|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 ||— ||— ||— |
|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 ||— ||— ||— |
|lin-14 gain-of-function mutation ||A gain-of-function mutation in lin-14 decreases lifespan . ||Worm ||— ||— ||— |
|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 ||— ||— |
|lars-2 mutation ||A mutation that impairs mitochondrial function was associated with a longer lifespan. Mutation of lrs-2/lars-2(mg312) extends lifespan and is associated with impaired mitochondrial function. The recessive allele mg312 of lars-2 extends lifespan by 200% at 20 degree Celsius and 30% at 25 degree Celsius. Lifespan extension by mg312 was not dependent on daf-16(mgDf47). Homozygous lars-2(mg312) worms had multiple pleotropies like lower rates of growth, pumping and defecation as well as remain the size of early L4 worms and are sterile, with an arrested gonad that exhibited no germ-cell differentiation lars-2 is ubiquitously express, with prominent expression in body-wall muscle and neurons, with a mitochondrial subcellular localisation. Mitochondria of lars-2 are noticeably disorganized, swollen and sometimes fused. lars-2 animals have lower ATP content and oxygen consumption . ||Worm ||+30 to +200 ||— ||— |
|Cisd2 overexpression ||A persistent level of Cisd2 achieved by transgenic expression extends mean, median and maximum lifespan without any apparent deleterious side effects . ||Mouse ||— ||— ||— |
|hebe overexpression ||Adult-specific overexpression of hebe increases the lifespan by 5-30% and modulates late-age female fecundity. Female and male mean lifespan is up to 11% and 24% higher . ||Fly ||+5 to +30 ||— ||— |
|magu overexpression ||Adult-specific overexpression of magu increases lifespan by 5-30% and modulates late-age fecundity . ||Fly ||+5 to +30 ||— ||— |
|MSRA overexpression ||Animals engineered to overexpress bovine MSRA in the nervous system have an extended median lifespan by up to 70% (relative to parental control), increased resistance to oxidative stress, and delayed the onset of senescence-induced decline in activity levels and reproductive capacity . ||Fly ||— ||+70 ||— |
|Atg2 overexpression ||Atg2 overexpression increases average female lifespan by 28% . ||Fly ||+28 ||— ||— |
|PNC1 overexpression ||Cells with 5 copies of PNC1 have a 70% longer replicative lifespan which is cancelled out by SIR2 deletion. Overexpression of PNC1 suppresses the effect of exogenously added nicotinamide on Sir2-dependent silencing at HM loci, telomeres and rDNA loci [12736687; 14729974]. PNC1 overexpression suppresses the inhibitory effect of exogenously added NAM on silencing, lifespan, and Hst1-mediated transcriptional repression . Increased expression of PNC1 is both necessary and sufficient for replicative lifespan extension by DR and low-intensity stress. Under non-stressing conditions (2% glucose, 30 degree Celsius), a strain with additional copies of PNC1 (5XPNC1) has 70% longer replicative lifespan than the wild-type and some cells live for more than 70 divisions. Neither DR nor heat stress further increase the lifespan of the 5XPNC1 strain . ||Yeast ||+70 ||— ||— |
|SGS101 chemical induced overexpression ||Chemical induced overexpression of SAG101 causes precocious senescence in both attached and detached leaves of transgenic plants . ||— ||— ||— ||— |
|SOD2 overexpression ||Combined overexpression of SOD1 and SOD2 extends chronological lifespan by 30% in EG103 strain .
||Yeast ||— ||— ||— |
|git3 constitutive activative mutation ||Constitutive activation of the G-alpha subunit acting downstream of Git3 accelerates aging and inhibits the 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) . || ||— ||— ||— |
|wis1 constitutive active mutation ||Constitutive active mutation of wis1 extends chronological lifespan and there is no further beneficial effect of DR . || ||— ||— ||— |
|Constitutive miR-277 expression ||Constitutive miR-277 expression shortens lifespan and synthetically lethal with reduced insulin signaling, indicating that metabolic control underlies this phenotype . ||Fly ||— ||— ||— |
|CTA1 overexpression ||CTA1 overexpression partially suppresses the shortened chronological lifespan by ISC1 mutation . ||Yeast ||— ||— ||— |
|cup-4 overexpression ||cup-4 overexpession reduces oxidative stress resistance and shortens lifespan of wild-type under AL . ||Worm ||— ||— ||— |
|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 ||— ||— |
|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 ||— ||— ||— |
|Hsp22 doxycyline-regulated overexpression ||Doxycyline-regulated overexpression of Hsp22 makes animals more sensitive to heat and oxidative stress as well as reduces the mean lifespan by up to 21%, particularly at higher culture temperature .
||— ||-21 ||— ||— |
|HES1 overexpression ||Elevation of HES1 levels by an ERG6 promoter reduces mean, median and maximum replicative lifespan by 25, 18 and 29% [Geber et al., unpublished] ||Yeast ||-25 ||-18 ||-29 |
|OSH6 overexpression ||Elevation of OSH6 levels by an ERG6 promoter extends mean, median and maximum replicative lifespan by 39, 52 and 18% which is non-additive with 0.5% glucose restriction. It also extends the lifespan of NYV1 mutant [Geber et al., unpublished].
The long lifespan of Perg6-OSH6 is not further extended by deletion of TOR1 .
OSH6 overexpression decreases total cellular sterol content and reduces Lst8 protein levels. The CC domain of Osh6 is dispensable for longevity [Fusheng Tang, personal communication]. ||Yeast ||+39 ||+52 ||+18 |
|Atg8a overexpression ||Enhanced expression of Atg8a in older fly brains extends average adult lifespan by 56% and promotes resistance to oxidative stress . ||Fly ||+56 ||— ||— |