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
    LAG1 Ceramide synthase component A gene deletion of LAG1 in haploid cells results in a pronounced increase (approximately 50%) in mean and in maximum replicative lifespan in the YPHDF-1A strain [8195187], but has no significant effect on lifespan in stains W303R or PSY316 (N. Bishop, G.Liszt, and L. Guarente, unpublished]. The LAG1 transcribed is preferentially expressed in young cells. LAG1 null mutant is viable and has no obvious phenotypes but shows delayed ER to Golgi transport when combined with DGT1 mutation [10198056] and is synthetical lethal with LAC1 deletion. Budding yeast
    lin-14 abnormal cell LINeage 14 A loss-of-function mutation in lin-14 extends lifespan by 31% while a gain-of-function mutation decreases lifespan. The life-extending effects is dependent on daf-16 and hsf-1. Also, lin-14 is a target of lin-4 [16373574]. lin-14(n719) mutation extends mean and maximum lifespan of control animals by 20 and 67%, respectively [23097426]. Knockdown of lin-14 only during adulthood is sufficient to extend lifespan and suppresses the short lifespan phenotype of lin-4 mutants. Nematode
    isp-1 Iron-Sulfur Protein A missense mutation in isp-1 leads to low oxygen consumption, decreased sensitivity to reactive oxygen species, and increased mean (60%) and maximum (100%) lifespan. An isp-1;daf-2 double mutant has a lifespan that is longer than either single mutant, but the lifespan extension of the double mutant is not addative relative to each single mutant [11709184]. Nematode
    Ctf1 Cardiotrophin 1 Absence of Ctf1 is associated with decreased arterial fibrosis, stiffness mad senescence and increased longevity. Ctf1-null mice have a decrease in arterial stiffness and decrease in levels of inflammatory, apoptotic and senescence, whereas telomere-linked and DNA repair proteins as well as antioxidant enzyme activities are increased. The median lifespan of Ctf1-null mice is increased by 5 month (18%) [23172930]. Wild-type and Ctf1-null mice exhibit an increase of senescence markers (p53, Mdm2, p21, and p16) with age but are lower in Ctf1-null mice. Ctf1-null mice have a diminished vascular NFκB signaling, lower inflammation and oxidative stress and reduced senescence. Ctf1-null mice have a 12% increase in body weight, 130% increased adiponectin levels and 51% decreased leptin concentrations [23172930]. Treatment of cells with CT-1 increases SA-β-galactosidase, and apotosis and senescence makers (p53, p21 and p16), without modifying Mdm2 expression [23172930]. House mouse
    Adcy5 adenylate cyclase 5 Adcy5 knockout mice are to cardiac stress and have an increased median lifespan of 30% as well as an increased maximal lifespan of 12%. Further, they are also protected from age-related reduced bone density and susceptibility to fractures, and reduced cardiac function [17662940]. House mouse
    ADE4 ADEnine requiring 4 ade4 mutation extends chronological lifespan, but not replicative lifespan, and is non-additive with 0.5% glucose or amino-acid DR on chronological lifespan extension. ADE4 deletion in atg16 mutants results only in a partial extension of the chronological lifespan by 0.5% glucose DR [20421943]. Budding yeast
    AIM4 Altered Inheritance rate of Mi 4 AIM4 (alias SOY1) deletion increases chronological and replication lifespan, which is non-additive with DR. On AL mean and maximum replicative lifespan are extended by 63 and 69%, respectively. DR appears to decrease aim4-induced replication lifespan extension, indicating a negative interaction. aim4 mutation does not change DR-induced chronological lifespan extension [21584246]. Budding yeast
    alpha-Man-I alpha Mannosidase I alpha-Man-I mutant fly exhibit enhanced resistance to paraquat and starvation an a 60% increase in mean lifespan for both sexes. After outcrossing, the mutant exhibit, under normal conditions, an increase in mean lifespan of 22% for females and 38% for males. Maximum lifespan is increased by 15%. alpha-Man-I RNAi knockdown results in a 39% increase in mean lifespan [19302370]. Fruit fly
    Gh1 growth hormone 1 Animals carrying a single copy of an anti-sense Gh1 transgene (tg/-) live on average 7-10% longer. However, animals carrying two copies of the transgene (tg/tg) have a slighlty shorter lifespan compared to -/- animals, indicating that an optimal dosage of Gh1 is nessary to achieve lifespan exentension and too little GH has a detrimental effect on longevity. tg/tg and tg/- animals are dwarfs and exhibit reduced levels of serum IGF1 [12057928]. Norway rat
    SAG101 senescence-associated protein 101 Antisense RNA interference of SAG101 in transgenic plants delays the onset of leaf senescence for approximately 4 days, whereas chemical induced overexpression of SAG101 causes precocious senescence in both attached and detached leaves of transgenic plants [11971136].
    PLD alpha Antisense suppression of PLD alpha retards abscisic acid- and ethylene-induced senescence. Leaves detached from PLD alpha-deficient transgenic plants when inbutated in abscisic acid and ethylene exhibit a slower rate of senescence that those from wild-type and transgenic controls. PLD alpha deficient strains are associated with retardation of senescence as evidenced by delayed leaf yellowing, lower ion leakage, greater photosynthetic activity, and higher content of cholorophyl and phospholipids [9437863]. Antisense suppression of PLD alpha does not affect natural plant growth and development [9437863].
    aps-1 AdaPtin, Small chain (clathrin associated complex) 1 aps-1 RNAi in the adulthood extends mean lifespan by 8% without any apparent effect on maximum lifespan [23144747]. Nematode
    asb-1 ATP Synthase B homolog asb-1 RNAi in the adulthood extends the mean lifespan by 7% without changing the maximum lifespan [23144747]. Nematode
    ATG11 AuTophaGy related 11 ATG11 deletion extends replicative lifespan under AL and abrogates DR-lifespan extension [18690010]. Budding yeast
    Bmcp Mitochondrial uncoupler Bmcp knockout flies live longer on low-calorie diets, have a decreased fertility, and gain less weight on high-calorie diets. Bmcp (ucp5) knockout mutants live longer than wild-type on low-calorie diets, but no longer on starvation or high-calorie diets. Ectopic neuronal expression of Bmcp transgene rescues starvation sensitive phenotype of Bmcp knockout mutants [16387864]. 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
    bwa brain washing bwa (alias Dacer) inactivation increases Drosophila pre-adult development time and anti-oxidative stress capacity. Mean lifespan is increased by 16% in females, by 21% in males and by 19% in total. Maximum lifespan of females, males is also extended by 20 and 12%, respectively [20112046]. Fruit fly
    rict-1 RICT0r (Rapamycin-Insensitive Companion of TOR) homolog C. elegans with mutations in the TORC2 complex gene rict-1 (Rictor) grow slowly and have small body size, and live slightly longer than wild-type when maintained on “rich” food such as the RNAi feeding strain HT115 and at elevuated temperature (25 degree Celsius) [Soukas et al., 2009 in (Robida-Stubbs et al., 2012)]. rict-1 RNAi at 20 degree Celsius in the adulthood increases mean, median, 75th %ile and maximum lifespan by 12-42, 22-29, 13-32 and 28-54%, respectively, dependent on skn-1. daf-16 is not required for lifespan to be increased by rict-1 RNAi, or when TORC1 and TORC2 are blocked by ragc-1;rict-1 RNAi. rict-1 RNAi extends mean, median, 75th %ile and maximum lifespan in the intestine-specific RNA stains VPS288 by 18, 19, 18 and 16%, respectively [22560223]. Nematode
    C26B2.2 C26B2.2 knockout mutations extend lifespan [15253933]. Nematode
    C47D12.2 TRRAP-like (transcription/transformation domain-associated protein) C47D12.2 RNAi in the adulthood extends mean and maximum lifespan by 6 and 9% [23144747]. Nematode
    dnc dunce cAMP phosphodiesterase-deficient dunce mutants have an extended maximum lifespan by about 70% [17369827]. Fruit fly
    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
    che-2 abnormal CHEmotaxis che-2 recessive loss-of-function mutations extend lifespan up to 50% (in Bristol N2) [10617200]. che-2 mutants are chemotactic defective, slightly small, defective for osmotic avoidance, have ciliated neurons with abnormal stunted ultrastructure, and are dauer defective [2428682; 1732156]. Nematode
    chn-1 C-term of Hsp70-iNteracting protein (CHIP family) 1 chn-1 RNAi in the adulthood extends mean and maximum lifespan by 7 and 9%, respectively [23144747]. Nematode
    SKN1 Suppressor of Kre Null 1 Chronological lifespan increased by 60% for single skn1 and double ipt1-skn1 deletion [16527275]. Budding yeast
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    • 25 of 478 factors
    Factors are an extension of GenAge and GenDR.

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