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Ageing Phenotype Observations List—Data Type 1

NOTE:

We distinguish between different types of ageing relevance evidence. Experimental studies on ageing factors result in observations with experimental ageing relevance evidence (1). According to our definition of ageing factors a comparison of two situations, with and without the action of the ageing factor, is required. Almost all data in AgeFactDB is of this type. There are however also a few lifespan data for populations or species included that are certainly relevant to ageing with a slightly different meaning of the term ageing relevance, however. But in this case there is no intervention study and therefore these data cannot be assigned to an ageing factor (2). Furthermore, there are experimental studies where no significant effect of an assumed ageing factor was found (3). And finally there are genes included that are homologous to known ageing-relevant genes for which there is no experimental evidence. They are considered as putative ageing-relevant genes with computational evidence (4).
Order of importance:

yes (Experimental Analysis)
yes, but no ageing factor assigned (Experimental Analysis)
no (Experimental Analysis)
putative (Computational Analysis)

The color indicating the ageing relevance type of an observation may differ from the corresponding color for the ageing factor related to this observation. The reason is that for ageing factors associated with more than one observation, the most important observation color is chosen as ageing factor color. This is always the color with the lowest number in the order given above.

Ageing phenotype observations are considered as experimental analysis. They confirm or reject the ageing relevance for particular ageing factor(s). For genes that are homologous to known ageing-relevant genes there is thus far no experimental evidence. They are considered as candidate genes.
Due to the different data structures of ageing phenotype observation data integrated from other databases we subdivide these observations into type 1 and 2. Observations of type 1 contain the phenotype data mostly unseparated within a single description. Observations of type 2 contain lifespan data in a more structured form (e.g.: separated into lifespan effect, lifespan change, lifespan value). Currently there might be an overlap between the observations of type 1 and 2 from the same source, namely GenAge. But we are working on a reduction of this overlap.

Ageing Relevance:

yes (Exp. Analysis)
yes, but no ageing factor assigned (Exp. Analysis)
no (Exp. Analysis)
putative (Comp. Analysis)

1 ... 100

#

Observation Stable ID

Species

Gene

Other Ageing Factor

Description

PubMed

Source

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
aak-2	181727

37% decrease in median lifespna in daf-2 background and 54% decrease in lifespan in a wild-type background

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
hsp-6	178873

Knockdown of HSP-6 by RNAi in young adult nematodes caused a reduction in the levels of ATP-2, HSP-60 and CLK-1, leading to abnormal mitochondrial morphology and lower ATP level. As a result, RNAi-treated worms had lower motility, defects in oogenesis, earlier accumulation of autofluorescent material and a shorter lifespan (15% reduction).

Drosophila melanogaster

Gene Symbol	NCBI Gene ID
Hsp26	39075

Overexpression increased stress resistance and extended the mean lifespan by 30%.

Drosophila melanogaster

Gene Symbol	NCBI Gene ID
Hsp27	39078

Overexpression increased stress resistance and extended the mean lifespan by 30%.

Gene Symbol	NCBI Gene ID
htr1b	15551

Knockout mice displayed a decreased lifespan and early age-related motor decline.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
hus-1	171939

RNA interference increased mean lifespan by 11%. In hus-1 mutants, RNA interference of cep-1 did not increase lifespan, suggesting both genes influence lifespan through the same pathway.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
ife-2	180393

Loss-of-function mutation increased maximum lifespan by about 20%. It did not extend the lifespan of daf-16(RNAi) animals. TOR RNA interference further extended lifespan.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
ife-2	180393

Loss of a specific eIF4E isoform (IFE-2) that functions in somatic tissues reduces global protein synthesis, protects from oxidative stress and extends maximum lifespan by 30% in C. elegans. Lifespan extension is independent of the forkhead transcription factor DAF-16, which mediates the effects of the insulin-like signalling pathway on ageing. Furthermore, IFE-2 deficiency further extends the lifespan of long-lived age (30%) and daf (15% maximum lifespan) nematode mutants. Knockdown of ife-2 extends the lifespan (50% maximum lifespan) of glp-4(bn2) mutant animals lacking a germ line. Similarly, lack of IFE-2 enhances the long-lived phenotype of clk (30% maximum lifespan) and dietary-restricted eat mutant animals (30% maximum lifespan). Knockdown of target of rapamycin (TOR), a phosphatidylinositol kinase that controls protein synthesis in response to nutrient cues, further increases the longevity of ife-2 mutants (10-15% maximum lifespan). Depletion of other eIF4E isoforms had no effect on longevity.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
ifg-1	174322

RNAi increased maximum lifespan by about 30%. Reducing the levels of eIF2β or eIF4G did not extend the lifespan of daf-16 mutants at all. eIF2β and eIF4G RNAi slightly shortened the lifespan of daf-2 mutants. sir-2.1 deletion mutant was subjected to sir-2.1(ok434), to RP, S6K, TOR or eIF RNAi - In each case, lifespan was extended.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
ifg-1	174322

Inhibition of ifg-1 during adulthood led to a 36% increase in maximum lifespan. Inhibition of at least one eIF4E isoform and two of the three poly(A)-binding proteins also has a significant effect on lifespan extension. Inhibition of let-363 increased lifespan in both the N2 background and when ifg-1 was inhibited. In the daf-2 (e1370) mutant background, inhibition of either ifg-1 or rsks-1 further extended lifespan by 70% and 24%, respectively. Inhibition of either ifg-1 or rsks-1 extended lifespan by 27% and 14%, respectively, in a daf-16 (mu86 ) background. Inhibition of either ifg-1 or rsks-1 in the clk-1(e2519) mutant background led to a further lifespan extension by 19% and 13%, respectively. Inhibition of either ifg-1 or rsks-1 extended lifespan in the eat-2 background by 54% and 11%, respectively. In a sir-2.1 mutant background, ifg-1 inhibition extended lifespan by 93% and rsks-1 inhibition by 33%.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
ifta-2	189055

Knockouts have an extended lifespan phenotype (40-50%) and are defective in dauer formation due to defects in daf-2 receptor signalling pathway in ciliatedsensory neurons. There was no additive effect of the ifta-2 mutation on the daf-2 longevity phenotype.

Gene Symbol	NCBI Gene ID
Igf1r	16001

Mice heterozygous for IGF1R live 26% longer than controls. Female Igf1r +/- mice live 33% longer, while male mice live 16% longer. Igf1r +/- mice have normal size, normal metabolism, normal nutrient uptake, fertility and reproduction, and seem to be oxidative stress resistant.

Gene Symbol	NCBI Gene ID
Igf1r	16001

Nearly 40% mean lifespan extension in heterozygotes knockout, however, the maximum lifespan was unchanged. Homozygotes KO mice showed the same average lifespan as controls.

Drosophila melanogaster

Gene Symbol	NCBI Gene ID
Indy	40049

Flies heterozygotic for a disruption have extended mean (87-92%) lifespan and maximum lifespan (45%). Homozygotes for the disruption show only a 10-20% increase in mean lifespan.

Drosophila melanogaster

Gene Symbol	NCBI Gene ID
InR	42549

Mutations result in dwarf females with extended lifespan of up to 85% and dwarf males with reduced late age-specific mortality.

Gene Symbol	NCBI Gene ID
Insr	16337

Homologous murine model was created by replacing Pro-1195 of insulin receptors with Leu. Homozygous mice died in the neonatal stage from diabetic ketoacidosis, whereas heterozygous mice showed the suppressed kinase activity of the insulin receptor but grew normally without spontaneously developing diabetes during adulthood. Under 80% oxygen, mutant female mice survived 33.3% longer than wild-type female mice, whereas mutant male mice survived 18.2% longer than wild-type male mice.

Gene Symbol	NCBI Gene ID
Irs1	16367

Median lifespan was extended 18% in knockouts from both sexes and 32% in females. Female animals displayed signs of resistance to ageing markers in skin, bone, immune system, and motor dysfunction, in spite of mild, lifelong insulin resistance. Heterozygous animals had normal lifespans.

Gene Symbol	NCBI Gene ID
Irs2	384783

Irs2 brain-specific knockout mice were overweight, hyperinsulinemic, glucose intolerant, yet more active and lived up to 18% longer.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
isp-1	177609

A missense mutation leads to low oxygen consumption, decreased sensitivity to reactive oxygen species, and increased mean (60%) and maximum (100%) lifespan.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
isp-1	177609

Treating the respiratory mutant isp-1(qm150) with rps-15 or S6K/rsks-1 RNAi further extended its lifespan by 25-30%.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
baf-1	176330

RNA interference decreased median lifespan by 28% in daf-2 mutants.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
jnk-1	177460

Mutant worms have a 30% shortened maximal lifespan.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
bar-1	180982

May play a role in regulating daf-16 during dauer formation, particularly in conditions of oxidative stress. Deletion of bar-1 reduces mean (45%) and maximal (35%) lifespan.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
cid-1	175707

RNA interference results in developmental abnormalities but also a significant increase in lifespan.

Gene Symbol	NCBI Gene ID
Kl	16591

Disruption results in infertility and signs of premature ageing such as a short lifespan, arteriosclerosis, skin atrophy, osteoporosis, and emphysema.

Gene Symbol	NCBI Gene ID
Kl	16591

Many advanced ageing-like KL -/- phenotypes are restored to normal whenever Klotho expression is induced. Conversely, decreasing Klotho expression in these rescued KL -/- mice induced several ageing-like KL -/- phenotypes.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
kri-1	191275

RNA interference suppressed glp-1 life-extension but did not shorten lifespan of wildtype strains.

Saccharomyces cerevisiae

Gene Symbol	NCBI Gene ID
KSS1	852931

Deletion resulted in increased sensitivity to heat shock and oxidative stress and a 33% reduction in median lifespan.

Saccharomyces cerevisiae

Gene Symbol	NCBI Gene ID
LAT1	855653

Deletion abolished the lifespan extension conferred by calorie restriction. Overexpression extended mean lifespan by 20%, did not further extend lifespan under CR, and was not dependent on the Sir2 family. Overexpression also extended cell survival during prolonged culture at stationary phase.

Gene Symbol	NCBI Gene ID
Bax	12028

Inactivation extended fertile potential and minimized age-related health problems, including bone and muscle loss, excess fat deposition, alopecia, cataracts, deafness, increased anxiety, and selective attention deficit. It did not extend lifespan.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
lbp-4	179161

RNA interference resulted in decreased lifespan and earlier accumulation of lipofuscin.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
lbp-6	172390

RNA interference resulted in decreased lifespan and earlier accumulation of lipofuscin.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
lbp-9	178686

RNA interference resulted in decreased lifespan and earlier accumulation of lipofuscin.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
ldb-1	181292

RNA interference resulted in decreased lifespan and earlier accumulation of lipofuscin.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
let-60	178104

Activating mutations weakly suppress constitutive dauer diapause in daf-2 and age-1 mutants and extend lifespan induced by mutation of daf-2.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
let-653	178120

RNA interference decreased median lifespan by 13% in wild type animals and 32% in daf-2 mutants.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
lin-14	181337

A loss-of-function mutation in lin-14 extended lifespan by 31% while a gain-of-function mutation decreased lifespan. The life-extending effects were dependent on daf-16 and hsf-1. Also, lin-14 is a target of lin-4.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
lin-2	181400

lin-1 inhibits the growth of gld-1 tumors. Up to 30% reduction in mean lifespan in daf-2 and gld-1 double mutant background; no mean lifespan change in daf-2 mutants or wild-type background; no significant changes in the maximum lifespan in all backgrounds except daf-2 and gld-1 double mutant background (40% reduction).

Drosophila melanogaster

Gene Symbol	NCBI Gene ID
bchs	33819

Mean lifespan is decreased 40-45% in bchs mutant adults. No pronounced developmental defects were observed and young adults have normal behaviors, indicating that the bchs gene is essential for normal adult survival and longevity.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
lin-4	266860

A loss-of-function mutation in lin-4 shortened lifespan and accelerated tissue ageing while overexpressing lin-4 extended lifespan.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
lmn-1	172687

RNAi led to a 39% decrease in median lifespan in daf-2 background, 12% decrease in lifespan in daf-2/daf-16 double mutant background and 12% decrease in median lifespan in a wild-type background.

Gene Symbol	NCBI Gene ID
Lmna	16905

Homozygous mice display signs of premature ageing, including a marked reduction in growth rate and death by 4 weeks of age.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
lsm-7	177988

RNA interference decreased median lifespan by 24% in wild type animals, 27% in a daf-2 background and 9% in daf-2/daf-16 double mutants.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
lys-8	173944

lys-8 appears to inhibit the growth of gld-1 tumours. RNA interference reduced mean lifespan up to 29% in wild type animals, up to 19% in daf-2 mutants, and up to 15% in daf-2/gld-1 mutants. It also reduced maximum lifespan 12% in daf-2 mutants and 25% in daf-2/gld-1 mutants.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
M05B5.2	187451

RNA interference decreased median lifespan by 45% in wild type animals, 46% in a daf-2 background and 44% in daf-2/daf-16 double mutants.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
M57.2	177113

RNA interference decreased median lifespan by 20% in wild type animals and 40% in daf-2 mutants.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
mag-1	173073

RNA interference decreased median lifespan by 15% in wild type animals and 35% in daf-2 mutants.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
mcm-2	174841

RNAi let to a 33% decrease in median lifespan in daf-2 background and a 14% decrease in lifespan in a wild-type background.

Gene Symbol	NCBI Gene ID
Mcm2	17216

Conditional knockouts with reduced expression develop normally but lifespan is greatly reduced with most animals living 10-12 weeks accompanied by deficiencies in the proliferative cell compartments of several tissues and increased cancer incidence.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
mdh-1	175936

RNA interference decreased median lifespan by 10% in wild type animals and 16% in daf-2 mutants.

Saccharomyces cerevisiae

Gene Symbol	NCBI Gene ID
MEC1	852433

Mutants have a 3-fold reduced mean and maximum chronological lifespan under conditions of medium depletion.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
BE10.2	176695

RNA interference decreased median lifespan by 30% in wild type animals and 60% in daf-2 mutants.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
mep-1	178074

RNA interference results in a 39% decrease in median lifespan in daf-2 mutants, 14% decrease in lifespan in daf-2/daf-16 double mutants and 8% decrease in median lifespan in a wild-type background.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
mes-1	181362

Mutation animals that lack germ cells live about 60% longer than controls.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
mev-1	260040

Mutants are hypersensitive to raised oxygen concentrations and their lifespan decreases dramatically as oxygen concentrations increase.

Gene Symbol	NCBI Gene ID
Mgat5	107895

Although grossly normal at birth, knockout mice display multiple deficiencies with age including hypersensitivity to autoimmune disease, higher oxidative metabolism, resistance to weight-gain, and signs of early ageing such as osteoporosis, decreased muscle mass, and depletion of adult stem cells. Interestingly, Mgat5-/-Pten+/- and Mgat5+/-Pten+/- mutant mice showed a small but significant increase in lifespan when compared to Pten+/- mice, accompanied by an apparent delay in the inevitable development of cancer in Pten+/- mice.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
mnk-1	174623

RNA interference shortened wild-type (20%) and ife-2 mutant (15%) maximum lifespan.

Drosophila melanogaster

Gene Symbol	NCBI Gene ID
Mnt	31331

A dMnt null allele results in flies with larger cells, increased weight, and decreased lifespan.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
bec-1	177345

Required for normal dauer morphogenesis and lifespan extension. RNA interference results in a shortened lifespan.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
bec-1	177345

16% lifespan reduction (compared to wild type) and 25% lifespan reduction (in a daf-2 mutant) for RNAi from beginning of life. For post developmental RNAi maximum lifespan was extended by 10-15% both in wild-type and daf2 mutants.

Saccharomyces cerevisiae

Gene Symbol	NCBI Gene ID
MPT5	852697

Average chronological lifespan decreased by 50%. Rescued to the wt level by PKC1 overexpression

Drosophila melanogaster

Gene Symbol	NCBI Gene ID
Eip71CD	39675

Overexpression in the nervous system extended lifespan by up to 70%, increased resistance to oxidative stress, and delayed the onset of senescence-induced decline in activity levels and reproductive capacity.

Gene Symbol	NCBI Gene ID
Msra	110265

Knockouts exhibit a shorter lifespan and enhanced sensitivity to oxidative stress.

Gene Symbol	NCBI Gene ID
Msra	110265

No effect on aging, as determined by lifespan.

Drosophila melanogaster

Gene Symbol	NCBI Gene ID
mth	38058

Mutants displayed approximately 35 percent increase in average lifespan and enhanced resistance to various forms of stress.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
mxl-2	175184

RNA interference decreased median lifespan by 7% in wild type animals, 39% in a daf-2 background and 27% in daf-2/daf-16 double mutants.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
blmp-1	172917

RNA interference decreased median lifespan by 17% in a daf-2 background and 20% in daf-2/daf-16 double mutants.

Drosophila melanogaster

Gene Symbol	NCBI Gene ID
mys	44885

Mutants exhibit ameliorated age-related declines in locomotor activity and an increase in mean lifespan of 20%.

Saccharomyces cerevisiae

Gene Symbol	NCBI Gene ID
NDE1	855176

Overexpression of Nde1 and Nde2 resulted in a longer replicative lifespan (20-25%) on 2% glucose, but not on 0.5% glucose.

Saccharomyces cerevisiae

Gene Symbol	NCBI Gene ID
NDE2	851474

Overexpression of Nde1 and Nde2 resulted in a longer replicative lifespan (20-25%) on 2% glucose, but not on 0.5% glucose.

Gene Symbol	NCBI Gene ID
Neil1	72774

Knockout mice develop severe obesity, dyslipidemia, fatty liver disease, increased levels of DNA damage in the mtDNA, and have a tendency to develop hyperinsulinemia.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
nfi-1	174225

Deletion results in animals with defects in movement, pharyngeal pumping and egg-laying, and with a reduced lifespan.

Drosophila melanogaster

Gene Symbol	NCBI Gene ID
Bmcp	39322

Knockout flies live longer on low-calorie diets, have a decreased fertility, and gain less weight on high-calorie diets.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
nhr-49	172839

RNA interference shortened lifespan and altered fatty acid composition.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
alg-2	173468

RNA interference decreased median lifespan by 24% in wild type animals and 50% in a daf-2 background.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
nhx-2	174242

Gene inactivation by RNA interference led to a loss of fat stores in the intestine and a 40% increase in lifespan.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
nnt-1	180884

nnt-1 appears to inhibit the growth of gld-1 tumours. RNA interference reduced mean lifespan up to 18% in wild type animals, 20% in daf-2 mutants and 16% in daf-2/gld-1 mutants.

Gene Symbol	NCBI Gene ID
Nos3	18127

Knockout males exhibited premature death and age-related cardiac dysfunction but not females.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
npp-2	172611

RNA interference decreased median lifespan by 11% in wild type animals, 38% in a daf-2 background and 22% in daf-2/daf-16 double mutants.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
npp-3	174823

RNA interference decreased median lifespan by 14% in wild type animals, 36% in a daf-2 background and 11% in daf-2/daf-16 double mutants.

Gene Symbol	NCBI Gene ID
Cebpa	12606

Replacing the CEBPA gene by CEBPB increased lifespan by about 20%.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
let-765	175934

RNA interference decreased median lifespan by 27% in wild type animals, 38% in a daf-2 background and 22% in daf-2/daf-16 double mutants.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
nuo-1	174696

Mutations result in developmental arrest and increased lifespan.

Gene Symbol	NCBI Gene ID
Brca1	12189

Deletion causes senescence in mutant embryos and cultured cells and tumorigenesis and signs of premature ageing in adult mice.

Gene Symbol	NCBI Gene ID
Brca1	12189

Brca1 heterozygotes appear to have a shortened life span with 70% tumor incidence. Lymphoma, but not ovarian and mammary gland tumors, occurs commonly in these mice. After a whole-body exposure to ionizing radiation, Brca1 heterozygous mice have a 3–5-fold higher incidence specific to ovarian tumors, but not lymphoma, when compared with the Brca1+/+ mice.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
odr-3	179806

Loss-of-function mutation extended mean lifespan by 10-30% but not maximum lifespan. Life-extension was dependent on daf-16 but cumulative with daf-2 mutations.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
pept-1	180919

Gene inactivation of nhx-2 by RNAi led to a loss of fat stores in the intestine and a 40% increase in longevity while double RNAi of nhx-2 and opt-2 led to 10-20% increase in longevity

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
pept-1	180919

Deletion of pept1 (also called opt-2, pep-2) results in retarded development, reduced body size and extended reproductive lifespan. It also further extends (60%) the life-extension caused by daf-2 mutations.

Drosophila melanogaster

Gene Symbol	NCBI Gene ID
Orco	40650

Loss-of-function mutation resulted in olfactory defects, altered adult metabolism, enhanced stress resistance, and life-extension. Female Or83b2 mutant flies showed a 56% increase in median lifespan and a 30% increase in maximum lifespan. Males were also long-lived, though to a smaller degree and maximum lifespan was not extended. Heterozygous mutants of both sexes showed an intermediate longevity. Dietary restriction further extended lifespan.

Drosophila melanogaster

Gene Symbol	NCBI Gene ID
ovo	31429

The dominant ovoD1 allele extends female lifespan by approximately 50%. It does not synergize or prevent life-extension caused by chico.

Drosophila melanogaster

Gene Symbol	NCBI Gene ID
p53	2768677

Expression of dominant-negative versions of p53 in adult neurons extended lifespan by 58% in females and 32% in males and increased resistance to genotoxic stress.

Drosophila melanogaster

Gene Symbol	NCBI Gene ID
p53	2768677

Expression of dominant-negative (DN) forms of Dmp53 in adult neurons, but not in muscle or fat body cells, extends median lifespan by 19% and maximum lifespan by 8%. The lifespan of calorie-restricted flies is not further extended by simultaneously expressing DN-Dmp53 in the nervous system, indicating that a decrease in Dmp53 activity may be a part of the CR lifespan-extending pathway in flies. Selective expression of DN-Dmp53 in only the 14 insulin-producing cells (IPCs) in the brain extends lifespan to the same extent as expression in all neurons and this lifespan extension is not additive with CR.

Gene Symbol	NCBI Gene ID
Pappa	18491

Genetic deletion of PAPPA extended mean and maximum lifespan by 30-40% and reduced cancer incidence with no reduction in food intake or secondary endocrine abnormalities.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
par-5	178113

RNA interference slightly shortens lifespan and suppresses life-extension by sir-2.1 overexpression but not by daf-2 mutants. Overexpression extends lifespan by 30%, but is suppressed by RNA interference of daf-16.

Gene Symbol	NCBI Gene ID
Pawr	114774

Par4-null mice are prone to develop tumours, both spontaneously and on carcinogenic treatment. The endometrium and prostate of Par4-null mice were particularly sensitive to the development of proliferative lesions. Most (80%) Par4-null females presented endometrial hyperplasia by 9 months of age, and a significant proportion (36%) developed endometrial adenocarcinomas after 1 year of age. Similarly, Par4- null males showed a high incidence of prostate hyperplasia and prostatic intraepithelial neoplasias, and were extraordinarily sensitive to testosterone-induced prostate hyperplasia. 25% reduction in mean LS was observed compared to WT and 20% reduction in MLS. Heterozygote KOLS did not differ significantly from the WT.

Gene Symbol	NCBI Gene ID
Pawr	114774

Mice overexpressing the pro-apoptotic protein domain were resistant to tumours. Transgenic animals showed normal fertility, viability, and ageing, though they were slightly longer-lived possibly because of the cancer-resistance.

Gene Symbol	NCBI Gene ID
Pck1	18534

Overexpression in skeletal muscle results in an increased number of mitochondria and extended lifespan. Transgenic mice ate 60% more than controls but had half the body weight and 10% of the body fat.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
aco-2	176121

30% mean lifespan extension in daf2 background; no lifespan measurement in wt background

Gene Symbol	NCBI Gene ID
Bub1b	12236

Knockout mutant mice exhibit symptoms of accelerated ageing such as short lifespan, lordokyphosis, and fat loss.

Caenorhabditis elegans

Gene Symbol	NCBI Gene ID
pha-4	180357

PHA-4 may play a role in the life-extending effects of dietary restriction. RNA interference decreased lifespan of wild-type worms, but not of daf-2 mutants or of animals with defective electron transport chains. Overexpression slightly increased longevity.