| 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 |
| Atg2 | Autophagy-specific gene 2 | Atg2 overexpression increases average female lifespan by 28% [18059160]. | 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 |
| Pka-C1 | cAMP-dependent protein kinase 1 | PKA-overexpressing flies (hsPKA*/+) have an about 30% extended maximum lifespan [17369827]. | Fruit fly |
| CPB2 | carboxypeptidase B2 (plasma) | Genotypes of the CPB2 gene were studied in 2224 men and women aged 65 or older at baseline. During 10 years of follow-up, men with the -438 A/A genotype had decreased mortality due to all causes, and lived, on average, longer than men with the -438 G allele. The effects of -438 G/A in women were smaller and not statistically significant [15939070].CPB2 was found to be associated with longevity [15939070]. | Human |
| Mnt | CG13316-PC, isoform C | A dMnt null allele results in flies with larger cells, increased weight, and decreased lifespan [16055719]. | Fruit fly |
| 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 |
| 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 |
| CETP | cholesteryl ester transfer protein, plasma | Homozygousity for the I405V variant of CETP is associated with exceptional longevity and larger HDL and LDL particle sizes as well as lower prevalence of hypertension, cardivascular disease, and metabolic disease among Askenazi Jews [14559957]. CETP I405V homozygousity is associated with exceptional longevity and preservation of cognitive function in Askenazi Jews [17190939].
V/V homozygotes tend to have a 9-23% CETP deficiency [9610775; 15243211]. A decrease in CETP function increases HDL (high density lipoproteins) levels in the body, and decreases LDL (low-density lipoprotein). The result of this s that HDL-c levels are approximately equal in individuals with the I/I or I/V genotypes, while there are ten percent higher in V/V individuals [9610775].
Therefore the V/V SNP acts kind like an endogenous *CEPT inhibitor*, which might be the responsible for the increase in longevity but may also have side effects.CETP was found to be associated with longevity [22336474].CETP was found to be associated with longevity [15621216].CETP was found to be associated with longevity [15888337]. CETP was found to be associated with longevity [22234866]. CETP was found to be associated with longevity [22336474]. CETP was found to be associated with longevity [23389097]. CETP was found to be associated with longevity [23389097]. CETP was found to be associated with longevity [15621216]. CETP was found to be associated with longevity [15888337]. CETP was not found to be associated with longevity [23389097]. CETP was found to be associated with longevity [14559957]. CETP was found to be associated with longevity [16602826]. CETP was found to be associated with longevity [23162014]. CETP was not found to be associated with longevity [14559957]. CETP was found to be associated with longevity [18034366]. CETP was not found to be associated with longevity [24468472]. | Human |
| CLU | clusterin | Overexpression of the secretory form of human Clusterin in fruit flies increases mean lifespan. hClu overexpression flies also have greater tolerance to heat shock, wet starvation, and oxidative stress and the whole body amounts of reactive oxygen species is lower [22465014].CLU was found to be associated with longevity [16804001]. | Fruit fly |
| F2 | Coagulation factor II (thrombin) | — | Human |
| 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 |
| 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 |
| CFB | complement factor B | Genetic variations in CFB are not associated with longevity in Italian [10219002]. | 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 |
| DNApol-gamma35 | DNA polymerase gamma 35kD | Overexpression of DNApol-gamma35 (DNA polymerase gamma) in the nervous system results in a decrease in the median lifespan ranging from 39% to 52% [17999718].
| Fruit fly |
| Drd4 | Dopamine D4 Receptor | Drd4 knockout mice, when compared with wild-type and heterozygous mice, display a 7 - 9.7% decrease in lifespan, reduced spontaneous locomotor activity, and no lifespan increase when reared in an enriched environment [23283341]. | House mouse |
| Dys | Dystroglycan | Loss of dys function in the heart leads to an age-dependent disruption of the myofibrillar organization within the myocardium as well as to alterations in cardiac performance. dys RNAi-mediated knockdown in the mesoderm also shortens lifespan. Mesodermal dys knockout results in a morderate maximum lifespan reduction (13%), but not when exclusively targeted to the heart. In contrast, half of the transheteozygous DysExel618/Dyskx43 deficiency flies die at 29 days compared to 63 days in controls. This indicates that a moderate dye loss-of-function in all muscles, but not in just the heart, reduces the normal lifespan [18221418]. | Fruit fly |
| EcR | Ecdysone receptor | Mutant heterozygotes in EcR live on mean 40%-50% longer than controls [12610309; reviewed in 12610294]. Homozygous mutants in EcR are inviable. The developmental time and weight of EcR+/- mutants is the same as control, but resistance to temperature, oxidative stress, and starvation is increased in heterozygotes [12610309]. | Fruit fly |
| Eip71CD | Ecdysone-induced protein 28/29kD | Overexpression of Eip71CD (alias MsrA) in nervous system extends the lifespan by up to 70%, increased resistance to oxidative stress, and delays the onset of senescence-induced decline in activity levels and reproductive capacity. Eip71CD is a downstream effector of foxo [22310715].
Mean and maximum lifespan is increased by up to 2-% in animals that overexpress Eip71CD [20655917]. | Fruit fly |
| Ef1alpha48D | Elongation factor 1alpha48D | Overexpression of Ef1alpha48D (transformed with a P-element vector and under control of hsp70 regulatory sequences) results in lifespan extension by 18-41%. The decrease in protein synthesis that accompanies aging is preceded by a decrease in EF-1 alpha protein and mRNA [2508089]. | Fruit fly |
| elav | embryonic lethal abnormal vision | elav mutation significantly decreases the lifespan. Median lifespan in males is 66% lower [20589912]. | Fruit fly |
| E(z) | Enhancer of zeste | Flies heterozygous for the protein null E(z)63 or the catalytically inactive E(z)731 mutation that are progeny of an out-cross to an Oregon-R (O-R) wild-type strain exhibit a substantially greater median lifespan than the O-R control (71% and 76%, respectively). When derived from an out-cross to a longer-lived Canton-S (C-S) wild-type strain, the median lifespan of E(z)63 heterozygous is 33% longer than the C-S control [20018689]. | Fruit fly |
