|dys knockout ||Loss of dys function in the heart leads to an age-dependent disruption of the myofibrillar organization within the myocardium as well as to alterations in cardiac performance. Mesodermal dys knockout results in a morderate maximum lifespan reduction (13%), but not when exclusively targeted to the heart. In contrast, half of the transheteozygous DysExel618/Dyskx43 deficiency flies die at 29 days compared to 63 days in controls. This indicates that a moderate dye loss-of-function in all muscles, but not in just the heart, reduces the normal lifespan . ||Fly ||— ||— ||-13 |
|Aut1 RNAi ||Aut1 depletion by RNAi form the first day of imaginal stage shortens lifespan by 28% on average in Drosophila and causes morphological behavioural features of premature aging . ||Fly ||-28 ||— ||— |
|rho-7 knockout ||rho-7 knockout flies have severe neurological defects and a much reduced lifespan . ||Fly ||— ||— ||— |
|Mnt Mutation ||A dMnt null allele results in flies with larger cells, increased weight, and decreased lifespan . ||Fly ||— ||— ||— |
|GCN4 Deletion ||Deletion of GCN4 increases the replicative lifespan by 10% in the alpha strain .
GCN4 deletion decreases the lifespan in the alpha and a strain .
The chronological lifespan of GCN4 deletion is strongly decreased in the a strain . ||Yeast ||+10 ||— ||— |
|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 . ||Mouse ||-7 to -9.7 ||— ||— |
|Fxn disruption ||Disruption results in reduced lifespan, increased oxidative stress, impaired respiration, and the development of hepatic tumors . ||— ||— ||— ||— |
|Foxm1 deletion ||Deletion of Foxm1 causes age-related deterioration in liver regeneration . ||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 .
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 . ||Mouse ||— ||— ||— |
|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 . ||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 .
The p21(-/-) strains like the Cdkn1a(tmi/Tyj) exhibits enormous regenerative capacities as it closes ear holes similar to MRL mice [20231440; 21722344]. ||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 . ||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 .
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 . ||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 .
Cells of Atm(-/-) mice exhibit slow growth also in culture and premature senescence, telomeres are extensively shortened in multiple tissues .
Mice mutant for Atm and Terc display progressive multi-organ system compromise and features of accelerated aging . ||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 . ||Mouse ||— ||— ||— |
|Ctf1 knockout ||Absence of Ctf1 is associated with decreased arterial fibrosis, stiffness mad senescence and increased longevity. Ctf1-null mice have a decrease in arterial stiffness and decrease in levels of inflammatory, apoptotic and senescence, whereas telomere-linked and DNA repair proteins as well as antioxidant enzyme activities are increased. The median lifespan of Ctf1-null mice is increased by 5 month (18%) .
Wild-type and Ctf1-null mice exhibit an increase of senescence markers (p53, Mdm2, p21, and p16) with age but are lower in Ctf1-null mice. Ctf1-null mice have a diminished vascular NFκB signaling, lower inflammation and oxidative stress and reduced senescence. Ctf1-null mice have a 12% increase in body weight, 130% increased adiponectin levels and 51% decreased leptin concentrations . ||Mouse ||— ||+18 ||— |
|AVT1 deletion ||Deletion of AVT1 accelerates the development of age-induced mitochondrial dysfunction without effecting the kinetics of vacuolar acidity decline and prevents the suppression of mitochondrial dysfunction by VMA1 and VPH2 overexpression without affecting vacuolar acidity. AVT1 deletion decreases mean, median and maximum lifespan by 21, 22, and 12%, respectively . ||Yeast ||-20.6 ||-22.4 ||-11.8 |
|VMA2 deletion ||VMA2 deletion mutants have a reduced ΔΨ and mitochondrial morphology similar to aged cells. The restoration of the vacuolar acidity in daughter cells requires V-ATPase activity as it is eliminated in VMA2 deletion mutant cells . VMA2 deletion mutation decreases the mean replicative lifespan by 80% in the alpha strain . Deletion of VMA2 decreases mean, median and maximum replicative lifespan by 84%, 84% and 70%, respectively. DR (0.5% glucose restriction) does not extend the replicative lifespan of VMA2 and shortens it even more . ||Yeast ||-80 to -83.9 ||-84.1 ||-70.0 |
|OSH2 deletion ||Deletion of OSH2 decreases mean chronological lifespan . ||Yeast ||— ||— ||— |
|AVO2 deletion ||Deletion of AVO2 extends chronological lifespan . ||Yeast ||— ||— ||— |
|AFG3 deletion ||Deletion of the mitochondrial AAA protease AFG3 increases replicative lifespan by 20% in the alpha and a strains , but decreases chronological lifespan by 37 - 51% in diploid cells .
AFG3 deletion changes mean, median and maximum lifespan by 15 to 26% 17 to 30% and -25 to +58%, respectively.
AFG3 deletion leads to reduced cytoplasmic mRNA translation and its lifespan extension is independent of Sir2 and Hac1, but requires Gcn4. AFG3 deletion further extends the lifespan of cell deficient in both SIR2 and FOB1, but fails to extend the lifespan of dietary restricted cells or cells lacking GCN4. Gcn4 protein levels are increased in afg3 mutants. The deletion of AFG3 fails to extend the replicative lifespan in the W303AR strain. AFG3 deletion does deletion extend the replicative lifespan at 15°C. ||Yeast ||-51 to +20 ||— ||— |
|YOL092W deletion ||Deletion of YOL092W decreases mean and maximum replicative lifespan by 36 and 21%, respectively. Lifespan of YOL092Y deletion mutants is extended by 0.5% glucose restriction . ||Yeast ||-36 ||— ||-21 |
|OSH6 deletion ||OSH6 deletion does not affect lifespan under normal conditions, but it abrogates the lifespan extension by 0.5% glucose restriction [Xia et al. unpublished]. ||Yeast ||— ||— ||— |
|OSH4 deletion ||Deletion of OSH4 decreases mean replicative lifespan by 18% [Xia et al., unpublished]. ||Yeast ||— ||— ||— |