| 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 | — | — | — |
| Melatonin supplementation | Melatonin administrated with drinking water increases anti-oxidant capacity of the brain and prolongs the mean lifespan by 20% of males but not females [11462771]. | Mouse | 0 to +20 | — | — |
| N-acetyl-serotonin administration | N-acetyl-serotonin (a melatonin precursor) administrated with drinking water increases anti-oxidant capacity of the brain and prolongs the mean lifespan by 20% of males but not females [11462771].
| Mouse | 0 to +20 | — | — |
| Fgf21 overexpression | Overexpression of Fgf-21 increases the mean lifespan by 30% for male mice and 39% for female mice [23066506].
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 [23066506]. | Mouse | +30 to +39 | — | — |
| 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 [17086191].
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 [18599363]. Even at high doses and when started in young adulthood reseveratrol supplementation does not increase lifespan on a normal diet [17578509; 20974732].
| Mouse | — | — | — |
| 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 |
| 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 | — | — | — |
| Coq7 knockout | Mice heterozygous in Coq7 live about 15 to 30% longer than controls [16195414]. | Mouse | +15 to +30 | — | — |
| 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 | — | — | — |
| 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 [18394430]. | Mouse | +30 | — | — |
| Methionine restriction | A diet with reduced methionine content extends lifespan and increases body fat [15924568]. | Mouse | — | — | — |
| Lep knockout | Lep knockout results in ob/ob mice which eats excessively and becomes profoundly obese. ob/ob mice live shorter on ad libitum, but achieve a lifespan similiar to control levels under DR, yet their precentage of body fat is much greater that that of controls [6608731]. | Mouse | — | — | — |
| Acacb knockout | Acacb-null animals (alias Acc2-/-) exhibit upon regular diet an increase triglyceride breakdown, leaner phenotype, increased insulin sensitivity and no effect on lifespan [17923673]. | 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 | — | — | — |
| 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 | — | — | — |
| Ercc2 mutation | Mutations in Ercc2 increases cancer incidence and appear to accelerate ageing. Homozyogus mutation of Ercc2 results in an extreme shortening (71%) of lifespan (mean lifespan = 7 months) relative to wild-type (mean lifespan = 24 months) [de Boer et al. 2002]. The shortened lifespan of the mutant mouse is accompanied by symptoms of premature aging including osteoporosis, early greying, cahexia, and infertility.
It provides a mouse model for the britte hair disorder trichothiodystrophy (TTD) as it phenotypes include britte hair, UV sensitivity, and developmental defects [9651581]. | Mouse | -71 | — | — |
| Trp63 knockout | Heterozygous Trp632 mutant mice have a shortened lifespan (by 21.5%) and display features of accelerated aging [16107615].
The decreased longevity in Trp63(+/-) mice is almost identical to that of Trp53(+/m) mice in which enhanced Trp53 activity provides resistance to spontaneous tumors while simultaneously accelerating aging [16107615]. Trp63(+/-) are not susceptible to spontaneous tumors [16107615]. | Mouse | -21.5 | — | — |
| Decreased Trp53 | Decreased activity of Trp53 results in increased cancer and decreased apoptosis. | 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 [11780111]. | Mouse | — | — | — |
| Top3b knockout | Homozygous disruption of Top3b results in a normal development but a shorter lifespan (by approximately 70%) accompanied by lesions in multiple organs in C57BL/6 [11331780]. | Mouse | -70 | — | — |
| 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 [10089885].
Cells from Terc(-/-) mice (G4 and upward) exhibit chromosomes lacking detectable teloemre repeats, aneuplody, and end-to-end fusions [9335332]. | Mouse | — | -26 | — |
| 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 [19776219]. | 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 [7493016]. 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 [8790408]. 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 [9462746]. | 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 [19633237]. | Mouse | — | — | — |
| 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 [16054100].
Sirt1-null mice do not exhibit lifespan extension upon Dietary Restriction [18335035]. | Mouse | — | — | — |
GenAge
GenDR
