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
    CKA2 CK2 subunit 2 CKA2 deletion approximately doubles mean chronological lifespan under starvation/extreme DR in BY4741 also increases as well as as heat-shock resistance in SDC medium in the W303-1A and DBY746 genetic backgrounds [20657825]. Budding yeast
    frh-1 FRataxin (involved in human Friedrich's ataxia) Homolog Complete absence of frataxin,the mitochondrial protein defective in individuals with Friedreich ataxia is lethal, while its partial deficiency extends animal lifespan in a p53 dependent manner. Frataxin knockdown via RNAi extends mean and maximum lifespan by 19 and 37%, respectively [23247094]. Substantial reduction of frataxin protein expression is required to extend lifespan, affect sensory neurons functionality, remodel lipid metabolism and trigger autophagy. Beclin and p53 genes are required to induce autophagy and concurrently reduce lipid storages and extend animal lifespan in response to frataxin suppression. Frataxin expression modulates autophagy in the absence of p53 [23247094]. Nematode
    mir-277 Constitutive miR-277 expression shortens lifespan and synthetically lethal with reduced insulin signaling, indicating that metabolic control underlies this phenotype. Transgenic inhibition with a miRNA sponge construct also shortens lifespan [23669073]. miR-277 is downregulated during adult life [23669073]. mir-277 controls branched-chain amino acid catabolism and as a result it can modulate the activity of TOR kinase [23669073]. Fruit fly
    COX4 Cytochrome c OXidase 4 COX4 (subunit of cytochrome oxidase) deletion decreases mitochondrial membrane potential in rho+ cells to a value intermediate between rho+ and rho0 as well as increases mean and maximum replicative lifespan by 24% and 55%, respectively. Deletion of either RTG2 or RTG3 abrogated the replicative lifespan extension by COX4 deletion. ERC levels in cox4Delta rho+ cells was the same or lower than in rho+ cells [22303396]. Budding yeast
    cup-4 Coelomocyte UPtake defective 4 cup-4 RNAi or overexpession reduces oxidative stress resistance and shortens lifespan of wild-type under AL. cup-4 RNAi significantly reduces the extended lifespan of eat-2 mutants, but failed to block lifespan extension of age-1 or clk-1 mutants. Lifespan of cup-4 mutants increases only moderately by sDR [19783783]. Nematode
    cyc1 cytochrome c(1) cyc1 mutants have a reduced growth rate, a reduced reactive oxygen species production, and are long-lived [17081785]. Podospora anserine
    daf-1 abnormal DAuer Formation daf-1(mk40) mutation increases mean lifespan by 18-46% and maximum lifespan by 29% [17900898]. The daf-1(m40) allele has no effect on lifespan and fails to prevent lifespan extension by sir-2.1 overexpression, but it results in a temperautre-sensitive, dauer-constitutive phenotype in larvae [11242085]. Nematode
    daf-14 abnormal DAuer Formation daf-14(m77) mutation increases mean lifespan by 21-44% and maximum lifespan by 29% [17900898]. Nematode
    daf-2 abnormal DAuer Formation 2 daf-2 mutants live more than twice as long as controls. daf-2(sa189) mutation extends mean and maximum lifespan by 133 and 129%, respectively, when shifted to 20 degree Celsius. The daf-2(e1370) mutation extends mean and maximum lifespan by 32 and 119%, respectively, when shifted to 25 degree Celsius and by 110 and 145%, respectively, at 20 degree Celsius. daf-2(sa189) mutation extends mean lifespan by 67% as well as maximum lifespan [8247153]. This lifespan extension requires the activity of daf-16 [8247153]. The lifespan extension of daf-2(e1370) mutants is cancelled out by daf-16(m26) mutation. daf-2 mutants still exhibit a long lifespan after ablation of the gonad and germ cells. [8247153]. daf-2(e1370) increases mean (95-118%) and maximum (165%) lifespan [18828672]. RNAi against daf-2 extends mean and maximum lifespan by 47 and 65% [12471266]. daf-2 mutation extends lifespan of wild-type and eat-2 mutants [9789046]. Long lifespan of daf-2 insulin receptor mutation is further extended by sDR. However, daf-2 mutation is not a null mutation, therefore it is still possible that part of sDR-induced increase in lifespan might depend on insulin receptor pathway [17900900]. DR by bacterial dilution extends lifespan of daf-2 mutants [17538612]. IF does not markedly extend lifespan of daf-2 mutants [19079239]. 2% glucose reduce fractions of animals that become dauers at 22.5 degree Celsius in daf-2 mutants. Glucose almost completely suppresses lifespan extension of daf-2 ligand binding domain and tyrosine kinase mutants back to wild-type levels [19883616]. daf-2 mutation increases average lifespan by 157%. Under AL daf-2 mutation increases lifespan by 30%. bDR increases lifespan by 65%. daf-2 mutation further increases lifespan under bDR by 40%. Resistance to oxidative stress is reduced daf-2 mutation [19924292]. daf-2 RNAi increases mean lifesapn by 89% [18828672]. daf-2(m577) mutation increases mean and maximum lifespan by 33 and 29%, respectively, while daf-2(e1370) mutation increases mean and maximum lifespan by 101 and 181%, respectively [16782295]. DR from eat-2(ad465) mutation has an addative effect on lifespan of daf-2(e1370) adults, but not on lifespan of daf-2(e1368) adults [18043747]. Mutation in daf-2 in combination with mutation of daf-12 results in nearly 300% increase in lifespan [7789761]. daf-2 mutants are dauer constitutive [7219552] and exhibit reduced brood size [9504918; 9725835]. daf-2 mutants synergize with germ line ablation for lifespan extension [10360574] and also exhibit synergy with clk-1 mutation for lifespan prolongation [8638122]. All the phenotypes of daf-2 mutants are suppressed by mutation of daf-16 [8247153; 8601482; 7789761; 9725835; 9504918]. Mutation of daf-2 increases expression of sod-3 [10428762]. daf-2(e1370) increases mean lifespan by 146% [23097426]. Reducing expression of daf-2 in the adult stage alone extends lifespan [12399591]. Nematode
    daf-4 abnormal DAuer Formation daf-4(e1374) mutation increases mean and maximum lifespan by 40-120% and 76-83%. daf-4(m63) allele has no effect on lifespan and fails to prevent lifespan extension by sir-2.1 [11242085]. mutation of daf-4 results in a temperature-sensitive, dauer-constitutive phenotype in larvae. sir-2.1 overexpression in the daf-4(m63) background results in an increase in the severity of the dauer-constitutive phenotype [11242085]. Nematode
    daf-7 abnormal DAuer Formation daf-7 mutation does not significantly change lifespan [8247153]. Mutations in daf-7 cause up to 50% mean and maximum life-extension. This effect is dependent upon daf-3 and on daf-16 but independent of daf-2. daf-7(e1372) increases mean and maximum lifespan by 13-39% and 55%, respectively. daf-7(m62) increases mean and maximum lifespan by 20-29% and 29% [17900898]. RNAi against daf-7 only in the adulthood increases mean and maximum lifespan by 26 and 7%, respectively [17900898]. Nematode
    daf-8 abnormal DAuer Formation daf-8 mutation in adults increases mean lifespan by 9-31% but it did not increase maximum lifespan [17900898]. Nematode
    dct-12 DAF-16/FOXO Controlled, germline Tumor affecting 12 dct-12 appears to stimulate the growth of gld-1 tumours. RNA interference of dct-12 increases mean lifespan by 14% in wild-type animals, 16% in daf-16 mutants and 12% in gld-1 mutants [17934462]. Nematode
    dct-13 DAF-16/FOXO Controlled, germline Tumor affecting 13 dct-13 appears to stimulate the growth of gld-1 tumours. RNA interference of dct-13 increases mean lifespan by 23% and maximum lifespan by 20% in wild-type animals. It also increases mean lifespan by 21% in daf-16 mutants and 13% in gld-1 mutants [17934462]. Nematode
    dct-14 DAF-16/FOXO Controlled, germline Tumor affecting 14 dct-14 appears to stimulate the growth of gld-1 tumours. RNA interference increases mean lifespan by 19% in wild-type animals, 21% in daf-16 mutants and 13% in gld-1 mutants [17934462]. Nematode
    dct-15 DAF-16/FOXO Controlled, germline Tumor affecting 15 dct-15 appears to stimulate the growth of gld-1 tumours. RNA interference of dct-15 increases mean lifespan up to 10% in wild-type animals and 9% in gld-1 mutants [17934462]. Nematode
    Dgat1 Diacylglycerol O-acyltransferase 1 Deficiency in Dagat1 promotes leanless and extends mean, median and oldest 10% survival by 23, 26 and 9% without limiting food intake [22291164]. House mouse
    BMH1 Brain Modulosignalin Homologue 1 Deleting BMH1 extends chronological lifespan by 25% and is associated with activated stress response, decreased ROS levels and increased heat-shock-element-driven transcription activity. BMH1 deletion was non-additive with the genetic DR mimetic cdc25 and tor1. Water starvation (a form of extreme DR) extends chronological lifespan of BMH1 mutant even more as it does in wild-type. BMH1 genetically interacts with DR as well as TOR- and PKA-signaling pathways to regulate lifespan. Phosphorylation of Ser238 on Bmh1 increases during chronological aging, which is delayed by DR or reduced TOR activity [19805817]. Budding yeast
    SNF4 Sucrose NonFermenting 4 Deleting SNF4 extends replicative lifespan by 10-20% in S288C strain [10921902]. Budding yeast
    RAS1 Deletion in RAS1 increases mean (23%) and maximum (29%) replicative lifespan (in SP1) [8034612]. RAS1 deletion increases replicative lifespan by 15% in the alpha strain [19030232]. However, deletion of RAS1 slightly shortens chronological lifespan (in SP1) [12586694]. No lifespan extension results from overexpression of RAS1 (in SP1) [8034612]. Budding yeast
    AGP1 high-Affinity Glutamine Permease 1 Deletion of AGP1 extends chronological lifespan [16418483]. Budding yeast
    ATH1 Acid TreHalase Deletion of ATH1 extend the mean chronological lifespan by 17% (at 30 degree Celsus in BY4742) [22783207]. ATH1 mutants have higher trehalose levels until the end of the post-diauxic growth phase, but reaches a plateau at the level of 50-70% of wild-type in the stationary phase [22783207]. Budding yeast
    ATP1 ATP synthase 1 Deletion of ATP1 increases chronological lifespan by up to 50% [17492370], but decreases replicative lifespan by 70% in the alpha strain [18340043]. Budding yeast
    AVO2 Adheres VOraciously (to TOR2) Deletion of AVO2 extends chronological lifespan [21641548]. Budding yeast
    BAS1 BASal 1 Deletion of BAS1 increases replicative lifespan by 30% in the alpha strain [16293764; 19030232]. Budding yeast
    Factors are an extension of GenAge and GenDR.

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