| Hsp27 overexpression | Overexpression of Hsp27 (by the UAS/GAL4 system) increases stress resistance and extends the mean lifespan by 30% [15308776]. | Fly | +30 | — | — |
| 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 | — | — | — |
| Activating let-60 mutation | The let-60(n1046gf) activating mutation greatly reduces lifespan of wild-type, weakly suppresses constitutive dauer diapause in daf-2 and age-1 mutants and extends lifespan induced by mutation of daf-2 [16164423]. | Worm | — | — | — |
| 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 [1128606].
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 | — | — | — |
| 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]. | — | — | — | — |
| 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 [12447374]. | Worm | +30 to +200 | — | — |
| 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 | — | — |
| 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 [11867705]. | Fly | — | +70 | — |
| 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 | — | — |
| RPL31A deletion | Deletion of RPL31A increases mean replicative lifespan by 45% [16293764]. 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 [22377630]. RPL31A deletion increases significantly replicative lifespan [17174052]. Deletion of RPL31A extends replicative lifespan and is not further extended by 0.05% glucose restriction [18423200]. | Yeast | +29 to +50 | — | — |
| 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 | — | — |
| 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 | — | — | — |
GenAge
GenDR
