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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  • Species: + -
  • symbol name observation species
    Atg7 Autophagy-specific gene 7 Knockouts of Atg7 are short-lived with a 30% reduction in maximum lifespan and are hypersensitive to nutrient and oxidative stress [18056421; 19550147]. Fruit fly
    Atg8a Autophagy-related 8a Mutations in Atg8a results in reduced lifespan and increased sensitivity to oxidative stress while enhanced expression in older fly brains extends average adult lifespan by 56% and promotes resistance to oxidative stress [18059160]. Atg8a mutation reduces the maximum lifespan by 25% under starvation conditions [17617737]. Loss-of-function mutation in Atg8a reduces mean lifespan by 11 - 25% and maximum lifespan by 3 - 22% [17435236]. Fruit fly
    bchs blue cheese Loss of function mutation in bchs results in a 40-45% decrease in mean lifespan and is associated with age-related neurodegenerative phenotype with reduced CNS size and altered morphology as well as accumulation of insoluble ubiquinated proteins and amyloid precursor-like proteins along with an increase in neuronal apoptosis. No pronounced developmental defects were observed and young adults have normal behaviours, indicating that the bchs gene is essential for normal adult survival and longevity [12598614]. bchs mutation reduces mean lifespan by 28 - 54% and maximum lifespan by 24 - 46% [17435236]. Alfy (autophagy-linked FYVE protein) is the conserved human bchs homolog [15292400]. Fruit fly
    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
    car carnation Loss-of-function mutation in car results in reduction of mean lifespan by 34 - 63% and maximum lifespan by 28 - 29% [17435236]. Fruit fly
    Cat Catalase Simultaneous overexpression of catalase and Sod1 results in a one-third (i.e. 30%) lifespan extension, a slower rate of mortality acceleration, and a delayed loss in physical performance, but neither has any effect on lifespan alone [8108730]. Targeted overexpression of CAT in the mitochondrial matrix has no effect on lifespan at 25 degree Celsius, slightly shortens lifespan at 29 degree Celsius as is associated with increased resistance to endogenous hydrogen peroxide, paraquat, and cold stress [12521602]. Fruit fly
    Cct1 CTP:phosphocholine cytidylyltransferase 1 Overexpression of Cct1 from a doxycycline-inducible promoter results in a 6 - 8% increase in mean lifespan (in the PdL x rtTA; Oregon-R x rtTA strain) [12620118]. Cct1 exhibits a non-coding region difference unique to animals under experimental evolution selected for longevity and is upregulated in head of animals that were selected for longevity at all ages beyond the day of eclosion [23106705]. Fruit fly
    Cdk5 Cyclin-dependent kinase 5 Cdk5 loss-of-function mutations result in defective axon guidance, age-dependent behavioral deficits and reduced lifespan by about one third [17368005]. Fruit fly
    cert ceramide transfer protein cert mutants exhibit a shortened lifespan accompanied by enhanced oxidative damage to cellular proteins and metabolic compromise, such as increasing glucose levels, reminiscent of premature aging [17592126]. Fruit fly
    cher cheerio Overexpression of cher from a doxycycline-inducible promoter results in a 7 - 9% increase in mean lifespan (in PdL x rtTA; Oregon-R x rtTA) [12620118]. Fruit fly
    chico Insulin receptor substrate-1 Mutation in chico extends mean, median, and maximum lifespan by 56%, 48%, and 42% in homozygotes and 44%, 36%, and 35% in heterozygotes. chico mutation produces dwarf, long-lived females at normal nutrition. Male heterozygous live 13% longer than wild-type, but male homozygous have a shortened lifespan [11292874]. Wild-type and chico mutant females have similar peak lifespan under DR, but the food concentration at which these are achieved is shifted to higher amounts. chico mutation induces a state equivalent to submaximal, DR-induced slowing of aging [11951037]. chico heterzoygous females have a reduced fecundity and homozygous recessive mutants are sterile. chico heterozygous mutants are resistant to starvation but not oxidative stress or temperature stress [11292874]. Fruit fly
    cm carmine Loss-of-function mutation in cm reduces mean lifespan by 43 - 53% and maximum lifespan by 40 - 44% [17435236]. Fruit fly
    DJ-1alpha DJ-1α RNA interference of DJ-1alpha shortens maximum lifespan by 13% and results in increased sensitivity to oxidative stress and motor impairments [17651920]. Fruit fly
    dj-1beta dj-1β Loss of function mutation in dj-1beta shortens maximum lifespan by 40% and results in increased sensitivity to oxidative stress and motor impairments [17651920]. Fruit fly
    DLP Daxx-like protein DLP mutants have a 20% shorter mean lifespan and reduced female fertility [17933869]. Fruit fly
    dnc dunce cAMP phosphodiesterase-deficient dunce mutants have an extended maximum lifespan by about 70% [17369827]. Fruit fly
    Mt2 DNA methyltransferase 2 Overexpression of Dnmt2 extends mean and maximum lifespan [15533947]. Fruit fly
    dor deep orange Loss-of-function mutation in dor reduces mean lifespan by 70 - 81% and maximum lifespan by 71 - 78% [17435236]. Fruit fly
    mld molting defective Female, but not male, heterozygous mutants display a 42% increase in mean lifespan at 29 degrees Celsius. DTS-3 +/- female adults exhibit a 50% reduced ecdysone titer and reduced fertility [12610309]. Female, but not male, heterozygoutes also exhibit a temperature-dependent increase in starvation resistance. 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
    egm enigma Mutation in egm confers resistance to oxidative stress and extends the lifespan [16434470]. Fruit fly
    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
    Fwd four wheel drive Overexpression of Fwd (from a doxycline-inducible promoter) increases mean lifespan by 7-9% [12620118]. Fwd regulates actin organization and ring canal formation during germline cytokinesis [10934029] by catalysing the first step in the synthesis of the key regulatory membrane phsopholipid PIP2, which is generated from PIP by a PI 4,5-kinase. 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
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    • 25 of 211 factors
    Factors are an extension of GenAge and GenDR.

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