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
    Naam Nicotinamide amidase Naam overexpression increases mean and maximum lifespan by 30% in both females and males. The lifespan extension is reversed by Sir2 mutants, indicating the it is dependent on Sir2 [18678867]. Fruit fly
    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
    Prx5 Peroxiredoxin 5 Prx5 overexpression causes an increase in mean and median lifespan under normal conditions. It also leads to a small increase in maximum lifespan. dprx5(-/-) null mutants are comparatively more susceptible to oxidative stress, have higher incidence of apoptosis, and a shortened mean lifespan, but thee is no significant difference in maximum lifespan (10% survival) [21826223]. 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
    sug sugarbabe Overexpression of sug (from a doxycycline-inducible promoter) results in a 5-9% increase in mean lifespan [12620118]. Fruit fly
    Sod1 Superoxide dismutase Simultaneous overexpression of catalase and Sod (alias Sod1) results in a one-third lifespan extension, a slower rate of mortality acceleration, and a delayed loss in physical performance, but neither has any effect on lifespan alone [8108730]. General overexpression of Sod (also known as Cu/ZnSOD) alone is sufficient to extend lifespan by up to 48%. Simultaneous overexpression of catalase with Cu/ZnSOD has no added benefit, presumably due to a pre-existing excess of catalase [9858546]. Sod1 reduction by knockdown or knockout blunts the lifespan extension by a high sugar-low protein diet, but not a low-calorie diet [22672579]. Sod mutant flies display infertility and a reduction in lifespan [2539600]. Fruit fly
    Sod2 Superoxide dismutase 2 (Mn) RNA interference of Sod2 results in increased oxidative stress and early-onset mortality in young adults [12456885]. Overexpression of Sod2 by 5-115% decreases lifespan by 4-5% without any compensatory changes in metablic rate, level of physical activity, or the levels of other antioxidants (Sod, Cat, and glutathione) [10545213]. Targeted overexpression of Sod2 in motor neurons alone extends lifespan by 30% [11113599]. Induced overexpression of Sod2 in adult animals extends lifespan up to 37% [12072463]. Overexpression of catalase in combination with SOD2 has no added benefit for lifespan [12072463]. Animals overexpressing SOD2 or catalase do not exhibit a decrease in metabolism as measured by oxgen consumption [12072463]. Sod2 overexpression results in a 20% increase in mean and maximum lifespan [18067683]. Fruit fly
    to TakeOut Overexpression of to in adult neurons, pericerbral or abdonimal fat body increases male and female lifespan. to overexpression in the adult nervous system, head fat body and abdominal fat body results in 25, 20 and 12-18% increase of mean lifespan. On average the mean lifespan is extended for males and females by 18 and 26%, while maximum lifespan of male and female is increased by 13 and 25% [20519778]. Starvation, DR and many longevity mutants (like Rpd3, Sir2, chico, methusalem) all upregulate takeout (to). to is a secreted potential juvenile hormone binding protein and its induction by starvation is blocked by all arrhythmic central clock mutants [20519778; 20622267]. Fruit fly
    Jafrac1 thioredoxin peroxidase 1 Neuronal overexpression of Jafrac1 significantly increases both mean and maximum lifespan, while neuronal knockdown as well as loss of function mutation, causes a reduction in lifespan by 30%. The mean lifespan is 26% and 29% higher in females and males, respectively. The maximum lifespan is increased by 22% and 26% in females and males, respectively [19720829]. There is a consistent and significant lifespan extension (15% mean lifespan increase) in both males and females when Jafrac1 is overexpressed in somatic cells. Jafrac1 overexpression using the weaker 5961FS driver moderately but significantly extends lifespan [20976250]. Fruit fly
    TrxT Thioredoxin T Overexpression of TrxT in neurons increases the level of locomotor activity in aged flies and extends the mean lifespan by 15% [17301052]. Fruit fly
    ttll-9 Tubulin Tyrosine Ligase Like Knockdown of ttll-9 throughout the entire life increases the lifespan by 3% [23698443]. Nematode
    UCP2 uncoupling protein 2 (mitochondrial, proton carrier) Overexpression of human UCP2 in the fly nervous system extends lifespan by 10-30%. Ubiquitous overexpression is lethal [16054055]. Human
    Zw Zwischenferment Mean lifespan of G6PD overexpressor flies is extended in comparison with driver and responder controls, armadillo-GAL4 (up to 38%), Tubulin-GAL4 (up to 29%), C23-GAL4 (up to 27%), da-GAL4 (up to 24%), D42-GAL4 (up to 18%) and Appl-GAL4 (up to 16%). The maximum lifespan is also increased [18809674]. G6PD enzymatic activity as well as levels of NADPH, NADH, and the GSH/GSSG ration are increased [18809674]. Fruit fly
    Factors are an extension of GenAge and GenDR.

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