|symbol ||name ||observation ||species |
|Cdkn2a ||cyclin-dependent kinase inhibitor 2A ||Cdkn2a encodes different transcripts involved mostly in cell cycle regulation and cellular senescence , but it can also act as a tumor suppressor. Its expression level increase with age in rodents . 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 . Loss of Cdkn2a in mice results in tumour susceptibility . Mice deficient in Cdkn2a have smaller age-related decline in self-renewal potential as this process is associated with increasing levels of Cdkn2a .
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 .
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 |
|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 . ||House mouse |
|miR-214 ||microRNA 214 ||Expression increases with age in mouse liver. The miRNA downregulates detoxification and regeneration genes, which may contribute to aging . ||House mouse |
|Mir669c ||microRNA 669c ||Expression increases with age in mouse liver. The miRNA downregulates detoxification and regeneration genes, which may contribute to aging . ||House mouse |
|Nudt1 ||nudix (nucleoside diphosphate linked moiety X)-type motif 1 ||hMTH1-Tg mice express high levels of the hMTH1 hydrolase that degrades 8-oxoGTP and 8-oxoGTP and excludess 8-oxoguanine from both DNA and RNA.
hMTH1-overexpresing mice have significantly lower steady-state levels of 8-oxoguanine in both nuclear and mitochondrial DNA of several organs, including the brain. hMTH1 overexpression prevents the age-dependent accumulation of DNA 8-oxoguanine that occurs in the wild-type mice. These lower levels of oxidized guanines are associated with increased longevity and hMTH1-Tg animals live significantly longer than their wild-type littermates .
||House mouse |
|Pten ||phosphatase and tensin homolog ||Increasing gene dosage via homogeneous and moderate overexpression, while retaining its normal pattern of tissue expression of Pten increases mean, median and maximum lifespan in both females and males. Mean lifespan is extended by 18% (males), 11% (females) and 14% (both). Median lifespan in males, females and both increases by 12%, 16% and 12%, respectively . Transgenic Pten mice carrying the additional genomic copies of Pten are protected from cancer and present a significant extension of lifespan that is independent of their lower cancer incidence. Pten(g) mice have an increased energy expenditure and protection from metabolic pathologies .
PTEN promotes oxidative phosphorylation and decreases glycolysis. PTEN aslo upregulates UCP1 expression in brown adipocytes, which enhances their nutrient burning capacity and decreases adiposity and associated pathologies 
||House mouse |
|Mir1 ||— ||miR-1 is associated with stem cell differentiation in mouse and human ESCs . ||House mouse |
|Mir133 ||— ||miR-133 is associated with stem cell differentiation in mouse and human ESCs . ||House mouse |
|MIR20A ||microRNA 20a ||Overexpression of MiR-20a in mouse embryonic fibroblasts induces senescence by lowering Lrf (a transcriptional repressor of the Mdm2 inhibitor p19ARF [15662416; 9529248]) protein levels and in turn increasing p19ARF levels . ||House mouse |
|Srf ||Serum Response Factor ||SRF is activated by the daily variations of a blood signal, resulting in significant changes in the structure and size of live cells throughout the course of the day .
Daily variations of plasma signal cyclically stimulates SRF. SRF is solicited in an antiphasic manner in humans and rats, a fact that is linked to their activity, diurnal and nocturnal, respectively. SRF activation is accompanied by a remodeling of the cellular "skeleton", resulting in morphological change in cells based on their activity .
||House mouse |