| Metformin treatment | Chronic treatment of female transgenic HER-2/neu mice with metformin slightly decreases food consumption but fails to reduce body weight or temperature, slows down age-related rise in blood glucose and triglycerides level, as well as the age-related switch-off of estrous function, prolongs mean lifespan by 8% (p < 0.05), the mean lifespan of last 10% survivors by 13.1% and maximum lifespan by 1 month. Metformin treatment significantly decreases incidence and size of mammary adenocarcinomas and increases the mean latency of the tumors [16125352].
Chronic treatment of female outbred SHR mice with metformin slightly modified food consumption but decreases the body weight after the age of 20 months, slows down the age-related switch-off of estrous function, increases mean lifespan by 37.8% mean lifespan of the last 10% survivor by 20.8%, and maximum lifespan by 2.8 month (+10.3%). Treatment with metformin fails to influence blood estradiol concentration and spontaneous tumor incidence in female SHR mice [18728386].
In female SHR mice, metformin increases lifespan lifespan and postpones tumors when started at young and middle but not at old age. Chronic treatment of female outbred SHR mice with metformin started at the age of 3, 9 or 15 months decreases body temperature and postpones age-related switch-off of estrous function. Treatment with metformin started at the age of 3 months increases mean lifespan by 14% and maximum lifespan by 1 month. Treatment started at the age of 9 months insignificantly increases lifespan by only 6%, whereas the treatment started at the age of 15 months fails to increase lifespan. The mean lifespan of tumor-free mice increases by 21% (started at 3 months), by 7% (started at 9 months) and in contrast is reduced by 13% (started at 15 months). If started at 3 and 9 months, metformin delays the first tumors by 22% and 25%, correspondingly [21386129].
Transgenic FVB/N female mice carrying HER-2/neu mammary cancer gene receiving metformin with drinking water 5 days a week starting from the age of 2 months exhibit a slight reduced food consumption without change in water consumption and dynamics of weight gain. Their mean lifespan increases by 8% in 10% of the long-lived mice it is prolonged y 13.1% and the maximum lifespan is prolonged by 1 month. The total incidence of mammary adenocarcinoma and their multiplicity does not change under the effect of metformin, while the latency of tumor development increases and the mean diameter of tumors decreases [16224592].
Chronic treatment of inbred 129/Sv mice with metformin slightly modifies food consumption but fails to influence the dynamics of body weight, decreases by 13.4% the mean lifespan of make mice and slightly increases the mean lifespan of female mice (by 4.4%). Metformin treatment fails to influence tumor incidence in male 129/Sv mice, decreases by 3.5 times the incidence of malignant neoplasms in female mice while somehowwhat stimulate formation of benign vascualr tumors in the latter [21164223]. | Mouse | — | — | — |
| 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 | — | — | — |
| Methionine restriction | A diet with reduced methionine content extends lifespan and increases body fat [15924568]. | Mouse | — | — | — |
| 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 |
| 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 | — | — | — |
| 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 |
| 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 |
| 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 | — | — |
| NAC treatment | Treatment with 10 mM of NAC has no effect on the lifespan of wild-type, but fully abolishes the increased longevity of nuo-6 and severly limits that of isp-1. At high concentration (> 10-15 nM) NAC can be become deleteroius even on the wild-type [21151885]. | Worm | — | — | — |
| 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 | — | — | — |
| 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 |
| NAM treatment | Treatment with NAM significantly decreases adult lifespan [17335870]. | Worm | — | — | — |
| 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 | — | — | — |
| 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 |
| 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 |
| Phloridzin treatment | Administration of the apple polyphenol phloridzin at doses of 3, 10, and 30 microMolar siginificantly prolongs the replicative lifespan in K6001 strain (p < 0.01; p < 0.001). Phloridizin improves the viability of cells under oxidative stress (7 microMolar H2O2) in a dose-dependent manner and increases the significantly the expression of SOD1, SOD2, and SIR2 [21597195]. | Worm | — | — | — |
| 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 | — |
| Procyanidin treatment | Treatment with 65 microgram/mL Procyanidins from apple extends the lifespan of N2 and FEM-1 by 12.1 to 8.4%, respectively and does not modify grwoth, food intake of fecundity. Procyanidin treatment has no effect on mev-1 or sir-2.1 mutants [20717869]. | Worm | +8.4 to +12.1 | — | — |
| 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 | — | — | — |
| 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 |
| 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 |
| 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 |
| Restriction of yeast | Restriction of yeast, the major source of protein in the lfy diet, robustly extends lifespan [15186745; 16000018]. | Fly | — | — | — |
| Resveratrol supplementation | Resveratrol significantly extends the lifespan [12939617]. | Yeast | — | — | — |
GenAge
GenDR
