| YPT7 | Yeast Protein Two 7 | YPT7 deletion decreases replicative lifespan by 15% in the alpha strain [18340043]. Deletion of YPT7 cancels out replicative lifespan extension of 0.5% glucose restriction and results under DR also into a shorter replicative lifespan than under AL [18690010]. | Budding yeast |
| YHC3 | Yeast Homolog of human Cln3 | YHC3 deletion decreases 10-20% shortened lifespan [16435200]. | Budding yeast |
| yata | — | yata mutation shortens the maximum lifespan by 68% and results in progressive deterioration of the nervous tissues and aberrant accumulation of Sec23 [19209226]. | Fruit fly |
| Xrcc6 | X-ray repair complementing defective repair in Chinese hamster cells 6 | XRCC5 and XRCC6 double knockout mice show decreased lifespan and signs of premature ageing without increase cancer incidence. | House mouse |
| VPS20 | Vacuolar Protein Sorting 20 | VPS20 deletion decreases mean and maximum replicative lifespan by 16% and 19%, respectively, and additionally cancels out the DR-induced replicative lifespan extension [22912585]. | Budding yeast |
| VMA2 | Vacuolar Membrane Atpase 2 | 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 [23172144]. VMA2 deletion mutation decreases the mean replicative lifespan by 80% in the alpha strain [18340043]. 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 [23172144]. | Budding yeast |
| VAM7 | VAcuolar Morphogenesis 7 | VAM7 deletion decreases replicative lifespan under AL and blocked DR-mediated lifespan extension. Replicative lifespan decreases by 70% on DR in VAM7 deletion mutant [18690010]. | Budding yeast |
| VAC14 | VACuole morphology and inheritance mutant 14 | VAC14 mutants have a single vacuole and shortened lifespan on normal media [16293764]. | Budding yeast |
| ATG16 | AuTophaGy related 16 | Under AL atg16 mutation shortens chronological, but not replicative lifespan. 0.5% glucose DR extends chronological lifespan of atg16 mutants, but amino-acid DR does not extend the short chronological lifespan of atg16 mutants (similar to several other autophagy mutants). ADE4 deletion in atg16 mutants results only in a partial extension of chronological lifespan by 0.5% glucose DR. The long chronological lifespan of tor1 mutants requires ATG16 [20421943]. | Budding yeast |
| Tsc1 | CG6147-PA Tuberous sclerosis complex genes 1 | Ubiquitously overexpression of UAS constructs (via the daughterless (da)-GAL-4 driver) containing dTSC1 extends mean lifespan at 29°C by 14% [15186745]. | Fruit fly |
| Cbs | — | Ubiquitous or neuron-specific transgenic overexpression of Cbs enhances longevity in fully-fed animals. Cbs RNAi partially abrogates increased lifespan by DR, but has no effect on fully fed animals. Cbs upregulation is required for increased lifespan under low-nutrient conditions. Response of male flies to DR is muted in comparison with females. Adult-specific ubiquitous expression of Cbs is sufficient to increase female mean and maximum lifespan by 12 - 43% and 10%, respectively. Males, whose lifespan is relatively less affected by DR, exhibite a smaller, but still significant increase in lifespan by 7% upon Cbs overexpression. Neuronal overexpression also increases lifespan, albeit modestly (approximately 12% mean and 15% maximum lifespan extension), whereas overexpression in the fat body and in the gut has no effect [21930912]. | Fruit fly |
| ubc-18 | UBiquitin Conjugating enzyme 18 | ubc-18 overexpression is unable to extend lifespan (possibly, UBC-18 is not limiting for WWP-1 function in lifespan). Loss of ubc-18 function by mutation or RNAi reduces lifespan at 25 degree Celsius, but only slightly at 20 degree Celsius. RNAi depletion of ubc-18 completely suppresses increased longevity of eat-2 mutants. RNAi depletion of ubc-18 has no effect on long lifespan of isp-1 or daf-2 mutants. Combined knockdown of wwp-1 and ubc-18 by RNAi does not shorten lifespan any further than RNAi of either single gene. Knockdown of ubc-18 suppresses extended lifespan of wwp-1 overexpression [19553937]. | Nematode |
| rut | rutabaga | Two rutabaga mutants, rut1 and rut2080, have significantly shortened lifespans [17369827]. | Fruit fly |
| Trx-2 | thioredoxin-2 | Trx-2 mutants have a 25% reduction in maximum lifespan and exhibit lower tolerance to oxidative stress while animals carrying multiple copies of Trx-2 exhibit higher tolerance [17567437]. | Fruit fly |
| IPT1 | InositolPhosphoTransferase 1 | Transposon-mediated mutation of IPT1 increases oxidative stress resistance and chronological lifespan by 40% [16527275]. IPT1 deletion decreases replicative lifespan by 30% in the alpha strain [19030232]. | Budding yeast |
| NDT80 | Non-DiTyrosine 80 | Transient overexpression of NDT80 rejuvenates old cells [21700873]. | Budding yeast |
| IME1 | Inducer of MEiosis 1 | Transient overexpression of IME1 resets the replicative lifespan of old cells back to that of young cells [21700873]. | Budding yeast |
| CDC7 | Cell Division Cycle 7 | Transient inactivation of CDC7 results in a shortened replicative lifespan [2698814]. CDC7 participates in silencing and RAS2 modulates its activity [1990268]. | Budding yeast |
| Plau | Plasminogen activator, urokinase | Transgenic mice (called alphaMUPA) overexpression Plau in many brain sites (including hypothalamus) consume (20%) less food, have a reduced body weight (by 20%) and length (by 6%), reduced temperature, and a prolonged lifespan (by 20%) [9060969].
alphaMUPA mice have reduced levels of blood sugar and smaller size and birth frequency compared to parental control [9060969] as well as a reduced body weight [10638529]. | House mouse |
| SNCA | synuclein, alpha (non A4 component of amyloid precursor) | 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) [16782295].
Mutation of SCNA (alias alpha synclein) is associated with Parkinson's disease [9197268], which is characterized with resting tremor, rigidity bradykinesia and posural instability that are associated with selective neurodegeneration of the pigmented neurons in the brain stem (substantia nigra and locus coerues) and the presence of intracytoplasmic inclusion bodies (Lewy bodies) [Yamamura et al. 1973]. The mutated protein (Ala53Thr or Ala30Pro) may misfold, aggregate and resist degradation [11433374].SNCA was found to be associated with longevity [22912757]. SNCA was not found to be associated with longevity [22912757]. | Human |
| Spargel | — | Tissue-specific overexpression of dPGC-1 in stem and progenitor cells within the digestive tract of females flies extends the mean and maximum lifespan of females by up to 33% and 37%. Those mutants display a delay in the onset of aging-related changes in the intestine, leading to improved tissue homoeostasis in old flies [22055505]. | Fruit fly |
| trx-1 | ThioRedoXin 1 | Thioredoxins regulate many cellular redox processes. trx-1 is mainly associated with neurons and is expressed in ASJ ciliated sensory neurons and to some extent also on the posterior-most internal cells. trx-1 reduces protein disulfides in the presence of a heterologous thioredoxin reductase. trx-1 null mutant display reduced mean and maximum lifespan [16387300]. Mutants with a deletion in the trx-1 gene display a decrease in lifespan and are sensitive to oxidative stress [16324156]. trx-1 overexpression extends lifespan in wild-type but not in eat-2 mutants. trx-1 deletion completely suppresses the lifespan extension caused by eat-2 mutation, but only partially suppresses that by daf-2 or osm-5 mutations. Ectopic expression of trx-1 in ASJ neurons (but not in the intestine) in trx-1 mutants rescues the lifespan-extension conferred by eat-2 mutation. trx-1 overexpression extends lifespan of wild-type but not in eat-2 mutants. trx-1 deletion almost completely suppresses lifespan extension induced by dietary deprivation (DD). DD upregulates trx-1 expression in ASJ neurons. DR activates trx-1 in ASJ neurons which in turn triggers a trx-1-dependent non-cell autonomous mechanism to extend adult lifespan [21334311].
| Nematode |
| EXO1 | exonuclease 1 | The rs1776180 C allele in the promoter of EXO1 is significantly enriched in female Germans centenarians and this can be replicated in 445 female French centenarians. The C allele leads to the loss of binding site for the basic helix-loop-helix transcription factor E47, resulting in higher EXO1 expression [19698732].EXO1 was found to be associated with longevity [19698732]. EXO1 was not found to be associated with longevity [23770741]. | Human |
| SOD1 | SuperOxide Dismutase 1 | The overexpression of Sods, mitochondrial Sod2 and cytosolic CuZnSod (Sod1), in combination delays the age-dependent reversible inactivation of mitochondrial aconitase, a superoxide-sensitive enzyme, and extends chronological lifespan by 30% [12586694]. Deletion of SOD1 decreases replicative lifespan by 40% [17460215]. Overexpression of SOD1 with CCS1 levuates the level of Cn, Zn-Sod activity and increased chronological lifespan. However overexpression of SOD1 without high cooper or simultonous overexpression of CCS1 shortened both chronological and replicative lifespan [15659212]. Overexpression of SOD1 has no effect on replicative lifespan [10224252]. Deletion of SOD1 shortens replicative lifespan by approximately 40%. The magnitude of the decrease in lifespan does not appear to dependent on oxygen concentration in the atmosphere [12020810]. Deletion of SOD1 shortens replicative lifespan [10547026]. Deletion of SOD1 shortens replicative as well as chronological lifespan [10222047].
Cells with a deletion of SOD1 exhibit a profound defect in entry into and survival during stationary phase (i.e. chronological lifespan) in the W303-B strain [8647826; 10222047], which is partially suppressed by expression of human Bcl-2 [9199172].
Hypersensitivity to oxygene and significantly decreased replicative lifespan of SOD1 deletion can be ameliorated by exogenous ascorbate. If acorbate's negative effects of auto-oxidation are prevented by exchange of medium, ascorbate prolongs mean and maximum replicative lifespan in the atmosphere of air and pure oxygene [15621721].
SOD1 deletion causes sensitivity to hyperoxia as well as methionine and lysine auxotrohies [9199172].
| Budding yeast |
| kermit | — | The disruption of kermit (alias dGIPC) function results in premature loss of locomotor activity and reduced mean lifespan [21029723]. | Fruit fly |
