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
    mrps-5 Knockdown of mrps-5 throughout the entire life increases the lifespan by 60%. mrps-5 RNAi prevents aging-associated functional decline and alters mitochondrial function. Knocking down mrps-5 after early development no longer affects nematode lifespan. When RNAi of mrps-5 was performed during the larval stages only, lifespan increases by 48%, whereas RNAi started from the L4 stage has no effect. mrps-5 RNAi results in fragmented mitochondria. mrps-5 RNAi increases lifespan by 40% in widltype, 37% in daf-16(mu86), 40% in sir-2.1(ok434) 69% in aak-2(ok524) and 112% in mev-1(kn1). Knockdown of cco-1 does not extend the lifespan of mrps-5 RNAi [23698443]. Nematode
    nkcc-1 Na-K-Cl Cotransporter homolog Knockdown of nkcc-1 throughout the entire life increases the lifespan by 23% [23698443]. Nematode
    ttll-9 Tubulin Tyrosine Ligase Like Knockdown of ttll-9 throughout the entire life increases the lifespan by 3% [23698443]. Nematode
    mrpl-1 Knockdown of mrpl-1 increases lifespan by 57% [23698443]. Nematode
    mrpl-2 Knockdown of mrpl-2 increases lifespan by 54% [23698443]. Nematode
    mrpl-37 Knockdown of mrpl-37 increases lifespan by 41% [23698443]. Nematode
    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
    foxo Forkhead box, sub-group O foxo overexpression extends lifespan. Activation of foxo in the adult pericerbral fat body is sufficient for lifespan extension [15175753]. Overexpression of foxo in the adult adipose tissue alone prolongs lifespan [15192154; 15175753]. Limited activation of foxo reduces the expression of Drosophila insulin-like peptide dilp-2 synthesized in neurons and, represses endogenous insulin-dependent signaling in peripheral fat body [15175753]. foxo is not required for DR, but its activity modulates the response. foxo null mutants are highly and significantly shorter-lived than wild-type on all food dilutions apart from 0.1 SY and under starvation. foxo null mutants are not more sensitive to starvation than wild-type. foxo overexpression in adult fat body under normal nutritional conditions leads to extension of lifespan of females and causes a right shift of the response curve of lifespan to DR [18241326]. Overexpression of dFOXO in adult fat body increases median, by 21-33%, and maximum lifespan as well as lowers the age-specific mortality at all ages, in two independent experiments. Overexpression of dFOXO increases lifespan by lowering the whole mortality trajectory, with no effect on slope (similar to DR). Initiation of dFOXO expression at different ages increases subsequent lifespan with the magnitude of increase decreasing as the animals were put on RU486 (which activates the foxo transgene via UAS) at older ages. The effects of removal of dFOXO overexpression at different ages closely mirrored those of induction of expression and produce shortest lifespan observed in animals taken of RU486 at the earlier ages [17465980]. Fruit fly
    Gclm Glutamate-cysteine ligase modifier subunit Overexpression of Gclm extends the mean lifespan by up to 24% [16148000]. Fruit fly
    EcR Ecdysone receptor Mutant heterozygotes in EcR live on mean 40%-50% longer than controls [12610309; reviewed in 12610294]. Homozygous mutants in EcR are inviable. The developmental time and weight of EcR+/- mutants is the same as control, but resistance to temperature, oxidative stress, and starvation is increased in heterozygotes [12610309]. Fruit fly
    Ef1alpha48D Elongation factor 1alpha48D Overexpression of Ef1alpha48D (transformed with a P-element vector and under control of hsp70 regulatory sequences) results in lifespan extension by 18-41%. The decrease in protein synthesis that accompanies aging is preceded by a decrease in EF-1 alpha protein and mRNA [2508089]. Fruit fly
    g garnet Loss-of-function mutation in g reduces mean lifespan by 11 - 42% and maximum lifespan by 7 - 30% [17435236]. Fruit fly
    Gclc Glutamate-cysteine ligase catalytic subunit Overexpression of Gclc extends mean and maximum lifespan by up to 50% [16148000]. Fruit fly
    Hsp26 Heat shock protein 26 Overexpression of Hsp26 (by the UAS/GAL4 system) increases stress resistance and extends the mean lifespan by 30% [15308776]. Fruit fly
    Hsp27 Heat shock protein 27 Overexpression of Hsp27 (by the UAS/GAL4 system) increases stress resistance and extends the mean lifespan by 30% [15308776]. Fruit fly
    Hsp68 Heat shock protein 68 Overexpression of Hsp68 extends modestly (by around 15%) median and maximum lifespan [14602080]. Hsp68 is activated by the JNK pathway and target gene of foxo [20976250]. There is a consistent and significant lifespan extension by 20% in both males and females when hsp68 is overexpressed in somatic cells. hsp68 overexpression using GMR-Gal4, and eye-specific driver that expresses Gal4 in salivary glands has no effects. Hsp78 overexpression using the weaker 5961FS driver moderately but significantly extends lifespan [20976250]. Fruit fly
    Mnt CG13316-PC, isoform C A dMnt null allele results in flies with larger cells, increased weight, and decreased lifespan [16055719]. Fruit fly
    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
    mys myospheroid mys mutants exhibit ameliorated age-related declines in locomotor activity and an increase in mean lifespan of 20% [14570233]. Fruit fly
    p53 Overexpression of wild-type p53 during adult life has no significant effect on lifespan. Expression of dominant-negative versions of p53 in adult neurons extends lifespan by 58% in females and by 32% in males and increases resistance to genotoxic stress and resistance to oxidative stress, but not to starvation or heat stress, while not affecting egg production or physical activity. Dominant negative p53 expression cancels out lifespan extension effect of DR, low calorie-food (5% SY). Muscle or fat body specific expression of a dominant negative form of p53 as well as globally lack of p53 decreases lifespan [16303568]. Loss of p53 activity slightly shortens the lifespan. Mutants that lack p53 survive well up to 50 days, but mortality rate increases relative to wild-type at later ages. p53 mutant animals are extremely sensitive to irradiation [12935877]. Expression of dominant-negative (DN) form of p53 in adult neurons, but not in muscle or fat body cells, extends median lifespan by 19% and maximum lifespan by 8%. The lifespan of dietary-restricted flies is not further extended by simultaneously expressing DN-DMp53 in the nervous system, indicating that a decrease in Dmp53 activity may be part of the DR lifespan-extending effect. Selective expression of DN-Dmp53 in only the 14 insulin-producing cell (IPCs) in the brain extends lifespan to the same extent as expression in all neurons and this lifespan extension is not additive with DR [17686972]. Fruit fly
    Pcmt Protein-L-isoaspartate (D-aspartate) O-methyltransferase Overexpression of Pcmt extends lifespan by 32-39% at 29 degrees but not at 25 degrees [11742076]. The adult lifespan of animals overexpressing Pcmt is extended [18772467]. Fruit fly
    Pka-C1 cAMP-dependent protein kinase 1 PKA-overexpressing flies (hsPKA*/+) have an about 30% extended maximum lifespan [17369827]. Fruit fly
    rb ruby Loss-of-function mutation reduces mean lifespan by 33% and maximum lifespan by 22% [17435236]. Fruit fly
    rho-7 rhomboid-7 rho-7 knockout flies have severe neurological defects and a much reduced lifespan [16713954]. Fruit fly
    sdhC succinate dehydrogenase, cytochrome b556 subunit Mutants expressing a dominant negative form of sdhC in the nervous system have a 22% reduced mean lifespan and signs of oxidative stress induction [17854771]. Fruit fly
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    • 25 of 223 factors
    Factors are an extension of GenAge and GenDR.

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