| Pro | L-proline | L-proline supplementation in nematodes increases lifespan by 5.8 and 13.6% (mean and maximum lifespan) [22482728]. | — |
| — | Phloridzin | Administration of the apple polyphenol phloridzin at doses of 3, 10, and 30 microMolar siginificantly prolongs the replicative lifespan in K6001 yeast strain (p < 0.01; p < 0.001). Phloridizin improves the viability of cells under oxidative stress (7 microMolar H2O2) in a dose-dependent manner and increases the significantly the expression of SOD1, SOD2, and SIR2 [21597195]. | — |
| — | Ganodermasides A | Application of Ganodermasides A extends the replicative lifespan of budding yeast in K6001 strain by regulating UTH1 expression [20093034]. | — |
| — | Ganodermasides B | Application of Ganodermasides B extends the replicative lifespan of budding yeast in K6001 strain by regulating UTH1 expression [20093034]. | — |
| — | 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]. | — |
| — | 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]. | — |
| 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]. | — |
| 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]. | — |
| BBE | Blueberry extract | In fruit fly, supplementation of the diet with 5 mg/mL blueberry extract significantly extends the mean lifespan by 10% and is accompanied by an up-regulation of superoxide dismutase (SOD), catalase (CAT), and Rpn11 and down-regulationg of Methuselah (MTH). Lifespan is only extended in Oregon-R wild-type but not in SOD(n108) or Cat(n1) mutant strains [22197903]. | — |
| Beau I | beauveriolide I | In budding yeast treatment with beauveriolide I (20 microgram/mL) extends chronological lifespan in BY4741 by around 50% [22790951]. | — |
| TRE | Trehalose | In nematodes treatment with trehalose starting from the young-adult stage extends the mean lifespan by over 30% without any side effects. Trehalose treatment starting even from the old-adult stage shortly thereafter retards the age-associated decline in survivorship and extends the remaining lifespan by 60%. Lifespan extension by trehalose lowers the age-independent vulnerability. Trehalose increases reproductive span and retards the age-associated decrease in pharyngeal-pumping rate and the accumulation of lipofuscin autofluorescence as well as enhances thermotolerance and reduces polyglutamine. The lifespan extending effect of trehalose is abolished in daf-2 mutants [20477758].
Trehalose is suggested to act as a stress protectant against heat, cold, desiccation, anoxia, and oxidation [20477758].
Treatment with trehalose reduces neurodegeneration in a transgenic mouse model of taupathy (human mutant P301S tau mouse. Neuronal survival is evaluated by trehalose. Trehalose induces autophagy in the brain, where the number of neurons containing tau inclusions is significantly reduced as well as the amount of insoluble tau protein and the protein levels of p62. However, trehalose fails to activate autophagy in the spinal cord, where it has no impact on the level of sarkosyl-insoluble tau. Trehalose has also no effect on the motor impairment of human mutant P301S tau transgenic mice [22689910]. | — |
| Spd | Spermidine | Administration of spermidine extends lifespan of yeast, flies and worms and human immune cells. In yeast spermidine treatment triggers deacetylation of H3 through inhibition of histone acetylatranserfases, suppresses oxidative stress and necrosis. Altered acetylation of the chromatin results in upregulation of various autophagy-related genes and triggers autophagy [19801973].
In nematodes 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). | — |
| — | Tyrosol | In nematodes treatment with tyrosol (250 microMolar) extends mean, median, and maximum, lifespan by 21, 21, and 11% [22824366]. | — |
| CS | Cynomorium songaricum | In fruit fly, the yang-tonifying herbal medicine cynomorium songaricum Repr. (CS) supplementation to the diet extends both the mean and the maximum lifespan of adult females, but insignificantly that of males. In females, maximum lifespan (determined by the 90th survival percentile) is increased by up to 11.4% with 10 mg/mL CS and 5.7% with both 20 and 30 mg/mL Cs. Mean lifespan is significantly extended by 15, 18 and 11% upon treatment with 10, 20, and 30 mg/mL CS, respectively (all P <0.001). Increased lifespan by CS is correlated with higher resistance to oxidative stress and starvation and lower lipid hydroxyperoxids levels as well as accompanied by beneficial effects, such as improved mating readiness, increased fecundity, and suppresion of age-related learning impairment in aged animals [22844336]. | — |
| — | 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]. | — |
| 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]. | — |
