| 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 | — | — | — |
| Metformin treatment | In fruit fly feeding metformin to adult s results in robust AMPK activation and reduces lipid stores, but does not increase lifespan in either males or females. Administration of high concentration are even toxic [23077661].
| Fly | — | — | — |
| 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 | — | — | — |
| Diabenol treatment | In female NMRI and transgenic HER-2/neu mice supplementation of diabenol with drinking water 5 times a week since the age of 2 months, increases survival and inhibits spontaneous carcinogenesis.
In NMRI diabenol does not influence body weight gain dynamics, food and water consumption, but slowed down age-related disturbances in estrous function and increases the lifespan of all and 10% most long-living ones. Diabenol treatment in NMRI mice also inhibits spontaneous tumor incidence (mammary and lymphomas mainly) and increases mammary tumor latency. Diabenol treatment slows down age-related changes in estrous function in HER-2/neu mice, but fails to influence survival and slightly inhibited the incidence and decrease the size of mammary adenocarcinoma metastasis into the lung [15754958]. | Mouse | — | — | — |
| 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 | — | — | — |
| (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 [9972869]. | Fly | — | — | — |
| 2-ME treatment | Animals fed a diet supplemented with 2-mercaptoethanol (2-ME) exhibit an increased mean and maximum lifespan [6334792].
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 [6334792]. | Mouse | — | — | — |
| 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 | — | — |
| 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 | — | — |
| 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 | — | — | — |
| 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 | — | — |
| DATS treatment | Treatment with 5-10 μM DATS increases lifespan even when treatment is started during young adulthood. DATS increases the lifespan of daf-2 and daf-16 mutants, but not that of eat-2 mutants.
DATS treatment leads to the induction of the skn-1 target gene gst-4 and this induction is dependent on skn-1. DATS effect on lifespan is dependent on skn-1 activity in both intestine and ASI neurons [21296648]. | Fly | — | — | — |
| 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 | — | — |
| Tyrosol treatment | Treatment with tyrosol (250 microMolar) extends mean, median, and maximum, lifespan by 21, 21, and 11% [22824366]. | Worm | +21 | +21 | +11 |
| 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 |
| 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 |
| L-proline supplementation | L-proline supplementation increases lifespan by 5.8 and 13.6% (mean and maximum lifespan) [22482728]. | Worm | +6 | — | +14 |
| 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 |
| LY294002 treatment | Treatment of Drosophila imago with 5 micromolar LY294002 increases median (by 14%) and maximum (by 16-22%) lifespan (p<0.001) in females and males, respectively [22661237].
Low dose of LY294002 (5 microM) slightly increase the median and maximum lifespan [20017609]. | Fly | — | +14 | +16 to +22 |
| 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 | 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 |
| 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 |
| 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 |
| Wortmannin treatment | Treatment of Drosophila imago with 0.5 micromolar wortmannin increases median (by 5%) and maximum (by 39%) lifespan in males (p < 0.001), but the lifespan differences in females were statistical insignificant (p > 0.05) [22661237].
Low dose of wortmannin (5 microM) slightly increase the median and maximum lifespan [20017609]. | Fly | — | +5 | +39 |
GenAge
GenDR
