| — | Rapamycin | Rapamcyin increases mouse lifespan even when administrated late in life [19587680]. | House mouse |
| DDS | 4,4'-diaminodiphenylsulfone | In nematode treatment with DDS extends the lifespan [20974969].
DDS causes the delay of aging and decreases the level of a mitochondrial complex as well as lowers oxygen consumption and enhances oxidative stress resistance [20974969].
Pyruvate kinase is bound and inhibited by DDS in vitro and in vivo [20974969].
Hansen disease patients in Korea, who usually have taken DDS for several decades, have a longer lifespan in spite of their socioeconomic disadvantages [19084552]. | House mouse |
| — | Diabenol | 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]. | House mouse |
| 2-ME | 2-Mercaptoethanol | 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]. | House mouse |
| 2-MEA | 2-Mercaptoethylanime hydrochloride | 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].
References
----------------
Harman, D., and Eddy, D. E. (1979). Free radical theory of aging: beneficial effect of adding antioxidants to the maternal mouse diet on life span of offspring: possible explanation of the sex difference in longevity. Age 2, 109-22. | House mouse |
| THC | Tetrahydocurcumin | 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].
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].
| Human |
| TSA | Trichostatin A | 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].
| Human |
| PDTC | Pyrrolidine dithiocarbamate | Treatment of Drosophila imago with PDTC increases median (by 11-13%) and maximum (by 11-14%) lifespan in females and males, respectively [22661237]. | Fruit fly |
| Laz | Lazarillo | Extracellular forms of Laz have autocrine and paracrine protecting effects for oxidative stress-challanged Drosophila S2 cells. Local effects of GPI-linked Laz inside and outside the nervous system promote survival upon different stress forms, and extend lifespan and healthspan of the flies in a cell-type dependent manner. Ectopic enhancement of Laz expression increases mean, median, and maximum lifespan. Laz overexpression (via the use of a ubiquitous da-GAL4 driver) increases median lifepan by 28.3% (p < 0.0005). Overexpression of Laz specifically in muscles and brain (via GAL4109(2)80 driver) increases median lifespan by 43.5%. Laz overxpression in dopaminergic and serotenergic neurons and epidermis increases median lifespan bt 31.4% (p < 0.0005) [22846641]. | Fruit fly |
| Oo | Olive oil | In rats 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].
In humans olive oil has positive effects on health and counteracts aging [11905662]. Its effect is suggested to be a function of the dose [19369055]. | Fruit fly |
| LY294002 | — | 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 of fruit fly [20017609]. | Fruit fly |
| Icariin | Icariin | Icariin and its derivate icariside II extend lifespan. Animals treated with icariin have high levels of icariside II [22216122]. | Nematode |
| Icariside II | Icariside II | Icariside II and its derivate icarrin extend lifespan. Animals treated with icariin have high levels of icariside II. Icariside II also increases thermo and oxidative stress tolerance, slow locomotion decline in late adulthood and delay the onset of paralysis mediated by polyQ and ABeta(1-42) proteotoxicity. Lifespan extension by Icariside II is dependent on IIS, since daf-16(mu86) and daf-2(e1370) fails to sho exhibit lifespan extension upon icariside treatment. Incariside II treatment upregulates expression of DAF-16 targets in wild-type. HSF-1 has also a role in icariside II-dependent lifespan extension [22216122]. | Nematode |
| CYT1 | cytochrome c1 | Deletion of CYT1 increases replicative lifespan by 15% in the alpha strain and decreases replicative lifespan by 20% in a strain. Deletion of CYT1 decreases replicative lifespan and cancels out replicative lifespan extension by HAP4 overexpression. Initially, it was shown that deletion of CYT1 also prevents lifespan extension by 0.5% glucose restriction [12124627], but later it was shown that either 0.5 or 0.05 % glucose restriction increases replicative lifespan of cyt1Delta cells [16311627]. | Budding yeast |
| — | Hesperidin | 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 [22484922]. | Budding yeast |
| HDA1 | Histone DeAcetylase 1 | Deletion of HDA1 has no effect on longevity under AL, but acts synergistically with 0.1% glucose restriction to increase replicative lifespan [12213553]. Deletion of HDA1 leads to a slightly increased chronological lifespan [19801973]. Deletion of HDA1 has no effect on the wild-type lifespan in the short-lifespan of YSK771 strain, but suppresses the short-lifespan of SIR3 mutants [10512855]. | Budding yeast |
| Quercitin | — | Quercitin significantly extends the lifespan in C. elegans. 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]. | — |
| NAD | Nicotinamide Adenine Dinucleotide | Supplementation with NAD extended lifespan of C. elegans and this extension was dependent on sir-2.1 and daf-16 and associated with upregulation of sod-3 [19370397]. | — |
| PC | Procyanidin | Treatment of C. elegans 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]. | — |
| Asc | Ascrobate | In budding yeast, the hypersensitivity to oxygene and significantly decreased replicative lifespan of SOD1 deletion can be ameliorated by exogenous ascorbate. If acorbate's negative effects of auto-oxidation are prevented by exchange of medium, ascorbate prolongs mean and maximum replicative lifespan in the atmosphere of air and pure oxygene [15621721]. | — |
| SHE-3 | Eleutherococcus senticosus | Treatment of nematodes with the 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]. | — |
| SHE-5 | Rhodiola rosea | Treatment of nematodes with the 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 weakerm wheras at the highest concentrations (250 microgram/mL) a lifespan shortenening effect of 15-25% (P < 0.001) occurs [18536978]. | — |
| DhHP-6 | Deterohemin-AlaHisThrValGluLys | 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 [20528576]. | — |
| DMSO | Dimethyl sulfoxide | 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]. | — |
| JUG | 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 [19597959]. | — |
