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
    nhr-62 Nuclear Hormone Receptor family NHR-62 is required for metabolic and physiologic responses associated with DR-induced longevity. *nhr-62* mediates the longevity response of *eat-2* mutants and blunts the longevity by bacterial food dilution [Heestand, et al. 2012]. Mutation in *nhr-62* suppresses the lifespan extension of eat-2(ad465) animals (p<0.001) [Heestand et al. 2013]. Wild-type (N2) worms with extrachromosomal array dhEx627 (carrying a wild-type nhr-62) exhibit a significant increase in lifespan compared to wild-type (p<0.001) [Heestand et al. 2013]. Nematode
    AVT1 Amino acid Vacuolar Transport 1 Overexpressing or deleting AVT1 is sufficient to extend or shorten replicative lifespan, respectively [23172144]. Overexpression of AVT1 prevents mitochondrial dysfunction, prevents alterations in mitochondrial structure and ΔΨ of aged cells even through the vacuolar acidity is reduced in these cells. AVT1 overexpression extends the mean, median and maximum replicative lifespan by 28, 28, and 22%, respectively [23172144]. Deletion of AVT1 accelerates the development of age-induced mitochondrial dysfunction without effecting the kinetics of vacuolar acidity decline and prevents the suppression of mitochondrial dysfunction by VMA1 and VPH2 overexpression without affecting vacuolar acidity. AVT1 deletion decreases mean, median and maximum replicative lifespan by 21, 22, and 12%, respectively [23172144]. Budding yeast
    VMA1 Vacuolar Membrane Atpase 1 Overexpression of VMA1 increases vacuolar acidity and suppresses age-induced mitochondrial dysfunction of aged cells (17 or 18 cell divisions) which requires the V-ATPase activity. VMA1 overexpression significantly increases mean, median and maximum lifespan by 39 - 45%, 39 - 48% and 50 - 60%, respectively. DR (0.5% glucose restriction) does not further increase the lifespan of VMA1 overexpression strain [23172144]. Budding yeast
    CG13890 Overexpression of CG13890 (DCI) throughout the whole body increases mean and median lifespan by 35 and 31%, but decreases maximum lifespan by 6%, increases stress resistant (to paraquat and starvation), consistently reduces the mortality rate across adult ages and reduces the lifespan extension of DR by 15% [22997544]. CG6783 overexpression increases the dFOXO nuclear localization in the fat-body. mRNA levels of dFOXO target genes l(2)efl and 4E-BP in the adult whole bodies increases in response to overexpression of CG6783 [22997544]. Fruit fly
    fabp fatty acid bindin protein Overexpression of fabp (CG6783) throughout the whole body increases mean, median and maximum lifespan by 77, 81 and 13%, increases stress resistant (to paraquat but not starvation), consistently reduces mortality rate across adult ages and reduces the lifespan extension of DR by 12% [22997544]. fabp overexpression increases the dFOXO nuclear localization in the fat-body. mRNA levels of dFOXO target genes l(2)efl and 4E-BP in the adult whole bodies increases in response to overexpression of fabp [22997544]. Females of the genotype Act-GS-Gal4 > UAS-CG6783 exhibit an increase in median lifespan compared to uninduced control in response to feeding with RU486-containing food from day 3 of adulthood (P < 0.0001). Mean lifespan is extended by 10, while maximum lifespan is decreased by 11% [22997544]. Fruit fly
    phi-50 RNA interference of phi-50 decreases mean lifespan by 29% and suppresses lifespan extension by isp-1 and eat-2 mutation but does not significantly affect lifespan extension by daf-2 [22829775]. Nematode
    nekl-2 NEK (NEver in mitosis Kinase) Like 2 RNA intereference of nekl-2 decreases lifespan by 24% and suppresses lifespan extension by eat-2 mutation [22829775]. Nematode
    wnk-1 mammalian WNK-type protein kinase homolog 1 RNA interference of wnk-1 decreases lifespan by 9% and suppresses lifespan extension by eat-2 mutation [22829775]. Nematode
    cpf-2 Cleavage and Polyadenylation Factor 2 RNA interference of cpf-2 decreases mean lifespan by 6% and suppresses lifespan extension by eat-2 mutation [22829775]. Nematode
    asp-3 ASpartyl Protease 3 RNA interference against asp-3 significantly reduces lifespan of eat-2(ad1116) mutants, without any significant affect on the lifespan of wild-type. Mean and 75%ile lifespan of eat-2 mutants is reduced by 13-14% and 5-9% by asp-3 RNAi. ASP-3 is upregulated in eat-2 mutants [22810224]. Nematode
    icl-1 IsoCitrate Lyase homolog 1 RNAi knockdown of icl-1 (alias gei-7) starting at hatching or only during the adulthood significantly extends lifespan of wild-type, but does not alter, or even shortens the lifespan of eat-2 mutants [22810224]. Nematode
    acdh-12 Acyl CoA DeHydrogenase 12 RNA interference of acdh-12 starting at hatching or only during the adulthood significantly decreases eat-2 lifespan without affecting the lifespan of wild-type [22810224]. Nematode
    fat-2 FATty acid desaturase 2 RNAi knockdown of fat-2 starting at hatching or only during the adulthood significantly extends lifespan of wild-type, but does not alter, or even shortens the lifespan of eat-2 mutants. FAT-2 is downregulated in eat-2 [22810224]. Nematode
    pod-2 Polarity and Osmotic sensitivity Defect 2 RNA interference of pod-2 starting at hatching or only during the adulthood significantly decreases eat-2 lifespan without affecting the lifespan of wild-type. POD-2 is downregulated in eat-2 [22810224]. Nematode
    acdh-1 Acyl CoA DeHydrogenase 1 RNAi knockdown of acdh-1 starting at hatching or only during the adulthood significantly decreases lifespan of eat-2 without affecting wild-type lifespan. ACDH-1 significantly upregulated in eat-2. Increased content of ACDH-1 is, at least partially, required for lifespan-extension by DR [22810224]. Nematode
    pyc-1 PYruvate Carboxylase 1 RNA interference of pyc-1 starting at hatching or only during the adulthood significantly decreases eat-2 lifespan without affecting the lifespan of wild-type. PYC-1 is downregulated in eat-2 mutants [22810224]. Nematode
    MXR2 peptide Methionine sulfoXide Reductase 2 Deletion or overexpression of MXR2 (alias MsrB) has no effect on replicative lifespan under normal growth conditions. Simulatonous deletion of MXR2 together with MXR1 dramatically reduces replicative lifespan by 63%. Overexpression of MXR2 under DR conditions extends replicative lifespan by 120% [15141092]. Budding yeast
    shk-1 SHaKer family of potassium channels 1 shk-1 encodes a shaker family of potassium channel which functions in muscle [21059759], is expressed in sensory neurons [16899454], and downregulated in space. Mutation or RNA interference of shk-1 extends lifespan on NGM agar covered with killed or live bacteria as well as in liquid culture medium. shk-1 RNAi extends mean, 75%ile, and maximum lifespan by 16, 15, and 22%. shk-1(RB1392) mutation extends mean, 75%ile, and maximum lifespan by 19-22, 19-21, and 20-24%. Lifespan extension by unc-17 mutation is totally abolished by RNAi inactivation of either daf-16 or skn-1. eat-2 RNAi shortens the lifespan of shk-1 mutants. RNAi inactivation of shk-1 reduces Q35 aggregation [22768380]. Mutation and RNAi of shk-1 enhance pheromone-induced dauer formation [22768380]. Nematode
    F57A8.4 Protein F57A8.4 F57A8.4 encodes a rhodopsin-like G-protein coupled receptor that is known to sense light [11493519] and is downregulated in space. Mutation or RNA interference of F57A8.4 extends lifespan on NGM agar covered with killed or live bacteria as well as in liquid culture medium. F57A8.4 RNAi extends the mean, 75%ile and maximum lifespan by 34, 39, and 61%. F57A8.4(tm4341) mutation extends the mean, 75%ile, and maximum lifespan by 18-38, 21-25, and 42-68%. Lifespan extension by gar-3 mutation is not abolished by RNAi inactivation of either daf-16 nor skn-1. eat-2 RNAi shortens the lifespan of F57A8.4 mutants [22768380]. Mutation and RNAi of F57A8.4 suppresses pheromone-induced dauer formation [22768380]. Nematode
    cha-1 abnormal CHoline Acetyltransferase 1 cha-1 encodes a choline acetyltransferase which is expressed in motor [18041778] neurons and downregulated in space. Mutation or RNA interference of cha-1 extends lifespan on NGM agar covered with killed or live bacteria as well as in liquid culture medium [22768380]. cha-1(TY1652) mutation extends mean, 75%ile, and maximum lifespan by 23, 29, and 38%. The cha-1(PR1152) allele extends mean, 75%ile, and maximum lifespan by 22-49, 18-25, and 11-21%. Lifespan extension by cha-1 mutation is not abolished by daf-16 RNAi inactivation. eat-2 RNAi shortens the lifespan of cha-1 mutants. RNAi inactivation of cha-1 reduces Q35 aggregation [22768380]. cha-1 participates in determining pharyngeal pumping rate to affect food intake [6698395]. Nematode
    rpr reaper Flies with ablated wings caused by overexpressing reaper (UAS-rpr) with a wing-specific Gal4 enhancer trap (1096-Gal4) exhibit only a 14% extension in lifespan compared to controls which exhibit a 61% extension upon DR [22768842]. Fruit fly
    CG7834 CG7834 gene product from transcript CG7834-RA Muscle specific RNAi knockdown of CG7834 which reduces its mRNA levels by 25-35%, significantly reduces the DR-dependent lifespan extension. CG7834 RNAi animals exhibit only a 14% increase compared to the 55% lifespan-increase in controls upon DR [22768842]. Fruit fly
    CG4389 CG4389 gene product from transcript CG4389-RA Muscle specific RNAi knockdown of CG489 which reduces its mRNA levels by 25-35%, significantly reduces the DR-dependent lifespan extension. CG4389 RNAi animals exhibit only 20% increase while controls display an lifespan increase by 123% upon DR [22768842]. 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
    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
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    • 25 of 172 factors
    Factors are an extension of GenAge and GenDR.

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