| tert knockout | First-generation tert(-/-) zebrafish die prematurely with shorter telomeres. tert(-/-) fish develop degenerative phenotypes, including premature infertility, gastrointestinal atrophy, and sarcopenia. tert(-/-) mutants have impaired cell proliferation, accumulation of DNA damage markers, and a p53 response leading to early apoptosis, followed by accumulation of senescence cells. Apoptosis is primarily observed in the proliferative niche and germ cells. Cell proliferation, but not apoptosis, is rescued in tp53(-/-)tert(-/-) mutants, underscoring p53 as mediator of telomerase deficiency and consequent telomere instability [http://denigma.de/url/3p]. | Zebra | — | — | — |
| Drd4 knockout | Drd4 knockout mice, when compared with wild-type and heterozygous mice, display a 7 - 9.7% decrease in lifespan, reduced spontaneous locomotor activity, and no lifespan increase when reared in an enriched environment [23283341]. | Mouse | -7 to -9.7 | — | — |
| Fxn disruption | Disruption results in reduced lifespan, increased oxidative stress, impaired respiration, and the development of hepatic tumors [16278235]. | — | — | — | — |
| Foxm1 deletion | Deletion of Foxm1 causes age-related deterioration in liver regeneration [14647066]. | Mouse | — | — | — |
| Fgf23 knockout | Fgf23 knockouts have a short lifespan and display premature aging-like symptoms including kyphosis, muscle wasting, osteopenia, emphysema, uncoordinated movement, atherosclerosis, and atrophy of the intestinal villi, skin, thymus, and spleen [16436465].
Lack of Fgf23 activities results in extensive premature aging-like features and early mortality of Fgf-23(-/-) mice, while restoring the systemic effects of FGF-23 significantly ameliorates these phenotypes, with the resultant effect being improved growth, restored fertility, and significantly prolonged survival of double mutants [18729070]. | Mouse | — | — | — |
| ERCC1 and ERCC4 deficieny | ERCC1-ERCC4-deficient mice exhibit signs of premature aging [17183314]. | — | — | — | — |
| Efemp1 knockout | Efemp1 knockout mice exhibited an early onset of aging-associated phenotypes including a 20% shorted median lifespan and 30% shorter maximum lifespan, decreased body mass, lordokyphosis, reduced hair growth, and atrophy [17872905]. | Mouse | — | +20 | +30 |
| Cdkn1a knockout | Deletion of Cdkna1 (alias p21) prolongs the lifespan of telomerase-deficient mice with dysfunctional telomeres and improves the repopulation capacity and self-renewal of hematopoietic stem cells [17143283].
The p21(-/-) strains like the Cdkn1a(tmi/Tyj) exhibits enormous regenerative capacities as it closes ear holes similar to MRL mice [20231440; 21722344]. | Mouse | — | — | — |
| Casp-2 deficiency | Loss of caspase-2 resulted in a shortened (10%) maximum lifespan and in enhanced aging-related traits such as impaired hair growth, increased bone loss, and reduced body fat content [17188333]. | Mouse | — | — | -10 |
| Brca1 deletion | Deletion of Brca1 causes senescence in mutant embryos and cultured cells and tumorigenesis and signs of premature aging in adults [12533509]. Brca1 heterozygous seem to have shortened lifespan with 70% of tumor incidence. Lymphoma, but not ovarian and mammary gland tumors, occurs commonly in these animals. After a whole-body exposure to ionizing radiation, Brca1 heterozygous mice have a 3-5-fold higher incidence to ovarian tumors, but not lymphoma, when compared with Brca1(+/+) mice [17420720]. | Mouse | — | — | — |
| Bax knockout | Inactivation of proapoptotic Bax extends fertile potential and minimized age-related health problems, including bone and muscle loss, excess fat deposition, alopecia, cataracts, deafness, increased anxiety, and selective attention deficit. Bax deficiency does not lead to an increase in tumor incidence. Despite the apparently increased quality of life of aging females lacing Bax, there is no significant differences in overall lifespan [17360389]. | Mouse | — | — | — |
| Atr knockout | Deletion of Atr in young adults eliminates 80-90% of proliferating cells and results in several age-related phenotypes accompanied by a depletion of stem and progenitor cells and exhaustion of tissue renewal and homeostatic capacity [18371340].
Atr mutant mice (so called Seckle mice) exhibit high levels of replicative stress during embryogenesis, when proliferation is widespread, but this is reduced to marginal amounts in postnatal life. In spite of this decrease, adult Seckel mice display accelerated aging, which is further aggravated in the absence of p53. Seckel mice die in less than half a year, exhibit pancytopenia, cachexia and signs of premature aging, including hair graying, kyphosis, osteoporosis, accumulation of fat in the bone marrow, decreased density of hair follicles and thinner epidermis [19620979]. | Mouse | — | — | — |
| Atm knockout | Atm-deficient mice are viable, retarded in growth, infertile (male produce no mature sperm and female no gametes), display neurological dysfunction, and exhibit severe defects in T cell maturation while going on to develop thymomas [8917548; 8689683]. The majority of mutant mice rapidly develop thymic lymphomas and die before 4 months of age [8843194].
Cells of Atm(-/-) mice exhibit slow growth also in culture and premature senescence, telomeres are extensively shortened in multiple tissues [8689683].
Mice mutant for Atm and Terc display progressive multi-organ system compromise and features of accelerated aging [12540856]. | Mouse | — | — | — |
| Arhgap1 knockout | Most Ahrgap1 knockout mice are weak and die during the neonatal period. Animals that survived have a shorter lifespan (median lifespan is 12 months) and show premature aging-like phenotypes, including a reduction in body mass, a loss of subdermal adipose tissue, lordokyphosis, and osteoporosis [17227869]. | Mouse | — | — | — |
| Sir2 knockdown | A diet-dependent lifespan phenotype of dSir2 knockdown in the fat-body, but not in muscles, negates the effects of background genetic mutants. dSir2 knockdown abrogates fat-body dFoxo-dependent lifespan extension [23246004]. | Fly | — | — | — |
| frh-1 RNAi | Complete absence of frataxin is lethal, while its partial deficiency extends animal lifespan in a p53 dependent manner. Frataxin knockdown via RNAi extends mean and maximum lifespan by 19 and 37%, respectively [23247094].
Substantial reduction of frataxin protein expression is required to extend lifespan, affect sensory neurons functionality, remodel lipid metabolism and trigger autophagy. Beclin and p53 genes are required to induce autophagy and concurrently reduce lipid storages and extend animal lifespan in response to frataxin suppression [23247094]. | Worm | +18.75 | — | +37.037037037 |
| Bub1b mutation | The median and maximum lifespan of mice with a nonsense mutation 2211insGTTA in BubR1 is significantly reduced. BubR1(+/GTTA) mice develop several aging-related phenotypes at an accelerated rate, including catarct formation, lordokyphosis, skeletal muscle wasting, impaired exercise ability, and fat loss. Further BubR1(+/GTTA) mice develop mild anaplodies and exhibit enhanced growth of carcinogen-induced tumors [Wijshake et al. 2012]. | Mouse | — | — | — |
| Sirt6 RNAi | Decreased expression of Sirt6 by RNA interference causes lethality during development. Sirt6 silencing in neurons shortens mean lifespan by 20% [17159295]. | Fly | -20 | — | — |
| Wrn mutation | Mice lacking the helicase domain fo the WRN ortholog exhibit many phenotypic features of Werner Syndrom, including a pro-oxidant status and a shorter mean lifespan. Mice with a deletion in the helicase domain [9789047] recapitulates most of the Werner syndrome phenotypes, including an abnormal hyaluronic acid excretion, higher reactive oxygen species levels, dyslipidemia, increased genomic instability, and cancer incidence. Wrn(Dehl/Dehl) mutant mice have a 10 - 15% decrease in their mean lifespan [12707040; 19741171]. | Mouse | -10 to -15 | — | — |
| wrn-1 mutation | A nonfunctional wrn-1 DNA helicase decreases the lifespan [23075628].
The expression of miR-124 in whole wrn-1 mutant worms is significantly reduced [23075628].
Supplementation of vitamin C normalizes the median lifespan of wnr-1 and mir-124 mutants [23075628]. | Worm | — | — | — |
| wrn-1 RNAi | RNAi kockdown of wrn-1 shortens the lifespan, increases sensitivity to DNA damage, and accelerates aging phenoypes [15115755]. | Worm | — | — | — |
| mir-124 mutation | Loss of mir-124 increases reactive oxygen species formation and accumulation of the aging marker lipofuscin, reduces whole body ATP levels and results in reduction in lifespan [23075628].
Supplementation of vitamin C normalizes the reduced median lifespan of mir-124 mutants [23075628]. | Worm | — | — | — |
| mir-80 mir-227(nDf53); mir-81-82(nDf54) | mir-80 mir-227(nDf53); mir-81-82(nDf54) mutation decreases the mean lifespan by 20% [22482727]. | Worm | -20 | — | — |
| mir-64-66 mir-229(nDf63) mutation | mir-64-66 mir-229(nDf63) mutation decreases the lifespan by 30% [22482727]. | Worm | -30 | — | — |
| mir-61 mir-250(nDf59) mutation | mir-61 mir-250(nDf59) mutation decreases the mean lifespan by 25% [22482727]. | Worm | -25 | — | — |
GenAge
GenDR
