|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 . ||Mouse ||— ||— ||— |
|Low calorie diet with low-sugar content ||A diet with low-calorie and low-sugar content increase the lifespan, but not resistance to acute oxiditive stress  ||Fly ||— ||— ||— |
|Methionine restriction ||A diet with reduced methionine content extends lifespan and increases body fat . ||Mouse ||— ||— ||— |
|High sugar low protein diet ||A high sugar low protein diet increases the lifespan, but not resistance to acute oxidative stress . ||Fly ||— ||— ||— |
|Resveratrol supplementation ||A maximum dose of resveratrol increases the median lifespan by 56% . ||Fish ||— ||+56 ||— |
|D-glucosamine treatment ||Addition of 0.5 mg/ml D-glucosamine to the growth media suppresses the short replicative lifespan and temperature sensitive growth of mpt5 mutant, but fails to extend the lifespan of wild-type cells . ||Yeast ||— ||— ||— |
|(R)-N-(2-heptyl)-N-methylpropargylamine treatment ||Addition of 0.66 ng/fly/day (R)-N-(2-heptyl)-N-methylpropargylamine to a sucrose-based diet resulted in no significant effect on lifespan, but lifespan reduction due to galactose feeding is partially suppressed by supplementation with (R)-deprenyl or (R)-N-(2-heptyl)-N-methylpropargylamine . ||Fly ||— ||— ||— |
|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% . ||Mouse ||+30 ||— ||— |
|Carboxyfullerene SOD mimetic treatment ||Administration of a small-molecule synthetic enzyme superoxide dismutase mimetic to wild-type (i.e. non-transgenicm non-senescence accelerated) mice starting at middle age significantly extends lifespan and reduces age-associated oxidative stress and mitochondrial radical production. Treatment also improves performance on Morris water maze learning and memory task and therefore rescues age-related cognitive impairment . ||— ||— ||— ||— |
|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 . ||Worm ||— ||— ||— |
|2-ME treatment ||Animals fed a diet supplemented with 2-mercaptoethanol (2-ME) exhibit an increased mean and maximum lifespan .
T-cell-dependent immune responses are higher in the 2-ME-fed mice compared to the controls when the animals are young. The accumulation of fluorescent products of lipid peroxidation damage is also delayed in the lymphocytes of the 2-ME-fed mice and tumor onset and incidence is reduced in these animals . ||Mouse ||— ||— ||— |
|Ganodermasides A treatment ||Application of Ganodermasides A extends the replicative lifespan in K6001 strain by regulating UTH1 expression . ||Yeast ||— ||— ||— |
|Ganodermasides B treatment ||Application of Ganodermasides B extends the replicative lifespan in K6001 strain by regulating UTH1 expression . ||Yeast ||— ||— ||— |
|Ganodermasides C treatment ||Application of gonadermasides C significantly increases the replicative lifespan in the K6001 strain by regulating UTH1 . ||Yeast ||— ||— ||— |
|Gonadermasides D treatment ||Application of gonadermasides D significantly increases the replicative lifespan in the K6001 strain by regulating UTH1 . ||Yeast ||— ||— ||— |
|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 .
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 .
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 .
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 .
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 . ||Mouse ||— ||— ||— |
|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 . *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% . 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 . ||Worm ||+39 ||— ||+21.4 |
|D-chiro-inositol supplementation ||D-chiro-inositol supplementation to the diet extends adult longevity in both male and female animals. 20 microMolar dose of D-chiro-inositol extends median lifespan by 16.7 (p < 0.001) for males and 13% (p < 0.001) for females. Lifespan extension by D-chrio-inositol is accompanied by protection against oxidative and starvation stresses, improvement in health span, and not reduction in fecundity. Nuclear localization of foxo increases in D-chiro-inositol-fed animals .
||Fly ||— ||+13 to +16.7 ||— |
|DhHP-6 treatment ||Deuterohemin containing peptide deterohemin-AlaHisThrValGluLys (DhHP-6) significantly increases mean lifespan (P < 0.05), but not maximum lifespan. DhHP-6 also improves survival rate in acute heat-stress (35 degree Celsius) and rescues sensitivity to paraquat in acute oxidative stress. DhHP-6 treatment up-regulates SOD-3 and also regulates stress resistance genes such as hsp-16.1, hsp16.49 and sir-2.1 daf-16 and sir-2.1 genes are essential for the beneficial effect of DhHP-6 . ||Worm ||— ||— ||— |
|Dietary restriction by 1% yeast medium ||Dietary restriction by be reducing yeast content in medium to 1% extends the lifespan . ||Fly ||— ||— ||— |
|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 . ||Mouse ||+36 ||— ||+36 |
|L744832 treatment ||Farnesyl inhibitor L744832 increases lifespan . ||Fly ||— ||— ||— |
|Hesperidin treatment ||Hesperidin derived from the Citrus genus extends replicative lifespan at doses of 5 and 10 microMolar. Hesperdin inihibts ROS and UTH1 gene expression, but increases Sir2 and SOD gene expression. UTH1 and SKN7 are involved in lifespan extension mediated by hesperidin . ||Yeast ||— ||— ||— |
|Jugelone treatment ||High jugelone concentrations led to premature death. Low juglone concentrations are tolerated well and cause a prolongation of lifespan that is associated with increased expression of small heat-shock protein HSP-16.2, enhanced glutathione levels, and nuclear translocation of DAF-16. Silencing or deletion of daf-16 prevents jugelone-induced adaptations. RNA-interference for SIR-2.1 has the same effects as daf-16 deletion but does not affect nuclear accumulation of DAF-16. DAF-16- and SIR-2.1-dependent alterations in gene expression after challenge with reactive oxygene species lead to lifespan extension . ||Worm ||— ||— ||— |
|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 .
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%) . ||Fly ||+25 ||— ||— |