|lin-14 gain-of-function mutation ||A gain-of-function mutation in lin-14 decreases lifespan . ||Worm ||— ||— ||— |
|Coq7 overexpression ||Transgenic overexpression of mouse Coq7 reverts the extended lifespan of clk-1 mutants . ||Worm ||— ||— ||— |
|aak-2 constitutive active mutation ||A constitutive active mutation of aak-2 is sufficient to cause increase stress resistance as well as to significantly extend lifespan. Both increased stress resistance and extended lifespan is reverted in daf-16 knockdown by RNAi . ||Worm ||— ||— ||— |
|Overexpression of constitutive nuclear DAF-16 ||Overexpression of constitutive nuclear forms of DAF-16 increases lifespan only slightly . ||Worm ||— ||— ||— |
|TSA1 activating mutation ||A gain-of-function allele of peroxiredoxin (thioredoxin peroxidase, Tsa1) causes a dominant oxidative stress-resistance and robust premature aging phenotype with reduced mean lifespan. These effect is not provoked by altered Tsa1 levels, nor can it be stimulated by deletion, haploinssufficiency or overexpression of wild-type allele . ||Yeast ||— ||— ||— |
|wis1 constitutive active mutation ||Constitutive active mutation of wis1 extends chronological lifespan and there is no further beneficial effect of DR . || ||— ||— ||— |
|gpa2 constitutive active mutation ||Constitutive active mutation of gpa2 (alias git8) decreases chronological lifespan under AL (2% glucose) and almost completely cancels out the lifespan extending effect of DR (0.2% glucose) . || ||— ||— ||— |
|git3 constitutive activative mutation ||Constitutive activation of the G-alpha subunit acting downstream of Git3 accelerates aging and inhibits the effect of DR . || ||— ||— ||— |
|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 . ||Mouse ||— ||— ||— |
|CKIepsilon mutation ||A mutation in CKIepsilon called tau, if homozygous, shortens the circadian period (by 20%), increases metabolic rate (by 20%), and increases lifespan by 14-16% under conditions of constant darkness .
Male and female wild-type hamsters are heavier than homozygous mutants throughout the entire lifespan, and heterozygous mutants have intermediate weight . ||Hamster ||+14 to +16 ||— ||— |
|SIR3 activating mutation ||The S755A allele of SIR3 (which prevents phosphorylation of Sir3) results in a 40% increase in mean and maximum lifespan . ||Yeast ||+40 ||— ||+40 |
|RPL31A deletion ||Deletion of RPL31A increases mean replicative lifespan by 45% . Mean replicative lifespan increases by 35% in the alpha strain and 50% in a strain [19030232; 18423200]. Mean replicative lifespan of the RPL31A deletion mutant increases by 35% in the ORF collection and by 29% in the remade strain . RPL31A deletion increases significantly replicative lifespan . Deletion of RPL31A extends replicative lifespan and is not further extended by 0.05% glucose restriction . ||Yeast ||+29 to +50 ||— ||— |
|Activating let-60 mutation ||The let-60(n1046gf) activating mutation greatly reduces lifespan of wild-type, weakly suppresses constitutive dauer diapause in daf-2 and age-1 mutants and extends lifespan induced by mutation of daf-2 . ||Worm ||— ||— ||— |
|LMNA mutation ||Dominant mutation in LMNA (lamin A/C) gene cause Hutchinson-Gilford progeria syndrome (HGPS) which is rare and characterized by prematurly senile appearing skin and hair, with death from coronary artery disease often by age 10 [Gilford 1904; Hutchinson 1886; OMIM]. The median age of death in HGPS individuals is 13.4 years. A C to T transition at nucleotide 1824 is associated with HGPS [Sandra-Giovannoli et al., 2003; Eriksson et al., 2003]. The 1824C-T allele appears to act in a dominant negative manner by interfering with normal splicing, resulting in production of both the normal transcript and a transcript deleted for 150 bp at the 3' end [Sandre-Giovannoli et al, 2003]. Cultured skin fibroblasts from individuals with progeria exhibit an increased fraction of hat-labile proteins .
Gilford (1904). Ateleiosis and progeria: continuous youth and premature old age. Brit Med J 2, 914-918.
Hutchinson, J. (1886). Case of congenital absence of hair, with atrophic condition of the skin and its appendages, in a boy whose mother had been almost wholly bald from alopecia areata from the age of six. Lancet 1, 923. ||Human ||— ||— ||— |
|Replacement of Cebpa by Cebpb ||Replacing the Cebpa gene by Cebpb increases mean lifespan by about 20% . C/ebpalpha(beta/beta) animals consume more food but weight less than controls , and have a slightly elevated body temperature (0.3-0.5 degree Celsius) . ||Mouse ||+20 ||— ||— |
|Constitutive active S6k overexpression ||Overexpression of a constitutively active form of S6k (alias dS6K) decreases mean lifespan by 34% at 29°C . ||Fly ||-34 ||— ||— |
|SNCA overexpression ||Transgenic lines overexpressing either human wild-type or mutant (A53T) forms of the SNCA (alpha-synclein) gene under a pan-neuronal promoter live on average about 25% longer, even in weak (m577) and strong (e1370) daf-2 mutant backgrounds, and exhibited decreased pharyngeal pumping and egg-laying. Wild-type SNCA crossed into eat-2(ad1113) does not significantly effect lifespan compared to that of the background strain. Pumping rate in wild-type SCNA and A53T SCNA overexpression mutants were less than control already at day 1 of adulthood. The attenuation of lifespan exptesion by SNCA overexpression by growing on thick bacterial lawns, suggests that DR may explain some fo the effects on lifespan. SCNA overexpression increases average lifespan by 21.3% (wild-type) and 16.3% (A53T) . ||Worm ||+26 to +34 ||— ||+19 to +31 |
|Overexpression of constitutive nuclear SKN-1 ||skn-1 transgenes that overexpress a constitutive nuclear form of SKN-1 in the intestine extend the mean lifespan by 5-21%, independently of DAF-16 . ||Worm ||+5 to +21 ||— ||— |