| 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]. | — |
| Res | Resveratrol | Resveratrol significantly extends the lifespan of yeast [12939617].
Resveratrol supplementation prolongs the lifespan of nematodes [15254550; 17460219], but not in any case [17875315].
In fruit flies supplementation with resveratrol extends the lifespan [15254550], but not in always [17875315].
In Nothobranchius furzeri a maximum dose of resveratrol increases the median lifespan by 56% [16461283].
Resveratrol conteracts the detrimental effects of a high-fat diet in mice an decreases the risk of death by 30% and thereby reverting it to the level of normal diet. It also partially corrected a subset of the abnormal gene expression profile and insulin as well as glucose metabolism [17086191].
Although resveratrol has range a of beneficial effects in elderly mice, it does not increase the longevity of *ad libitum* fed mice when started midlife [18599363]. Even at high doses and when started in young adulthood reseveratrol supplementation does not increase lifespan on a normal diet [17578509; 20974732]. | — |
| MEL | Melatonin | Melatonin administrated to mice with drinking water increases anti-oxidant capacity of the brain and prolongs the mean lifespan by 20% of males but not females [11462771]. | — |
| NAS | N-acetyl-serotonin | N-acetyl-serotonin (a melatonin precursor) administrated in mice with drinking water increases anti-oxidant capacity of the brain and prolongs the mean lifespan by 20% of males but not females [11462771]. | — |
| — | 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]. | — |
| C3 | Tris-malonic acid derivate of the fullerene C60 molecule | Tris-malonic acid derivate of the fullerene C60 molecule (C3) increases the lifespan of Sod2(-/-) mice by 300% [15451059]. | — |
| CSODM | Carboxyfullerene SOD mimetic | Administration of a small-molecule synthetic enzyme superoxide dismutase mimetic to wild-type (i.e. non-transgenic; 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 [17079053].
Carboxyfullerene SOD mimetic is an antioxidant with mitochondrial activity and nervous system penetration capability [17079053]. | — |
| Met | Metformin | In nematode 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].
In fruit fly feeding metformin to adult 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].
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].
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]. | — |
| — | 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]. | — |
| 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]. | — |
| — | Wortmannin | 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]. | — |
| 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]. | — |
| L-Theanine | L-Theanine | L-Theanine promotes paraquat resistance and extends lifespan of adult *C. elegans* [22422488]. | — |
| C60 | [60]fullerene | Oral administration of C60 dissolved in olive oil (0.8 mg/ml) at reiterated doses (1.7 mg/kg of body weight) for just about 7 months to rats not only does not entail chronic toxicity but it almost doubles the lifespan. The effects on lifespan is mainly due to the attenuation of age-associated increases in oxidative stress. Dissolved C60 is absorbed by the gastro-intestinal tract and eliminated in a few tens of hours [22498298].
C60-olive oil can increase the mean, median and maximum lifespan by 114, 91 and 74%. C60-olive oil extends the lifespan of animals with a probability of 0.999 and 0.995 with respect to water and olive oil treatments, respectively [22498298].
The GSSG/GSH ratio of animals treated by C60-olive oil is significantly less (about twice as less) as compared to controls [22498298].
C60 solutions have a characteristic purple color. C60 can cross the blood-brain barrier [21787853]. The elimination process follows a non-urinary route as it is mainly eliminated through the bile ducts [16351219; 21787853]. C60 reacts inside the liver cells with vitamin A following a Diels-Alder like reaction both in mice and rats [16351219]. | — |
| 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 |
| 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 |
| 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 |
| 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 |
