|Transplantation of young thymus ||Lifespan extension . ||Mouse ||— ||— ||— |
|Homozygous knock-in of proof-reading deficient Polg ||Mice with a proof-reading-deficient version of Polg display an increased amount of mtDNA mutations (by 3 to 5-fold) and signs of premature ageing including a reduced lifespan, weight loss, reduced subcutaneous fat, alopecia, kyphosis, osteoporosis, anaemia, reduced fertility, and heart enlargement. Median lifespan of homozyous Polg mutant knock-in mice is 48 months . ||Mouse ||— ||— ||— |
|Homozygous Prdx1 knockout ||Homozygous Prdx1 knockout mice have a lifespan significant shorter than +/+ and +/- littermates and develop severe haemolytic anaemia and several malignant cancers (starting at about 9 months of age)  ||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 ||— ||— ||— |
|Rgn knockout ||Survival among make animals lacking Rgn (alias SMP30) is 50% at 180 days compared to 100% among controls [N. Maruyama, unpublished data].
SMP30-/- mutant mice are indstuguishibale form their SMP30+/+ littermates in terms of development and fertilization capacity . However, -/- mice were more susceptible to liver injury after treatment with anti-FAS antibody. SMP30-/- hepatocytes cultures in vitro are more susceptible to apoptosis induced by tumor-necrosis factor (TNF-alpha) plus actinomycin D (ActD) than SMP30+/+ hepatocytes.
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|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 ||— |
|Sirt1 knockout ||Sirt1 knock-out mouse embryonic fibroblasts (MEFs) have a significant greater replicative capacity in culture. p19ARF levels are significantly reduced in Sirt1 knock-out MEFs .
Sirt1-null mice do not exhibit lifespan extension upon Dietary Restriction . ||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 ||— ||— ||— |
|Sod2 homozygous knockout ||Sod2(-/-) mice are born smaller, pale and less vigorous, and die with 7-10 days. The major problems are dilated cardiomyopathy, accumulaiton of lipid in various tissues particularly liver and skeletal muscle, and metabolic acidosis . In another strain background Sod2(-/-) mice have severe anemia, degeneration of neurons in the basal ganglia and brainstem, and progressive weakness, fatigue, and cricling behavior . Treatment of Sod(-/-) mice with superoxide dismuate/catalase mimetics (EUK-8, EUK-134, or EUK-189) partially rescues the short lifespan (mean lifespan 14-28 days) and other phenotypes . ||Mouse ||— ||— ||— |
|Sod2 heterozyogous knockout ||Life-long reduction in MnSOD activity leads to increased levels of oxidative DNA damage and increase cancer incidience, but does not appear to affect aging. Sod2(+/-) mice that have a 50% reduction in MnSOD activity in all tissues throughout the life have increased oxidative damage as evidenced by significantly elevated levels of 8-oxo-2-deoxyguanosine in nuclear DNA (in all tissues) as well as in mitochondrial DNA (in lver and brain). Increased oxidative damage to DNA is associated with a 100% increase in tumor incidience in old Sod2(+/-) mice. However, mean and maximum lifespan of Sod2(+/-) and wild-type mice is identical. Biomarkers of aging, such as catarct formation, immune response, and formation of glycooxidation products carboxylmethyl lysine and pentosidine in skin collagen changes with age to the same extent in both wild-type and Sod2(+/-) mice.
Sod2(+/-);Gpx(-/-) animals exhibit no reduction in lifespan, despite increased levels of oxidative damage and neoplasms as well as tumorgenesis . ||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 ||— ||— ||— |
|Klotho disruption ||Klotho disruption results in infertility and signs of premature ageing such as a short lifespan, arteriosclerosis, skin atrophy, osteoporosis, and emphysema. Klotho is highly expressed in brain and kidney . The circulating form of Klotho binds to a cell-surface receptor and represses intracellular signals of insulin and IGF1. Perturbing insulin and IGF1 alleviates the aging-like phenotypes in Klotho-deficient mice . kl/kl mice initially develop normally but exhibit growth retardation starting at 3-4 weeks of age. Their average lifespan is 61 days (none more than 100 days). These mice gradually become inactive, with reduced stride length, atrophic genital organs, thymus atrophy, arteriosclerosis (medial calcification and intimal thickening), ectopic calcification in arterial walls, osteroposis, skin atrophy, impaired maturation of gonadal cells, emphysema, reduced growth hormone-producing cells in the pituitary gland, slight hypercalcemia, and hyperphosphatemia . kl/kl mice have decreased insulin production and increased insulin sensitivity . ||Mouse ||— ||— ||— |
|Klotho overexpression ||Klotho overexpression leads to lifespan extension . ||Mouse ||— ||— ||— |
|Resveratrol supplementation ||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 .
Although resveratrol has a range of beneficial effects in elderly mice, it does not increase the longevity of *ad libitum* fed mice when started midlife . Even at high doses and when started in young adulthood reseveratrol supplementation does not increase lifespan on a normal diet [17578509; 20974732].
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|Terc deletion ||Telomerase null mice exhibit age-dependent telomere shortening and shortened lifespan with succeeding generations. Median lifespan is reduced by 26% in G6 Terc(-/-) mice compared to wild-type or G1-G3 Terc(-/-) (18 months vs. 24 months). G6 Tec(-/-) display hair greying, hair loss, and ulcerative skin lesions, as well as impaired response to wound healing and hematoitopitic ablation, and an increased incidence of cancer .
Cells from Terc(-/-) mice (G4 and upward) exhibit chromosomes lacking detectable teloemre repeats, aneuplody, and end-to-end fusions . ||Mouse ||— ||-26 ||— |
|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 ||— ||— ||— |
|Decreased Trp53 ||Decreased activity of Trp53 results in increased cancer and decreased apoptosis. ||Mouse ||— ||— ||— |
|p53 deletion 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 . ||Mouse ||— ||— ||— |
|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 ||— ||— ||— |
|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 ||— ||— ||— |