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
    Surf1 surfeit gene 1 Surf1 knockdown results in larval lethality. However, knockdown in the central nervous system (CNS) not only bypasses the larval lethality but it results in an increase in maximum lifespan of about 20-30% [16172499]. Fruit fly
    sun Stunted sun mutations increases lifespan and resistance to oxidative stress [15133470] Fruit fly
    sug sugarbabe Overexpression of sug (from a doxycycline-inducible promoter) results in a 5-9% increase in mean lifespan [12620118]. Fruit fly
    Srf Serum Response Factor SRF is activated by the daily variations of a blood signal, resulting in significant changes in the structure and size of live cells throughout the course of the day [23374345]. Daily variations of plasma signal cyclically stimulates SRF. SRF is solicited in an antiphasic manner in humans and rats, a fact that is linked to their activity, diurnal and nocturnal, respectively. SRF activation is accompanied by a remodeling of the cellular "skeleton", resulting in morphological change in cells based on their activity [23374345]. House mouse
    Spargel Tissue-specific overexpression of dPGC-1 in stem and progenitor cells within the digestive tract of females flies extends the mean and maximum lifespan of females by up to 33% and 37%. Those mutants display a delay in the onset of aging-related changes in the intestine, leading to improved tissue homoeostasis in old flies [22055505]. 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
    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
    snz snazarus Mutation in snz increases maximum lifespan of both sexes by up to 66%, while the median female lifespan is approximately 85% higher and that of males around 72% [18478054]. Fruit fly
    SNF4Agamma SNF4/AMP-activated protein kinase gamma subunit Deletion of SNF4Agamma from the first day of the imaginal stage shortens mean lifespan by 23% and causes morphological and behavioural features of premature aging [18219227]. Fruit fly
    SLC6A4 solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 Two alleles, 44-bp insertion (l allele) or deletion (s allele) in the promoter region of SLC6A4, were examined in 265 Japanese centenarians and control subjects. The frequency of the l/l genotype and the l allele was significantly greater in centenarians than in younger control subjects, particularly women [16095668].SLC6A4 was found to be associated with longevity [22985157]. Human
    Sirt6 Decreased expression of Sirt6 by RNA interference causes lethality during development. Sirt6 silencing in neurons shortens mean lifespan by 20% [17159295]. Fruit fly
    Sirt2 Decreased expression of Sirt2 by RNA interference causes lethality during development. Silencing in neurons shortened mean lifespan by 20% [17159295]. Fruit fly
    SIRT1 sirtuin 1 SIRT1 was found to be associated with longevity [21972126; 16257164; 16257164; 16257164; 16257164; 16257164; 21972126; 20633545]. SIRT1 was not found to be associated with longevity [16257164; 18765803].SIRT1 was found to be associated with longevity [23505545]. SIRT1 was found to be associated with longevity [23450480]. SIRT1 was not found to be associated with longevity [23450480]. Human
    Sir2 Overexpression of Sir2 (alias dSir2) extends lifespan by up to 57% and specifically median lifespan by 40-60%, whereas a decrease in Sir2 activity by mutation blocks the life-extending effect of caloric reduction or rpd3 mutations [15520384]. rpd3 mutants fed normal food and wild-type fed a low-calorie diet increase dSir2 expression two-fold [12459580]. Sir2 mutation does not reduce lifespan under AL. Ubiquitous Sir2 overexpression causes a 4-fold increase in Sir2 mRNA expression and an up to 57% increase in average lifespan (29% for females and 18% for males). A 10 - 20% increase in Sir2 mRNA levels causes no lifespan extension. High levels of Sir2 protein is found in nuclei of neurons and in nuclei and cytoplasm of fat body cells. Neuronal Sir2 overexpression extends average lifespan by 52% in females and 20% in males. Motor-neuronal specific expression fails to cause lifespan extension. Flies with no or with several decreased Sir2 gene function have no lifespan extension under DR. DR fails to cause further increase in lifespan or even reduces lifespan toward normal of Sir2 overexpression mutants. Mild Sir2 overexpression in the fat-body extends lifespan and reduces relative body fat content in both males and females [22661237]. Sir2 in the adult fat body regulates longevity in a diet-depending manner. A diet-dependent lifespan phenotype of Sir2 perturbations (both knockdown and overexpression) in the fat-body, but not in muscles, negates the effects of background genetic mutants. Sir2 knockdown abrogates fat-body dFoxo-dependent lifespan extension [23246004]. Decreased expression of Sir2 and Sir2-like genes in all cells causes lethality during development. Suppression of the Sir2 in neurons decreases the median lifespan by 10-30%, while ubiquitinous silinecing of the Sir2-like genes shortens lifespan. The effects are server at 28°C that at 25°C [17159295]. Fruit fly
    Sh Shaker Genetic mutation in Sh decreases lifespan by accelerating the aging process. At 25 degree mean and maximum lifespan is reduced by 16 and 22%, while by 18 degree Celsius the reduction is 32 and 21% [8582611]. 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
    RIMBP2 RIMS binding protein 2 RIMBP2 was found to be associated with longevity [22174011]. Human
    rho-7 rhomboid-7 rho-7 knockout flies have severe neurological defects and a much reduced lifespan [16713954]. Fruit fly
    REN renin Polymorphic repeats in intron 7 (short and long alleles) were examined in 196 centenarians (143 females and 53 makes) and 358 controls (196 females and 162 male; 10-85 years old). No significant difference in genotype frequencies was found between centenarians and controls [9887369].REN was found to be associated with longevity [15105583]. REN was not found to be associated with longevity [9887369]. Human
    Rbp9 RNA-binding protein 9 Rbp9 mutation significantly decreases longevity with a 33% reduction in median lifespan of males [20589912]. Fruit fly
    rb ruby Loss-of-function mutation reduces mean lifespan by 33% and maximum lifespan by 22% [17435236]. Fruit fly
    RAGE Human
    RAD52 RAD52 homolog (S. cerevisiae) RAD52 was found to be associated with longevity [22406557]. Human
    RAD23B RAD23 homolog B (S. cerevisiae) RAD23B was found to be associated with longevity [22406557]. Human
    QKI quaking homolog, KH domain RNA binding (mouse) SNPs close to SQKI were associated with longevity [22773346]. Human
    Factors are an extension of GenAge and GenDR.

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