| — | D-glucosamine | In budding yeast addition of 0.5 mg/ml D-glucosamine to the growth media suppresses the short replicative lifespan and temperature sensitive growth of mpt5 mutant, but fails to extend the lifespan of wild-type cells [11805047]. | — |
| arf-3 | ADP-Ribosylation Factor related 3 | RNA interference of arf-3 does not affect lifespan of wild-type but suppresses lifespan extension by isp-1 mutation [22829775]. | — |
| 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]. | — |
| 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]. | — |
| git3 | — | git3 encodes a G protein-coupled receptor for glucose. git3 deletion increases chronological lifespan in conditions where glucose consumption is not affected. Constitutive activation of the G-alpha subunit acting downstream of Git3 accelerates aging and inhibits the effect of DR. The anti-aging effect of DR and git3 deletion mutation is accompanied by increased respiration and lower ROS production [19266076]. | Fission yeast |
| ATG18 | — | The replicative lifespan of ATG18 deletion mutant is not shorter than that of wild-type under DR [18690010]. | Budding yeast |
| APD1 | Actin Patches Distal 1 | Although APD1 was identified as a potential long-lived mutant strain in a bar-code screen, deletion of APD1 does not significantly affect chronological lifespan under starvation/extreme DR [20657825]. | Budding yeast |
| SSN2 | Suppressor of SNf1 | Although SSN2 was identified as a potential long-lived mutant strain in a bar-code screen, deletion of SSN2 does not significantly affect chronological lifespan under starvation/extreme DR [20657825]. | Budding yeast |
| BUL1 | Binds Ubiquitin Ligase 1 | Deletion of BUL1 does non-significantly reduces mean chronological lifespan under starvation/extreme DR [20657825]. | Budding yeast |
| PAN2 | Poly(A)-binding protein-dependent poly(A) riboNuclease 2 | Deletion mutant of PAN2 live approximately as long as wild-type under starvation/extreme DR [20657825]. | 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 |
| GAL83 | GALactose metabolism 83 | Deletion of GAL83 has no effect on replicative lifespan in S228C [10921902] and general GAL83 mutants have no obvious phenotype [10990457]. | Budding yeast |
| RAD1 | RADiation sensitive 1 | Deletion of RAD1 has no effect on replicative lifespan [10207108]. | Budding yeast |
| RAD26 | RADiation sensitive 26 | Deletion of RAD26 has no effect on replicative lifespan in PSY316 [10207108]. | Budding yeast |
| RAD7 | RADiation sensitive 7 | Deletion of RAD7 has no effect on replicative lifespan in PSY316 [10207108].
Mutation in RAD7 results in decrease repair of the non-transcribed strand in rDNA [8604332]. | Budding yeast |
| SLT2 | Suppression at Low Temperature 2 | Deletion of SLT2 has no effect on replicative lifespan in W303 strain [12640455].
SLT2 deletion increases rDNA silencing and rDNA recombination and decreases silencing at the telomeres and HM loci [Ray et al., 2003] as well as results in decreased phosphorylation of Sir3 [12640455]. | Budding yeast |
| CPR7 | Cyclosporin-sensitive Proline Rotamase 7 | Deletion of CPR7 has no effect on lifespan replicative lifespan, but increases chronological lifespan [11361336] | Budding yeast |
| DNL4 | DNA Ligase 4 | DNL4 deletion does not affect lifespan [10521401], although it renders cells defective for non-homologous end-joining [9242411] | Budding yeast |
| TAD1 | tRNA-specific Adenosine Deaminase 1 | Deletion of TAD1 does non-significantly increase the mean replicative lifespan by 14% [20550517]. | Budding yeast |
| FCY1 | FluoroCYtosine resistance 1 | Deletion of FCY1 does non-significantly decrease mean and maximum replicative lifespan by 4% and 8%, respectively [20550517]. | Budding yeast |
| SML1 | Suppressor of Mec1 Lethality 1 | Deletion of SML1 increases non-significantly mean replicative lifespan by 3% and non-significantly maximum lifespan by 16% [20550517]. | Budding yeast |
| TPS2 | Trehalose-6-phosphate PhoSphatase 2 | Deletion of TPS2 has no effect on replicative lifespan and does not prevent lifespan extension by high osmolarity [12391171].
TPS2 is required for trehalose biosynthesis in response to osmotic stress [8444170]. | Budding yeast |
| MXR2 | peptide Methionine sulfoXide Reductase 2 | Deletion or overexpression of MXR2 (alias MsrB) has no effect on replicative lifespan under normal growth conditions. Simulatonous deletion of MXR2 together with MXR1 dramatically reduces replicative lifespan by 63%. Overexpression of MXR2 under DR conditions extends replicative lifespan by 120% [15141092]. | Budding yeast |
| UGA2 | Utilization of GAba 2 | Deletion of UGA2 does not affect replicative lifespan [21371425]. | Budding yeast |
| UGA4 | Utilization of GAba 4 | Deletion of UGA4 does not effect replicative lifespan [21371425]. | Budding yeast |
