| 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 [11780111]. | Mouse | — | — | — |
| 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 | — | — |
| Ghr knockout | Ghr knockouts (the so called Laron mice) are dwarfs with significantly extended lifespan by 40-50% [12933651]. 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 [16682650]. Intermittent fasting also fails to extend the long lifespan of GHRKO mice [19747233].
Lifespan of mice with a deletion in the Ghr gene live almost 5 years [21123740]. In C57BL/6J this mutation increases life expectancy by 16 to 26% depending on gender [12933651] and in mice of mixed genetic background the increases amounted to 36-55% [9371826]. Serum levels of GH are elevated in mutant mice [9371826] and mutants are smaller than wild-type. IGF-1 and IGFBP-3 levels are also reduced in Ghr mutant mice [10875265]. The age-associated decline in memory retention is delayed in Ghr mutants [11336996]. | 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 [12426394]. | Mouse | — | — | — |
| 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 | — | — |
| 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 [11780111]. | 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 | — | — |
| 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 [15520276]. | 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 [22560220]. | Mouse | — | — | — |
| Rapamycin treatment | Rapamcyin increases mouse lifespan and healthspan even when administrated late in life (20 months) [19587680].
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 [22107964]. | Mouse | — | — | — |
| 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 | — | — | — |
| Coq7 knockout | Mice heterozygous in Coq7 live about 15 to 30% longer than controls [16195414]. | Mouse | +15 to +30 | — | — |
| 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 | — | — |
| 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 | — | — | — |
| 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 [15688016]. | 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 [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 | — | — | — |
| 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 [22585399].
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 [22585399].
| Mouse | +13 to +24 | — | +13 to +20 |
| 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 | — | — | — |
| 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 | — | — | — |
| 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 | — | — | — |
| Dietary restriction on low-fat diet | DR under a low-fat diet increases mean and maximum lifespan by 20% and 25%, respectively [22509016]. | 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 [22509016]. | 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 [22509016]. | Mouse | -20 | — | -20 |
GenAge
GenDR
