| Arhgap1 knockout | Most Ahrgap1 knockout mice are weak and die during the neonatal period. Animals that survived have a shorter lifespan (median lifespan is 12 months) and show premature aging-like phenotypes, including a reduction in body mass, a loss of subdermal adipose tissue, lordokyphosis, and osteoporosis [17227869]. | Mouse | — | — | — |
| 2-ME treatment | Animals fed a diet supplemented with 2-mercaptoethanol (2-ME) exhibit an increased mean and maximum lifespan [6334792].
T-cell-dependent immune responses are higher in the 2-ME-fed mice compared to the controls when the animals are young. The accumulation of fluorescent products of lipid peroxidation damage is also delayed in the lymphocytes of the 2-ME-fed mice and tumor onset and incidence is reduced in these animals [6334792]. | Mouse | — | — | — |
| (R)-N-(2-heptyl)-N-methylpropargylamine treatment | Addition of 0.66 ng/fly/day (R)-N-(2-heptyl)-N-methylpropargylamine to a sucrose-based diet resulted in no significant effect on lifespan, but lifespan reduction due to galactose feeding is partially suppressed by supplementation with (R)-deprenyl or (R)-N-(2-heptyl)-N-methylpropargylamine [9972869]. | Fly | — | — | — |
| Sir2 knockdown | A diet-dependent lifespan phenotype of dSir2 knockdown in the fat-body, but not in muscles, negates the effects of background genetic mutants. dSir2 knockdown abrogates fat-body dFoxo-dependent lifespan extension [23246004]. | Fly | — | — | — |
| frh-1 RNAi | Complete absence of frataxin is lethal, while its partial deficiency extends animal lifespan in a p53 dependent manner. Frataxin knockdown via RNAi extends mean and maximum lifespan by 19 and 37%, respectively [23247094].
Substantial reduction of frataxin protein expression is required to extend lifespan, affect sensory neurons functionality, remodel lipid metabolism and trigger autophagy. Beclin and p53 genes are required to induce autophagy and concurrently reduce lipid storages and extend animal lifespan in response to frataxin suppression [23247094]. | Worm | +18.75 | — | +37.037037037 |
| Bub1b mutation | The median and maximum lifespan of mice with a nonsense mutation 2211insGTTA in BubR1 is significantly reduced. BubR1(+/GTTA) mice develop several aging-related phenotypes at an accelerated rate, including catarct formation, lordokyphosis, skeletal muscle wasting, impaired exercise ability, and fat loss. Further BubR1(+/GTTA) mice develop mild anaplodies and exhibit enhanced growth of carcinogen-induced tumors [Wijshake et al. 2012]. | Mouse | — | — | — |
| Pdf overexpression | Overexpression of Pdf suppresses age-associated changes in the period and strength of free-running locomotor rhythms and amplifies TIM oscillations in many pacemaker neurons in the elder flies [23223368]. | 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 | — | — | — |
| Bub1b overexpression | Sustained high-level expression of BubR1 preserves genomic integrity and reduces tumorgenesis (even in the presence of genetic alterations that strongly promote aneuplodization and cancer, such as oncogenic Ras) and extends the lifespan and delays age-related deterioriation and aneuploidy in several tissues [23242215].
BubR1 overabundance exerts its protective effect by correcting mitotic checkpoints defects [23242215].
BubB1 overexpression extends maximum lifespan by 20 - 41% compared to GFP-carrying control transgenic mice [23242215]. | Mouse | — | — | +20 to +41.3 |
| Sirt6 RNAi | Decreased expression of Sirt6 by RNA interference causes lethality during development. Sirt6 silencing in neurons shortens mean lifespan by 20% [17159295]. | Fly | -20 | — | — |
| Diabenol treatment | In female NMRI and transgenic HER-2/neu mice supplementation of diabenol with drinking water 5 times a week since the age of 2 months, increases survival and inhibits spontaneous carcinogenesis.
In NMRI diabenol does not influence body weight gain dynamics, food and water consumption, but slowed down age-related disturbances in estrous function and increases the lifespan of all and 10% most long-living ones. Diabenol treatment in NMRI mice also inhibits spontaneous tumor incidence (mammary and lymphomas mainly) and increases mammary tumor latency. Diabenol treatment slows down age-related changes in estrous function in HER-2/neu mice, but fails to influence survival and slightly inhibited the incidence and decrease the size of mammary adenocarcinoma metastasis into the lung [15754958]. | 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 | — | — | — |
| 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 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 | 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 | — | — | — |
| Wrn mutation | Mice lacking the helicase domain fo the WRN ortholog exhibit many phenotypic features of Werner Syndrom, including a pro-oxidant status and a shorter mean lifespan. Mice with a deletion in the helicase domain [9789047] recapitulates most of the Werner syndrome phenotypes, including an abnormal hyaluronic acid excretion, higher reactive oxygen species levels, dyslipidemia, increased genomic instability, and cancer incidence. Wrn(Dehl/Dehl) mutant mice have a 10 - 15% decrease in their mean lifespan [12707040; 19741171]. | Mouse | -10 to -15 | — | — |
| wrn-1 mutation | A nonfunctional wrn-1 DNA helicase decreases the lifespan [23075628].
The expression of miR-124 in whole wrn-1 mutant worms is significantly reduced [23075628].
Supplementation of vitamin C normalizes the median lifespan of wnr-1 and mir-124 mutants [23075628]. | Worm | — | — | — |
| wrn-1 RNAi | RNAi kockdown of wrn-1 shortens the lifespan, increases sensitivity to DNA damage, and accelerates aging phenoypes [15115755]. | Worm | — | — | — |
| mir-124 mutation | Loss of mir-124 increases reactive oxygen species formation and accumulation of the aging marker lipofuscin, reduces whole body ATP levels and results in reduction in lifespan [23075628].
Supplementation of vitamin C normalizes the reduced median lifespan of mir-124 mutants [23075628]. | Worm | — | — | — |
| Carboxyfullerene SOD mimetic treatment | Administration of a small-molecule synthetic enzyme superoxide dismutase mimetic to wild-type (i.e. non-transgenicm 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]. | — | — | — | — |
| C3 treatment | Tris-malonic acid derivate of the fullerene C60 molecule (C3) increases the lifespan of Sod2(-/-) mice by 300% [15451059].
| Mouse | +300 | — | — |
| C60-olive oil treatment | 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-oil is significantly less (about twice as less) as compared to controls [22498298].
| Rat | +113.8 | +90.9 | +73.7 |
| Olive oil treatment | 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]. | Rat | +41.4 | +18.2 | +52.6 |
| mir-80 mir-227(nDf53); mir-81-82(nDf54) | mir-80 mir-227(nDf53); mir-81-82(nDf54) mutation decreases the mean lifespan by 20% [22482727]. | Worm | -20 | — | — |
| mir-64-66 mir-229(nDf63) mutation | mir-64-66 mir-229(nDf63) mutation decreases the lifespan by 30% [22482727]. | Worm | -30 | — | — |
GenAge
GenDR
