| SIR2RP1 | NAD-dependent SIR2 | Overexpression of SIR2RP1 results in a significant increase in survival of the vertebrate stage under normla axenic culture conditions, but has no effect on survival of the insect stage of the parasite. SIR2RP1 is mainly localized within the cytoplasm [12383511]. | — |
| MSRA | methionine sulfoxide reductase A | 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 [11867705]. | — |
| lyz | lysozyme | Overexpression of lyz increases mean, median, and maximum lifespan by 26, 30 and 44% [22737090]. | — |
| sod1 | sod1 superoxide dismutase 1, soluble | Overexpression of sod1 in C. elegans increases mean, median, and maximum lifespan by 21, 25, and 29% [22737090]. | — |
| ucp2 | uncoupling protein 2 | Overexpression of zebrafish's ucp2 in nematode increases mean, median, and maximum lifespan by 42, 40, and 26%, which is non-additive with sDR [22737090]. | — |
| SAG12 | — | Introduction of a SAG12 via bacterial gene transfer (pSAG12:ipt) increases longevity. The gene results in enhanced production of the hormone Cytokinin which affects growth and development as well as stimulates cell division and thereby extends the lifespan. pSAG::ipt transgenic plants exhibit delayed leaf senescence, increased branching and reduced internodal length. The leaves and flowers of the pSAG12:ipt plants are reduced in size and display a more intense coloration [http://www.wissenschaft.de/wissenschaft/news/316062.html; http://www.biomedcentral.com/1471-2229/12/156/abstract; Garcia-Sogo et al. 2012]. | — |
| wis1 | — | Constitutive active mutation of wis1 extends chronological lifespan and there is no further beneficial effect of DR [20075862]. | Fission yeast |
| ATG7 | Autophagy-related protein and dual specificity member of the E1 family of ubiquitin-activating enzymes; mediates the conjugation of Atg12p with Atg5p and Atg8p with phosphatidylethanolamine, required steps in autophagosome formation | ATG7 deletion reduces chronological lifespan by 70% [19302372]. | Budding yeast |
| BCY1 | Bypass of CYclase mutations | Disruption in BCY1 by mutation results decreases mean and maximum replicative lifespan by 37 and 16% and is associated with increased PKA activity [8195187]. | Budding yeast |
| CCR4 | Carbon Catabolite Repression 4 | Deletion of CCR4 increases mean chronological lifespan by 20 - 41% (20, 33, 41) in diploid cells [21447998]. In W303R CCR4 deletion shortens replicative lifespan by approximately 80% and results in temperature sensitivity that is suppressed by SSD1-V. SSD1-V partially suppresses the short-lifespan of ccr4 mutant. CCR4 mutation is synthetically lethal in combination with deletion of MPT5 in the absence of SSD1-V [11805047]. | 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 |
| COQ3 | COenzyme Q 3 | Deletion of COQ3 decreases chronological lifespan and renders cells respiratory deficient and sensitive to hydrogen peroxide [12586694]. | Budding yeast |
| CTF4 | Chromatin-associated protein, required for sister chromatid cohesion; interacts with DNA polymerase alpha (Pol1p) and may link DNA synthesis to sister chromatid cohesion | Deletion of CTF4 results in an approximately 75% reduced mean replicative lifespan [12024027]. | Budding yeast |
| DNA2 | DNA synthesis defective 2 | Mutants in DNA2 exhibit an accelerated ageing phenotype including extended cell cycle time, age-related transcriptional silencing defects, and nucleolar reorganization, which are all phenotypes of old wild-type cells. Lifespan of DNA2 mutants is extended by expression of an additional copy of SIR2 or by deletion of FOB1 and therefore the lifespan shortening partially suppressed. Three different alleles of DNA2 (dna2-1, dna2-2, and dna2-20) result in a significant shortened lifespan up to 85%. DNA2 mutation shorten the already short lifespan of SGS1 mutants [12024027]. | Budding yeast |
| GPD1 | Glycerol-3-Phosphate Dehydrogenase 1 | GPD1 deletion shortens replicative lifespan by 25% and prevents lifespan extension by high osmolarity [12391171]. Transcripational regulation of GPD1 by osmotic stress requires HOG1 [8196651]. | Budding yeast |
| HAP5 | Heme Activator Protein 5 | Deletion of HAP5 shortens replicative lifespan by approximately 40%. This is not a premature aging phenotype as "old" HAP5 cells do not become premature sterile or exhibit other biomarkers of yeast aging [9271578]. HAP5 null mutants are unable to grow on a non-fermentable carbon source [7828851]. | Budding yeast |
| YKU80 | Subunit of the telomeric Ku complex (Yku70p-Yku80p) | Deletion of YKU80 significantly shortens replicative lifespan, but does not accelerate the normal aging process [10521401]. YKU80 null mutant is defective for non-homologous end-joining [8754818] and for telomere silincing [9501103; 9635192] | Budding yeast |
| YKU70 | Subunit of the telomeric Ku complex (Yku70p-Yku80p) | Deletion fo YKU70 shortens lifespan, but does not accelerate the normal aging process [10521401]. YKU70 null mutants are defective for non-homologous end-joining [8754818] and for telomeric silencing [9635192]. | Budding yeast |
| HSC80 | — | Deletion of HSC82 has no effect on replicative lifespan, but shortens chronological lifespan [11361336]. | Budding yeast |
| HSP104 | Heat shock protein that cooperates with Ydj1p (Hsp40) and Ssa1p (Hsp70) to refold and reactivate previously denatured, aggregated proteins; responsive to stresses including: heat, ethanol, and sodium arsenite; involved in [PSI+] propagation | Deletion of HSP104 leads to a 14% [9851879] to 40% [17908928] reduction in mean replicative lifespan, therfore it is required for required for longevity. Overexpression of HSP104 driven by GAL promoter is insufficient to extend replicative lifespan [9851879]. Overproduction of HSP104 in wild-type cells has no effect on replicative life span, but suppresses the reduced lifespan of Sir2-deficient cells [17908928]. Exposure of cells to transient sub-lethal heat-stress extends mean lifespan by 12% while decreasing maximum lifespan by 14%. This effect does not occur in an HSP104 null mutant [9851879]. HSP104 null mutant is viable but displays reduced high temperature survival and its overproduction is sufficient to induce thermotolerance [8643570]. | Budding yeast |
| LAG2 | Protein involved in determination of longevity | Deletion of LAG2 in haploid SP1 strain does not affect growth, but results in a 50% decrease in the mean and maximum replicative lifespan. When LAG2 is overexpressed, the mean and maximum replicative lifespan is extended by about 36% and 54%, respectively. Overexpression induced at generation 12 similarly increases replicative lifespan [8760941]. | Budding yeast |
| NCA3 | Nuclear Control of ATPase 3 | Disruption in NCA3 shortens mean (87% of normal), nut not maximum replicative lifespan without causing any other gross changes in cell cycle parameters of growth characteristics [8810036].
In combination with an NCA2 disruption, NCA3 disruption causes a cryosensitive phenotype on non-fermentable carbon sources due to a defect in the F1-F0 ATP synthetase due to misbalancing of alternate spliceforms of mitochondrial mRNA encoding subunits 6 and 8 of the synthase [7586026]. | Budding yeast |
| PDE2 | High-affinity cyclic AMP phosphodiesterase, component of the cAMP-dependent protein kinase signaling system, protects the cell from extracellular cAMP, contains readthrough motif surrounding termination codon | Deletion of PDE2 decreases mean replicative lifespan by 26% [11000115] and also results in a shorter chronological lifespan [21076178]. PDE2 null mutant are sentive to oxidative stress [10394911].
PDE2 null mutant are sensitive to oxidative stress [10394911]. | Budding yeast |
| PHB1 | ProHiBitin 1 | Deletion of PHB1 results in a slight reduction in mean and maximum replicative lifespan and a defect in mitochondrial membrane potential. When both PHB1 and PHB2 genes are deleted, the mean replicative lifespan is reduced by one third (30%) that of the wild-type strain [9259555]. Deletion of PHB1 decreases replicative lifespan by 20% [12882345]. Phenotypic changes characteristic of aging cells (e.g. lengthening of cell cycle and specific morphological changes) suggests that PHB1;PHB2 double mutants undergo premature aging, not simply reduction of viability [9259555].
There is no reduction in stress resistance or bulk growth rate in PHB1 mutants. PHB1;PHB2 double mutant have a strong defect in mitochondrial potential, while PHB1 mutant have only a slight defect [9259555]. PHB1 deletion is synthetical lethal with mutation of outer mitochondrial membrane proteins, Mdm12, Mdm10, or Mmm1 [9632789]. | Budding yeast |
| PHB2 | Subunit of the prohibitin complex (Phb1p-Phb2p), a 1.2 MDa ring-shaped inner mitochondrial membrane chaperone that stabilizes newly synthesized proteins; determinant of replicative life span; involved in mitochondrial segregation | PHB2 deletion leads to a slight reduction in both mean and maximum replicative lifespan, and when both PHB1 and PHB2 genes are deleted, the mean replicative lifespan is reduced by 40% [9259555]. Deletion of PHB2 decreases replicative lifespan by 30% [12882345]. Phenotypic changes characteristic of aging cells (e.g. lengthening of cell cycle and specific morphological changes) suggests that PHB1;PHB2 double mutants undergo premature aging, not simply reduction of viability [9259555].
PHB2 mutants exhibit no reduction in stress resistance or bulk growth rate. PHB1;PHB2 double mutant have a strong defect in mitochondrial potential [9259555].
Prohibitin-dependent mutation pbd1 and pdb2 behave in a different manner and probaly affect different aspects of prohibitin function. pdb1 mutants slightly extended lifespan by 11%, whereas in contrast, the pdb2 mutation results in a shortening in both the mean- and the maximum-lifespan (by 28 and 17%, respectively). pdb1 mutation also reduces chronological lifespan. Reducing the expression of the PHB2 in the pbd mutants retards the rate of growth and affects replicative lifespan [16710639]. | Budding yeast |
