| 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 |
| concA treatment | The specific V-ATPase inhibitor concanatmycin A (concA) blocks VMA1 or VPH2 overexpression mutations ability to produce normal, tubular mitochondria. Treatment of young cells causes vacuolar acidity and loss of mitochondrial depolarization. Loss of ΔΨ is followed by mitochondrial fragmentation and aggregation that resembles mitochondrial phenotypes present in aged cells [23172144]. | Yeast | — | — | — |
| THC treatment | Tetrahydocurcumin extends the lifespan and reduces oxidative stress in male and female fruit flies. THC extends lifespan of Drosophila and inhibits the oxidative stress response by regulating *FOXO* and *Sir2* [22156377]. | Fly | — | — | — |
| Apple polyphenol supplementation | Supplemention of the diet with apple polyphenol significantly extends mean lifespan by 10% and is accompanied by up-regulation of SOD1, SOD2 and CAT as well as downregulation of MTH in aged animals [21319854]. | Fly | +10 | — | — |
| Resveratrol supplementation | Supplementation with resveratrol extends the lifespan [15254550], but not in always [17875315]. | Fly | — | — | — |
| NAD supplementation | Supplementation with NAD extended lifespan and this extension was dependent on sir-2.1 and daf-16 and associated with upregulation of sod-3 [19370397]. | Worm | — | — | — |
| Black tea extract supplementation | Supplementation of the diet with black tea extract extends the lifespan by 10% (from 51 to 56 days) and is associated with higher SOD1 and CAT expression [19770032]. | Fly | +10 | — | — |
| Blueberry extract supplementation | Supplementation of the diet with 5 mg/mL blueberry extract significantly extends the mean lifespan by 10% and is accompanied by an up-regulation of superoxide dismutase (SOD), catalase (CAT), and Rpn11 and down-regulationg of Methuselah (MTH). Lifespan is only extended in Oregon-R wild-type but not in SOD(n108) or Cat(n1) mutant strains [22197903]. | Fly | +10 | — | — |
| Resveratrol supplementation | Resveratrol supplementation prolongs the lifespan [15254550; 17460219], but not in any case [17875315]. | Worm | — | — | — |
| Resveratrol supplementation | Resveratrol significantly extends the lifespan [12939617]. | Yeast | — | — | — |
| Resveratrol supplementation | Resveratrol conteracts the detrimental effects of a high-fat diet in mice an decreases the risk of death by 30% and thereby reverting it to the level of normal diet. It also partially corrected a subset of the abnormal gene expression profile and insulin as well as glucose metabolism [17086191].
Although resveratrol has a range of beneficial effects in elderly mice, it does not increase the longevity of *ad libitum* fed mice when started midlife [18599363]. Even at high doses and when started in young adulthood reseveratrol supplementation does not increase lifespan on a normal diet [17578509; 20974732].
| Mouse | — | — | — |
| Restriction of yeast | Restriction of yeast, the major source of protein in the lfy diet, robustly extends lifespan [15186745; 16000018]. | Fly | — | — | — |
| 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 |
| 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 | — | — | — |
| 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 | — | — | — |
| 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 | — | — | — |
| Rhodiola rosea treatment | Plant adaptogen Rhodiola rosea (SHE-5) increase stress resistance and mean lifespan in a dose-dependent manner. 10-25 microgram/ml SHE-5 signinifanclty increases lifespan between 10 and 20% 9 (P < 0.001), increase maximum lifepsan with 2-3 days and pospones the moment when the first individuals die. With higher concentrations, the effect is weaker whereas at the highest concentrations (250 microgram/mL) a lifespan shortenening effect of 15-25% (P < 0.001) occurs. Treatment with SHE-5 induces translocation of DAF-16 and activation of HSP-16 [18536978]. | Worm | +10 to +20 | — | — |
| Eleutherococcus senticosus treatment | Plant adaptogen Eleutherococcus senticosus (SHE-3; alias Acantopanax senticosus) increase stress resistance and mean lifespan in a dose-dependent manner. 250 microgram/ml SHE-3 signinifanclty increases lifespan between 10 and 20% 9 (P < 0.001), increase maximum lifepsan with 2-3 days and pospones the moment when the first individuals die. With higher concentrations, the effect is weakerm wheras at the highest concentrations (2500 microgram/mL) a lifespan shortenening effect of 15-25% (P < 0.001) occurs. Treatment with SHE-3 induces translocation of DAF-16 and activation of HSP-16 [18536978]. | Worm | +10 to +20 | — | — |
| Pinitol supplementation | Pinitol (a 3-methoxy analogue of D-chiro-inositol) supplementation to the diet. For both males and females, a 20 microMolar dose of pinitol significantly extends median lifespan by 13% (p < 0.05) and 12.5% (p < 0.05), respectively. Lifespan extension by pinitol is accompanied by protection against oxidative and starvation stresses, improvement in health span, and no reduction in fecundity. Pinitol increases organismal lifespan of both in dietary restriction and ad libitum conditions. Nuclear localization of foxo increases in pinitol-fed animals. Pinitol treatment significantly activates JNK and S6K, but not AKT [22843669]. | Fly | — | +12.5 to +13 | — |
| 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 |
| 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 |
| Oligomycin treatment | Oligomycin (a specific inhibitor of complex V) feeding exends lifespan on ad libitum and prevents an increase in longevity under DR (started in the adulthood) in males [19968629]. | Fly | — | — | — |
| N-acetyl-serotonin administration | N-acetyl-serotonin (a melatonin precursor) administrated with drinking water increases anti-oxidant capacity of the brain and prolongs the mean lifespan by 20% of males but not females [11462771].
| Mouse | 0 to +20 | — | — |
| 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 |
| Mianserin Treatment | Mianserin a serotonin receptor antagonist (used as antidepressant in humans), can increase C. elegans lifespan when given only during adulthood. Lifespan extension is reduced or abolished by mutations that affect serontonin synthesis or serotonin reuptakte at synapses [14,16]. It requires a serontonin receptor and an octopamine receptor which are both inhibited by Mianserin. Mianserin plus DR increase lifespan only by 4% more than DR alone and totally failed to extend lifepan in eat-2(ad1116) mutants. However, mianserin does not appear to reduce food intake [14]. On average, mianserin increases lifespan by 31% by an optimal dose of 50 micromolar, but had little or no effect when given at 250 micromolar. Mianserin failes to increase the lifepsna of mutants lacking serotonin synthesis enzyme TPH-1 and causes a lifespan increase of only 13% in mutant lacking serontin reuptake transporter MOD-5. Mianserin does not increase lifepan of SER-4 or SER-4 mutants. Mianserin increases lifespan by31% when given throughout adulthood, but it only result in 10% lifespan extension when it was gieven beginning at adult day 5. Mianserin also failed to increase lifespan in liquid lifespan assay and in animals grown on solid agarose plates lacking ill-defined component of commoly used agar plates (agar and Bacto peptone). Mianserin increases lifespan of animlas grown at 20 but not at 25 degree Celsius [19686215]. | Worm | — | — | — |
GenAge
GenDR
