| symbol | name | observation | species | | Fgf23 | Fibroblast growth factor 23 | 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]. | House mouse | | Efemp1 | Epidermal growth factor-containing fibulin-like extracellular matrix protein 1 | 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]. | House mouse | | Cav1 | caveolin, caveolae protein 1 | Knockout mice are viable and fertile but exhibit an approximately 50% reduction in lifespan probably due to a combination of pulmonary fibrosis, pulmonary hypertension, and cardiac hypertrophy [14690422]. | House mouse | | Casp2 | caspase 2 | 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]. | House mouse | | Bub1b | budding uninhibited by benzimidazoles 1 homolog, beta (S. cerevisiae) | Bub1b hypomorphic mutation decreases median lifespan by 60% (from 15 to 6 months) and such mutant mice that procude low levels of the protein are prone to aneuplody and develop many phenotypes suggestive of accelerated aging, including short lifespan, growth retardation, sarcopenia, lordokyphosis, progressive bilateral cataracts, substantial loss of sub dermal adipose tissue, spinal kyphosis, muscle atrophy, reduced dermal thickness and decreased wound healing [15208629; 17272762; 16781018; 18516091].
Moreover, there is a pronounced increase in senescent associated Beta-galactosidase expression in late generation Bub1b mutant mice, indicative of increased rate of cellular senescence. Homozyogous knockout of Bub1b results in lethality, while heterozygous animals exhibit no aging phenotypes [15208629].
Sustained high-level expression of BubR1 preserves genomic integrity and reduces tumorgenesis (even in the presence of genetic alterations that strongly promote aneuplodization and cancer, such as oncogenic Ras) and extends the lifespan and delays age-related deterioriation and aneuploidy in several tissues [23242215].
BubR1 overabundance exerts its protective effect by correcting mitotic checkpoints defects [23242215].
BubR1 expression level declines with age in various tissues [15208629; 17272762; 16781018].
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].
| House mouse | | Brca1 | Breast cancer 1 | Deletion of Brca1 causes senescence in mutant embryos and cultured cells and tumorigenesis and signs of premature aging in adults [12533509]. Brca1 heterozygous appear 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]. | House mouse | | Atr | Ataxia telangiectasia and Rad3 related | 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]. | House mouse | | Atm | Ataxia telangiectasia mutated homolog (human) | 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]. | House mouse | | Arntl | aryl hydrocarbon receptor nuclear translocator-like | Arntl knockout mice display symptoms of premature aging including a shorter lifespan, sarcopenia, cataracts, less subcutaneous fat, and organ shrinkage [16847346]. | House mouse | | Arhgap1 | Rho GTPase activating protein 1 | 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]. | House mouse | |
