| Trehalose treatment | 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]. | Mouse | — | — | — |
| Dnmt gene therapy | Injecting a virus that contains extra copies of a Dnmt into elderly mice restored their faulty memories to it oiriganal capacity of young ones. Halving the amount of Dnmt produced by younger mice, deteriotes their memory to that of non-treated older mice [http://www.medicaldaily.com/news/20120702/10573/aging-memory-dna-enzyme-forgetfulness-young-old.htm]. | Mouse | — | — | — |
| Tert re-activation | Re-activation of telomerase in a model of premature aging caused by accelerated telomere shortening (duo to telomerase deficiency) was enough to revert some age-associated phenotypes [21113150].
Mice lacking telomerase age more rapedely and died earlier, as an abundance of critically short telomeres developed. Reawakening of Tert, leads to disappearment of age-related symptoms and rejuvenation occurred in several organs including their brains [http://www.isagenixhealth.net/blog/2012/05/16/telomerase-stimulation-extends-lifespan-in-mice/]. | Mouse | — | — | — |
| Mir20a Overexpression | Overexpression of MiR-20a in mouse embryonic fibroblasts induces senescence by lowering Lrf (a transcriptional repressor of the Mdm2 inhibitor p19ARF [15662416; 9529248]) protein levels and in turn increasing p19ARF levels [18596985]. | Mouse | — | — | — |
| Lamp2a expression restoration | Maintaining the amount of the Lamp2a (in a double transgenic mice) specifically in the liver at levels found in young adults prevents age-dependent decrease in receptor abundance at the cellular and organ levels. In this mice CMA activity is maintained until advanced ages which results in preservation of the autophagic activity and is associated with lower intracellular accumulation of damaged proteins, better ability to handle protein damage and improved organ function [19115216; 18690243]. Lamp2a expression restored not only CMA but also macrophagy and proteasomal degradation to the level observed in young liver as well as youthful mitochondrial function and cellular ATP abundance and overall youthful liver functions [18776878]. | Mouse | — | — | — |
| Ctf1 knockout | Absence of Ctf1 is associated with decreased arterial fibrosis, stiffness mad senescence and increased longevity. Ctf1-null mice have a decrease in arterial stiffness and decrease in levels of inflammatory, apoptotic and senescence, whereas telomere-linked and DNA repair proteins as well as antioxidant enzyme activities are increased. The median lifespan of Ctf1-null mice is increased by 5 month (18%) [23172930].
Wild-type and Ctf1-null mice exhibit an increase of senescence markers (p53, Mdm2, p21, and p16) with age but are lower in Ctf1-null mice. Ctf1-null mice have a diminished vascular NFκB signaling, lower inflammation and oxidative stress and reduced senescence. Ctf1-null mice have a 12% increase in body weight, 130% increased adiponectin levels and 51% decreased leptin concentrations [23172930]. | Mouse | — | +18 | — |
| HNRNPD deletion | HNRNPD deletion leads to accelerated aging as evidenced by strinking telomere erosion, markedly increased DNA damage repsosne at telomere ends, pronounced cellular senescence and rapid premature aging that increases with successive generations [Pont et al., 2012]. | Mouse | — | — | — |
| Adcy5 knockout | Adcy5 knockout mice are to cardiac stress and have an increased median lifespan of 30% as well as an increased maximal lifespan of 12%. Further, they are also protected from age-related reduced bone density and susceptibility to fractures, and reduced cardiac function [17662940]. | Mouse | — | +30 | +12 |
| Prkar2b knockout | Loss of function of Prkar2b results in mice that are lean and insulin sensitive. Both median and maximum lifespan is increased by 14%. Median lifespan is increasesd (from 884 to 1005) and 80% lifespan increased from 941 to 1073 days. There is no difference either in median or 80% lifespan in female genotypes [19536287]. | Mouse | — | +0 to +14 | +0 to +14 |
| Ubiquitinous SOD1 overexpression | Ubiquitous overexpression of SOD1 does not extend lifespan in mice. Homozygous transgenic mice with two- to five-fold overexpression of SOD1 in various tissues exhibit a light reduction in lifespan. Hemizygous transgenic mice, with 1.5- to 3-fold overexpression of SOD1 display no difference in lifespan compared with nontransgenic litermate controls [10719757]. Transgenic mice with a mutant SOD1 transgene develop neuronal cytoskeletal lesions resembling the human amytrophic lateral sclerosis (ALS) phenotype [8610185]. Transgenic mice overexpressing SOD1 (and having 3.1-fold higher cellular Cu,Zn SOD activity in the brain) have reduced infarct size following experimental cerebral ischemia [1763030]. | Mouse | — | — | — |
| TXN overexpression | Overexpression of TXN1 in transgenic C57BL/6 mice resulted in extended median (35%) and maximum (22%) lifespan. Telomerase activity in spleen tissues of TXN1 overexpressing mice is higher than tha in wild-type [12230882]. | Mouse | — | +35 | +22 |
| 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 | — | — | — |
| 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 | — | — | — |
| Sirt6 knockout | Sirt6 knockout mice develop signs of premature ageing including a short lifespan [16439206].
Mice without Sirt6 have a higher risk of gastrointestinal cancers. Loss of Sirt6 increases the number, size and aggressiveness of tumors. Sirt6 loss leads to tumor formation even without activation of oncogenes. Transformed SIRT6-deficient cells exhibit increased glycolysis and tumor growth [23217706].
| Mouse | — | — | — |
| 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 overexpression | Overexpression of Sirt6 in male mice lengthens the median lifespan by 9.9-14.5% and maximum lifespan by 13.1-15.8% [22367546]. | Mouse | — | +9.9 to +14.5 | +13.1 to +15.8 |
| 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 | — | — | — |
| 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 | — | — | — |
| 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 | — | — | — |
| Atm knockout | Atm-deficient mice are viable, retarded in growth, infertile (male produce no mature sperm and female no gametes), display neurological dysfunction, and exhibit severe defects in T cell maturation while going on to develop thymomas [8917548; 8689683]. The majority of mutant mice rapidly develop thymic lymphomas and die before 4 months of age [8843194].
Cells of Atm(-/-) mice exhibit slow growth also in culture and premature senescence, telomeres are extensively shortened in multiple tissues [8689683].
Mice mutant for Atm and Terc display progressive multi-organ system compromise and features of accelerated aging [12540856]. | Mouse | — | — | — |
| Atr knockout | Deletion of Atr in young adults eliminates 80-90% of proliferating cells and results in several age-related phenotypes accompanied by a depletion of stem and progenitor cells and exhaustion of tissue renewal and homeostatic capacity [18371340].
Atr mutant mice (so called Seckle mice) exhibit high levels of replicative stress during embryogenesis, when proliferation is widespread, but this is reduced to marginal amounts in postnatal life. In spite of this decrease, adult Seckel mice display accelerated aging, which is further aggravated in the absence of p53. Seckel mice die in less than half a year, exhibit pancytopenia, cachexia and signs of premature aging, including hair graying, kyphosis, osteoporosis, accumulation of fat in the bone marrow, decreased density of hair follicles and thinner epidermis [19620979]. | Mouse | — | — | — |
| Gh antagonist overexpression | Overexpression of a growth hormone antagonist (a mutated bovine growth hormone that competes with the endogenous one) has no effect on lifespan [12933651]. | Mouse | — | — | — |
| Bax knockout | Inactivation of proapoptotic Bax extends fertile potential and minimized age-related health problems, including bone and muscle loss, excess fat deposition, alopecia, cataracts, deafness, increased anxiety, and selective attention deficit. Bax deficiency does not lead to an increase in tumor incidence. Despite the apparently increased quality of life of aging females lacing Bax, there is no significant differences in overall lifespan [17360389]. | Mouse | — | — | — |
| 30% Dietary restriction | 30% dietary restriction starting at 2 months of age increases overall, average, median and maximal lifespan. Knockout of Ghr failed to respond with lifespan extension to this regimen [16682650]. | Mouse | — | — | — |
| Brca1 deletion | Deletion of Brca1 causes senescence in mutant embryos and cultured cells and tumorigenesis and signs of premature aging in adults [12533509]. Brca1 heterozygous seem to have shortened lifespan with 70% of tumor incidence. Lymphoma, but not ovarian and mammary gland tumors, occurs commonly in these animals. After a whole-body exposure to ionizing radiation, Brca1 heterozygous mice have a 3-5-fold higher incidence to ovarian tumors, but not lymphoma, when compared with Brca1(+/+) mice [17420720]. | Mouse | — | — | — |
GenAge
GenDR
