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
    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
    LBR Lamin B receptor Overexpression of Lamin B receptor in the adult muscle and in the abdominal fat body results in a 54% and 46% reduction of mean lifespan, respectively [18494863]. Fruit fly
    Lnk Loss of Lnk function results in increased median (14% in females and 17.5 in males) and maximum lifespan, reduced female fecundity and improves survival under conditions of oxidative stress and starvation. Heterozygousity does not result in any significant differences in lifespan in either males or females. Moreover, lifespan extension in one of the female homozygous mutant is fully rescued by the introduction of a Lnk genomic rescue construct [20333234]. Fruit fly
    Loco locomotion defects Reduced expression of Loco due to hetero-deficient results in a 17-20% longer mean lifespan for both male and females, besides the fact that the homozygous deficiency of loco is lethal. Several of these long-lived mutants are more resistant to stresses such as starvation, oxidation and heat. Additionally, mutants have higher Manganese-containing superoxide dismutase (MnSOD) activity, increased fat content an diminished cAMP levels. Loco's RGS domain is required for the regulation of longevity as deletion analysis suggest [21776417]. Fruit fly
    magu Adult-specific overexpression of magu increases lifespan by 5-30% and modulates late-age fecundity [19011900]. Fruit fly
    mle maleless Homozygous mutant animals (mle napts) display a shortened median lifespan and increased frailty in both males and females [18208580]. Fruit fly
    Mlp84B Muscle LIM protein at 84B RNA interference of Mlp84B specifically in the heart results in bradycardia and heart rthym abnormalities as well as a shorter mean lifespan in males but not in females [18083727]. Fruit fly
    MTF-1 Metal response element-binding Transcription Factor-1 MTF-1 overexpression in either the peripheral nervous system or motorneurons extends both mean and maximum lifespan by 40% in males [18775584]. Fruit fly
    Naam Nicotinamide amidase Naam overexpression increases mean and maximum lifespan by 30% in both females and males. The lifespan extension is reversed by Sir2 mutants, indicating the it is dependent on Sir2 [18678867]. Fruit fly
    Nlaz Neural Lazarillo Absence of Nlaz, which is homologous to ApoD, results in a reduced lifespan in both sexes. Median lifespan is 30.8% and 22.5% lower in females and males, respectively. Maximum lifespan is reduced by 12% and 30% in females and males [21376794]. Fruit fly
    Pi3K92E Phosphatidylinositol-3-kinase Heterozyogous mutation in Pi3K92E fails to extend lifespan [11292874] and it is recessive lethal. Overexpression of a dominant-negative Pi3K92E (DP110) results in mutants that have impaired regeneration of the intestinal epithelium and are short lived with a reduction of the mean lifespan by 2.8% for males and 5.0% for females [20976250]. Fruit fly
    pex16 peroxin 16 pex16 mutation lead to a reduced mean lifespan of one-third in females and on-fourth in males. The short lifespan can be rescued by the simultaneous overexpression of pex16 in the fat body and differentiated neurons [21826223]. Mutant flies lack normal peroxisomes, have an reduced adult body size (70%-85% smaller than controls) and rozy eyes, show locomotion defects in the development of the nervous system [21826223]. Fruit fly
    Factors are an extension of GenAge and GenDR.

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