|— ||— ||— ||— ||— ||— |
|PEP4 overexpression ||— ||Yeast ||— ||— ||— |
|272N18 Treatment ||272N18 (3-(3-nitrophenyl)-11-phenyl-2,3,4,5,10,11-hexohydro-1H-dibenzo[b,e] [1,4]diazepin-1-one dihdrochloride) increases lifespan by 20%, bears a structural resemblance to certain human antidepressants that affect signalling by the neurotransmitter serotonin. ||Worm ||— ||— ||— |
|30% Dietary restriction ||30% dietary restriction starting at 2 months of age increases overall, average, median and maximal lifespan. Knockout of Ghr failed to respond with lifespan extension to this regimen . ||Mouse ||— ||— ||— |
|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 ||— ||— ||— |
|Sir2 mutation ||A decrease in Sir2 (alias dSir2) blocks the life-extending effect of caloric reduction or rpd3 mutations . Sir2 mutation does not reduce lifespan under AL . ||Fly ||— ||— ||— |
|Low calorie diet with low-sugar content ||A diet with low-calorie and low-sugar content increase the lifespan, but not resistance to acute oxiditive stress  ||Fly ||— ||— ||— |
|Methionine restriction ||A diet with reduced methionine content extends lifespan and increases body fat . ||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 . ||Fly ||— ||— ||— |
|Mnt Mutation ||A dMnt null allele results in flies with larger cells, increased weight, and decreased lifespan . ||Fly ||— ||— ||— |
|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 ||— ||— ||— |
|LAG1 deletion ||A gene deletion of LAG1 in haploid cells results in a pronounced increase (approximately 50%) in mean and in maximum replicative lifespan in the YPHDF-1A strain , but has no significant effect on lifespan in stains W303R or PSY316 (N. Bishop, G.Liszt, and L. Guarente, unpublished]. The LAG1 transcribed is preferentially expressed in young cells. LAG1 null mutant is viable and has no obvious phenotypes but shows delayed ER to Golgi transport when combined with DGT1 mutation  and is synthetical lethal with LAC1 deletion. ||Yeast ||+50 ||— ||+50 |
|High sugar low protein diet ||A high sugar low protein diet increases the lifespan, but not resistance to acute oxidative stress . ||Fly ||— ||— ||— |
|hypomoprhic hep mutation ||A hypomorphic allele of hep (hep1) laerlgy prevents lifespan extension caused by puc heterozygosity . ||Fly ||— ||— ||— |
|Hells mutation ||A hypomorphic deletion of helicase domains 3, 4 and part of 2, leads to expression of a C-terminal truncated Hells protein causing an extremely short lifespan. with 60% of homozyogous mutants dying after birth and remaining 40% surviving up to seven weeks (around 25 days) .
Hells disruption results in genomic hypomethylation, de-repression of silenced genes, and premature aging, characterized by decreased proliferation, increased replicative senescence, and altered expression of Bmi-1 and p16INK4a. Hells mutant exhibit significant hypoglycemia, low birth weight and growth retardation, and signs of premature aging such as greying hair and balding, reduced fat deposition, unstable gait, cachexia, and kyphosis . ||Mouse ||— ||— ||— |
|lin-14 loss-of-function mutation ||A loss-of-function mutation in lin-14 extends lifespan by 31% . lin-14(n719) mutation extends mean and maximum lifespan of control animals by 20 and 67%, respectively .
The life-extending effects is dependent on daf-16 and hsf-1 . Inactivation of lin-14 does not increase the lifespan of pash-1 mutants .
||Worm ||+20 to +31 ||— ||+67 |
|Resveratrol supplementation ||A maximum dose of resveratrol increases the median lifespan by 56% . ||Fish ||— ||+56 ||— |
|isp-1 mutation ||A missense mutation in isp-1 leads to low oxygen consumption, decreased sensitivity to reactive oxygen species, and increased mean (60%) and maximum (100%) lifespan. An isp-1;daf-2 double mutant has a lifespan that is longer than either single mutant, but the lifespan extension of the double mutant is not addative relative to each single mutant . ||Worm ||+60 ||— ||+100 |
|hsf-1 mutation ||A mutant allele of hsf-1 slightly decreases lifespan under AL, but cancels out the lifespan extension effect of bDR. hsf-1 RNAi also prevents lifespan extension by bDR. Glucose or glycerol does not shorten the lifespan of hsf-1 mutants. Glucose treatment completely suppresses the long lifespan caused by hsf-1 overexpression . sDR extends the lifespan of hsf-1 mutant with a premature stop codon, that eliminates activation domain, and that of wild-type to a similar extent . ||Worm ||— ||— ||— |
|nrh-49 mutation ||A mutant allele, nhr(nr2041) results in a short lifespan. nhr-49 mutant animals accumulate fat, due to decreased expression of enzymes involved in fatty acid beta-oxidation . ||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 ||— ||— |
|wrn-1 mutation ||A nonfunctional wrn-1 DNA helicase decreases the lifespan .
The expression of miR-124 in whole wrn-1 mutant worms is significantly reduced .
Supplementation of vitamin C normalizes the median lifespan of wnr-1 and mir-124 mutants . ||Worm ||— ||— ||— |
|Cisd2 overexpression ||A persistent level of Cisd2 achieved by transgenic expression extends mean, median and maximum lifespan without any apparent deleterious side effects . ||Mouse ||— ||— ||— |