| MAPT overexpression | Expression of wild-type human MAPT (tau) moderately shortened lifespan. Expression of a mutant form of human MAPT (Arg406 Trp), associated with an early onset familial form of demetia, results in a several shortened lifespan. MAPT is implicated in the pathogenesis of Alzeimer's disease and related disorders in humans. Transgenic flies exhibit key features of the human disorders: adult onset, progressive neurodegeneration, early death, enhanced toxicity of mutant tau, accumulation of abnormal tau, and relative anatomic selectivity. However, neurodegeneration occurred without the neurofibrillary formation that is observed in humans disease and some rodent taupathy models [11408621]. | Fly | — | — | — |
| INS overexpression | Expression of human insulin under an inducible heat shock promoter increases nematode lifespan by 25% and is also able to enhance the lifespan of daf-2 mutants [11274053]. | Worm | +25 | — | — |
| ins-1 overexpression | Increased dosage of ins-1 under its own promoter as well as a heat shock promoter increases lifespan by 25% and is also able to increase the lifespan of daf-2 mutants. Overexpression of ins-1 also causes an increase in dauer formation and can enhance the dauer formation of daf-2 mutants [11274053]. | Worm | +25 | — | — |
| Klotho overexpression | Klotho overexpression leads to lifespan extension [16123266]. | Mouse | — | — | — |
| LAG2 overexpression | When LAG2 is overexpressed in SP1 strain, the mean and maximum replicative lifespan is extended by about 36% and 54%, respectively. Overexpression induced at generation 12 similarly increases replicative lifespan [8760941]. | Yeast | +36 | — | +54 |
| SIR2RP1 overexpression | Overexpression of SIR2RP1 (alias LmSIR2) 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]. | — | — | — | — |
| MORF4 overxpression | Overexpression of MORF4 reverses the immortal phenotype of immortal cell lines in complementation group B [9891081]. Cellular senescence is dominant over immortality in fused hybrids of normal and immortal human cell in culture [6879195]. Fusion of immortal cell lines with each other led to the idenetification of four complementation groups for immortality [3413074]. MORF4 rescues the immortal phenotype [9891081]. | Human | — | — | — |
| HSPA9 overexpression | Overexpression of HSPA9 (mortalin) increases the proliferation potential of normal fibroblasts [11959102]. Transfection of normal human fibroblasts with human HSPA9 (or the murine Hspa9) overexpression vectors led to an increase in the number of population doublings the cells could sustain before senescing (increase varying from 32-60%, depending on the exact construct used). Transfected cells retain a youthful morphology longer than the controls cells, and there is an dealy in appearance of senescence associated beta-galactosidase activity [10838077]. Mot-2 overexpressing cells exhibit a reduction in p53 transcriptional activation (as measured by expression from vectors containing either luciferase or beta-glactosidase driven by p53 binding sites) [10838077], which might partially or wholly explain the effects of Mot-2 on proliferative potential. HSPA9 is differentially distributed and/or translated in normal vs. transformed cells [8454632]. | Human | — | — | — |
| MPT5 overexpression | Overexpression of MPT5 from the ADH promoter extends replicative lifespan by about 20% in W303R [11805047] and by 25% in PSY142 [9150138].
MPT5 overexpression suppresses the temperature phenotype of POP2 mutant [9504907]. | Yeast | +20 to +25 | — | — |
| Npy overexpression | Overexpression of Npy under the control of its own promoter results in increased mean and maximum lifespan. However the observed lifespan extension is relatively small (p = 0.0059 by Wilcoxin test and p = 0.05 by t-test; n = 20) [12668588].
The blood pressure of Npy transgenic rats was significantly lower as compared with nontransgenic siblings. Food intake and weight were not significantly different compared to controls [12668588]. | Rat | — | — | — |
| Plau overexpression | 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]. | Mouse | +20 | — | — |
| 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 [14729974]. 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 [12736687]. | Yeast | +70 | — | — |
| RAS1 overxpression | No lifespan extension results from overexpression of RAS1 (in SP1) [8034612]. | Yeast | — | — | — |
| Rdh overexpression | Overexpression of Rdh from a doxycycline-inducible promoter results in a 6-17% increase in mean lifespan [12620118].
Rdh is an open reading frame in the first intron of the encore gene [12620118]. | Fly | +6 to +17 | — | — |
| SGS101 antisense RNAi | Antisense RNA interference of SAG101 in transgenic plants delays the onset of leaf senescence for approximately 4 days [11971136]. | — | — | — | — |
| SGS101 chemical induced overexpression | Chemical induced overexpression of SAG101 causes precocious senescence in both attached and detached leaves of transgenic plants [11971136]. | — | — | — | — |
| SCP1 overexpression | Overexpression of SCP1 leads to elevuated ROS levels and reduces chronological lifespan [15024029]. | Yeast | — | — | — |
| SGS1 overexpression | Overexpression of SGS1 extends the maximum lifespan of cells lacking SRS2, but not the mean lifespan [11861900]. | Yeast | — | — | — |
| SIR2 overexpression | Integration of a second copy of SIR2 into the wild-type strain leads to an extension of replicative lifespan by around 35% in W303R strain[10521401]. 0.05% glucose restriction further extends replicative lifespan of SIR2 overexpression mutant [15328540]. Overexpression extends replicative lifespan in several strains, but not in PSY316 | Yeast | +35 | — | — |
| 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) [16782295]. | Worm | +26 to +34 | — | +19 to +31 |
| SNF1 overexpression | Overexpression (high-copy 2 micro expression) of SNF1 shortens replicative lifespan to 75% of wild-type and is accompanied by signs of premature ageing, including proegressive sterility, enlargment and fragmentation of the nucleus, redistribution of Sir3 to the nucleus, and more rapid accumulation of extrachromosomal rDNA circles [10921902]. SNF1 overexpression also reduced chronological lifespan [19164565]. | Yeast | -25 | — | — |
| SOD1 overexpression | 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]. 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].
| Yeast | — | — | — |
| Sod2 overexpression | Two-fold overexpression of Sod2 in young (4-6 months) and old (26-28 months) throughout the life results in decreased lipid peroxidation, increased resistance against paraquat-induced oxidative stress, and decreased age-related decline in mitochondrial ATP production, without any change on lifespan or age-related pathology [19633237]. | Mouse | — | — | — |
| SOD2 overexpression | Combined overexpression of SOD1 and SOD2 extends chronological lifespan by 30% in EG103 strain [12586694].
| Yeast | — | — | — |
| Ubiquitinous SOD1 overexpression | Ubiquitous overexpression of SOD1 does not extend lifespan in mice. Homozygous transgenic mice with two- to five-fold overexpression of SOD1 in various tissues exhibit a light reduction in lifespan. Hemizygous transgenic mice, with 1.5- to 3-fold overexpression of SOD1 display no difference in lifespan compared with nontransgenic litermate controls [10719757]. Transgenic mice with a mutant SOD1 transgene develop neuronal cytoskeletal lesions resembling the human amytrophic lateral sclerosis (ALS) phenotype [8610185]. Transgenic mice overexpressing SOD1 (and having 3.1-fold higher cellular Cu,Zn SOD activity in the brain) have reduced infarct size following experimental cerebral ischemia [1763030]. | Mouse | — | — | — |
GenAge
GenDR
