| HSPA1A | heat shock 70kDa protein 1A | (A/C)-110 polymorphism in the HSPA1A gene was examined in 591 subjects (263 males and 328 females; age range 18-109 years; 36 male and 84 female centenarians). A significant age-related decrease of the frequency of allele (A)-110 was observed in females, while no difference was observed in the males [14501185].HSPA1A was found to be associated with longevity [16804002]. HSPA1A was found to be associated with longevity [14501185]. HSPA1A was found to be associated with longevity [16804002]. HSPA1A was found to be associated with longevity [20388090]. HSPA1A was found to be associated with longevity [20388090]. | Human |
| MLH1 | mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) | 3 SNPs in the coding region of MLH1 were analyzed in 85 Korean centenarians and in 106 Korean controls. The CAT haplotype (C670, A676 and T1172) frequency was significantly higher in the centenarians than in the controls [16474933]. MLH1 was found to be associated with longevity [22406557]. | Human |
| MTR | 5-methyltetrahydrofolate-homocysteine methyltransferase | 329 healthy individuals were examined for 2576A-->G (D919G) polymorphism in the MTR gene. Prevalence of the G-allele was significantly higher in the older than in the younger individuals. Separate analysis of female and male subjects revealed that the influence of the MTR genotype on male subjects became relevant at a younger age as opposed to female subjects suggesting a gender-dependent effect [16142417]. | Human |
| TGFB1 | transforming growth factor, beta 1 | 4 SNPs (-800 G/A, -509 C/T, +869 T/C and +915 G/C) in the TGFB1 gene were analysed in 419 subjects from Northern and Central Italy, including 172 centenarians and 247 younger controls. Significant differences were found at the +915 site as far as the C allele and GC genotype were concerned, both of them being lower in centenarians than in young controls, but none of the other tested genetic variants was significantly different between centenarians and controls. Moreover, a particular haplotype combination (G -800/C -509/C 869/C 915) was notably lower in centenarians than in younger individuals [15569360].TGFB1 was found to be associated with longevity [21299522]. TGFB1 was found to be associated with longevity [21299522]. TGFB1 was found to be associated with longevity [15569360]. | Human |
| INSR | insulin receptor | 5 intronic and 1 exonic polymorphisms in the INSR gene were examined in 122 semisupercentenarians (older than 105, 107 female, 15 male, mean age 106.8 years) and 122 healthy younger controls (105 female, 17 male, mean age 33.33). One haplotype, which was comprised of 2 intronic SNPs in linkage disequilibrium, was more frequent in semisupercentenarians than in younger controls [15582274].INSR was found to be associated with longevity [15582274]. INSR was not found to be associated with longevity [15582274]. INSR was not found to be associated with longevity [19489743]. | Human |
| HMOX1 | heme oxygenase (decycling) 1 | A (GT)n repeat polymorphism in the promoter region of the human HO-1 gene was examined in younger (60 years, 59 male and 45 female) and older (60-75 years, 95 male and 106 female) subjects. The proportion of allelic frequencies in class L with a large size of (GT)n repeat, as well as the genotypic frequencies in group I with class L alleles, was significantly lower in the oldest male subjects than in the younger males. In contrast, in the oldest female subjects this was not observed [12566526].HMOX1 was found to be associated with longevity [12566526]. | Human |
| Mnt | CG13316-PC, isoform C | A dMnt null allele results in flies with larger cells, increased weight, and decreased lifespan [16055719]. | Fruit fly |
| YTHDF2 | YTH domain family, member 2 | A locus associated with human longevity corresponds to (TG)n microsatellite is located in the YTHDF2 gene. 412 participants of different ages, including 137 centenarians, were genotyped. The increased homozygosity in centenarians at this locus was confirmed, and observed a concomitantly increased frequency of the most frequent allele and the corresponding homozygous genotype. The same genotype was associated with increased YTHDF2 messenger RNA levels in immortalized lymphocytes. [16799135].YTHDF2 was found to be associated with longevity [16799135]. | 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 |
| IGF2 | insulin-like growth factor 2 (somatomedin A) | A/G ApaI site SNP in the IGF2 gene was examined 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). An increase in the A allele was observed in older Ashkenazi females and a highly significant increase was observed in the AA genotype in these subjects [15621215].IGF2 was found to be associated with longevity [19367319]. IGF2 was not found to be associated with longevity [19367319]. IGF2 was found to be associated with longevity [17989723]. IGF2 was found to be associated with longevity [15621215]. | Human |
| Nlaz | Neural Lazarillo | Absence of Nlaz, which is homologous to ApoD, results in a reduced lifespan in both sexes. Median lifespan is 30.8% and 22.5% lower in females and males, respectively. Maximum lifespan is reduced by 12% and 30% in females and males [21376794]. | Fruit fly |
| hebe | — | Adult-specific overexpression of hebe increases the lifespan by 5-30% and modulates late-age female fecundity. Female and male mean lifespan is up to 11% and 24% higher [19011900]. | Fruit fly |
| magu | — | Adult-specific overexpression of magu increases lifespan by 5-30% and modulates late-age fecundity [19011900]. | 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 |
| Atg2 | Autophagy-specific gene 2 | Atg2 overexpression increases average female lifespan by 28% [18059160]. | Fruit fly |
| 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 |
| F7 | coagulation factor VII (serum prothrombin conversion accelerator) | Blood coagulation factor VII (FVII) R/Q353 and FVII-323ins10 SNPs were examined in 187 centenarians (47 males and 140 females) and 201 controls (20-64 years). R/Q353 and FVII-323ins10 manifest significant influences on survival in males, with reduced hazards of death for carriers of the Q353 allele and the FVII-323P10 allele [11602206].F7 was found to be associated with longevity [15621215]. F7 was found to be associated with longevity [10744171]. F7 was found to be associated with longevity [10744171]. F7 was found to be associated with longevity [11602206]. | Human |
| CG3776 | — | Both overexpression and underexpression of CG3776 (alias Jhebp29) reduces the mean lifespan, where the reduction in males is slightly higher.
The lifespan of male flies with under- and overexpressed CG3776 is reduced by 38.8 and 42.6%, respectively when compared with Oregon R flies.The lifespan of female flies with under- and overexpressed CG3776 is reduced by 31.6 and 35%, respectively when compared to Oregon R flies.
Among the males and females, relatively to Oregon R and EP835/CyO, the age-specific survival of EP835/EP835 and EP835/Gal4 is reduced in both log-rank and Wilcoxon tests (P < 0.001); survival of EP835/EP835 and EP835/Gal4 differed using the log-rank-test (male: P<0.001; female: P=0.027) [18275960].
| Fruit fly |
| HFE | hemochromatosis | C282Y, H63D and S65C polymorphisms in the HFE gene were studied in 106 young controls (age range from 22 to 55 years; 40 men and 66 women) and 35 elderly subjects (age range from 91 to 105 years; seven men and 28 women). A significant difference was observed only in women in frequencies of C282Y alleles between the young and the elderly subjects. Concerning H63D polymorphisms, no significant differences were observed, between old and young people [11857056].HFE was found to be associated with longevity [11857056]. HFE was found to be associated with longevity [11857056]. HFE was found to be associated with longevity [11857056]. HFE was found to be associated with longevity [11857056]. HFE was found to be associated with longevity [11857056]. HFE was found to be associated with longevity [12714263]. HFE was not found to be associated with longevity [11857056]. HFE was not found to be associated with longevity [12714263]. | Human |
| Cdkn2a | cyclin-dependent kinase inhibitor 2A | Cdkn2a encodes different transcripts involved mostly in cell cycle regulation and cellular senescence [12882406], but it can also act as a tumor suppressor. Its expression level increase with age in rodents [15520862]. super-Ink4a/Arf mice carrying a transgenic copy of a large genomic segment containing an intact and complete copy of the Cdkn2a (a.k.a. Ink4a/Arf) gene are significantly protected from cancer and had no indication of accelerated aging. Cells derived from super-Ink4a/Arf mice have increased resistance to in vitro immortalization and oncogenic transformation [15520276]. Loss of Cdkn2a in mice results in tumour susceptibility [11544530]. Mice deficient in Cdkn2a have smaller age-related decline in self-renewal potential as this process is associated with increasing levels of Cdkn2a [16957738].
Increased levels of p16 are associated with aging (Krishnamurthy et al., 2006; Molofsky et al., 2006) and a bona fide marker of cellular senescence (Collado et al., 2007). p16INK4a accumulates in many tissues as a function of advancing age (Krishnamurthy et al., 2004; Nielsen et al., 1999; Zindy et al., 1997) and is an effector of senescence (Campisi, 2003; Park et al., 2004),
p16INK4a is a potent inhibitor of proliferative kinase Cdk4 (Lowe and Sherr, 2003) which is essential for pancreatic ?-cell proliferation in adult mammals (Rane et al., 1999; Tsutsui et al., 1999). p16INK4a constrains islet proliferation and regeneration in an age-dependent manner. Expression of the p16INK4a transcript is enriched in purified islets compared with the exocrine pancreas and islet-specific expression of p16INK4a increases markedly with aging (Krishnamurthy et al., 2006).
Aging in mammals is associated with reduced regenerative capacity in tissues that contain stem cells (Chien and Karsenty, 2005) which is probably partially caused by senescence of progenitors with age (Campisi, 2005; Lombard et al., 2005).
Progenitor proliferation in subventricular zone and neurogenesis in the olfactory bulb as well as multipotent progenitor frequency and self-renewal potential, all decline with ageing the mouse forebrain. The decline in progenitor frequency and function correlate with increased expression of p16INK4a (Molofsky et al., 2006).
Aging p16INK4a-deficient mice exhibit a significantly smaller decline in subventricular zone proliferation, olfactory bulb neurogenesis and the frequency and self-renewal potential of multipotent progenitors (Molofsky et al., 2006).
p16 expression in skin cells is significantly lower the the group that has a strong family history of longevity. As such a younger biological age associates with lower levels of p16INKfa positive cells [22612594].
p16 expression increases exponentially with age. Expression of p16INK4a with age does not predict cancer development. p16INK4a activation is a characteristic of all emerging cancers [http://denigma.de/url/3n].
| House mouse |
| Sirt2 | — | Decreased expression of Sirt2 by RNA interference causes lethality during development. Silencing in neurons shortened mean lifespan by 20% [17159295]. | Fruit fly |
| Sirt6 | — | Decreased expression of Sirt6 by RNA interference causes lethality during development. Sirt6 silencing in neurons shortens mean lifespan by 20% [17159295]. | Fruit fly |
| GSTT1 | glutathione S-transferase theta 1 | Deletion in the GSTT1 was examined in 94 nonagenarians and centenarians and 418 control subjects of younger age. A significant difference in the proportion of nonagenarians and centenarians homozygotes for the deletion was observed in comparison to control subjects [11162685].GSTT1 was found to be associated with longevity [11162685]. GSTT1 was found to be associated with longevity [16574194]. GSTT1 was not found to be associated with longevity [11162685]. GSTT1 was not found to be associated with longevity [15195682]. | Human |
