| NAM treatment | Treatment with NAM reduces mean and maximum replicative lifespan by 28 and 37%. NAM treatment blocks the lifespan extending effect of rapamycn [20947565]. | Yeast | -28 | — | -37 |
| High fat diet | Lifelong feeding of a high-fat diet markedly reduces lifespan of mice by about 20% for both mean and maximum lifespan [22509016]. | Mouse | -20 | — | -20 |
| C60-olive oil treatment | Oral administration of C60 dissolved in olive oil (0.8 mg/ml) at reiterated doses (1.7 mg/kg of body weight) for just about 7 months to rats not only does not entail chronic toxicity but it almost doubles the lifespan. The effects on lifespan is mainly due to the attenuation of age-associated increases in oxidative stress. Dissolved C60 is absorbed by the gastro-intestinal tract and eliminated in a few tens of hours [22498298].
C60-olive oil can increase the mean, median and maximum lifespan by 114, 91 and 74%. C60-olive oil extends the lifespan of animals with a probability of 0.999 and 0.995 with respect to water and olive oil treatments, respectively [22498298].
The GSSG/GSH ratio of animals treated by C60-oil is significantly less (about twice as less) as compared to controls [22498298].
| Rat | +113.8 | +90.9 | +73.7 |
| Olive oil treatment | Oral treatment with Olive oil (at the age of 10 month for 7 months) increases mean, median and maximum lifespan by 41, 18 and 53%, respectively. Olive oil extends the lifespan with a probability of 0.99 [22498298]. | Rat | +41.4 | +18.2 | +52.6 |
| Moderate DR | Moderate DR is the restriction of glucose concentration from 2% (*ad libitum*) to 0.5%, which extends the mean, median and maximum replicative lifespan by 45 - 52%, 43 - 50% and 50 - 52%, respectively [23172144]
Moderate DR increases vacuolar acidity in young cells and prevents the decline of vacuolar acidity in aging cells. DR also suppresses mitochondrial dysfunciton of aged cells (21 divisions) in a V-ATPase-dependent manner [23172144].
Constitutively activating PKA signaling by deleting the Ras GTPase-activating protein IRA2 reduces vacuolar acidity and accelerates the development of mitochondrial dysfunction in aging cells and prevents DR-mediated enhancement of vacuolar acidity and suppression of mitochondrial dysfunction [23172144].
Lifespan extension by DR is prevented in a strain lacking V-ATPase activity [23172144]. | Yeast | +45.2 to +51.7 | +42.9 to +50.0 | +50.0 to +52.0 |
| Cynomorium songaricum supplementation | The yang-tonifying herbal medicine cynomorium songaricum Repr. (CS) supplementation to the diet extends both the mean and the maximum lifespan of adult females, but insignificantly that of males. In females, maximum lifespan (determined by the 90th survival percentile) is increased by up to 11.4% with 10 mg/mL CS and 5.7% with both 20 and 30 mg/mL Cs. Mean lifespan is significantly extended by 15, 18 and 11% upon treatment with 10, 20, and 30 mg/mL CS, respectively (all P <0.001). Increased lifespan by CS is correlated with higher resistance to oxidative stress and starvation and lower lipid hydroxyperoxids levels as well as accompanied by beneficial effects, such as improved mating readiness, increased fecundity, and suppresion of age-related learning impairment in aged animals [22844336]. | Fly | +11 to +18 | — | +5.7 to +11.4 |
| Wortmannin treatment | Treatment of Drosophila imago with 0.5 micromolar wortmannin increases median (by 5%) and maximum (by 39%) lifespan in males (p < 0.001), but the lifespan differences in females were statistical insignificant (p > 0.05) [22661237].
Low dose of wortmannin (5 microM) slightly increase the median and maximum lifespan [20017609]. | Fly | — | +5 | +39 |
| Dietary restriction on high-fat diet | Dietary restriction on a high-fat diet increases both mean and maximum lifespan by 36% compared to the high-fate diet control group [22509016]. | Mouse | +36 | — | +36 |
| Rapamycin treatment | Treatment of Drosophila imago with rapamycin induces increases of median (by 5-6%) lifespan (p < 0.01) in males and females, respectively and increase of maximum lifespan (by 33%) in females (p < 0.01) [22661237].
Low dose of LY294002 (5 microM) slightly increase the median and maximum lifespan [20017609]. | Fly | — | +5 to +6 | +33 |
| Minocycline treatment | Treatment with minocycline (0.87mM) prolongs mean, median and maximum lifespan of wild-type (Oregon strain) of both genders. In females mincocycline extend mean and maximum lifespan by 57 and 78%, respectively. In males minocycline results in a mean and maximum lifespan extension by 114 and 28%, respectively [23185716]. | Fly | +57.1 to +114.3 | — | +28.1 to +78.3 |
| Curcumin treatment | Curcumin increases lifespan in and is associated with reduced ROS and lipofuscin during aging. Curcumin lifespan extension is attributed to its antioxidative properties. Lifespan extension had effects on body size and pharyngeal pumping rate but not on reproduction. Lifespan-extension by curcumin is abolished in osr-1, sek-1, mek-1, skn-1, unc-43, sir-2.1 and age-1 mutants, whereas curcumin treatment prolongs lifespan of mev-1 and daf-16 mutants [21855561]. *C. elegans* feed low concentration of curcumin have a decreased lipofuscin levels and enhanced the resistance to heat stress and increased mean lifespan by 39% and a maximum lifespan extended by 21.4% [23325575]. In fruit fly that survive an average of 64 days, an increase of mean lifespan to 80 days occurs in flies, with females of one strain and males of another strain experiencing an extension in lifespan. The lifespan response to curcimun exhibits variation in male and female, although the compound extends lifespan in both genders [23325575]. | Worm | +39 | — | +21.4 |
| Rapamycin treatment | Treatment with rapamcyin increases mean, median, 75th %ile and maximum lifespan by 19-29, 17-29, 24-32 an 19%, respectively on OP50. On HT115 rapamycyin extends mean, median and 75th %ile of lifespan by 8-36, 4-46 and 12-44%, respectively. Rapamycin robustly increases lifespan in two daf-16 mutants (mgDf47 and mu86) with or without FUdR and with growth on either the standard strain OP50 or the feeding RNAi strain HT115 [22560223]. | Worm | +8 to +29 | +4 to +46 | +19 |
| LY294002 treatment | Treatment of Drosophila imago with 5 micromolar LY294002 increases median (by 14%) and maximum (by 16-22%) lifespan (p<0.001) in females and males, respectively [22661237].
Low dose of LY294002 (5 microM) slightly increase the median and maximum lifespan [20017609]. | Fly | — | +14 | +16 to +22 |
| Methionine restriction | Restriction of the methionine content in the culture extends mean and maximum lifespan by up to 29 and 16% (1/10 methionine content) [15141092]. | Yeast | +29 | — | +16 |
| Rapamycin treatment | Treatment with rapamcyin increases mean and maximum replicative lifespan by 19 and 16% Rapamycin fails to extend the lifespan of sir2 mutants or NAM treated wild-type cells [20947565]. Rapamcyin treatment increases mean chronological lifespan by by approximately by 80% in BY4742 [22790951].
Rapamycin extends chronological lifespan proportional with increasing concentrations from 100 pg/mL to 1 ng/mL [16418483] | Yeast | +19 to +50 | — | +16 |
| L-proline supplementation | L-proline supplementation increases lifespan by 5.8 and 13.6% (mean and maximum lifespan) [22482728]. | Worm | +6 | — | +14 |
| Spermidine treatment | Treatment with 0.2 mM spermidine extends mean and maximum lifespan of wild-type by 16 and 13% significantly (<0.005) as well as the mean and maximum lifespan in sir-2.1(ok434) by 12 and 11% significantly (<0.01). | Worm | +16 | — | +13 |
| PDTC treatment | Treatment of Drosophila imago with PDTC increases median (by 11-13%) and maximum (by 11-14%) lifespan in females and males, respectively [22661237]. | Fly | — | +11 to +13 | +11 to +14 |
| Tyrosol treatment | Treatment with tyrosol (250 microMolar) extends mean, median, and maximum, lifespan by 21, 21, and 11% [22824366]. | Worm | +21 | +21 | +11 |
| Icariin treatment | Icariin and its derivate icariside II extend lifespan. Animals treated with icariin have high levels of icariside II [22216122]. | Worm | — | — | — |
| Icariside II treatment | Icariside II and its derivate icarrin extend lifespan. Animals treated with icariin have high levels of icariside II. Icariside II also increases thermo and oxidative stress tolerance, slow locomotion decline in late adulthood and delay the onset of paralysis mediated by polyQ and ABeta(1-42) proteotoxicity. Lifespan extension by Icariside II is dependent on IIS, since daf-16(mu86) and daf-2(e1370) fails to sho exhibit lifespan extension upon icariside treatment. Incariside II treatment upregulates expression of DAF-16 targets in wild-type. HSF-1 has also a role in icariside II-dependent lifespan extension [22216122]. | Worm | — | — | — |
| Quercetin treatment | Quercitin significantly extends the lifespan. Lifespan extension by quercitin has no effect on reproduction and body length. Quercitin induced lifespan extenison was neither dependent on a dietary restriction mimetic nor on sir-2.1 [19043800]. | Worm | — | — | — |
| 30% Dietary restriction | 30% dietary restriction starting at 2 months of age increases overall, average, median and maximal lifespan. Knockout of Ghr failed to respond with lifespan extension to this regimen [16682650]. | Mouse | — | — | — |
| Intermittent fasting | Intemittent fasting diet increases survivorship and improves insuli sensitivity of normal males, but fails to affect either parameter in GHRKO mice [19747233]. | Mouse | — | — | — |
| 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 | — | — | — |
GenAge
GenDR
