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. 2017 May 31;7(5):335–404. doi: 10.1007/s13659-017-0135-9

Table 1.

Compounds from natural products with anti-aging activities

CAS Chemicals Structure Source Anti-aging activity and proposed anti-aging mechanism
With anti-aging activities in a variety of aging models
 501-36-0 Resveratrol graphic file with name 13659_2017_135_Figa_HTML.gif Polygonum cuspidatum Sieb.et Zucc. In mice: 4.7% increase in mean lifespan; increasing insulin sensitivity, reducing insulin-like growth factor-1 (IGF-I) levels, increasing AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) activity, increasing mitochondrial number, and improving motor function [44, 46–51]
In D. melanogaster: extends mean lifespan of females fed the low sugar–high protein diet by ∼15.0%, fed the high-fat diet by ∼10.0%; modulating genetic pathways that can reduce cellular damage [45]
In C. elegans: 18.0% increase in mean lifespan; regulating AMPK, SIR-2.1, autophagy, and proteasomal degradation [28, 52, 53]
In cell: increasing NAD(+) and the activity of AMPK and Sirt1, inhibiting PDE4, JAK2/STAT3 [89–92]
In S. cerevisiae: 70.0% increase in mean lifespan; regulating Sir2 and SNF1 [93, 94]
In Nothobranchius guentheri: antioxidant [95]
 62-46-4 α-Lipoic acid graphic file with name 13659_2017_135_Figb_HTML.gif Cell metabolite In SAMP8 mice: improving memory and oxidative stress in extremely old SAMP8 mice, but decreasing lifespan [56]
In D. melanogaste: 12.0% increase in mean lifespan and antioxidant [54]
In C. elegans: 24.0% increase in mean lifespan and antioxidant, enhancing chemotaxis index [55]
 472-61-7 Astaxanthin graphic file with name 13659_2017_135_Figc_HTML.gif Carotenoid In d-galactose-induced brain aging in rats: antioxidant, upregulating BDNF expression [58, 59]
In D. melanogaster: antioxidant [57]
In C. elegans: 29.0% increase in mean lifespan and regulating DAF-16 [29]
 154-23-4 Catechin graphic file with name 13659_2017_135_Figd_HTML.gif Green tea, cocoa, grapes, and apples In senescence-accelerated (SAMP10) mice: preventing memory regression and DNA oxidative damage [62]
In D. melanogaster: 16.0% increase in mean lifespan and antioxidant [61, 96]
In C. elegans: 13.0% increase in mean lifespan and antioxidant, regulating DAF-2, AKT-2, MEV-1, and NHR-8; decreasing insulin-like growth factor-1 [60]
 458-37-7 Curcumin graphic file with name 13659_2017_135_Fige_HTML.gif Curcuma longa L. In C57BL6/N mice: antioxidant, increasing collagen and AGEs [64]
In D. melanogaster: 25.8% increase in mean lifespan and antioxidant [65]
In C. elegans: 25.0% increase in mean lifespan and antioxidant [63]
 3351-86-8 Fucoxanthin graphic file with name 13659_2017_135_Figf_HTML.gif Natural substances in human diet In hairless mice: lessening UVB-induced epidermal hypertrophy, VEGF, and MMP-13 expression [67]
In D. melanogaster: 33.0% increase in mean lifespan and antioxidant [66]
In C. elegans: 14.0% increase in mean lifespan and antioxidant [66]
 124-20-9 Spermidine graphic file with name 13659_2017_135_Figg_HTML.gif Natural polyamine In D. melanogaster: 30.0% increase in mean lifespan and autophagy [68]
In C. elegans: 15.0% increase in mean lifespan and autophagy [68]
In S. cerevisiae: autophagy [68, 69]
With anti-aging activities in two aging models
 480-44-4 Acacetin graphic file with name 13659_2017_135_Figh_HTML.gif Naturally occurring flavonoid In D. melanogaster: decreasing APP protein expression, BACE-1 activity, and Aβ production [97]
In C. elegans: 27.3% increase in mean lifespan and upregulating SOD-3 and GST-4 [98]
 64-19-7 Acetic acid graphic file with name 13659_2017_135_Figi_HTML.gif Vinegars In C. elegans: 23.0% increase in mean lifespan and regulating insulin/IGF-1 pathway [99]
In S. cerevisiae: stimulating growth signaling pathways, increasing oxidative stress and replication stress [100]
 1005344-44-4 Antcin M graphic file with name 13659_2017_135_Figj_HTML.gif Antrodia cinnamomea In cell: antioxidant, regulating Nrf2 and SIRT-1 [101]
In C. elegans from oxidative stress: ~10.0% increase in mean lifespan and antioxidant [101]
 306-60-5 Agmatine graphic file with name 13659_2017_135_Figk_HTML.gif Generated by arginine decarboxylase In male sprague–dawley rats: suppressing age-related elevation in nitric oxide synthase activity in the dentate gyrus of the hippocampus and prefrontal cortex [102]
In C. elegans: 16.0% increase in mean lifespan and needs further research [103]
 328-50-7 α-Ketoglutarate graphic file with name 13659_2017_135_Figl_HTML.gif Tricarboxylic acid cycle intermediate In mice: decreasing TBARS level and the activity of superoxide dismutase, increasing glutathione peroxidase activity [104]
In C. elegans: 50.0% increase in mean lifespan and inhibiting ATP synthase and TOR signaling [105]
 491-67-8 Baicalein graphic file with name 13659_2017_135_Figm_HTML.gif Scutellaria baicalensis Lamiaceae In C. elegans: 24.0% increase in mean lifespan and antioxidant, regulating SKN-1 [106]
In PC12 cell: suppressing mitochondria dysfunction and apoptosis [107]
 107-43-7 Betaine graphic file with name 13659_2017_135_Fign_HTML.gif Nitrogen containing metabolite In aged rats: upregulating IKK/MAPKs, attenuating NF-κB activation [108, 109]
In C. elegans: 9.0% increase in mean lifespan and needs further research [103]
 331-39-5 Caffeic acid graphic file with name 13659_2017_135_Figo_HTML.gif Tomatoes, carrots, strawberries, blueberries and wheat In Sprague–Dawley rats and intra-cerebroventricular streptozotocin induced experimental dementia in rats: antioxidant, restoring cholinergic functions [110, 111]
In C. elegans: 11.0% increase in mean lifespan and regulating OSR-1, SEK-1, SIR-2.1, UNC-43, and DAF-16 [112]
 305-84-0 Carnosine graphic file with name 13659_2017_135_Figp_HTML.gif Endogenous dipeptide In aged rats: preventing oxidative stress and apoptosis [113, 114]
In D. melanogaster: 26.0% increase in mean lifespan and antioxidant [115, 116]
 2415-24-9 Catalpol graphic file with name 13659_2017_135_Figq_HTML.gif Rehmannia glutinosa In senescent mice induced by d-galactose: improving cholinergic function, reducing inflammatory cytokines; In rats: rebalancing E2 and P4 levels in aged rats [117, 118]
In C. elegans: 28.5% increase in mean lifespan and antioxidant, regulating SKN-1/Nrf and DAF-16 [119]
 327-97-9 Chlorogenic acid graphic file with name 13659_2017_135_Figr_HTML.gif Coffee and tea In d-galactose-induced mice: antioxidant, reducing tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) protein levels [120]
In C. elegans: 20.1% increase in mean lifespan and antioxidant, regulating IIS pathway [121]
 303-98-0 Coenzyme Q10 graphic file with name 13659_2017_135_Figs_HTML.gif Mitochondrial respiratory chain component In mice: ameliorating age-related impairment, reducing protein oxidation [122]
In C. elegans: 18.0% increase in mean lifespan and scavenging reactive oxygen species [123]
 3416-24-8 d-Glucosamine graphic file with name 13659_2017_135_Figt_HTML.gif Hexosamine pathway In mice: 6.0% increase in mean lifespan; enhancing expression of several murine amino-acid transporters, increasing amino-acid catabolism [124]
In C. elegans: 11.0% increase in mean lifespan and mimicking a low-carbohydrate diet by regulating AMPK and SKN-1 [124]
 75-18-3 Dimethyl sulfide graphic file with name 13659_2017_135_Figu_HTML.gif Metabolite of marine algae or fermentative bacteria In D. melanogaster: 24.2% increase in mean lifespan and antioxidant [17]
In C. elegans: 24.3% increase in mean lifespan and antioxidant [17]
 490-46-0 (−)-Epicatechin graphic file with name 13659_2017_135_Figv_HTML.gif Cocoa In obese diabetic mice: antioxidant, improving skeletal muscle stress output, reducing systematic inflammation and serum LDL cholesterol [61]
In D. melanogaster: ~8.0% increase in mean lifespan and needs further research [61]
 989-51-5 Epigallo-catechin gallate graphic file with name 13659_2017_135_Figw_HTML.gif Tea polyphenols In d-galactose-induced mice: increasing oxidative stress and the expression of EGFR proteins [125]
In C. elegans: 13.0% increase in mean lifespan and antioxidant, regulating IIS pathway [126]
 149-91-7 Gallic acid graphic file with name 13659_2017_135_Figx_HTML.gif Beverages (red wines and green teas), plant leaves (beriberry) In senescence accelerated mice: antioxidant [127]
In C. elegans: 25.0% increase in mean lifespan and antioxidant [27]
 527-07-1 Gluconate graphic file with name 13659_2017_135_Figy_HTML.gif Sugars metabolite In D. melanogaster: 22.0% increase in mean lifespan and antioxidant [128]
In lacking nitrogen on C. elegans: 16.0% increase in mean lifespan and antioxidant [103]
 56-81-5 Glycerol graphic file with name 13659_2017_135_Figz_HTML.gif Sugars metabolite In lacking nitrogen on C. elegans: 21.0% increase in mean lifespan and needs further research [103]
In rotifer: 50.0% increase in mean lifespan; increasing resistance to starvation, heat, oxidation, and osmotic stress, but not UV stress [129]
 520-26-3 Hesperidin graphic file with name 13659_2017_135_Figaa_HTML.gif Citrus genus In Murine model of sepsis: antioxidant [130]
In S. cerevisiae: 37.0% increase in mean lifespan and antioxidant, regulating Sir2, UTH1 [131]
 489-32-7 Icariin graphic file with name 13659_2017_135_Figab_HTML.gif Herba epimedii In mice: inducting antioxidant protein superoxide dismutase (SOD) activity, decreasing oxidative marker malondialdehyde (MDA) [132]
In C. elegans: 20.7% increase in mean lifespan and regulating IIS pathway [133]
 74-79-3 Arginine graphic file with name 13659_2017_135_Figac_HTML.gif Amino acid In C. elegans: 27.0% increase in oxidative stress; 370% in heat stress and antioxidant, regulating insulin/IGF signaling pathway [103, 134]
In Megalobrama amblycephala: antioxidant [134]
 50-21-5 Lactate graphic file with name 13659_2017_135_Figad_HTML.gif Metabolite In D. melanogaster: 15.0% increase in mean lifespan and antioxidant [128]
In C. elegans: 6.0% increase in mean lifespan and antioxidant [103]
 500-38-9 Nordi-hydroguaiaretic acid graphic file with name 13659_2017_135_Figae_HTML.gif Creosote plant (Larrea tridentata: Zygophyllaceae) In mice:12.0% increase in mean lifespan; decreasing the absorption or increasing the utilization of calories [135–138]
In Mosquito: 64.0% increase in mean lifespan and needs further research [137]
 508-02-1 Oleanolic acid graphic file with name 13659_2017_135_Figaf_HTML.gif Olea europaea, Viscum album L., and Aralia chinensis L. In d-galactose-induced mice: anti-oxidative, anti-glycative, and anti-apoptotic [139]
In C. elegans: 16.6% increase in mean lifespan and antioxidant, regulating DAF-16 [140]
 851983-55-6 Oligonol graphic file with name 13659_2017_135_Figag_HTML.gif Grape seed or lychee fruit In mice: Regulating AMPK, SIRT1, autophagy, and increasing cell proliferation [141, 142]
In C. elegans: regulating AMPK and autophagy [141]
 27208-80-6 Polydatin graphic file with name 13659_2017_135_Figah_HTML.gif Grape juice In mice: anti-oxidative, anti-inflammatory, and anti-apoptotic [143]
In C. elegans: 30.0% increase in mean lifespan and regulating DAF-2, SIR-2.1, SKN-1, SOD-3, and DAF-16 [144]
 537-15-5 Rosmarinic acid graphic file with name 13659_2017_135_Figai_HTML.gif Subfamily Nepetoideae of the Lamiaceae In aging mice: antioxidant [145]
In C. elegans: 10.0% increase in mean lifespan and regulating SIR-2.1, OSR-1, SEK-1, UNC-43, and DAF-16 [112]
 607-80-7 Sesamin graphic file with name 13659_2017_135_Figaj_HTML.gif Sesame seeds In D. melanogaster: 12.0% increase in mean lifespan and antioxidant [146]
In C. elegans:14.0% increase in mean lifespan and regulating DAF-2, SKN-1, PMK-1, and DAF-16 [147]
 36062-04-1 Tetra-hydrocurcumin graphic file with name 13659_2017_135_Figak_HTML.gif Biotransformed metabolite of curcumin contained in turmeric of Indian curry In mice: 12.0% increase in mean lifespan; attenuating oxidative stress, hypertension, vascular dysfunction, and baroreflex dysfunction [148–151]
In D. melanogaster: ~28.0% increase in mean lifespan and regulating Sir2 and FoxO [152]
 1143-70-0 Urolithin A graphic file with name 13659_2017_135_Figal_HTML.gif Pomegranate fruit, nuts and berries In mouse models of age-related decline of muscle function: improving exercise capacity [153]
In C. elegans: 45.4% increase in mean lifespan and regulating mitochondrial function, mitophagy [153]
 3681-93-4 Vitexin graphic file with name 13659_2017_135_Figam_HTML.gif Vigna angularis In d-galactose-aged mice: antioxidant [154]
In C. elegans: 17.0% increase in mean lifespan and antioxidant [155]
With anti-aging activities in rats or mice
 118-00-3 Guanosine graphic file with name 13659_2017_135_Figan_HTML.gif Endogenous nucleoside In Wistar rats: antioxidant [156]
 70579-26-9 Porphyra-334 graphic file with name 13659_2017_135_Figao_HTML.gif Red alga Porphyra rosengurttii In mice skin: antioxidant, Hsp70 [157]
 73112-73-9 Shinorine graphic file with name 13659_2017_135_Figap_HTML.gif Red alga Porphyra rosengurttii In mice skin: antioxidant, Hsp70 [157]
 70363-87-0 Sargaquinoic acid graphic file with name 13659_2017_135_Figaq_HTML.gif Sargassum sagamianum In mice skin: inducing apoptosis [158]
 70363-89-2 Sargachromenol graphic file with name 13659_2017_135_Figar_HTML.gif Sargassum sagamianum In mice skin: inducing apoptosis [158]
 1094-61-7 β-Nicotinamide mononucleotide graphic file with name 13659_2017_135_Figas_HTML.gif Turnover of the oxidized form of nicotinamide adenine dinucleotide (NAD+) In rats: increasing NAD+ level [159]
 1339070-29-9 TA-65 graphic file with name 13659_2017_135_Figat_HTML.gif Root of Astragalus membranaceus In mice: activating telomerase [160]
 34157-83-0 Celastrol graphic file with name 13659_2017_135_Figau_HTML.gif Traditional Chinese medicinal herbs of the Celastraceae family In transgenic mouse model of amyotrophic lateral sclerosis: 13.0% increase in mean lifespan and regulating HSP70, blocking neuronal cell death [161]
 57-00-1 Creatine graphic file with name 13659_2017_135_Figav_HTML.gif Natural ergogenic compound In mice: 9.0% increase in mean lifespan and upregulating genes implicated in neuronal growth, neuroprotection, and learning [162]
 42553-65-1 Crocin graphic file with name 13659_2017_135_Figaw_HTML.gif Kashmiri saffron (Crocus sativus) In mice: 44.0% increase in mean lifespan and impacting on hematological parameters [163]
 61276-17-3 Acteoside graphic file with name 13659_2017_135_Figax_HTML.gif Roots of Incarvillea younghusbandii Sprague In senescent mouse model induced by a combination of d-gal and AlCl3: decreasing nitric oxide, the activity of nitric oxide synthase and the expression of caspase-3 [164]
 11096-26-7 Erythropoietin Glycoprotein Glycoprotein hormone In rats: antioxidant, regulating ERK/Nrf2-ARE [165]
 62499-27-8 Gastrodin graphic file with name 13659_2017_135_Figay_HTML.gif A number of plants and herbs In vascular dementia rats induced by chronic ischemia: antioxidant, regulating ADH7, GPX2, GPX3 and NFE2L2 [166]
 22427-39-0 Ginsenoside Rg1 graphic file with name 13659_2017_135_Figaz_HTML.gif Panax ginseng In d-galactose-induced mice: antioxidant, regulating the level of proinflammatory cytokines and telomerase system, activating the Wnt/β-catenin signaling [167, 168]
With anti-aging activities in Drosophila melanogaster
 87-89-8 Chiro-inositol graphic file with name 13659_2017_135_Figba_HTML.gif Inositol family 16.7% increase in mean lifespan and antioxidant, regulating dFOXO [169]
 526-95-4 Gluconic acid graphic file with name 13659_2017_135_Figbb_HTML.gif Glucose catabolism 22.0% increase in mean lifespan and antioxidant [128]
Glycoside acteoside graphic file with name 13659_2017_135_Figbc_HTML.gif Roots of Incarvillea younghusbandii Sprague 15.0% increase in mean lifespan and antioxidant [170]
 127-40-2 Lutein graphic file with name 13659_2017_135_Figbd_HTML.gif Major carotenoids in most fruits and vegetables 11.0% increase in mean lifespan and antioxidant [171]
 1004313-10-3 S,S-Trolox-carnosine graphic file with name 13659_2017_135_Figbe_HTML.gif Trolox acylated derivatives 36.0% increase in mean lifespan and antioxidant [116]
 4670-05-7 Theaflavins graphic file with name 13659_2017_135_Figbf_HTML.gif Black tea 10.0% increase in mean lifespan and antioxidant [172]
 353-09-3 β-Guani-dinopropionic acid graphic file with name 13659_2017_135_Figbg_HTML.gif Metabolites 13.0% in female, 90% in male increase in mean lifespan and regulating AMPK-Atg1-autophagy signaling [173]
 19545-26-7 Wortmannin graphic file with name 13659_2017_135_Figbh_HTML.gif Penicillium funiculosum 5.0% increase in mean lifespan and inhibiting PI3K [174]
 139-85-5 3,4-Dihydro-xybenzaldehyde graphic file with name 13659_2017_135_Figbi_HTML.gif Sasa senanensis leaves 23.0% increase in mean lifespan and inhibiting the 2-oxoglutarate binding sites of prolyl 4-hydroxylase [175]
With anti-aging activities in Caenorhabditis elegans
 57-91-0 β-Estradiol graphic file with name 13659_2017_135_Figbj_HTML.gif Hormone 7.0% increase in mean lifespan and antioxidant [176]
 1406-65-1 Chlorophyll graphic file with name 13659_2017_135_Figbk_HTML.gif Green vegetables 25.0% increase in mean lifespan and antioxidant [177]
 730-08-5 Dipeptide Tyr-Ala graphic file with name 13659_2017_135_Figbl_HTML.gif Hydrolyzed maize protein 12.4% increase in mean lifespan and antioxidant [178]
 934822-64-7 Ferulsinaic acid graphic file with name 13659_2017_135_Figbm_HTML.gif Sesquiterpene coumarins from the genus Ferula 20.0% increase in mean lifespan and antioxidant [179]
 446-72-0 Genistein graphic file with name 13659_2017_135_Figbn_HTML.gif Vigna angularis 27.9% increase in mean lifespan and antioxidant [180, 181]
Quercetin 3-O-β-d-glucopyranoside-(4 → 1)-β-d-glucopyranoside graphic file with name 13659_2017_135_Figbo_HTML.gif Onion 12.4% increase in mean lifespan and antioxidant [182]
 69-72-7 Salicylic acid graphic file with name 13659_2017_135_Figbp_HTML.gif Plant hormone 14.0% increase in mean lifespan and antioxidant [183]
 72514-90-0 Specioside graphic file with name 13659_2017_135_Figbq_HTML.gif Stereospermum suaveolens 15.5% increase in mean lifespan and antioxidant [184]
 480-18-2 Taxifolin graphic file with name 13659_2017_135_Figbr_HTML.gif Citrus fruits and onion 51.0% increase in mean lifespan and antioxidant [185]
 3081-61-6 Theanine graphic file with name 13659_2017_135_Figbs_HTML.gif Camellia sinensis ~5.0% increase in mean lifespan and antioxidant [186]
 6829-55-6 Tocotrienols graphic file with name 13659_2017_135_Figbt_HTML.gif Vitamin E members ~20.0% increase in mean lifespan and antioxidant [187]
 53188-07-1 Trolox graphic file with name 13659_2017_135_Figbu_HTML.gif Vitamin E analog 31.0% increase in mean lifespan and antioxidant [185]
 528-48-3 Fisetin graphic file with name 13659_2017_135_Figbv_HTML.gif Apples, onions and grapes and many more herbal edibles 6.0% increase in mean lifespan of thermal stress and antioxidant, regulating DAF-16 [188]
 215112-16-6 4-Hydroxy-E-globularinin graphic file with name 13659_2017_135_Figbw_HTML.gif Premna integrifolia 18.8% increase in mean lifespan and antioxidant, regulating DAF-16 [189]
 521-48-2 Iso-xanthohumol graphic file with name 13659_2017_135_Figbx_HTML.gif Humulus lupulus L. 10.2% increase in mean lifespan and antioxidant, regulating DAF-16 [190]
 520-18-3 Kaempferol graphic file with name 13659_2017_135_Figby_HTML.gif Apples, onions and grapes and many more herbal edibles 10.0% increase in mean lifespan and antioxidant,regulating DAF-16 [188]
 117-39-5 Quercetin graphic file with name 13659_2017_135_Figbz_HTML.gif Onions, apples, and broccoli as well as in red wine, tea, and extracts of Ginkgo biloba 15.0% increase in mean lifespan and antioxidant, regulating DAF-16 [191]
 50932-19-9 Verminoside graphic file with name 13659_2017_135_Figca_HTML.gif Stereospermum suaveolens 20.8% increase in mean lifespan and antioxidant, regulating DAF-16 [192]
 113558-15-9 Icariside II graphic file with name 13659_2017_135_Figcb_HTML.gif Icariin active metabolite 20.0% increase in mean lifespan and regulating IIS signaling [133]
 99-20-7 Trehalose graphic file with name 13659_2017_135_Figcc_HTML.gif Disaccharide of glucose 32.0% increase in mean lifespan and regulating IIS signaling [193]
 32911-62-9 Withanolide A graphic file with name 13659_2017_135_Figcd_HTML.gif Ayurvedic 29.7% increase in mean lifespan and regulating IIS pathway and neural activity [194]
 501-94-0 Tyrosol graphic file with name 13659_2017_135_Figce_HTML.gif Extra virgin olive oil 10.8% increase in mean lifespan and regulating IIS pathway and heat shock response [195–197]
 4339-71-3 Piceatannol graphic file with name 13659_2017_135_Figcf_HTML.gif Grapes and white tea ~18.3% increase in mean lifespan and regulating IIS pathway and SIR-2.1 [198]
 52-89-1 Cysteine graphic file with name 13659_2017_135_Figcg_HTML.gif Amino acids 16.0% increase in mean lifespan and regulating AMPK and DAF-16 [103]
 6537-80-0 Chicoric acid graphic file with name 13659_2017_135_Figch_HTML.gif Caffeoyl derivative 21.0% increase in mean lifespan and regulating AMPK [199]
 328-42-7 Oxaloacetate graphic file with name 13659_2017_135_Figci_HTML.gif Citric acid cycle metabolite 25.0% increase in mean lifespan and regulating AMPK [200]
 29700-22-9 Oxy-resveratrol graphic file with name 13659_2017_135_Figcj_HTML.gif Isomer of hydroxylated resveratrol 31.1% increase in mean lifespan and regulating calorie restriction, AMPK, and SIR-2.1 [201]
β-Dihydro-agarofuran-type sesquiterpenes graphic file with name 13659_2017_135_Figck_HTML.gif Seeds of Celastrus monospermus 38.0% increase in mean lifespan and rapamycin mimetics [202]
 13095-47-1 (R)-2-Hydro-xyglutarate graphic file with name 13659_2017_135_Figcl_HTML.gif Oncometabolite 43.0% increase in mean lifespan and inhibiting ATP synthase and mTOR signaling [203]
 13095-48-2 (S)-2-Hydroxyglutarate graphic file with name 13659_2017_135_Figcm_HTML.gif Oncometabolite 32.0% increase in mean lifespan and inhibiting ATP synthase and mTOR signaling [203]
 765-01-5 10-Hydroxy-2-decenoic acid graphic file with name 13659_2017_135_Figcn_HTML.gif Major lipid component of Royal Jelly 10.0% increase in mean lifespan and regulating dietary restriction and mTOR signaling [204]
Ascr#2 graphic file with name 13659_2017_135_Figco_HTML.gif Pheromone 14.0% increase in mean lifespan and regulating SIR-2.1 [205]
Ascr#3 graphic file with name 13659_2017_135_Figcp_HTML.gif Pheromone 14.0% increase in mean lifespan and regulating SIR-2.1 [205]
 1740-19-8 Dehydro-abietic acid graphic file with name 13659_2017_135_Figcq_HTML.gif P. densiflora, P. sylvestris, Abies grandis 15.5% increase in mean lifespan and regulating SIR-2.1 [206]
 7783-06-4 Hydrogen sulfide graphic file with name 13659_2017_135_Figcr_HTML.gif Naturally produced in animal cells 74.0% increase in mean lifespan and antioxidant, regulating SIR-2.1 [207, 208]
 932-30-9 Salicylamine graphic file with name 13659_2017_135_Figcs_HTML.gif Phenolic amines 56.0% increase in mean lifespan and regulating SIR-2.1 and ETS-7 [209]
 481-39-0 Juglone graphic file with name 13659_2017_135_Figct_HTML.gif Roots, leaves, woods and fruits of Juglandaceae walnut trees 29.0% increase in mean lifespan and regulating SIR-2.1 and DAF-16 [210]
Deutero-haemin-AlaHisThrValGluLys Peptides Porphyrin-peptide 19.1% increase in mean lifespan and regulating SIR-2.1and DAF-16 [211]
 53-84-9 Nicotinamide adenine dinucleotide graphic file with name 13659_2017_135_Figcu_HTML.gif Tricarboxylic acid cycle intermediate 15.0% increase in mean lifespan and regulating SIR-2.1 and DAF-16 [212]
 149-61-1 Malate graphic file with name 13659_2017_135_Figcv_HTML.gif Tricarboylic acid (TCA) cycle metabolite 14.0% increase in mean lifespan and regulating dietary restriction, SIR-2.1, and DAF-16 [213]
 70-47-3 Asparagine graphic file with name 13659_2017_135_Figcw_HTML.gif Amino acid 5.0% increase in mean lifespan and regulating SKN-1 [103]
 2050-87-5 Diallyl trisulfide graphic file with name 13659_2017_135_Figcx_HTML.gif Garlic 12.6% increase in mean lifespan and regulating SKN-1 [214]
 481-42-5 Plumbagin graphic file with name 13659_2017_135_Figcy_HTML.gif Plumbago zeylanica L. 15.0% increase in mean lifespan and regulating SKN-1 [215]
 77-59-8 Tomatidine graphic file with name 13659_2017_135_Figcz_HTML.gif Unripe tomato fruits, leaves and stems 7.0% increase in mean lifespan and regulating SKN-1/Nrf2 pathway, mitophagy [216]
 21593-77-1 S-Allylcysteine graphic file with name 13659_2017_135_Figda_HTML.gif Allium sativum L. 17.0% increase in mean lifespan and antioxidant, regulating SKN-1 [217]
 2281-22-3 S-Allylmercapto-cysteine graphic file with name 13659_2017_135_Figdb_HTML.gif Allium sativum L. 20.9% increase in mean lifespan and antioxidant, regulating SKN-1 [217]
 61-90-5 Leucine graphic file with name 13659_2017_135_Figdc_HTML.gif Amino acids 16.0% increase in mean lifespan and regulating SKN-1and DAF-16 [103]
 62333-08-8 Isolappaol A graphic file with name 13659_2017_135_Figdd_HTML.gif A. lappa seeds 11.0% increase in mean lifespan and regulating JNK-1 and DAF-16 [218]
 64855-00-1 Lappaol C graphic file with name 13659_2017_135_Figde_HTML.gif A. lappa seeds 12.0% increase in mean lifespan and regulating JNK-1 and DAF-16 [218]
 69394-17-8 Lappaol F graphic file with name 13659_2017_135_Figdf_HTML.gif A. lappa seeds 13.0% increase in mean lifespan and regulating JNK-1 and DAF-16 [218]
 580-72-3 Matairesinol graphic file with name 13659_2017_135_Figdg_HTML.gif Arctium lappa 25.0% increase in mean lifespan and regulating JNK-1 and DAF-16 [218]
 7770-78-7 Arctigenin graphic file with name 13659_2017_135_Figdh_HTML.gif Arctium lappa 14.0% increase in mean lifespan and antioxidant, regulating JNK-1 and DAF-16 [218]
 20362-31-6 Arctiin graphic file with name 13659_2017_135_Figdi_HTML.gif Arctium lappa 15.0% increase in mean lifespan and antioxidant, regulating JNK-1 and DAF-16 [218]
 484-68-4 Pinitol graphic file with name 13659_2017_135_Figdj_HTML.gif Fine wood, alfalfa, and legumes 13.0% increase in mean lifespan and regulating JNK, S6K, and DAF-16 [169]
 56-41-7 Alanine graphic file with name 13659_2017_135_Figdk_HTML.gif Amino acid 11.0% increase in mean lifespan and regulating AAK-2, SKN-1, and DAF-16 [103]
 56-87-1 Lysine graphic file with name 13659_2017_135_Figdl_HTML.gif Amino acids 8.0% increase in mean lifespan and regulating AAK-2, SKN-1, and DAF-16 [103]
 338-69-2 d-Alanine graphic file with name 13659_2017_135_Figdm_HTML.gif Amino acids 16.0% increase in mean lifespan and regulating AAK-2, SIR-2.1, and DAF-16 [103]
 56-85-9 Glutamine graphic file with name 13659_2017_135_Figdn_HTML.gif Amino acids 16.0% increase in mean lifespan and regulating EAT-2, AAK-2, and SKN-1 [103]
 87-44-5 β-Caryophyllene graphic file with name 13659_2017_135_Figdo_HTML.gif Edible plants 22.0% increase in mean lifespan and regulating SIR-2.1, SKN-1 and DAF-16 [219]
 60-18-4 Tyrosine graphic file with name 13659_2017_135_Figdp_HTML.gif Amino acids 10.0% increase in mean lifespan and regulating SIR-2.1, SKN-1, and DAF-16 [103]
 107-95-9 β-Alanine graphic file with name 13659_2017_135_Figdq_HTML.gif Amino acid 13.0% increase in mean lifespan and regulating AAK-2, SIR-2.1, SKN-1, and DAF-16 [103]
Acacetin 7-O-α-l-rhamnopyranosyl (1–2) β-d-xylopyranoside graphic file with name 13659_2017_135_Figdr_HTML.gif Premna integrifolia 39.0% increase in mean lifespan and regulating EAT-2, SIR-2.1, SKN-1, HSF-1, MEV-1, and DAF-16 [220]
 15502-74-6 Arsenite graphic file with name 13659_2017_135_Figds_HTML.gif Natural and anthropogenic sources (10 μM) 10.0% increase in mean lifespan, (>100 μM) 12.0% decrease and antioxidant, regulating SKN-1, MTL-2, TIN-9, and DAF-16 [221, 222]
 625-72-9 d-β-Hydroxybutyrate graphic file with name 13659_2017_135_Figdt_HTML.gif Ketone body 26.0% increase in mean lifespan and regulating AAK-2, SIR-2.1, SKN-1, and DAF-16; inhibiting histone deacetylase [223]
 71-00-1 Histidine graphic file with name 13659_2017_135_Figdu_HTML.gif Amino acids 12.0% increase in mean lifespan and regulating EAT-2, AAK-2, SIR-2.1, SKN-1, BEC-1, HIF-1, GAS-1, IFE-2, GCN-2, and DAF-16 [103]
 37159-97-0 Proline graphic file with name 13659_2017_135_Figdv_HTML.gif Amino acids 19.0% increase in mean lifespan and regulating EAT-2, AAK-2, SIR-2.1, SKN-1, BEC-1, and DAF-16 [103]
 56-45-1 Serine graphic file with name 13659_2017_135_Figdw_HTML.gif Amino acids 22.0% increase in mean lifespan and regulating EAT-2, AAK-2, SIR-2.1, SKN-1, HIF-1, BEC-1, and DAF-16 [103]
 73-22-3 Tryptophan graphic file with name 13659_2017_135_Figdx_HTML.gif Amino acids 14.0% increase in mean lifespan and regulating EAT-2, AAK-2, SIR-2.1, SKN-1, BEC-1, GCN-2, and DAF-16 [103]
 1405-87-4 Bacitracin graphic file with name 13659_2017_135_Figdy_HTML.gif Bacillus subtilisvar Tracy 59.0% increase in mean lifespan and regulating CBP-1, improving proteotoxcity [224]
 142-42-7 Fumarate graphic file with name 13659_2017_135_Figdz_HTML.gif Tricarboxylic acid (TCA) cycle metabolite 16.0% increase in mean lifespan and increasing the amount of oxidized NAD and FAD cofactors [213]
 63-68-3 Methionine graphic file with name 13659_2017_135_Figea_HTML.gif Amino acids 14.0% increase in mean lifespan and regulating mitochondrial unfolded protein response [103]
 62-75-9 N-Nitrosodimethylamine graphic file with name 13659_2017_135_Figeb_HTML.gif Ubiquitously distributed organic xenobiotic compounds 6.0% increase in mean lifespan and reducing transcription of many stress response genes [225]
 25166-14-7 2,3-Dehydrosily-bin A/B graphic file with name 13659_2017_135_Figec_HTML.gif Potential active components of silymarin 16.1% increase in mean lifespan and antioxidant, regulating FGT-1, improving proteotoxic stress [226]
 476-66-4 Ellagic acid graphic file with name 13659_2017_135_Figed_HTML.gif Strawberry and raspberry ~10.0% increase in mean lifespan and antioxidant, CR mimetics, antimicrobial [27]
 1259-86-5 Glau-carubinone graphic file with name 13659_2017_135_Figee_HTML.gif Different species of the tropical plant family Simaroubaceae ~80.0% increase in mean lifespan and promoting mitochondrial metabolism, reducing body fat [227]
 529-44-2 Myricetin graphic file with name 13659_2017_135_Figef_HTML.gif Tea, different vegetables, onions, berries, grapes and medical plants 34.3% increase in mean lifespan and regulating DAF-16; enhanced quality of life during aging [63, 228]
 106758-54-7 Otophylloside B graphic file with name 13659_2017_135_Figeg_HTML.gif Cynanchum otophyllum 11.3% increase in mean lifespan and regulating DAF-2, SIR-2.1, CLK-1, and DAF-16 [229]
 14937-32-7 Pentagalloyl glucose graphic file with name 13659_2017_135_Figeh_HTML.gif Eucalyptus leaves 18.0% increase in mean lifespan and regulating dietary restriction, IIS pathway, SIR-2.1 and mitochondrial electron transport chain [230]
 7512-17-6 N-Acetyl-glucosamine graphic file with name 13659_2017_135_Figei_HTML.gif Hexosamine Pathway Metabolite 50.0% increase in mean lifespan and enhancing autophagy, ER-associated protein degradation, and proteasomal activity [231]
Quercetin 3′-O-β-d-glucopyranoside graphic file with name 13659_2017_135_Figej_HTML.gif Onion 20.9% increase in mean lifespan and regulating DAF-2, OLD-1, OSR-1,and AEK-1 [182]
 50-70-4 Sorbitol graphic file with name 13659_2017_135_Figek_HTML.gif S. cerevisiae 35.0% increase in mean lifespan and regulating DR and osmotic response [232]
 1401-55-4 Tannic acid graphic file with name 13659_2017_135_Figel_HTML.gif Grapes and green tea 19.0% increase in mean lifespan and regulating TGF-β, p38 MAPK pathways, and DAF-12 [233, 234]
 77-92-9 Citrate graphic file with name 13659_2017_135_Figem_HTML.gif Tricarboxylic acid cycle intermediate 13.0% increase in mean lifespan and inducing ER stress response [103]
 107-35-7 Taurine graphic file with name 13659_2017_135_Figen_HTML.gif Nitrogen containing metabolites 11.0% increase in mean lifespan and inducing ER stress response [103]
 38748-32-2 Triptolide graphic file with name 13659_2017_135_Figeo_HTML.gif Tripterygium wilfordii 20.1% increase in mean lifespan and antioxidant, regulating HSP16.2 and SOD-3 [235]
 67-97-0 Vitamin D3 graphic file with name 13659_2017_135_Figep_HTML.gif Vitamins 39.0% increase in mean lifespan and regulating SKN-1, IRE-1, XBP-1, DAF-12, and proteostasis [236]
 57-88-5 Cholesterol graphic file with name 13659_2017_135_Figeq_HTML.gif Cyclo-pentanoper-hydro-phenanthrene ring Regulating cholesterol-binding protein NSBP-1and DAF-16 [237]
 949004-12-0 Dafachronic acid graphic file with name 13659_2017_135_Figer_HTML.gif Bile acid-like steroid 17.0% increase in mean lifespan and “antiaging” in the germ-line longevity pathway [238]
 145-13-1 Pregnenolone graphic file with name 13659_2017_135_Figes_HTML.gif Hormonal steroids 20.0% increase in mean lifespan and relating to germline-defective regulated longevity [239]
 1315285-41-6 Royalactin Glycoprotein Royal jelly 34.0% increase in mean lifespan and regulating EGF signaling [240]
 104594-70-9 Caffeic acid phenethyl ester graphic file with name 13659_2017_135_Figet_HTML.gif Propolis 9.0% increase in mean lifespan and regulating DAF-16 [241]
 64-17-5 Ethanol graphic file with name 13659_2017_135_Figeu_HTML.gif Metabolites Serving as a carbon and energy source and/or by inducing a stress response [242]
N-γ-(l-Glutamyl)-l-seleno-methionine graphic file with name 13659_2017_135_Figev_HTML.gif Garlic as and primary metabolic product of SeMet Antioxidant, regulating sele-noprotein TRXR-1 [243]
 74-81-7 Caprylate graphic file with name 13659_2017_135_Figew_HTML.gif Metabolites In lacking nitrogen on C. elegans: 7.0% increase in mean lifespan and needs further research [51]
 6893-26-1 d-Glutamate graphic file with name 13659_2017_135_Figex_HTML.gif Amino acids 18.0–114.0% increase in mean lifespan and needs more research [103]
 10257-28-0 Galact-opyranose graphic file with name 13659_2017_135_Figey_HTML.gif Sugars metabolites In lacking nitrogen on C. elegans: 6.0% increase in mean lifespan and needs more research [103]
 56-40-6 Glycine graphic file with name 13659_2017_135_Figez_HTML.gif Amino acids 10.0% increase in mean lifespan and needs more research [103]
 6027-13-0 Homocysteine graphic file with name 13659_2017_135_Figfa_HTML.gif Nitrogen containing metabolites 13.0% increase in mean lifespan and needs more research [103]
 87-89-8 Inositol graphic file with name 13659_2017_135_Figfb_HTML.gif Metabolites In lacking nitrogen on C. elegans: 17.0% increase in mean lifespan and needs more research [103]
 320-77-4 Isocitrate graphic file with name 13659_2017_135_Figfc_HTML.gif TCA cycle intermediate 13.0% increase in mean lifespan and needs more research [103]
 7004-09-3 Isoleucine graphic file with name 13659_2017_135_Figfd_HTML.gif Amino acids 3.0% increase in mean lifespan and needs more research [103]
 70-26-8 Ornithine graphic file with name 13659_2017_135_Figfe_HTML.gif Amino acids 8.0% increase in mean lifespan and needs more research [103]
 138-08-9 Phosphoenol-pyruvate graphic file with name 13659_2017_135_Figff_HTML.gif Metabolites In lacking nitrogen on C. elegans: 12.0% increase in mean lifespan and needs more research [103]
 98-98-6 Picolinic acid graphic file with name 13659_2017_135_Figfg_HTML.gif Endogenous metabolite of the kynurenine pathway 7.0% increase in mean lifespan and needs further research [103]
 10257-32-6 Ribopyranose graphic file with name 13659_2017_135_Figfh_HTML.gif Sugars metabolites In lacking nitrogen on C. elegans: 9.0% increase in mean lifespan and needs more research [103]
 56-14-4 Succinate graphic file with name 13659_2017_135_Figfi_HTML.gif TCA cycle intermediates 11.0% increase in mean lifespan and needs more research [103]
 72-19-5 Threonine graphic file with name 13659_2017_135_Figfj_HTML.gif Amino acids 8.0% increase in mean lifespan and needs more research [103]
 72-18-4 Valine graphic file with name 13659_2017_135_Figfk_HTML.gif Amino acids 13.0% increase in mean lifespan and needs more research [103]
 58-86-6 Xylose graphic file with name 13659_2017_135_Figfl_HTML.gif Sugars metabolites In lacking nitrogen on C. elegans: 6.0% increase in mean lifespan and needs more research [103]
With anti-aging activities in other aging models
 32619-42-4 Oleuropein graphic file with name 13659_2017_135_Figfm_HTML.gif Olea europea leaf In cell: 15.0% increase in mean lifespan; and increasing proteasome-mediated degradation rates, retaining proteasome function and Nrf2/heme oxygenase-1 pathway [244]
 84605-18-5 Cyclo-astragenol graphic file with name 13659_2017_135_Figfn_HTML.gif Astragalus membranaceus In PC12 cells and primary neurons: inducing telomerase activity and cAMP response element binding (CREB) [245]
 528-58-5 Cyanidin graphic file with name 13659_2017_135_Figfo_HTML.gif Fruits and vegetables In cell: antioxidant, decreasing expressions of nuclear factor-kappaB, cyclooxygenase-2, and nitric oxide synthase [246]
 88095-77-6 Dieckol graphic file with name 13659_2017_135_Figfp_HTML.gif Eckloina cava In radiation-induced cell damages: protecting effects on UV-B [247]
 1229519-12-3 HDTIC-1 graphic file with name 13659_2017_135_Figfq_HTML.gif Herb Astragalus membranaceus var. mongholicus In cell: antioxidant, improving proliferation, inhibiting glycation end product formation, slowing down telomere shortening rate [248, 249]
 1229519-13-4 HDTIC-2 graphic file with name 13659_2017_135_Figfr_HTML.gif Herb Astragalus membranaceus var. mongholicus In cell: antioxidant, improving proliferation, inhibiting glycation end product formation, slowing down telomere shortening rate [248, 249]
 87798-94-5 Quercetin caprylate graphic file with name 13659_2017_135_Figfs_HTML.gif Quercetin derivative In cell: antioxidant, proteasome activator [250]
 501334-35-6 Collemin A graphic file with name 13659_2017_135_Figft_HTML.gif Lichenized ascomycete Collema cristatum In cell and human skin: preventing pyrimidine dimer formation and UV-B induced erythema [251]
 87425-34-1 Nolinospiroside F graphic file with name 13659_2017_135_Figfu_HTML.gif Ophiopogon japonicus In S. cerevisiae: 23.0% increase in mean lifespan and antioxidant [252, 253]
 57103-57-8 (−)-Glyceollin I graphic file with name 13659_2017_135_Figfv_HTML.gif Soybeans In S. cerevisiae: calorie restriction mimetic [254]
 487-52-5 Butein graphic file with name 13659_2017_135_Figfw_HTML.gif Toxicodendron vernicifluum In S cerevisia: 31.0% increase in mean lifespan and regulating Sir2 [255]
 1341-23-7 Nicotinamide riboside graphic file with name 13659_2017_135_Figfx_HTML.gif NAD(+) precursor In S. cerevisiae: 20.0% increase in mean lifespan and increasing net NAD(+) synthesis and Sir2 function [252, 253]
 434-13-9 Lithocholic acid graphic file with name 13659_2017_135_Figfy_HTML.gif Major bile acids excreted by mammals In S. cerevisiae: 100.0% increase in mean lifespan and modulating housekeeping longevity assurance processes [256, 257]
 57-94-3 Curare graphic file with name 13659_2017_135_Figfz_HTML.gif Chondrodendron tomentosum, Menispermaceae or Strychnos In Asplanchna brightwelli: 34.0% increase in mean lifespan and needs further research [258]