| 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 |
| Celsr3 | Cadherin EGF LAG seven-pass G-type receptor 3 | Celsr3 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 |
| Chmp2a | charged multivesicular body protein 2a | Chmp2a 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 |
| Col4a5 | collagen, type IV, alpha 5 | Col4a5 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 |
| Cox14 | COX14 cytochrome c oxidase assembly | Cox14 (D3ZWG6_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 |
| Cox5a | Cytochrome c oxidase subunit 5A, mitochondrial | Cox5a 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 |
| Cox7c | cytochrome c oxidase, subunit VIIc | Cox7c 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 |
| Cyth2 | Cytohesin-2 | Cyth2 is transcriptional uprgulated 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 |
| D3ZTB8_RAT | — | D3ZTB8_RAT 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 |
| D3ZWG6_RAT | — | D3ZWG6_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 |
| D4ACK9_RAT | — | D4ACK9_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 |
| 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 |
| SNF4Agamma | SNF4/AMP-activated protein kinase gamma subunit | Deletion of SNF4Agamma from the first day of the imaginal stage shortens mean lifespan by 23% and causes morphological and behavioural features of premature aging [18219227]. | 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 |
| Egln3 | Egl nine homolog 3, mitochondrial | Egln3 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 |
| elav | embryonic lethal abnormal vision | elav mutation significantly decreases the lifespan. Median lifespan in males is 66% lower [20589912]. | Fruit fly |
| Eml5 | Echinoderm microtubule-associated protein-like 5 | Eml5 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 |
| INS | insulin | Expression of human insulin under an inducible heat shock promoter increases nematode lifespan by 25% and is also able to enhance the lifespan of daf-2 mutants [11274053]. INS was found to be associated with longevity [22406557; 19367319; 17989723; 19489743]. | Human |
| Fam107a | family with sequence similarity 107, member A | Fam107a 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 |
| tert | telomerase reverse transcriptase | First-generation tert(-/-) zebrafish die prematurely with shorter telomeres. tert(-/-) fish develop degenerative phenotypes, including premature infertility, gastrointestinal atrophy, and sarcopenia. tert(-/-) mutants have impaired cell proliferation, accumulation of DNA damage markers, and a p53 response leading to early apoptosis, followed by accumulation of senescence cells. Apoptosis is primarily observed in the proliferative niche and germ cells. Cell proliferation, but not apoptosis, is rescued in tp53(-/-)tert(-/-) mutants, underscoring p53 as mediator of telomerase deficiency and consequent telomere instability [http://denigma.de/url/3p]. | Zebrafish |
