| — | Germline | Sterilization prolongs lifespan, in species from insect to humans.
In hermaphrodite C. elegans, removing sperm and egg-producing cells extends lifespan by 50%. Removing those cells triggers a reaction in the surrounding tissue. The signal is send out in the form of a steroid hormone, that turns on a molecular switch, which switches them into a kind of survival mode. Specifically, remaining gonadal cells trigger production of a steroid hormone dafachronic acid. Dafachronic acid activates miRNAs, which work as tiny molecular switch causing changes in gene expression that promote longevity. The same steroid hormone-miRNA switch is part of the developmental clock. The loss of the germ cells ultimately causes the worm to use developmental timers to put in motion a lifespan-prolonging programme [23239738]. | — |
| ABP1 | Actin Binding Protein 1 | ABP1 deletion increases replicative lifespan by 30% in the alpha strain and decreases replicative lifespan by 20% in the a strain [18340043]. Deletion of ABP1 increases replicative lifespan by 20% in the alpha strain and decreases replicative lifespan by 20% in the a strain [19030232]. | Budding yeast |
| ACB1 | Acyl-CoA-Binding 1 | ACB1 deletion extends chronological lifespan under starvation/extreme DR. Similar heat-shock resistance and resistance to a very hight concentration of acetic acid (but not resistance to oxidative stress) was enhanced by the deletion of ACB1. Deletion of ACB1 in W303-1A and DBY746 genetic backgrounds on synthetic complete media causes severe growth defects and sightly shorter lifespan and also heat-sensitivity [20657825]. | Budding yeast |
| arf-3 | ADP-Ribosylation Factor related 3 | RNA interference of arf-3 does not affect lifespan of wild-type but suppresses lifespan extension by isp-1 mutation [22829775]. | — |
| Arntl | aryl hydrocarbon receptor nuclear translocator-like | Arntl knockout mice display symptoms of premature aging including a shorter lifespan, sarcopenia, cataracts, less subcutaneous fat, and organ shrinkage [16847346]. | House mouse |
| ARO7 | AROmatic amino acid requiring 7 | Under starvation/extreme DR deletion of ARO7 increases mean chronological lifespan and confers higher resistance to heat-shock, but made cell more sensitive to acetic acid and leads to growth defects. In W303-1A background ARO7 deletion causes an even more severe growth defect and mutants are short-lived [20657825]. | Budding yeast |
| Atm | Ataxia telangiectasia mutated homolog (human) | Atm-deficient mice are viable, retarded in growth, infertile (male produce no mature sperm and female no gametes), display neurological dysfunction, and exhibit severe defects in T cell maturation while going on to develop thymomas [8917548; 8689683]. The majority of mutant mice rapidly develop thymic lymphomas and die before 4 months of age [8843194].
Cells of Atm(-/-) mice exhibit slow growth also in culture and premature senescence, telomeres are extensively shortened in multiple tissues [8689683].
Mice mutant for Atm and Terc display progressive multi-organ system compromise and features of accelerated aging [12540856]. | House mouse |
| baf-1 | Barrier to Autointegration Factor 1 | RNA interference of baf-1 decreases median lifespan by 28% in daf-2 mutants [18006689]. | Nematode |
| bax | Bcl2-associated X protein | Inactivation of proapoptotic Bax extends fertile potential and minimized age-related health problems, including bone and muscle loss, excess fat deposition, alopecia, cataracts, deafness, increased anxiety, and selective attention deficit. Bax deficiency does not lead to an increase in tumor incidence. Despite the apparently increased quality of life of aging females lacing Bax, there is no significant differences in overall lifespan [17360389]. | House mouse |
| BUB1B | budding uninhibited by benzimidazoles 1 homolog beta (yeast) | Mutations in BUB1B are associated with mosaic variegated aneuplody, a rare human syndrome characterized by aneuplodization, tumour predisposition and several progeroid traits, including short lifespan, growth and mental retardation, cataracts and facial dysmorphisms [16411201; 15475955; 20651707]. | Human |
| Bub3 | budding uninhibited by benzimidazoles 3 homolog (S. cerevisiae) | Haploinsufficiency of Bub3 and Rae1, but not haploinsufficiency of either gene by itself, reduces lifespan by 12% and appears to accelerate aging [16476774]. | House mouse |
| C29F9.1 | — | RNA interference of C29F9.1 decreases median lifespan by 35% in daf-2 mutants [18006689]. | Nematode |
| CCL11 | chemokine (C-C motif) ligand 11 | CCL11 is an age-related systemic factor associated with decreased neurogenesis. Relative levels of CCL11 increase in the plasma during aging an in young mice during Heterochronic Parabiosis [21886162]. | House mouse |
| CCL11 | chemokine (C-C motif) ligand 11 | CCL11 exhibits an age-related increase in the plasma and cerebrospinal fluid from healthy human individuals between 20 and 90 years [21886162]. | Human |
| CCL2 | chemokine (C-C motif) ligand 2 | CCL2 levels are evaluated in old unpaired and young heterochronic (with old animals) paired mice [21886162]. | House mouse |
| CCL2 | chemokine (C-C motif) ligand 2 | CCL2 levels in plasma increase with age and it is part of the senescence-associated secretory phenotype [19648977]. | Human |
| Cdkn1a | Cyclin-dependent kinase inhibitor 1A | Deletion of Cdkna1 (alias p21) prolongs the lifespan of telomerase-deficient mice with dysfunctional telomeres and improves the repopulation capacity and self-renewal of hematopoietic stem cells [17143283].
The p21(-/-) strains like the Cdkn1a(tmi/Tyj) exhibits enormous regenerative capacities as it closes ear holes similar to MRL mice [20231440; 21722344]. | House mouse |
| 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 |
| Chek2 | CHK2 checkpoint homolog (S. pombe) | Mice hypomorphic for Brca1 and double mutant for chk2 exhibit signs of premature ageing. | House mouse |
| Chromosome 4 | epithelial cell adhesion molecule | — | Human |
| cit-1.2 | CyclIn T 1.2 | RNA interference cit-1.2 decreases median lifespan by 27% in daf-2 mutants [18006689]. | Nematode |
| cku-70 | Caenorhabditis KU 70 | RNA interference of cku-70 further increases the lifespan of daf-2 mutants. Lifespan of daf-16 mutants is slightly decreased by cku-70 RNAi [16099946]. | Nematode |
| CTA1 | CaTalase A 1 | CTA1 overexpression partially suppresses the shortened chronological lifespan by ISC1 mutation [21707788]. | Budding yeast |
| cul-1 | CULlin 1 | RNAi of cul-1 decreases lifespan of daf-2 mutant, but not of wild-type or glp-1 mutant. The CUL-1 complex functions in postmitotic, adult somatic tissues of insulin/insulin-like growth factor-1-signaling mutants to enhance longevity. It may act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO [17392428]. | Nematode |
| daf-12 | Abnormal DAuer Formation | Mutations in daf-2 and daf-12, but not mutations in daf-12 alone, nearly quadruples lifespan [7789761]. Recessive loss of function mutation in daf-12 shortens lifespan. daf-12 activity is required for lifespan extension after germ line ablation [10360574]. daf-12 mutation suppresses the lifespan extension by mutation in daf-28 [8807293]. daf-12 mutants are dauer defective and heterochronic [7219552]. Some daf-12 alleles exhibit synthetic lethality with mutation of age-1 [8807293] or daf-12 [1732156]. | Nematode |
