. Hsp22 shows beneficial effects on early-aging events since the premortality phase displays the same increase as the mean lifespan [14734639]. Animals that do not express Hsp22 (due to a transposition into its transcriptional starting site) have a 40% decrease in lifespan, exhibit a 30% decrease in locomotor activity and are sensitive to mild stress [20036725]. Doxycyline-regulated overexpression of Hsp22 makes animals more sensitive to heat and oxidative stress as well as reduces the mean lifespan by up to 21%, particularly at higher culture temperature [15491684]. Hsp22-promoter driven reporter overexpression reduces mean and maximum lifespan [19420297]. Histone deacetylase inhibitor Trichostatin A (TSA) extends the lifespan of *Drosophila melanogaster* by promoting the hsp22 gene transcription, and affecting the chromatin morphology at the locus of hsp22 gene along the polytene chromosome [15346199]. Fruit fly
    Ilp2 Insulin-like peptide 2 Flies with an ablation of median neurosecretary cells (which eliminates Ilp2 expression) exhibit a significant increase in mean and maximum lifespan over that of control flies and an increase to oxidative stress and starvation. The mutants also exhibit increased storage of lipid and carbohydrate, reduced fecundity, and reduced tolerance of heat and cold [15708981]. The median and maximum lifespan of females is increased by 33.5% and 40%, respectively. In males the median and maximum lifespan is increased by 10.5% and 27%, respectively [15708981]. Ilp2 RNA interference results in a 24% to 47% increase in median lifespan [19005568]. Ilp2 is transcriptional down-regulated in long-lived mutants. Ilp2 null mutants are significant longer-lived with a 8-13% longer median lifespan, but have a normal DR response. Ilp2 Ilp3 Ilp5 triple null mutants fail to have a normal response to DR. Their response is right shifted, with mutants shorter-lived compared to wild-type on low but longer-lived on high yeast concentrations [20195512]. Fruit fly
    Jafrac1 thioredoxin peroxidase 1 Neuronal overexpression of Jafrac1 significantly increases both mean and maximum lifespan, while neuronal knockdown as well as loss of function mutation, causes a reduction in lifespan by 30%. The mean lifespan is 26% and 29% higher in females and males, respectively. The maximum lifespan is increased by 22% and 26% in females and males, respectively [19720829]. There is a consistent and significant lifespan extension (15% mean lifespan increase) in both males and females when Jafrac1 is overexpressed in somatic cells. Jafrac1 overexpression using the weaker 5961FS driver moderately but significantly extends lifespan [20976250]. Fruit fly
    CG3776 Both overexpression and underexpression of CG3776 (alias Jhebp29) reduces the mean lifespan, where the reduction in males is slightly higher. The lifespan of male flies with under- and overexpressed CG3776 is reduced by 38.8 and 42.6%, respectively when compared with Oregon R flies.The lifespan of female flies with under- and overexpressed CG3776 is reduced by 31.6 and 35%, respectively when compared to Oregon R flies. Among the males and females, relatively to Oregon R and EP835/CyO, the age-specific survival of EP835/EP835 and EP835/Gal4 is reduced in both log-rank and Wilcoxon tests (P < 0.001); survival of EP835/EP835 and EP835/Gal4 differed using the log-rank-test (male: P<0.001; female: P=0.027) [18275960]. Fruit fly
    kermit The disruption of kermit (alias dGIPC) function results in premature loss of locomotor activity and reduced mean lifespan [21029723]. Fruit fly
    kuk kugelkern Overexpression of kugelkern in the adult muscle results in a 60% reduction of mean lifespan [18494863]. Fruit fly
    l(3)neo18 lethal (3) neo18 RNA interference of l(3)neo18 in females increases mean lifespan by 14-18% when applied during development and adulthood in the whole organism and by 8-24% when applied in the neurons. The effect is more variable in males. A consistent increase (8-18%) is however observed for whole organisms RNAi in adults [19747824]. l(3)neo18 (alias CG9762) is translational upregulated upon DR. Under rich nutritional conditions lifespan of l(3)neo18 RNAi knockout animals is indistinguishable from wild-type, while upon DR, lifespan extension is diminished in males and females [19804760]. Fruit fly
    Factors are an extension of GenAge and GenDR.

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