| 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 | — | — |
| 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 | — | — |
| 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 |
| 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 | — | — |
| 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 |
| 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 | — | — |
| L-proline supplementation | L-proline supplementation increases lifespan by 5.8 and 13.6% (mean and maximum lifespan) [22482728]. | Worm | +6 | — | +14 |
| 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 |
| Beauveriolide I treatment | Treatment with beauveriolide I (20 microgram/mL) extends chronological lifespan in BY4741 by around 50% [22790951]. | Yeast | +50 | — | — |
| Apply polyphenol treatment | Treatment with 100 microgram/mL apple polyphenol increases mean lifespan of wild-type N2 and FEM-1 by 12.0 and 5.3%, respectively [20717869]. | Worm | +5.3 to 12.0 | — | — |
| 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 |
| 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 |
| 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 |
| 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 |
| C3 treatment | Tris-malonic acid derivate of the fullerene C60 molecule (C3) increases the lifespan of Sod2(-/-) mice by 300% [15451059].
| Mouse | +300 | — | — |
| Trehalose treatment | Treatment with trehalose starting from the young-adult stage extends the mean lifespan by over 30% without any side effects. Trehalose treatment starting even from the old-adult stage shortly thereafter retards the age-associated decline in survivorship and extends the remaining lifespan by 60%. Lifespan extension by trehalose lowers the age-independent vulnerability. Trehalose increases reproductive span and retards the age-associated decrease in pharyngeal-pumping rate and the accumulation of lipofuscin autofluorescence as well as enhances thermotolerance and reduces polyglutamine. The lifespan extending effect of trehalose is abolished in daf-2 mutants [20477758]. | Worm | +30 to +60 | — | — |
| 2-MEA treatment | Addition of 1% by weight 2-MEA to the diet of male LAF mice, started shortly after weaning, increases average lifespan by approximately 30%, but does not extend maximum lifespan [5723482; 11795501].
Addition of 2-MEA to the maternal diet of female mice increases the lifespan of male and female offspring by 15 and 8%, respectively [Harman & Eddy, 1979; 11795501].
Addition of 2-MEA of an antioxidant mixture containing ethoxyquin and 2-MEA to the diet of dietary restricted mice shortens lifespan approximately 20% [2394907]. | Mouse | +30 | — | — |
| 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 |
| Trichostatin A supplementation | Histone deacetylase inhibitor Trichostatin A (TSA) extends the lifespan of Drosophila melanogaster by promoting the hsp22 gene transcription, and affecting the chromatin morphology at the locus of hsp22 gene along the polytene chromosome [15346199].
hsp70 and hsp22 RNA levels are higher in long-lived than in short-lived fly lines. The HDAC inhibitor TSA causes a higher expression of hsp22 and hsp70, and strikingly influences the lifespan in both long and short-lived lines, with variable degrees (up to 25%) [15695762]. | Fly | +25 | — | — |
| DMSO treatment | Treatment with 0.5 and 2% DMSO increases lifespan by 24.4 and 23.0%, respectively. 0.5% DMSO does not affect progeny number or lifespan under thermal stress. Treatment with 0.5% DMSO enhances the mRNA levels of hsp-16.2, hsp-70, lys-7, old-1, and sod-5 by 2.5, 2.9, 1.3, 2.3, and 4.5-fold, respectively, as well as the protein level of lys-7 by 1.5-fold. Lifespan extension confered by DMSO depends on sir-2.1 and daf-16 but not on eat-2 or hsf-1 [20828537]. | Worm | +23.0 to +24.4 | — | — |
| Tyrosol treatment | Treatment with tyrosol (250 microMolar) extends mean, median, and maximum, lifespan by 21, 21, and 11% [22824366]. | Worm | +21 | +21 | +11 |
| 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 |
| 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 |
| 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 | — | — |
GenAge
GenDR
