Interventions

  • Species: + -
  • name effect species mean median maximum
    DHEA treatment DHEA treatment increases the lifespan of female fruit flies [Li et al., 2000]. Fly
    pex1 mutation Mutation of the promoter region of pex1(S4868), results in lower expression levels and increases lifespan in males and females by 16% and 13%, respectively. pex1 mutation increases mean and maximum lifespan and males/females by 27-23/14-19% and 0-15%, respectively [22509016]. Fly +14 to +27 0 to +15
    pex13 Mutation Mutation of pex13(KG04339), located in its promoter region, results in lower gene expression and increased lifespan by around 16% and 13% in males and females. pex13 mutation increases mean and maximum lifespan by 23-27/14-19% and 11%, respectively [22509016]. Fly +14-27 +11
    Selection for starvation resistance Selecting for increased starvation resistance extends mean, median and maximum lifespan under three different food levels (malnutrition, optimal food and overfeeding) [22559237]. Fly
    Pink1 overexpression Overexpression of Pink1 and overexpression of Pink1 with alpha-synclein results in an increase in lifespan which is accompanied by an increase in healthspan (as measured by mobility) when driven by a dopaminergic cells targeting TH-Gla4 transgene [22653599]. Fly
    Curcumin treatment In fruit fly, 0.5 an 1.0 mg/g curcumin in the diet increases mean lifespan by 6.2 and 25% in females and by 15.5 and 12.6 in males, respectively. Lifespan extension by curcumin was associated with the increased superoxide dismutase (SOD) activity, upregulation of Ms-SOD and CuZn-SOD genes, and the downregulation of *dInR*, *ATTD*, *Def*, *CecB* and, *DptB* genes as well as reduction of lipofuscin, malondialdehyde and lipid peroxidation [22653297; 23325575]. Curcumin prolongs life and enhances activity of fruit fly Alzheimer diseased flies [22348084]. Fly +6.2 to +25
    Propargylglycine treatment Propargylglycine (PPG) inhibits gamma-cystathioinase, the second enzyme of the trans-sulfuration pathway (TSP). PPG is a specific suicidal inhibitor of gamma-cystathionase. Gluthatione (GSH) levels are decreased by PPG administration in flies subjected to DR, whereas there is no effect on fully fed animals. PPG robustly suppresses DR lifespan extension, while longevity of fully fed flies is not affected in different strains. Thus, indicating that the effect of PPG is specific to DR. PPG abrogates changes in lifespan that are normally observed when flies are maintained in different dietary concentrations and compositions [21930912]. Fly
    Cbs overexpression Ubiquitous or neuron-specific transgenic overexpression of Cbs enhances longevity in fully-fed animals. Adult-specific ubiquitous expression of Cbs is sufficient to increase female mean and maximum lifespan by 12 - 43% and 10%, respectively. Males, whose lifespan is relatively less affected by DR, exhibite a smaller, but still significant increase in lifespan by 7% upon Cbs overexpression. Neuronal overexpression also increases lifespan, albeit modestly (approximately 12% mean and 15% maximum lifespan extension), whereas overexpression in the fat body and in the gut has no effect [21930912]. Fly +12 to +43 +10 to +15
    Ilp2/Ilp3/Ilp5 mutation Ilp5 null mutants have a normal lifespan under AL and a normal DR response. Ilp2 Ilp3 Ilp5 triple null mutants fail to have a normal response to DR. Their response is right shifted, with mutants being shorter-lived compared to wild-type on low but longer-lived on high yeast concentrations [20195512]. Fly
    Ilp2 mutation Ilp2 null mutants are significant longer-lived with a 8-13% longer median lifespan [20195512]. Fly +8 to +13
    l(3)neo18 RNAi Under rich nutritional conditions lifespan of l(3)neo18 (alias CG9762) RNAi knockout animals is indistinguishable from wild-type, while upon DR, lifespan extension is diminished in males and females [19804760]. Fly
    Dietary restriction by 1% yeast medium Dietary restriction by be reducing yeast content in medium to 1% extends the lifespan [19968629]. Fly
    Malnutrition by 0.2% yeast medium Reduction of the yeast concentration in the medium from 1 to 0.2% shortens the lifespan by invoking malnutrition [19968629]. Fly
    CG5389 RNAi RNAi of complex V subunit CG5389 results in increased mean longevity under standard laboratory food conditions (3% yeast) in males. RNAi started from the development results in a mild lifespan increase in both sexes (3-11% in females and 3-8% in males). Post-developmental RNAi and silencing limited to neurons has variable effects with reduction in lifespan of up to 9% [19747824]. Under rich media conditions CG5389 knockdown throughout development and adulthood increases mean lifespan by 26% and abolished the lifespan extension by DR (started in the adulthood) in males. Suppression of CG5389 only during the adulthood either via RNAi by tub-GS or via oligomycin (a specific inhibitor of complex V) feeding prevents an increase in longevity under DR (started in the adulthood) in males [19968629]. Fly -9 to +26
    p53 dominant negative overexpression 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 Dmp53 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 Dmp53 as well as globally lack of Dmp53 decreases lifespan [16303568]. 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]. Fly +32 to +58 +19 +8
    Thor mutation Null mutation in Thor (alias d4E-BP) causes a significant decrease in longevity (-25% median lifespan in males). foxo (alias dFOXO) and Thor null mutants are compromised in stress resistant. Stress resistance of foxo null mutants is rescued by Thor overexpression [16055649]. Thor null mutants cancel out DR-induced lifespan extension, because mutants exhibit a diminished change in lifespan when nutrient conditions were varied. Thor null mutants have a wild-type similar reduction in egg production upon DR [19804760]. Fly -25
    Thor overexpression Ubiquitously overexpression of wild-type Thor (alias d4E-BP) causes no change under AL, but an activated allele (with more than 3-fold increased binding activity to delF4E) significantly extends lifespan of females (weak allele) and females as well as males (strong allele). Mean lifespan is extended by 11 to 40%. Median lifespan of males and females is enhanced by by 11 and 22%, respectively. Maximum lifespan is extended by 16 and 18% for males and females, respectively. Under DR (0.25% YE) there is no lifespan extension, beyond the effect of DR alone, in all (wild-type, weak and strong) Thor alleles [19804760]. Lifespan of animals with increased Pten and 4E-BP activity in muscle exhibit and extended mean and maximum lifespan by 20% and 15.8% [21111239]. Fly +11 to +40 +11 to +22 +16 to +18
    foxo overexpression 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 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]. Fly +21 to +33
    foxo mutation 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 [18241326]. Fly
    Indy mutation Flies heterozygotic for a disruption in Indy gene have extended mean (87-92%) and maximum (45%) lifespan. Homozygotes for the disruption show only a 10 - 20% increase in mean lifespan [11118146]. Heterozygous insertion of a p-element in the non-coding region of Indy locus leads to a reduction in Indy mRNA expression and causes a significant median lifespan extension in male and female by about 29% and 34%, respectively. At normal or high calorie conditions Indy heterozygote mutants have a significant lifespan extension, but under low calorie conditions, Indy heterozygous mutants have minimal median lifespan extension. Reduction of calorie content from high to normal calorie condition results in 19% decline in Indy mRNA and from normal to low calorie condition results in additional 9% decrease in Indy mRNA. Reduction of calorie content from high to normal calorie conditions in heterozygous Indy mutants leads to 20% reduction in Indy mRNA expression without any additional decrease upon further reduction to low calorie food. Maximum lifespan extension is associated with Indy mRNA levels between 25 - 75% of normal. Long-lived heterozygous Indy mutants on high-calorie food and normal wild-type on low-calorie food have several phenotypes in common: 50 - 60 % reduced mRNA expression levels of Ilp2, Ilp3 and Ilp 5; similar high percentage of anti-FOXO-positive nuclei in fat body cells; higher sensitivity to starvation; do not gain weight; similar decrease in triglycerides and fat storage; normal food intake [19470468]. Mutations in Indy dramatically extend lifespan without a loss in fertility, physical activity, flight velocity or metabolic rate [11118146; 12626742]. Indy encodes a high-affinity dicarboxylate/citrate plasma membrane transporter found most abundantly in adult fat body, oenocytes and midgut cells, the primary sites of intermediary metabolism [12391301]. Indy mutation alters metabolism in a manner similiar to DR and mutants have several phenotypes with long-lived DR files in common, including decreases insulin-like signaling, lipid storage, weight gain, and resistance to starvation, and an increase in spontaneous physical activity [19470468]. Of the Indy206 and Indy302 mutation only one of the two has lower mRNA levels and both do not extend lifespan of female flies in any genetic background. In original genetic background only Indy mutation associated with altered RNA expression extends the lifespan of males. This effect is abolished by back-crossing into standard out-bred genetic backgrounds and is associated with an unidentified locus on the X chromosome. Original Indy line with long-lived males is infected by the cytoplasmic Wolbachia. Longevity of Indy males disappear after tetracycline clearance of this endosymbiont [17571923]. Fly +10 to +92 +45
    Sir2 overexpression Overexpression of Sir2 (alias dSir2) extends lifespan by up to 57% and specifically median lifespan by 40-60%. 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. Neuronal Sir2 overexpression extends average lifespan by 52% in females and 20% in males. Motor-neuronal specific expression fails to cause lifespan extension. DR fails to cause further increase in lifespan or even reduces lifespan toward normal of dSir2 overexpression mutants [15520384]. Mild Sir2 overexpression in the fat-body extends lifespan and reduces relative body fat content in both males and females [22661237]. A diet-dependent lifespan phenotype of dSir2 overexpression in the fat-body, but not in muscles, negates the effects of background genetic mutants [23246004]. Fly +18 to + 57 +4- to +60
    Sir2 mutation A decrease in Sir2 (alias dSir2) blocks the life-extending effect of caloric reduction or rpd3 mutations [15520384]. Sir2 mutation does not reduce lifespan under AL [15520384]. Fly
    Dominant negative Tor Expression of a dominant-negative form of Tor extends lifespan [15186745]. Ubiquitious overexpression of dTOR with the da-GAL4 driver of UAS-dTOR(FRB) which contains the 11kDA FKB12-rapamycin binding domain led to a mean and maximum lifespan increase of 15% (24%) and 29% at 29°C and of 50% (26%) and 13% at 25°C, respectively [15186745]. Overexpression of the dominant-negative form of Tor specifically in the fat and muscle tissues is sufficient to extend the mean and maximum lifespan by 24 and 19%, respectively [15186745]. Overexpression of UAS-dTOR(WT) or UAS-dTOR(TED) prevents eclosion to adulthood [15186745]. Fly +15 to +50 +13 to +29
    Dominant-negative S6k Ubiquitous overexpression of a dominant-negative form of S6k (alias dS6K) increases mean lifespan by 22%. Overexpression of a dominant-negative form of S6k protects mutants from deleterious effects of rich food, as if mimicking the effect of DR [15186745]. Fly +22
    Constitutive active S6k overexpression Overexpression of a constitutively active form of S6k (alias dS6K) decreases mean lifespan by 34% at 29°C [15186745]. Fly -34
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    • 25 of 232 interventions
    Interventions are an extension of GenAge and GenDR.