| Black rice extract supplementation | In fruit fly, 30 mg/ml black rice extract prolonges mean lifespan by 14% which is accompanied with mRNA up-regulation of SOD1, SOD2, CAT and Rpn11 Rpn11 and with downregulation of Mth [22930061]. | Fly | +14 | — | — |
| THC treatment | In male mice supplementation with tetrahydrocurcumin beginning at the age of 13 month increases the mean lifespan by an average of 84 days, i.e. an increase of 11.7% [17516143]. | Mouse | +11.7 | — | — |
| Metformin treatment | In rats metformine treatment reduces body weight significantly (despite similar food intake) but fails to significantly extend the lifespan at any quantile (25th, 50th, 75th, or 90th), overall or maximum lifespan (p > 0.05) [20304770]. | Rat | — | — | — |
| L-proline supplementation | L-proline supplementation increases lifespan by 5.8 and 13.6% (mean and maximum lifespan) [22482728]. | Worm | +6 | — | +14 |
| LA treatment | LA confers a memory effect, by fixing the lifespan of previous feeding regimen. When animals are switched early in life (12 months) from DR to AL and supplemented with α-lipoic acid the DR typical lifespan extension is maintained, but switching early from AL supplemented with α-lipoic acid to DR blocks the lifespan extending effect [18486188].
LA exhibits the ability to compensate for age-related, long-term memory deficits in old rats [8309958].
| Rat | — | — | — |
| Melatonin supplementation | Melatonin 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 | — | — |
| Metformin treatment | Metformin treatment extends healthspan, slows lipofuscin accumulation, extends mean lifespan and prolongs healthful locomotory ability in a dose-dependent manner as well as reduces fecundity. AMPK and its activating kinase LKB1 are essential for these health benefits. Oxidative stress-responsive transcription factor SKN-1/Nrf2 is essential for metformin-confered healthspan too as it must be expressed in both neurons and intestines [20090912]. | Worm | — | — | — |
| 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 | — | — | — |
| 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 | — | — |
| 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 | — | — | — |
| 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 |
| 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 | — |
| 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 | — | — |
| 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 | — | — |
| 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 | — | — | — |
| 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 | — | — | — |
| 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 | — | — | — |
| Resveratrol supplementation | Resveratrol significantly extends the lifespan [12939617]. | Yeast | — | — | — |
| Resveratrol supplementation | Resveratrol supplementation prolongs the lifespan [15254550; 17460219], but not in any case [17875315]. | Worm | — | — | — |
| 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 | — | — |
| 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 | — | — |
| 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 | — | — | — |
| Resveratrol supplementation | Supplementation with resveratrol extends the lifespan [15254550], but not in always [17875315]. | 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 | — | — |
GenAge
GenDR
