| Eleutherococcus senticosus treatment | 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]. | Worm | +10 to +20 | — | — |
| Ganodermasides A treatment | Application of Ganodermasides A extends the replicative lifespan in K6001 strain by regulating UTH1 expression [20093034]. | Yeast | — | — | — |
| Ganodermasides B treatment | Application of Ganodermasides B extends the replicative lifespan in K6001 strain by regulating UTH1 expression [20093034]. | Yeast | — | — | — |
| Ganodermasides C treatment | Application of gonadermasides C significantly increases the replicative lifespan in the K6001 strain by regulating UTH1 [21512225]. | Yeast | — | — | — |
| GGTI-298 treatment | Treatment with type 1 geranylgeranyl transferase inhibitor GGTI-298 increases lifespan [22737247]. | Fly | — | — | — |
| Gonadermasides D treatment | Application of gonadermasides D significantly increases the replicative lifespan in the K6001 strain by regulating UTH1 [21512225]. | Yeast | — | — | — |
| Hesperidin treatment | 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]. | Yeast | — | — | — |
| Icariin treatment | Icariin and its derivate icariside II extend lifespan. Animals treated with icariin have high levels of icariside II [22216122]. | Worm | — | — | — |
| Icariside II treatment | 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]. | Worm | — | — | — |
| 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]. | Worm | — | — | — |
| L-proline supplementation | L-proline supplementation increases lifespan by 5.8 and 13.6% (mean and maximum lifespan) [22482728]. | Worm | +6 | — | +14 |
| L744832 treatment | Farnesyl inhibitor L744832 increases lifespan [22737247]. | Fly | — | — | — |
| LA treatment | LA confers a memory effect, by fixing the lifespan of previous feeding regimen. When animals are switched early in life (12 months) from DR to AL and supplemented with α-lipoic acid the DR typical lifespan extension is maintained, but switching early from AL supplemented with α-lipoic acid to DR blocks the lifespan extending effect [18486188].
LA exhibits the ability to compensate for age-related, long-term memory deficits in old rats [8309958].
| Rat | — | — | — |
| LY294002 treatment | 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 [20017609]. | Fly | — | +14 | +16 to +22 |
| Melatonin supplementation | Melatonin administrated with drinking water increases anti-oxidant capacity of the brain and prolongs the mean lifespan by 20% of males but not females [11462771]. | Mouse | 0 to +20 | — | — |
| Metformin treatment | 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]. | Worm | — | — | — |
| Metformin treatment | In fruit fly feeding metformin to adult s 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].
| Fly | — | — | — |
| Metformin treatment | 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]. | Mouse | — | — | — |
| Metformin treatment | 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]. | Rat | — | — | — |
| Mianserin Treatment | Mianserin a serotonin receptor antagonist (used as antidepressant in humans), can increase C. elegans lifespan when given only during adulthood. Lifespan extension is reduced or abolished by mutations that affect serontonin synthesis or serotonin reuptakte at synapses [14,16]. It requires a serontonin receptor and an octopamine receptor which are both inhibited by Mianserin. Mianserin plus DR increase lifespan only by 4% more than DR alone and totally failed to extend lifepan in eat-2(ad1116) mutants. However, mianserin does not appear to reduce food intake [14]. On average, mianserin increases lifespan by 31% by an optimal dose of 50 micromolar, but had little or no effect when given at 250 micromolar. Mianserin failes to increase the lifepsna of mutants lacking serotonin synthesis enzyme TPH-1 and causes a lifespan increase of only 13% in mutant lacking serontin reuptake transporter MOD-5. Mianserin does not increase lifepan of SER-4 or SER-4 mutants. Mianserin increases lifespan by31% when given throughout adulthood, but it only result in 10% lifespan extension when it was gieven beginning at adult day 5. Mianserin also failed to increase lifespan in liquid lifespan assay and in animals grown on solid agarose plates lacking ill-defined component of commoly used agar plates (agar and Bacto peptone). Mianserin increases lifespan of animlas grown at 20 but not at 25 degree Celsius [19686215]. | Worm | — | — | — |
| Minocycline treatment | 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]. | Fly | +57.1 to +114.3 | — | +28.1 to +78.3 |
| N-acetyl-serotonin administration | N-acetyl-serotonin (a melatonin precursor) administrated with drinking water increases anti-oxidant capacity of the brain and prolongs the mean lifespan by 20% of males but not females [11462771].
| Mouse | 0 to +20 | — | — |
| NAC treatment | Treatment with 10 mM of NAC has no effect on the lifespan of wild-type, but fully abolishes the increased longevity of nuo-6 and severly limits that of isp-1. At high concentration (> 10-15 nM) NAC can be become deleteroius even on the wild-type [21151885]. | Worm | — | — | — |
| NAD supplementation | Supplementation with NAD extended lifespan and this extension was dependent on sir-2.1 and daf-16 and associated with upregulation of sod-3 [19370397]. | Worm | — | — | — |
| NAM treatment | Treatment with NAM reduces mean and maximum replicative lifespan by 28 and 37%. NAM treatment blocks the lifespan extending effect of rapamycn [20947565]. | Yeast | -28 | — | -37 |
GenAge
GenDR
