|Nudt1 Overexpression ||hMTH1-Tg mice express high levels of the hMTH1 hydrolase that degrades 8-oxoGTP and 8-oxoGTP and excludess 8-oxoguanine from both DNA and RNA.
hMTH1-overexpresing mice have significantly lower steady-state levels of 8-oxoguanine in both nuclear and mitochondrial DNA of several organs, including the brain. hMTH1 overexpression prevents the age-dependent accumulation of DNA 8-oxoguanine that occurs in the wild-type mice. These lower levels of oxidized guanines are associated with increased longevity and hMTH1-Tg animals live significantly longer than their wild-type littermates . ||Mouse ||— ||— ||— |
|Foxm1 overexpression ||Increased hepatocyte expression in 12-month-old (aged) transgenic mice of Foxm1b alone is sufficient to restore hepatocyte proliferation to levels found in 2-month-old (young) regenerating liver . ||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 .
BubR1 overabundance exerts its protective effect by correcting mitotic checkpoints defects .
BubB1 overexpression extends maximum lifespan by 20 - 41% compared to GFP-carrying control transgenic mice . ||Mouse ||— ||— ||+20 to +41.3 |
|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 . ||Mouse ||— ||— ||— |
|Fgf21 overexpression ||Overexpression of Fgf-21 increases the mean lifespan by 30% for male mice and 39% for female mice .
Mice overproducing Fgf21 are lean throughout their lives and remain lean even while eating slightly more than wild-type mice. Fgf21 overproducers tend to be smaller than wild-type mice and female mice were infertile. Although Fgf21 overproducers have significantly lower bone density than wild-type, Fgf21-abundant mice exhibit no ill effects from the reduced bone density and remain active into old age without any broken bones . ||Mouse ||+30 to +39 ||— ||— |
|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% . ||Mouse ||— ||+9.9 to +14.5 ||+13.1 to +15.8 |
|Pck1 overxpression ||Overexpression of Pck1 in skeletal muscle results in an increased number of mitochondria, markedly increase in activity, and extended lifespan by 30%. Transgenic mice ate 60% more than controls but had half the body weight and 10% of the body fat [17716967; Hakimi, Berger and Hanson, unpublished]. Pck1 overxpression leads to increased storage and utilization of fatty acids in muscle for energy purposes and mutants store up to 5-times more triglyceride in their skeletal muscle, and exhibit increased levels of physiological activity . ||Mouse ||+30 ||— ||— |
|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 . ||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 ||— ||— ||— |
|Heterozyogus Trp53 truncation mutation ||Mice heterozyogous for an allele of p53 that removes the 5' portion of the protein demonstrate decreased cancer, permature aging phenotypes, and shortened lifespan in the mixed inbred C57BL/6â129/Sv background. It has been proposed that the this allele of p53 results in increased activity/overexpression . ||Mouse ||— ||— ||— |
|Sod2 overexpression ||Two-fold overexpression of Sod2 in young (4-6 months) and old (26-28 months) throughout the life results in decreased lipid peroxidation, increased resistance against paraquat-induced oxidative stress, and decreased age-related decline in mitochondrial ATP production, without any change on lifespan or age-related pathology . ||Mouse ||— ||— ||— |
|Plau overexpression ||Transgenic mice (called alphaMUPA) overexpression Plau in many brain sites (including hypothalamus) consume (20%) less food, have a reduced body weight (by 20%) and length (by 6%), reduced temperature, and a prolonged lifespan (by 20%) .
alphaMUPA mice have reduced levels of blood sugar and smaller size and birth frequency compared to parental control  as well as a reduced body weight . ||Mouse ||+20 ||— ||— |
|Pcmt overexpression ||Overexpression of Pcmt extends lifespan by 32-39% at 29 degrees but not at 25 degrees .
The adult lifespan of animals overexpressing Pcmt is extended . ||Mouse ||0 to 39 ||— ||— |
|Overexpression of mitochondrial targeted CAT ||Overexpression of human catalase targeted to mitochondria (MCAT) extends mean and maximum lifespan by about 20% in mice. Inactivation of aconitase in heat mitochondria and mitochondrial damage is also reduced in long-lived CAT mutant mice .
The MCAT strain has a reduced severity of age-dependent arteriosclerosis and increased genomic stability, as indicated by an decrease in oxidative stress and mitochondrial deletions in heart and muscle tissues. Median and maximum lifespan in increased about 17 - 21% . ||Mouse ||+20 ||+17 to +21 ||+17 to +21 |
|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 . ||Mouse ||— ||+35 ||+22 |
|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 . Transgenic mice with a mutant SOD1 transgene develop neuronal cytoskeletal lesions resembling the human amytrophic lateral sclerosis (ALS) phenotype . 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 . ||Mouse ||— ||— ||— |
|Klotho overexpression ||Klotho overexpression leads to lifespan extension . ||Mouse ||— ||— ||— |
|GH overexpression ||Overexpression of GH is associated wtih markedly reduced lifespan and various indices of premature aging . Transgenic mice overexpressing bovine Gh1 are bigger than controls and display early onset of pathological changes in the kidneys such glomerulosis and glomerulonephritis as well as signs of premature aging such as a shortened lifespan, increased astrogliosis, shortened reproductive lifepsan and early onset of age-related changes in cognitive function, hypothalamic neurotransmitter turnover, and plasma corticosterone levels . ||Mouse ||— ||— ||— |
|Replacement of Cebpa by Cebpb ||Replacing the Cebpa gene by Cebpb increases mean lifespan by about 20% . C/ebpalpha(beta/beta) animals consume more food but weight less than controls , and have a slightly elevated body temperature (0.3-0.5 degree Celsius) . ||Mouse ||+20 ||— ||— |
|Cisd2 overexpression ||A persistent level of Cisd2 achieved by transgenic expression extends mean, median and maximum lifespan without any apparent deleterious side effects . ||Mouse ||— ||— ||— |
|Tert gene therapy ||Mice treated with an adeno-assoicated virus vector expressing TERT at the age of one lived 24% longer on average and those treated at the age of two, by 13%. Maximum lifespan of the mice treated at 1 and 2 years was also extended by and 13% and 20%, respectively. AAV9-mTERT treated mice also had improved health, delayed onset of age-related diseases (like osteoporosis and insulin resistance) as well as improved readings in ageing indicators like neuromuscular coordination .
The gene therapy consists of a single injected via tail vein and achieved a transduction efficiency of 20-50%. Already 1 month after treatment, the treated mice at both age groups had longer telomeres and a decrease in the short telomeres in multiple tissues, while the controls exhibit an increase in short telomerase. In contrast to their control littermates at 3 and 8 months post-treatment the blood of most of the AAV9-treated mice at 1 year had no decrease or exhibit even a net increase in average telomere length and had also no increase or even a marked decrease in percentage of short telomeres with time. Thus, the therapy achieved in perhipheral blood leukocytes a prevention of telomere shortening. Treated mice had lower leves of fasting insulin, improved glucose tolerance and better homeostatic model assessment. Two years old treated mice had higher IGF1 levels. Treated mice at both ages had improved memory scores. AAV9-mTERT treatment increased cyclinD1 positive cells in various tissues. Upon AAV9-mTERT treatment levels of p16 decreased in most organs (with exception of heart). The metabolic and mitochondrial decline in 2 years old mice treated was not as apparent as in controls .
||Mouse ||+13 to +24 ||— ||+13 to +20 |
|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 .
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 ||— ||— ||— |
|K5-Tert overxpression ||Overexpression of telomerase results in a high cancer incidence but also a modest mean (10%) and maximum lifespan extension accompanied by a lower incidence of some age-related degenerative diseases, in particular those related to kidney function and germline integrity . ||Mouse ||+10 ||— ||— |
|Tert overexpression ||Mice genetically modified to express telomerase lived 40% longer and do not develop cancer. Overexpression of Tert in mice engineered to be cancer-resistant by means of ehanced expression of p53, p16 and p19ARF (Sp53/Sp16/SARF/TgTERT) decreased telomere shortening with age, delayed aging and increases mean and median longevity by 40% . ||Mouse ||+40 ||+40 ||— |
|Pten overexpression ||Increasing gene dosage via homogeneous and moderate overexpression, while retaining its normal pattern of tissue expression of Pten increases mean, median and maximum lifespan in both females and males. Mean lifespan is extended by 18% (males), 11% (females) and 14% (both). Median lifespan in males, females and both increases by 12%, 16% and 12%, respectively . Transgenic Pten mice carrying the additional genomic copies of Pten are protected from cancer and present a significant extension of lifespan that is independent of their lower cancer incidence. Pten(g) mice have an increased energy expenditure and protection from metabolic pathologies . ||Mouse ||+14 ||+12 ||— |