Table 1.
Selected human candidate genes for involvement in lifespan determination
| Gene names or genetic defects (symbol) | Protein function | Phenotype | Populations/study locations | References |
|---|---|---|---|---|
| Apolipoprotein E (APOE) | Ligand for the LDL receptor | Consistently associated with survival and longevity | Multiple | 55 |
| Apolipoprotein C3 (APOC3) | Major component of VLDL and chylomicron remnants | Associated with cardiovascular risk factors and longevity in one study | Ashkenazi Jews | 57 |
| Microsomal triglyceride transfer protein (MTTP) | Transport of triglycerides, cholesteryl esters and phospholipids | Inconsistent linkage and association results for longevity | United States | 44,104 |
| France | 45 | |||
| Germany | 58 | |||
| Denmark | 59 | |||
| Cholesteryl ester transfer protein (CETP) | Transfer of cholesteryl esters | Inconsistent association results for longevity | Ashkenazi Jews | 105 |
| Italy | 106 | |||
| Angiotensin I-converting enzyme (ACE) | Hydrolyses angiotensin I to angiotensin II | Inconsistent association results for longevity | Germany | 61 |
| Denmark | 62,63 | |||
| Insulin-like growth factor 1 receptor (IGF1R) | Energy-status signalling | One study shows association with longevity | Italy | 65 |
| Growth hormone 1 (GH1) | Growth hormone (insulin signalling component) | One study shows association with survival at age 85+ | Holland | 66 |
| Catalase (CAT) | Catalyses the decomposition of hydrogen peroxide | No association with survival | Denmark | 107 |
| Superoxide dismutases 1 and 2 (SOD1 and SOD2) | Catalyses the breakdown of superoxide radicals | One study shows association with longevity | Italy | 99 |
| Heat shock proteins (HSPA1A and HSPA1L) | Protein folding and transport; immune system functions | Various associations but not replicated | Italy | 108 |
| Ireland | 109 | |||
| Paraoxonase 1 (PON1) | Preserves HDL function and protects LDL from oxidative modification | Inconsistent association results for longevity | Denmark | 110 |
| Italy and Ireland | 111 | |||
| Interleukin 6 (IL6) | An immunoregulatory cytokine | Inconsistent, but longitudinal studies show association with longevity | Denmark | 79 |
| Finland | 80 | |||
| Hereditary haemochromatosis (HFE) | Regulation of iron absorption in the intestine | Inconsistent association results for longevity | Denmark | 67 |
| France | 69 | |||
| Italy | 112 | |||
| Methylenetetrahydrofolate reductase (MTHFR) | Re-methylation of homocysteine to methionine | Inconsistent association results for longevity | Denmark | 63 |
| Switzerland | 113 | |||
| Multiple | 114 | |||
| Ashkenazi Jews | 115 | |||
| Sirtuin 3 (SIRT3) | Unknown | Various associations but not replicated | Italy | 116,117 |
| Tumour protein p53 (TP53) | Tumour suppressor gene | Inconsistent association results for longevity | Holland | 66 |
| Italy | 118 | |||
| Transforming growth factor β 1 (TGFB1) | Regulation of proliferation and differentiation; various other functions | One study shows association with longevity | Italy | 119 |
| Klotho (KL) | A type-1 membrane protein that is related to β-glucosidases; function is still unclear | Heterozygous survival advantage in two populations | Czech Republic | 120 |
| Ashkenazi Jews | 121 | |||
| Werner syndrome (WRN) | Maintenance and repair of DNA; DNA replication | One study shows association with age but not replicated | Mexico and Finland | 122 |
| Holland | 90 | |||
| mutL homologue 1 (MLH1) | DNA mismatch repair enzyme | One study shows association with age | Korea | 123 |
| Mitochondrial mutations(Mt5178A, Mt8414T, Mt3010A and J haplotype) | Mitochondrial energy production | Single studies or inconsistent association results for longevity | Japan | 81 |
| Italy | 82–84 |
HDL, high-density lipoprotein; LDL, low-density lipoprotein; VLDL, very-low-density lipoprotein.