Table 1.
Reviewed candidate genes for their possible association with human longevity.
| Gene names | Protein function | Populations/study locations | Genotype and phenotype data | Reference |
|---|---|---|---|---|
| AKT | IIS signaling | Three cohorts enrolled Caucasian and African-American participants from the United States, including Study of Osteoporotic Fractures (SOF), Cardiovascular Health Study (CHS), and Ashkenazi Jewish Centenarians (AJC). | An intronic SNP (rs3803304) in AKT1 was identified to be significantly associated with lifespan. | Pawlikowska et al. (2009) |
| APOE (Apolipoprotein E) | Lipoprotein metabolism | A Swedish population which is composed of 407 healthy Swedish individuals, 244 men and 163 women, ages 17–86 years. | The ɛ4 allele frequency correlated positively with LDL cholesterol, and decreased with increasing age, and was significantly lower in individuals >60 years of age. | Eggertsen et al. (1993) |
| A population of centenarians (n = 338) and adults aged 20–70 years. | The ɛ4 allele of APOE is significantly less frequent in centenarians than in controls, while the frequency of the ɛ2 allele is significantly increased. | Schächter et al. (1994) | ||
| FOXO1A (forkhead box O1A) | IIS signaling | 817 centenarians and younger individuals in Han Chinese. | Two intronic SNPs (rs2755209, rs2755213) showed a reduced minor allele frequency in the female centenarian group. | Li et al. (2009a) |
| A community-based sample which was composed of up to 1345 Framingham Study participants from 330 families. | Two SNPs (rs10507486 and rs4943794) intronic to FOXO1A, showed association with age at death. | Lunetta et al. (2007) | ||
| FOXO3A (forkhead box O3A) | IIS signaling | 213 long-lived American men of Japanese ancestry from the island of Oahu (Hawaii) (minimum age 95 years) with 402 average-lived subjects. | The long-lived Japanese had one or more copy of the “G” allele of rs2802292 (variable name: FOXO3A3). | Willcox et al. (2008) |
| 1762 German subjects, including 1031 unrelated centenarians/nonagenarians (age range 95–110 years; mean age 98.4 years) and 731 younger controls (age range 60–75 years, mean age 67.2 years). | Polymorphism of rs3800231 had a highly significant association with human longevity. | Flachsbart et al. (2009) | ||
| 817 centenarians and younger individuals in Han Chinese. | Three SNPs (rs2253310, rs2802292, rs4946936) were found to have strong associations with longevity in sex-combined centenarians with an average age of 102 years. | Li et al. (2009a) | ||
| A large cohort of Italians (age range 90–108 years). | One SNP, rs2802292, was postulated to play a beneficial role in lifespan by increasing FOXO3A expression and then enhancing the downstream targets. | Anselmi et al. (2009) | ||
| Three cohorts enrolled Caucasian and African-American participants from the United States, including Study of Osteoporotic Fractures (SOF), Cardiovascular Health Study (CHS), and Ashkenazi Jewish Centenarians (AJC). | Two intronic SNPs (rs1935949, rs4946935) were significantly associated with female lifespan. | Pawlikowska et al. (2009) | ||
| A community-based sample which was composed of up to 1345 Framingham Study participants from 330 families. | Genome-wide scan data revealed the SNP, rs6910534 near FOXO3A, is strongly associated with human longevity. | Lunetta et al. (2007) | ||
| GH1 (growth hormone 1) | IIS signaling | 1576 individuals (aged >85) from Dutch, or Leiden. | Female carriers of the intron 4 A allele had reduced height and mortality. | van Hemmst et al. (2005) |
| IGF1 (insulin-like growth factor) | IIS signaling | 1576 individuals (aged >85) from Dutch, or Leiden. | CA repeats (191 bp minor allele) seem to contribute most to female longevity. | van Hemmst et al. (2005) |
| IGF2 (insulin growth factor 2) | IIS signaling | 224 older (75 years) Jewish Jerusalem residents of Ashkenazi ethnicity and 441 younger subjects (22 years). | Increased A allele of RFLP marker (Apa I) was found in the older subjects. | Stessman et al. (2005) |
| IGF1R (insulin-like growth factor 1 receptor) | IIS signaling | 496 Italian health subjects, including 278 young people (mean age 54.8 years; 76 males and 202 females) and 218 long-lived people (mean age 98.0 years; 56 males and 162 females). | Subjects carrying at least one A allele of codon 1013 had lower free IGF1 plasma levels, and were more represented among long-lived people than in young people. | Bonafè et al. (2003) |
| INSR (insulin receptor) | IIS signaling | 122 Japanese semisupercentenarians (older than 105, mean age 106.8 years) and 122 healthy younger controls. | One INSR haplotype comprised of two intronic SNPs (rs3745548 and rs2252637) in linkage disequilibrium, and was more frequent in semisupercentenarians than in younger controls. | Kojima et al. (2004) |
| IRS1 (insulin receptor substrate 1) | IIS signaling | 1576 individuals (aged >85) from Dutch, or Leiden. | Arg allele of codon 972 seems to contribute to longevity in females. | van Hemmst et al. (2005) |
| 496 Italian health subjects, including 278 young people (mean age 54.8 years; 76 males and 202 females) and 218 long-lived people (mean age 98.0 years; 56 males and 162 females). | AA, GA, or GG genotype of codon 972 had identical levels of plasma IGF1, and had no association with longevity. | Bonafè et al. (2003) | ||
| P21 (CDKN1A) | Cell-cycle inhibitor | 184 centenarians and 184 younger subjects in the Italian population. | The rare alleles of two exon-derived SNPs (rs1801270, rs1059234), were significantly underrepresented among the centenarians. | Gravina et al. (2009) |
| PON1 (Paraoxonase 1) | Detoxication and lipoprotein metabolism | 308 centenarians and 579 controls enrolled from Italy. | The percentage of carriers of the B allele at codon 192 is higher in centenarians than in controls (0.539 versus 0.447). | Bonafè et al. (2002) |
| 256 healthy French Caucasian men (mean age 69.8 years). | Gln homozygotes of codon 192 were more frequent in aging than in Arg allele carriers. | Xia et al. (2003) | ||
| 100 healthy octogenarians and 200 adults of Sicilian. | Octagenerians had a higher percentage of (−107) CC genotype compared with controls, and displayed significant higher levels of PON1 activity. | Campo et al. (2004) | ||
| A community-based sample which was composed of up to 1345 Framingham Study participants from 330 families. | One SNP, rs2374983 located near PON1 showed association with both age at death and morbidity-free survival at age 65. | Lunetta et al. (2007) | ||
| TP53 (tumor protein p53) | Tumor suppressor | Centenarians and younger controls from continental Italy and Sardinia. | The carriers of P72 allele of rs1042522 were slightly increased in centenarians, though showing no statistic significance. | Bonafè et al., 1999a, Bonafè et al., 1999b |
| 66 nonagenarians/centenarians and 150 young healthy volunteers enrolled from Northern Italy. | The absence of any TP53 polymorphisms and of GSTT1 deletion, and the simultaneous presence of the three identified TP53 polymorphisms and of GSTT1 deletion, were much more frequent in young subjects than in centenarians. | Gaspari et al. (2003) | ||
| 1226 people aged 85 years and over. | The carriers of the PP genotype of rs1042522 have a 41% increased survival. | van Heemst et al. (2005) | ||