| — | Oligomycin | In fruit fly, Oligomycin feeding exends lifespan on ad libitum and prevents an increase in longevity under DR (started in the adulthood) in males [19968629]. | — |
| — | Pinitol | In fruit flies, 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]. | — |
| DCI | D-chiro-inositol | In fruit flies, 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 [22843669]. | — |
| — | 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 |
| — | Mincoycline | In Drosophila melongaster 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]. | — |
| 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]. | — |
| Rapa | Rapamycin | In budding yeast 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].
Treatment with rapamcyin in nemaotdes 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].
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]. Rapamcyin increases mouse lifespan even when administrated late in life [19587680].
Low dose of rapamycin (5 microM) slightly increase the median and maximum lifespan in fruit fly [20017609].
Rapamcyin increases mouse lifespan and healthspan even when administrated late in life (20 months) [19587680].
Rapamycin enhances learning and memory in young mice and improves these faculties in old mice thereby negating the normal decline in these functions with age. Rapamycin boost levels of neurotransmitters associated with neural plasticity. Rapamycin also lowered anxiety and depressive-like behaviour at all ages from 4, 12 and 28 months. "Happy, feel-good" neurotransmitters such as serotonin, dopamine and norepinephrine are all significantly augmented in the midbrains of rapamycin treated mice [http://denigma.de/url/37].
Treatment with rapamycin increased lifespan and suppresses spontanous tumorgenesis in inbred female mice [22107964]. | — |
| Beau I | beauveriolide I | In budding yeast treatment with beauveriolide I (20 microgram/mL) extends chronological lifespan in BY4741 by around 50% [22790951]. | — |
| — | Gonadermasides D | In budding yeast application of gonadermasides D significantly increases the replicative lifespan in the K6001 strain by regulating UTH1 [21512225]. | — |
| — | Gonadermasides C | In budding yeast application of gonadermasides C significantly increases the replicative lifespan in the K6001 strain by regulating UTH1 [21512225]. | — |
| 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 |
| Icariin | Icariin | Icariin and its derivate icariside II extend lifespan. Animals treated with icariin have high levels of icariside II [22216122]. | Nematode |
| 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 |
| 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]. | — |
| — | 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 |
| 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 |
| 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]. | — |
| 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 |
| 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 |
| DATS | Diallyl Trisulfide | DATS increases longevity apparently by enhancing skn-1.
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]. | — |
| — | Curcumin | Curcumin increases lifespan in *C. elegans* 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].
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]. | — |
| BTE | Black tea extract | Black tea extract is a mixture of epicatechins and theaflavins. In fruit fly, upplementation of the diet with black tea extract extends the lifespan by 10% (from 51 to 56 days) and is associated with higher SOD1 and CAT expression [19770032]. | — |
| — | Ganodermasides B | Application of Ganodermasides B extends the replicative lifespan of budding yeast in K6001 strain by regulating UTH1 expression [20093034]. | — |
| — | Ganodermasides A | Application of Ganodermasides A extends the replicative lifespan of budding yeast in K6001 strain by regulating UTH1 expression [20093034]. | — |
| AP | Apple polyphenol | Apple polyphenols mainly consists of procyanidins, which are composed of (-)-epicatechins and (+)-catechins. Treatment of C. elegans with 100 microgram/mL apple polyphenol increases mean lifespan of wild-type N2 and FEM-1 by 12.0 and 5.3%, respectively [20717869].
In fruit flies, supplemention of the diet with apple polyphenol significantly extends mean lifespan by 10% and is accompanied by up-regulation of SOD1, SOD2 and CAT as well as downregulation of MTH in aged animals [21319854]. | — |
