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
    Fgf21 Fibroblast growth factor-21 Overproduction of Fgf-21 increases mean lifespan of males by 30% and that of females by 39% [23066506]. Mice overproducing Fgf21 are lean throughout their lives and remain lean even while eating slightly more than wild-type mice. Fgf21 overproducers tend to be smaller than wild-type mice and female mice were infertile. Although Fgf21 overproducers have significantly lower bone density than wild-type, Fgf21-abundant mice exhibit no ill effects from the reduced bone density and remain active into old age without any broken bones. Fgf21 seems to provide its health benefits by increasing insulin sensitivity and blocking the growth hormone/insulin-like growth factor-1 signaling. Fgf21 acts as a hormone, is secreted by the liver during fasting and helps the body to adapt to starvation. House mouse
    SAG12 Introduction of a SAG12 via bacterial gene transfer (pSAG12:ipt) increases longevity. The gene results in enhanced production of the hormone Cytokinin which affects growth and development as well as stimulates cell division and thereby extends the lifespan. pSAG::ipt transgenic plants exhibit delayed leaf senescence, increased branching and reduced internodal length. The leaves and flowers of the pSAG12:ipt plants are reduced in size and display a more intense coloration [http://www.wissenschaft.de/wissenschaft/news/316062.html; http://www.biomedcentral.com/1471-2229/12/156/abstract; Garcia-Sogo et al. 2012].
    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
    PEP4 carboxyPEPtidase Y-deficient 4 Overexpression of vacuolar aspartyl protease (PEP4) extends chronological lifespan by increasing cytosolic polyamine and S-adenosylmethionine (SAM) levels. Deletion of PEP4 results in both apoptotic and necrotic cell death during chronological aging [21593793]. PEP4 is not DR-essential [18690010]. Budding yeast
    pck-1 Phosphoenolpyruvate CarboxyKinase 1 RNA interference of pck-1 during the adulthood significantly shortens lifespan of both wild-type and eat-2 mutants. RNAi knockdown of pck-1 from hatching cases larval lethality. Overexpression of pck-1 greatly increases content of PEPCK-C, markedly induces enzyme activity and significantly increases mean, 75%ile, and maximum lifespan by 19-23%, 17-22%, and 21% [22810224]. Nematode
    MAPK1 mitogen-activated protein kinase 1 Overexpression of human MAPK1 (alias ERK2) confers resistance to heat shock and oxidative stress extends median chronological lifespan by 24% and was statistically non-addative with cyr1-1 mutation [17662940].MAPK1 was not found to be associated with longevity [23020224]. MAPK1 was found to be associated with longevity [23020224]. Human
    Hsp70Bb Hsp70Bb Heat-shock-protein-70Bb Overexpression of the Hsp70 locus (containing Hsp70Bb and Hsp70Bc) in transgenic flies extends lifespan as much as 7.9% [9363888]. Fruit fly
    Akh Adipokinetic hormone Knockdown of the adipokinetic hormone (Akh) by RNAi (with an RU486-inducible and ubiquitously expressing Actin 5C-GS Gal4 strain) does not by itself affect lifespan, but significantly inhibits DR-dependent increase in lifespan across a range of yeast concentrations in both females and males. While control females and males exhibit a 113%/22% increase in lifespan under DR, upon Akh inhibition there was a significant reduction in lifespan extension with DR (52%/5%). Global Akh knockdown reduces starvation resistance by 24% upon DR, but no significant change upon AL. Also Akh RNAi repressed the DR-dependent increase in cold-stress resistance. Fat body and neuronal-specific inhibition of Akh by using RU486-inducible S(1)106-GS-Gal4 and Elav-GS-Gal4 enhancer traps, respectively, does not reduce lifespan extension upon DR. But, muscle-specific inhibition of Akh using RU486-inducible muscle enhancer trap (Mhc-GS-Gal4) reduces the DR-dependent increase in lifespan. While control exhibit a 47.2% lifespan extension, animals with muscle-specific Akh inhibition fails to result in any increase upon DR (i.e. completely blocked the DR lifespan extension). Muscle-specific Akh inhibition diminishes the increase in triglyceride synthesis and breakdown present normally under DR. A significant reduction in lifespan extension also occurs with a noninducible muscle driver (Mhc-Gal4). Controls on DR exhibit significant higher levels of spontaneous activity compared to Akh RNAi-inhibited animals at all ages. Akh inhibition reduces the protective effect of DR on age-related decline in muscle function/activity [22768842]. Fat-body specific Akh RNAi results in increased spontaneous activity and a small but significant increase in lifespan upon AL [22768842]. Overexpression of Akh in a ubiquitousness manner enhances fat metabolism (significant increase in triglyceride synthesis and breakdown under AL), spontaneous activity (148% on AL and 154% on DR), and lifespan on AL (33%). However, despite and increase in movement under DR, lifespan is not increased under a restricted diet [22768842]. Fruit fly
    NDT80 Non-DiTyrosine 80 Transient overexpression of NDT80 rejuvenates old cells [21700873]. Budding yeast
    IME1 Inducer of MEiosis 1 Transient overexpression of IME1 resets the replicative lifespan of old cells back to that of young cells [21700873]. Budding yeast
    Npy neuropeptide Y Overexpression of Npy under the control of its own promoter results in increased mean and maximum lifespan. However the observed lifespan extension is relatively small (p = 0.0059 by Wilcoxin test and p = 0.05 by t-test; n = 20) [12668588]. The blood pressure of Npy transgenic rats was significantly lower as compared with nontransgenic siblings. Food intake and weight were not significantly different compared to controls [12668588]. Norway rat
    NNT1 Nicotinamide N-methylTransferase 1 Deletion of NNT1 decreases mean and maximum lifespan by 9 and 19%. 0.5% glucose DR extends the mean and maximum lifespan of NNT1 deletion mutants by 35 and 40%. Overexpression of NNT1 by 5-fold extends mean and maximum replicative lifespan by 18 and 23%, which is approximately of the same magnitude as the lifespan extension obtained from DR. DR in NNT1 overexpression mutant fails to significantly affect the lifespan and only results in extended mean lifespan by 12% and reduced maximum lifespan by 11%. NNT1 overexpression increases rDNA silincing, whereas deletion decreases rDNA silencing. Overexpression of human nicotinamide N-methyltransferase also increases rDNA silencing [12736687]. Budding yeast
    Eip71CD Ecdysone-induced protein 28/29kD Overexpression of Eip71CD (alias MsrA) in nervous system extends the lifespan by up to 70%, increased resistance to oxidative stress, and delays the onset of senescence-induced decline in activity levels and reproductive capacity. Eip71CD is a downstream effector of foxo [22310715]. Mean and maximum lifespan is increased by up to 2-% in animals that overexpress Eip71CD [20655917]. Fruit fly
    SIR2RP1 NAD-dependent SIR2 Overexpression of SIR2RP1 results in a significant increase in survival of the vertebrate stage under normla axenic culture conditions, but has no effect on survival of the insect stage of the parasite. SIR2RP1 is mainly localized within the cytoplasm [12383511].
    INS insulin Expression of human insulin under an inducible heat shock promoter increases nematode lifespan by 25% and is also able to enhance the lifespan of daf-2 mutants [11274053]. INS was found to be associated with longevity [22406557; 19367319; 17989723; 19489743]. Human
    TERT telomerase reverse transcriptase Telomerase-expressing cells (human foreskin fibroblasts, retinal pigment epithelial cells) maintain normal length of telomeres and continue to divide vigorously [9454332]. Cells expression telomerase have reduced staining for beta-galactosidase (a biomarker of cellular senescence) [9501072]. TERT expression is also able to prevent the accelerated replicative senescence observed in cells taken from Werner's patients [10615119]. A haplotype of TERT was correlated with both longer both longer telomere length and exceptional longevity. Mutations in TERT were overpresented in Ashkenazi centenarians [19915151].TERT was not found to be associated with longevity [22136229]. TERT was found to be associated with longevity [23562826]. Human
    HSPA9 heat shock 70kDa protein 9 (mortalin) Overexpression of HSPA9 (mortalin) increases the proliferation potential of normal fibroblasts [11959102]. Transfection of normal human fibroblasts with human HSPA9 (or the murine Hspa9) overexpression vectors led to an increase in the number of population doublings the cells could sustain before senescing (increase varying from 32-60%, depending on the exact construct used). Transfected cells retain a youthful morphology longer than the controls cells, and there is an dealy in appearance of senescence associated beta-galactosidase activity [10838077]. Mot-2 overexpressing cells exhibit a reduction in p53 transcriptional activation (as measured by expression from vectors containing either luciferase or beta-glactosidase driven by p53 binding sites) [10838077], which might partially or wholly explain the effects of Mot-2 on proliferative potential. HSPA9 is differentially distributed and/or translated in normal vs. transformed cells [8454632]. Human
    hep hemipterous Overexpression of hey significantly extends median (50%) and maximum (25%) lifespan. A hypomorphic allele of hep (hep1) laerlgy prevents lifespan extension caused by puc heterozygosity [14602080]. Fruit fly
    hsb-1 Heat Shock factor Binding protein hsb-1(cg116) mutation at 20 degree Celsius extends mean, 75%ile, and maximum lifespan by 57-60%, 52-59%, and 37-69%. Nematode
    lyz lysozyme Overexpression of lyz increases mean, median, and maximum lifespan by 26, 30 and 44% [22737090].
    ucp2 uncoupling protein 2 Overexpression of zebrafish's ucp2 in nematode increases mean, median, and maximum lifespan by 42, 40, and 26%, which is non-additive with sDR [22737090].
    sod1 sod1 superoxide dismutase 1, soluble Overexpression of sod1 in C. elegans increases mean, median, and maximum lifespan by 21, 25, and 29% [22737090].
    lmp-2 LAMP (lysosome-associated membrane protein) homolog Overexpression of lmp-2 increases mean, median and, maximum lifespan by 25, 35, and 48% [22737090]. Nematode
    sod-1 SOD (superoxide dismutase) sod-1 overexpression increases mean, median, and maximum lifespan by 32, 25, and 35% [22737090]. Nematode
    aakg-2 AMP-Activated protein Kinase Gamma subunit 2 aakg-2 overexpression extends mean, median, and maximum lifespan by 47, 45, and 35%. Overexpression of aakg-2 toegther with D. rerio ucp2 was non-additive with sDR [22737090]. Nematode
    Factors are an extension of GenAge and GenDR.

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