Factors

We need to know every factor which determines lifespan.

Lifespan factors often but not always originate from defined genetic elements. They are not just genes, by definition they can be anything for which a Classifications schema can be build for that is related to the regulation of lifespan, such entities may include Single-Nucleotide Polymorphism, transcript variants, proteins and their complexes, compounds (i.e. small molecules like metabolites and drugs), etc. A factor should be based on a defined molecular entity or genomic position and been classified. It shall be highly flexible and scalable Concept.

While individual lifespan factors within each species or precise defined molecular entities will be captured within the Lifespan App, Data Entries of the Data App may summarize for instance the relevance of each factor class (e.g. homologous group; chemical derivate of related structure and properties, etc.) as well as draw overall conclusions. o

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  • symbol name observation species
    TUBB4B tubulin, beta 2C TUBB4B was found to be associated with longevity [22174011]. Human
    14-3-3epsilon CG31196 gene product from transcript CG31196-RA Loss of 14-3-3ε results in increased stress-induced apoptosis, growth repression and extended lifespan of flies, in a foxo-dependent manner. Mean lifespan of males and females is increased by 25% and 49%, respectively. Increased 14-3-3ε expression also reverts foxo-induced growth defects. No effect of lifespan is observed when overexpressing 14-3-3ε in adipose tissue, indicating that endogenous foxo activity in this tissue is low under normal conditions [18665908]. Fruit fly
    ABCA1 ATP-binding cassette, sub-family A (ABC1), member 1 The R219K SNP was examined in 256 centenarians and 190 healthy younger controls. The allelic frequency were not different between the two groups [12601526]. Human
    Abca2 ATP-binding cassette sub-family A member 2 Abca2 is transcriptional downregulated in the cerebral cortex at the age 28 months under different longevity conditions such as under dietary restriction (DR) as well as in feeding switch regimens that result in extended lifespan, like early age switch to DR as well as the reverse switch under the influence of the DR-mimetic α-lipoic acid (i.e. DR switched to ad libitum+ lipoic acid) [Shona et al. 2013]. Norway rat
    ACE angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 The I/D polymorphism in ACE was a examined in centenarians (n = 338) and in adults aged 20-70 years. A variant of ACE which predisposes the coronary heat disease was more frequently in centenarians with a significant increase of the homozygous genotype [8136829]. I/D polymorphism was examined in 182 women and 100 men aged >84 years and in 100 boys and 100 girls younger than 17 years. The I/I polymorphism was depleted in the elderly males but not in the elderly females. Furthermore, significant differences were observed between ACE genotypes in elderly men and elderly women [9105559]. I/D polymorphism was examined in 394 French centenarians (13% men and 87% women) and controls (238) from 20 to 70 years of age (140 men and 98 women). Both the ACE D allele and ACE D/D genotype were more frequent in centenarians in comparison with controls, without sex-related differences nor significant correlation with a cardiovascular pathology [9761238]. I/D polymorphism was examined in 424 subjects comprising 227 Uighur individuals, 108 Kazakh individuals, and 89 Han individuals. All subjects in the latter two groups ranged in age from 65 to 70 years, whereas the Uighur subjects comprised two different age groups: those ranging in age from 59 to 70 years and those ranging in age from 90 to 113 years. Within the Uighur group, frequency of the D allele was significantly higher in the group aged >90 than in the group aged <70. The overall distributions of alleles in the three groups did not differ significantly [11773214]. Alleles of ACE was found to be associated with longevity [12547486; 22456784].ACE was found to be associated with longevity [11773214]. ACE was found to be associated with longevity [16960022]. ACE was found to be associated with longevity [19502260]. ACE was found to be associated with longevity [12634288]. ACE was found to be associated with longevity [23389097]. ACE was found to be associated with longevity [12547486]. ACE was found to be associated with longevity [22456784]. ACE was found to be associated with longevity [14528043]. ACE was found to be associated with longevity [8136829]. ACE was found to be associated with longevity [21614448]. ACE was found to be associated with longevity [21330423]. ACE was found to be associated with longevity [19502260]. ACE was found to be associated with longevity [9105559]. ACE was found to be associated with longevity [9761238]. ACE was not found to be associated with longevity [11280044]. ACE was not found to be associated with longevity [14528043]. ACE was not found to be associated with longevity [21330423]. ACE was not found to be associated with longevity [9761238]. ACE was found to be associated with longevity [23623925]. Human
    Adcy8 Adenylate cyclase type 8 Adcy8 is transcriptional downregulated in the cerebral cortex at the age 28 months under different longevity conditions such as under dietary restriction (DR) as well as in feeding switch regimens that result in extended lifespan, like early age switch to DR as well as the reverse switch under the influence of the DR-mimetic α-lipoic acid (i.e. DR switched to ad libitum+ lipoic acid) [Shona et al. 2013]. Norway rat
    ADIPOQ adiponectin, C1Q and collagen domain containing Human
    AGT angiotensinogen (serpin peptidase inhibitor, clade A, member 8) M/T235 SNP in the AGT gene was examined in 187 centenarians (47 males and 140 females) and 201 controls (20-64 years) and a significant influences on survival in males were observed, with reduced hazards of death for carriers of the M235 allele [11602206].AGT was found to be associated with longevity [15621215]. AGT was found to be associated with longevity [11602206]. AGT was not found to be associated with longevity [15621215]. Human
    AKAP10 A kinase (PRKA) anchor protein 10 Male (n= 4766) and female (n = 6202) divided into young (183-9 years) and old (60 years) groups were examined for polymorphisms. A polymorphism that results in an amino acid change from Ile to Val showed the strongest correlation with age. The Val variant was associated with a statistically significant decrease in the length of the electrocardiogram PR interval. An A to G polymorphism in the 3'UTR of D-AKAP2 showed a significant decrease of the G allele in the older sample of both genders. Additionally, the I646V polymorphism was found to be significantly different between young and old in both males and females [12646697]. Human
    Akt1 CG4006 gene product from transcript CG4006-RA RNA interference of Akt1 in intestinal stem cells, results in impaired regeneration of the intestinal epithelium and a short lifespan. In males and females on mean lifespan is 11.4% and 7.4% lower [20976250]. Fruit fly
    alpha-Man-I alpha Mannosidase I alpha-Man-I mutant fly exhibit enhanced resistance to paraquat and starvation an a 60% increase in mean lifespan for both sexes. After outcrossing, the mutant exhibit, under normal conditions, an increase in mean lifespan of 22% for females and 38% for males. Maximum lifespan is increased by 15%. alpha-Man-I RNAi knockdown results in a 39% increase in mean lifespan [19302370]. Fruit fly
    APOA1 apolipoprotein A-I APOA1-MspI-RFLP (-75 nt from the transcription starting site) polymorphism was examined in a healthy population with 304 subjects aged 18-45 years, 267 subjects aged 46-80 years and 229 subjects aged 81-109 years (including 184 subjects, 43 males and 141 females, older than 100 years). The APOA1 allele P, which increases serum LDL-C at middle-age and is over-represented in cardiovascular diseases, tends to increase its frequency in the centenarians males [12556235].APOA1 was found to be associated with longevity [12556235]. Human
    APOA4 apolipoprotein A-IV Two restriction polymorphisms, HinfI347 (Thr347/Ser) and Fnu4HI360 (Gln360/His), and a VNTR (alleles 3, 4) at the 3 region of the APOA4 gene were examined in 71 centenarians (18 men and 53 women, 100-107 years of age, mean 102.3 years) and 100 unrelated adults (21 men and 79 women, 19-59 years of age, mean 35.7 years). The Hinf347 genotype distribution was significantly different in centenarians [9622284].APOA4 was found to be associated with longevity [9533408]. APOA4 was found to be associated with longevity [9622284]. APOA4 was not found to be associated with longevity [9622284]. APOA4 was not found to be associated with longevity [12556235]. Human
    APOB apolipoprotein B (including Ag(x) antigen) A sample of 143 centenarians and a control sample of 158 individuals were examined for polymorphism in APOB restriction fragment length (RFLP) (XbaI2488 and EcoRI4154) and variable number of tandem repeat (VNTR) (3'APOB-VNTR) polymorphisms. Neither the XbaI-RFLP nor the EcoRI-RFLP was able to discriminate between centenarians and controls, while the 3'APOB-VNTR multiallelic system revealed significant differences between the samples: the frequency of alleles with fewer than 35 repeats was lower in centenarians than in controls [9050915].apoB was found to be associated with longevity [17393087].APOB was found to be associated with longevity [15028112]. APOB was found to be associated with longevity [17393087]. APOB was not found to be associated with longevity [17393087]. APOB was found to be associated with longevity [9050915]. APOB was not found to be associated with longevity [11592926]. APOB was not found to be associated with longevity [8018664]. APOB was not found to be associated with longevity [9050915]. Human
    APOC3 apolipoprotein C-III Several small nucleotide polymorphisms in the APOC3 gene were associated with longevity [8018664; 11193221; 16602826]. The Sst I polymorphism was examined in 179 Finnish centenarians. The S2 allele (Sst I restriction site present) occurred more often in the centenarians (frequency, 12.9%) than in the youngest reference population (frequency, 8.8%) [8018664]. Human
    APOE apolipoprotein E In humans APOE is located on chromosome 19. There are three common allelic variants of APOE (ε2 to ε4). The resulting proteins are referred to as ApoE2, ApoE3 and ApoE4. The respective proteins differ only in single amino acid, but have a dramatic influence on the life of affected humans. The frequency of the epsilon 2 allele of ApoE is significantly increased in centenarians relative the overall control population, while the epsilon 4 allele is significantly decreased in centenarians [8136829]. Among individuals 85 years or older how had good cognition, the mortality of those that had the 2/3 genotype was half that in those who carried the epsilon 3/3 genotype and the mortality in subjects with the epsilon 3/4 genotype is twice that of those who carry the epsilon 3/3 genotype. This 4-fold variation results in 2-year difference in survival [8624216]. The epsilon 4 allele is also associated with higher cholesterol levels and cardiovascolar disease [10818513; 8624216] as well as risk factor for cognitive impariment under age 85 [8624216]. However the APOE polymorphism is not a risk factor for cognitive impairment in individuals older than 85 years [8624216]. The Polymorphism (E2, E3, and E4) was examined in a sample of 228 healthy Italian subjects (124 men and 104 women) aged 18-93, with the result that the frequency of E4 decreased with age and was not found in subjects aged 75 and older [8541369]. By Examining the common polymorphism was in 182 women and 100 men aged > 84 years and in 100 boys and 100 girls younger than 17 years (English, Cambridge) a difference between genotypes in the elderly women and the young sample was observed. However, this did not retain significance when the genotype frequencies of the young sample were adjusted to values expected from the allele frequencies on the basis of Hardy-Weinberg equilibrium and compared to observed genotypes in elderly men and women [9105559]. In a Braxiallian population the common polymorphism was examined in 70 elderly patients aged 80 years or more. No association was observed between the genotypes and longevity, though individuals with the E3E4 genotype had a mean age greater than those with the E3E3 genotype [12185856]. In a Korean population the common polymorphism examination of 103 centenarians (13 men and 90 women, mean age 102.4 +/- 2.6 years) and 6435 adults (5008 men and 1427 women) of mean age 50.7 +/- 7.9 years found that the frequencies of genotypes and alleles of the centenarians were not significantly different from those of the control groups. The frequency of the E4 allele was significantly higher in centenarians with dementia than in centenarians without definitive dementia [12634288]. Examination of the common polymorphism in 224 older (75 years) Jewish Jerusalem residents of Ashkenazi ethnicity (150 males and 74 females) and a group of 441 younger subjects (22 years) revealed that the Ashkenazi older subjects were characterized by an increased percentage of the E2 allele and a decreased percentage of the E4 allele [15621215]. A study of APOE polymorphisms in a samples of 538 Colombian subjects (aged 18-106 years) did not find any differences between young and old subjects [16971231]. APOE correlated highly with longevity in a plethora of genetic signatures and has been associated with Alzheimer's disease [22279548]. ε3 and *ε4 are much more efficient binding lipoprotein receptors [11882522]. The various APOE isoforms interact differently with specific lipoprotein receptors, ultimately altering circulating levels of cholesterol. APOE from VLDL, chylomirons and chylomicron remnants binds to specific receptor cells in the liver. Carriers of the *ε2 allele are less efficient at making and transferring VLDLs and chylomicrons from the blood plasma to the liver because of its binding properties. By contrast, carriers of the ε3 are much more efficient in these processes. While APOE4 and APOE3 bind with approximately equal affinity to lipoprotein receptors, APOE2 binds with less than 2% of this strength [7628082]. Thus, compared with carriers of the *ε3 or *ε4 allele, carriers of the *ε2 allele are slower to clear dietary fat from their blood [3479440]. The difference lipoprotein particles results in differences in regulating hepatic low density lipoprotein (LDL) receptors which in turn contribute to genotypic differences in total and LDL cholesterol levels [1998654; 3277611; 8696954; 8018666; 1867194; 3698268]. While APOE was not found to be associated with longevity in some studies [16799145; 21703254], APOE was found to be associated with longevity in many others [11780357; 11213279; 16487435; [23286790; 15621215; 8018664; 21418511; 8136829; 9792194; 22445811; 12185856; 10069711; 21703254; 17934638; 17234815; 11788960; 17934638; 10643896; 11280044; 14615589; 23040522; 18034366]. APOE was found to be associated with longevity [22445811]. APOE was not found to be associated with longevity [24924924]. APOE was found to be associated with longevity [24924924]. APOE was found to be associated with longevity [24688116]. APOE was found to be associated with longevity [24534555]. APOE was found to be associated with longevity [24244950]. APOE was found to be associated with longevity [24126160]. Human
    Atg2 Autophagy-specific gene 2 Atg2 overexpression increases average female lifespan by 28% [18059160]. Fruit fly
    Atp5j2 ATP synthase, H+ transporting, mitochondrial Fo complex, subunit F2 Atp5j2 is transcriptional upregulated in the cerebral cortex at the age 28 months under different longevity conditions such as under dietary restriction (DR) as well as in feeding switch regimens that result in extended lifespan, like early age switch to DR as well as the reverse switch under the influence of the DR-mimetic α-lipoic acid (i.e. DR switched to ad libitum+ lipoic acid) [Shona et al. 2013]. Norway rat
    ATP8_RAT ATP synthase protein 8 ATP8_RAT is transcriptional upregulated in the cerebral cortex at the age 28 months under different longevity conditions such as under dietary restriction (DR) as well as in feeding switch regimens that result in extended lifespan, like early age switch to DR as well as the reverse switch under the influence of the DR-mimetic α-lipoic acid (i.e. DR switched to ad libitum+ lipoic acid) [Shona et al. 2013]. Norway rat
    Aut1 Aut1 depletion form the first day of imaginal stage shortens lifespan by 28% on average in Drosophila and causes morphological behavioural features of premature aging [18219227]. Fruit fly
    bam bag of marbles Bam mutants have an extended lifespan due to germ cell loss. Lifespan of females is on average up to 50% higher and that of males on average s up to 27.8% higher [18434551]. Fruit fly
    Bbs1 Bardet-Biedl syndrome 1 protein Bbs1 is transcriptional downregulated in the cerebral cortex at the age 28 months under different longevity conditions such as under dietary restriction (DR) as well as in feeding switch regimens that result in extended lifespan, like early age switch to DR as well as the reverse switch under the influence of the DR-mimetic α-lipoic acid (i.e. DR switched to ad libitum+ lipoic acid) [Shona et al. 2013]. Norway rat
    C3 complement component 3 Genetic variations in C3 are not associated with longevity in Italian [10219002]. Human
    C4A complement component 4A (Rodgers blood group) Genetic variations in C4A are not associated with longevity in Italian [10219002]. Human
    C4B complement component 4B (Chido blood group) Genetic variations in C4B are not associated with longevity in Italian [10219002]. Human
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    • 25 of 223 factors
    Factors are an extension of GenAge and GenDR.

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