|Transplantation of young thymus ||Lifespan extension . ||Mouse ||— ||— ||— |
|Dietary restriction on low-fat diet ||DR under a low-fat diet increases mean and maximum lifespan by 20% and 25%, respectively . ||Mouse ||+20 ||— ||+25 |
|Dietary restriction on high-fat diet ||Dietary restriction on a high-fat diet increases both mean and maximum lifespan by 36% compared to the high-fate diet control group . ||Mouse ||+36 ||— ||+36 |
|High fat diet ||Lifelong feeding of a high-fat diet markedly reduces lifespan of mice by about 20% for both mean and maximum lifespan . ||Mouse ||-20 ||— ||-20 |
|Ghr knockout ||Ghr knockouts (the so called Laron mice) are dwarfs with significantly extended lifespan by 40-50% . Ghr-/- mice are significantly longer lived as Ghr+/+ or Ghr+/- mice (by 40-50%) in both females and males [10875265; 19370397]. 30% DR fails to affect overall survival, average or median long-lifespan of Growth hormone receptor knockout (GHRKO) mice and increased maximal lifespan only in females. Insulin sensitivity in GHRKO mutants is greater than in wild-type and is not further increased by DR . Intermittent fasting also fails to extend the long lifespan of GHRKO mice .
Lifespan of mice with a deletion in the Ghr gene live almost 5 years . In C57BL/6J this mutation increases life expectancy by 16 to 26% depending on gender  and in mice of mixed genetic background the increases amounted to 36-55% . Serum levels of GH are elevated in mutant mice  and mutants are smaller than wild-type. IGF-1 and IGFBP-3 levels are also reduced in Ghr mutant mice . The age-associated decline in memory retention is delayed in Ghr mutants . ||Mouse ||+16 to +55 ||— ||— |
|super-Trp53 ||super-p53 mice generate by integrating a transgenic copy of a large genomic segment containing an intact and complete copy of p53 have an ehanced response to DNA damage, are significantly protected from cancer and had no indication of accelerated aging . ||Mouse ||— ||— ||— |
|ectopic Trp53 overexpression ||Mutant mice with activated Trp53 display enhanced resistance to spontaneous tumours and signs of premature ageing including reduced lifespan, osteoporosis, organ atrophy and a diminished stress tolerance . ||Mouse ||— ||— ||— |
|super-Ink4a/Arf ||super-Ink4a/Arf mice carrying a transgenic copy of a large genomic segment containing an intact and complete copy of the Cdkn2a (a.k.a. Ink4a/Arf) gene are significantly protected from cancer and had no indication of accelerated aging. Cells derived from super-Ink4a/Arf mice have increased resistance to in vitro immortalization and oncogenic transformation . ||Mouse ||— ||— ||— |
|super-Ink4a/Arf/p53 ||super-Ink4a/Arf/p53 mice have a synergic protection against cancer and delayed aging [Workshop RoSyBa 2011]. ||Mouse ||— ||— ||— |
|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 ||— |
|Whole-body Sirt1 deletion in the adulthood ||Whole-body deletion of Sirt1 in the adulthood results in mice which are seemingly normal in every way. When mice were given low doses of resveratrol after Sirt1 was disabled, there were no discernible improvement in mitochondrial function or any paramenter, while mice with normal Sirt1 function given reservatrol showed dramatic increases in energy, mitochondrial biogenesis and function, AMPK activation and increased NAD+ levels in skeletal muscle. When mice lacking Sirt1 were given low doses of reserveratrol, AMPK was unaffected. When doses were significantly increased in these mice, AMPK was activated in a SIRT1-indepent manner, but still no benefit to mitochondrial function resulted . ||Mouse ||— ||— ||— |
|Rapamycin treatment ||Rapamcyin increases mouse lifespan and healthspan even when administrated late in life (20 months) .
Rapamycin enhances learning and memory in young mice and improves these faculties in old mice thereby negating the normal decline in these functions with age. Rapamycin boost levels of neurotransmitters associated with neural plasticity. Rapamycin also lowered anxiety and depressive-like behaviour at all ages from 4, 12 and 28 months. "Happy, feel-good" neurotransmitters such as serotonin, dopamine and norepinephrine are all significantly augmented in the midbrains of rapamycin treated mice [http://denigma.de/url/37].
Treatment with rapamycin increased lifespan and suppresses spontanous tumorgenesis in inbred female mice . ||Mouse ||— ||— ||— |
|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 ||— |
|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 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 ||— ||— ||— |
|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 |
|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 . ||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 . ||Mouse ||— ||+0 to +14 ||+0 to +14 |
|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 . ||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 . ||Mouse ||— ||— ||— |
|Intermittent fasting ||Intemittent fasting diet increases survivorship and improves insuli sensitivity of normal males, but fails to affect either parameter in GHRKO mice . ||Mouse ||— ||— ||— |
|Cisd2 overexpression ||A persistent level of Cisd2 achieved by transgenic expression extends mean, median and maximum lifespan without any apparent deleterious side effects . ||Mouse ||— ||— ||— |
|Cisd2 knockout ||Cisd2 knockout shortens lifespan resulting in premature aging . ||Mouse ||— ||— ||— |
|Bub1b mutation ||Bub1b mutation decreases median lifespan by 60% (from 15 to 6 months). Bub1b mutant mice develop many phenotypes suggestive of accelerated aging, including: progressive bilateral cataracts, substantial loss of sub dermal adipose tissue, spinal kyphosis, muscle atrophy, and decreased wound healing. Moreover, there is a pronounced increase in senescent associated Beta-galactosidase expression in late generation Bub1b mutant mice, indicative of increased rate of cellular senscence. Homozyogous knockout of Bub1b results in lethality, while heterozygous animals exhibit no aging phenotypes . ||Mouse ||— ||-60 ||— |