Редактирование: EGR1

Early growth response protein 1 (EGR-1) (AT225) (Nerve growth factor-induced protein A) (NGFI-A) (Transcription factor ETR103) (Transcription factor Zif268) (Zinc finger protein 225) (Zinc finger protein Krox-24) [KROX24] [ZNF225]

==Publications==

{{medline-entry
|title=Glucocorticoids delay RAF-induced senescence promoted by [[EGR1]].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31371485
|abstract=Expression of hyperactive RAF kinases, such as the oncogenic B-RAF-V600E mutant, in normal human cells triggers a proliferative arrest that blocks tumor formation. We discovered that glucocorticoids delayed the entry into senescence induced by B-RAF-V600E in human fibroblasts, and allowed senescence bypass when the cells were regularly passaged, but that they did not allow proliferation of cells that were already senescent. Transcriptome and siRNA analyses revealed that the [[EGR1]] gene is one target of glucocorticoid action. Transcription of the [i][[EGR1]][/i] gene is activated by the RAF-MEK-ERK MAPK pathway and acts as a sensor of hyper-mitogenic pathway activity. The [[EGR1]] transcription factor regulates the expression of p15 and p21 (encoded by [i]CDKN2B[/i] and [i]CDKN1A[/i], respectively) that are redundantly required for the proliferative arrest of BJ fibroblasts upon expression of B-RAF-V600E. Our results highlight the need to evaluate the action of glucocorticoid on cancer progression in melanoma, thyroid and colon carcinoma in which B-RAF-V600E is a frequent oncogene, and cancers in which evasion from senescence has been shown.
|mesh-terms=* Amino Acid Substitution
* Cell Line
* Cellular Senescence
* Cyclin-Dependent Kinase Inhibitor p15
* Cyclin-Dependent Kinase Inhibitor p21
* Early Growth Response Protein 1
* Fibroblasts
* Glucocorticoids
* Humans
* MAP Kinase Signaling System
* Mutation, Missense
* Proto-Oncogene Proteins B-raf
|keywords=* B-RAF-V600E
* CDKN1A
* CDKN2B
* EGR1
* Glucocorticoid
* Oncogene-induced senescence
|full-text-url=https://sci-hub.do/10.1242/jcs.230748
}}
{{medline-entry
|title=[[EGR1]] promotes the cartilage degeneration and hypertrophy by activating the Krüppel-like factor 5 and β-catenin signaling.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31201921
|abstract=Osteoarthritis is one of the most common orthopedic diseases in elderly people who have lost their mobility. In this study，we observed abnormally high [[EGR1]] expression in the articular cartilage of patients with osteoarthritis. We also found significantly high [[EGR1]] expression in the articular cartilage of mice with destabilized medial meniscus (DMM)-induced osteoarthritis and 20-month-old mice. In vitro experiments indicated that IL-1β could significantly enhance [[EGR1]] expression in primary mouse chondrocytes. [[EGR1]] over-expression in chondrocytes using adenovirus could inhibit COl2A1 expression and enhance [[MMP9]] and [[MMP13]] expression. And silencing [[EGR1]], using RNAi, had the opposite effects. Moreover, [[EGR1]] over-expression accelerated chondrocyte hypertrophy in vitro, and [[EGR1]] knockdown reversed this effect. We then explored the underlying mechanism. [[EGR1]] over-expression increased Kruppel-Like Factor 5 ([[KLF5]]) protein level without influencing its synthesis. Enhanced [[EGR1]] expression induced its integration with [[KLF5]], leading to suppressed ubiquitination of [[KLF5]]. Moreover, [[EGR1]] prompted β-catenin nuclear transportation to control chondrocyte hypertrophy. Ectopic expression of [[EGR1]] in articular cartilage aggravated the degradation of the cartilage matrix in vivo. The [[EGR1]] inhibitor, ML264, protected chondrocytes from IL-1β-mediated cartilage matrix degradation in vitro and DMM-induced osteoarthritis in vivo. Above all, we demonstrate the effect and mechanisms of [[EGR1]] on osteoarthritis and provide evidence that the ML264 might be a potential drug for treating osteoarthritis in the future.
|mesh-terms=* Aging
* Animals
* Cartilage, Articular
* Chondrocytes
* Early Growth Response Protein 1
* Heterocyclic Compounds, 3-Ring
* Humans
* Interleukin-1beta
* Kruppel-Like Transcription Factors
* Matrix Metalloproteinase 9
* Mice
* Mice, Inbred C57BL
* Osteoarthritis
* RNA Interference
* RNA, Small Interfering
* Signal Transduction
* Ubiquitin
* Ubiquitination
* Up-Regulation
* beta Catenin
|keywords=* Chondrocyte
* EGR1
* KLF5
* Osteoarthritis
|full-text-url=https://sci-hub.do/10.1016/j.bbadis.2019.06.010
}}
{{medline-entry
|title=Identification of key genes and transcription factors in aging mesenchymal stem cells by DNA microarray data.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30641220
|abstract=Mesenchymal stem cells ([[MSC]]s) are multipotent cells that can be widely used in stem cell therapy. However, few studies have revealed the potential mechanisms of the changes in aging [[MSC]]. In this study, microarray data GSE35955 was downloaded from the Gene Expression Omnibus database. Then limma package in R was used to filtrate differentially expressed genes (DEGs), Transcription factors ([[TF]]s) were predicted by DCGL package. After predicting [[TF]]s, protein-protein interaction (PPI) network and [[TF]]-mediated transcriptional regulation network were constructed. The functional and pathway enrichment analysis of screened DEGs, hub genes and [[TF]]s were conducted by the DAVID. Totally 156 up-regulated DEGs and 343 down-regulated DEGs were obtained. 6 hub genes ([[CTNNB1]], [[PPP2R1A]], [[FYN]], [[MAPK1]], [[PIK3C2A]] and [[EP300]]) were obtained from PPI network. 11 [[TF]]s (CREB1, [[[[CUX1]]]], [[EGR1]], [[EP300]], [[FOXC1]], [[HSF2]], [[MEF2A]], [[PLAU]], [[SP1]], [[STAT1]] and USF1) for DEGs were predicted and 2 highly scored co-expression relationships ([[EP300]]-[[PPP2R1A]] and [[STAT1]]-[[FOXC1]]) were acquired from the [[TF]]-mediated transcriptional regulation network. The discovery of the hub genes, [[TF]]s and pathways might contribute to the understanding of genetic and molecular functions of aging-related changes in [[MSC]]. Further validation studies on genes and [[TF]]s such as [[CTNNB1]], [[FYN]], [[PPP2R1A]], [[MAPK1]], [[EP300]] and related biological processes and pathways, including adherens junction, DNA damage caused from oxidative stress, attribution of telomere, [[MSC]] differentiation and epigenetic regulation, are urgent for clinical prevention and treatment.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Gene Expression Profiling
* Gene Expression Regulation
* Humans
* Mesenchymal Stem Cells
* Middle Aged
* Mitogen-Activated Protein Kinase 1
* Oligonucleotide Array Sequence Analysis
* Protein Interaction Maps
* Protein Phosphatase 2
* Proto-Oncogene Proteins c-fyn
* Transcription Factors
* beta Catenin
|keywords=* Differentially expressed genes
* Enrichment analysis
* Gene Expression Omnibus
* Hub genes
* Microarray analysis
* Protein-protein interaction network
* Transcriptional regulatory network
|full-text-url=https://sci-hub.do/10.1016/j.gene.2018.12.063
}}
{{medline-entry
|title=Hypoxia-inducible transcription factors, [[HIF1A]] and HIF2A, increase in aging mucosal tissues.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29338076
|abstract=Hypoxia (i.e. oxygen deprivation) activates the hypoxia-signalling pathway, primarily via hypoxia-inducible transcription factors (HIF) for numerous target genes, which mediate angiogenesis, metabolism and coagulation, among other processes to try to replenish tissues with blood and oxygen. Hypoxia signalling dysregulation also commonly occurs during chronic inflammation. We sampled gingival tissues from rhesus monkeys (Macaca mulatta; 3-25 years old) and total RNA was isolated for microarray analysis. [[HIF1A]], HIF1B and HIF2A were significantly different in healthy aged tissues, and both [[HIF1A]] and [[HIF3A]] were positively correlated with aging. Beyond these transcription factor alterations, analysis of patterns of gene expression involved in hypoxic changes in tissues showed specific increases in metabolic pathway hypoxia-inducible genes, whereas angiogenesis pathway gene changes were more variable in healthy aging tissues across the animals. With periodontitis, aging tissues showed decreases in metabolic gene expression related to carbohydrate/lipid utilization (GBE1, [[PGAP1]], TPI1), energy metabolism and cell cycle regulation (IER3, [[CCNG2]], PER1), with up-regulation of transcription genes and cellular proliferation genes (FOS, [[EGR1]], [[MET]], JMJD6) that are hypoxia-inducible. The potential clinical implications of these results are related to the epidemiological findings of increased susceptibility and expression of periodontitis with aging. More specifically the findings describe that hypoxic stress may exist in aging gingival tissues before documentation of clinical changes of periodontitis and, so, may provide an explanatory molecular risk factor for an elevated capacity of the tissues to express destructive processes in response to changes in the microbial biofilms characteristic of a more pathogenic microbial challenge.
|mesh-terms=* Age Factors
* Aging
* Animals
* Basic Helix-Loop-Helix Transcription Factors
* Gene Expression
* Hypoxia
* Hypoxia-Inducible Factor 1, alpha Subunit
* Macaca mulatta
* Mucous Membrane
* Periodontitis
* Signal Transduction
|keywords=* aging
* hypoxia
* mucosal tissues
* non-human primates
* periodontitis
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002220
}}
{{medline-entry
|title=The p16/miR-217/[[EGR1]] pathway modulates age-related tenogenic differentiation in tendon stem/progenitor cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29036495
|abstract=Previous studies have shown that the differentiation potential declines with the age of progenitor cells and is linked to altered levels of senescence markers. The purpose of this study was to test whether senescence marker p16 affects age-related tenogenic differentiation in tendon stem/progenitor cells (TSPCs). Young and aged TSPCs were isolated from young/healthy and aged/degenerated human Achilles tendons, respectively. Cellular aging and capacity for tenogenic differentiation were examined. The results showed that the tenogenic differentiation capacity of TSPCs significantly decreases with advancing age. TSPCs from elderly donors showed upregulation of senescence-associated β-galactosidase and p16 and concurrently a decrease in Type I collagen concentration and in the expressions of tendon-related markers: Scx, Tnmd, Bgn, Dcn, Col1, and Col3. Overexpression of p16 significantly inhibited tenogenic differentiation of young TSPCs. Analysis of the mechanism revealed that this effect is mediated by microRNA-217 and its target [[EGR1]]. These results indicated that p16 inhibits tenogenic differentiation of TSPCs via microRNA signaling pathways, which may serve as a potential target for the prevention or treatment in the future.
|mesh-terms=* Adolescent
* Adult
* Age Factors
* Aged
* Cell Differentiation
* Cyclin-Dependent Kinase Inhibitor p16
* Early Growth Response Protein 1
* Humans
* MicroRNAs
* Middle Aged
* Signal Transduction
* Stem Cells
* Tendons
* Young Adult
|keywords=* aging
* miR-217
* p16
* progenitor cell
* tendon stem
|full-text-url=https://sci-hub.do/10.1093/abbs/gmx104
}}
{{medline-entry
|title=Age-associated up-regulation of [[EGR1]] promotes granulosa cell apoptosis during follicle atresia in mice through the NF-κB pathway.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27436181
|abstract=Follicular atresia is the main process responsible for the loss of follicles and oocytes from the ovary, and it is the root cause of ovarian aging. Apoptosis of granulosa cells ([[GC]]s) is the cellular mechanism responsible for follicular atresia in mammals. Recent advances have highlighted fundamental roles for [[EGR1]] in age-related diseases via the induction of apoptosis. In the present study, we found that the expression of [[EGR1]] was significantly increased in aged mouse ovaries compared with young ovaries. Immunohistochemical analysis revealed strongly positive [[EGR1]] staining in atretic follicles, especially in apoptotic granulosa cells. We further showed that [[EGR1]] up-regulation in mouse primary granulosa cells inhibited cell proliferation and promoted apoptosis. In addition, the promotion of apoptosis in [[GC]]s by [[EGR1]] increases over time and with reactive oxygen species (ROS) stimulation. Our mechanistic study suggested that [[EGR1]] regulates [[GC]] apoptosis in a mitochondria-dependent manner and that this mainly occurs through the NF-κB signaling pathway. In conclusion, our results suggested that age-related up-regulation of [[EGR1]] promotes [[GC]] apoptosis in follicle atresia during ovarian aging.
|mesh-terms=* Aging
* Animals
* Apoptosis
* Cell Proliferation
* Early Growth Response Protein 1
* Female
* Follicular Atresia
* Gene Expression Regulation, Developmental
* Granulosa Cells
* Mice, Inbred C57BL
* Mitochondria
* NF-kappa B
* PTEN Phosphohydrolase
* Signal Transduction
* Tumor Suppressor Protein p53
* Up-Regulation
|keywords=* EGR1
* NF-κB
* apoptosis
* follicular atresia
* granulosa cell
* ovarian aging
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5105915
}}
{{medline-entry
|title=RNA-Seq analysis reveals new evidence for inflammation-related changes in aged kidney.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27153548
|abstract=Age-related dysregulated inflammation plays an essential role as a major risk factor underlying the pathophysiological aging process. To better understand how inflammatory processes are related to aging at the molecular level, we sequenced the transcriptome of young and aged rat kidney using RNA-Seq to detect known genes, novel genes, and alternative splicing events that are differentially expressed. By comparing young (6 months of age) and old (25 months of age) rats, we detected 722 up-regulated genes and 111 down-regulated genes. In the aged rats, we found 32 novel genes and 107 alternatively spliced genes. Notably, 6.6% of the up-regulated genes were related to inflammation (P < 2.2 × 10-16, Fisher exact t-test); 15.6% were novel genes with functional protein domains (P = 1.4 × 10-5); and 6.5% were genes showing alternative splicing events (P = 3.3 × 10-4). Based on the results of pathway analysis, we detected the involvement of inflammation-related pathways such as cytokines (P = 4.4 × 10-16), which were found up-regulated in the aged rats. Furthermore, an up-regulated inflammatory gene analysis identified the involvement of transcription factors, such as [[STAT4]], [[EGR1]], and [[FOSL1]], which regulate cancer as well as inflammation in aging processes. Thus, RNA changes in these pathways support their involvement in the pro-inflammatory status during aging. We propose that whole RNA-Seq is a useful tool to identify novel genes and alternative splicing events by documenting broadly implicated inflammation-related genes involved in aging processes. 
|mesh-terms=* Aging
* Alternative Splicing
* Animals
* Biomarkers
* Down-Regulation
* Early Growth Response Protein 1
* Feasibility Studies
* Gene Expression Profiling
* Inflammation
* Kidney
* Male
* Proto-Oncogene Proteins c-fos
* RNA
* Rats
* Rats, Sprague-Dawley
* STAT4 Transcription Factor
* Sequence Analysis, RNA
* Signal Transduction
* Specific Pathogen-Free Organisms
* Transcriptome
* Up-Regulation
|keywords=* Gerotarget
* RNA-Seq
* aging
* alternative splicing
* differentially expressed genes
* inflammation
* novel genes
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058662
}}
{{medline-entry
|title=Minocycline enhances hippocampal memory, neuroplasticity and synapse-associated proteins in aged C57 BL/6 mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25838119
|abstract=Previous studies have suggested that minocycline can attenuate cognitive deficits in animal models of conditions such as Alzheimer's disease and cerebral ischemia through inhibiting microglia associated anti-inflammatory actions. However the pathway that minocycline targets to enhance cognitive performance is not fully defined. Here we examined the effects of minocycline on learning and memory in aged (22-month-old) C57 BL/6 mice. We treated one group of mice with minocycline (30 mg/kg/day), and another group of mice with donepezil (2 mg/kg/day) as a positive control. The Morris water maze and passive avoidance tests were used to evaluate the effects of minocycline on learning and memory deficits. We also used high-frequency stimulation-induced long-term potentiation and Golgi-Cox staining to assess the effect of minocycline on synaptic plasticity and synaptogenesis. The effects of minocycline on synapse-associated signaling proteins were determined by western blot. We found that minocycline ameliorates cognitive deficits, enhances neuroplasticity, activates brain-derived neurotrophic factor- extracellular signal-regulated kinases signaling and increases expression of Arc, [[EGR1]] and [[PSD]]-95 in the [[CA1]] and dentate gyrus regions of the hippocampus in aged mice. The effects of minocycline in aged mice were similar to those of donepezil. Our results suggest that minocycline could improve learning and memory through enhancing synaptic plasticity and synaptogenesis, modulating the expression of synapse-associated signaling proteins, which provide a rationale for exploring the viability of using minocycline treatment in cognitive deficits.
|mesh-terms=* Aging
* Animals
* Avoidance Learning
* Brain-Derived Neurotrophic Factor
* Cytoskeletal Proteins
* Dendritic Spines
* Donepezil
* Early Growth Response Protein 1
* Hippocampus
* Indans
* Long-Term Potentiation
* MAP Kinase Signaling System
* Male
* Maze Learning
* Memory
* Mice
* Mice, Inbred C57BL
* Minocycline
* Nerve Tissue Proteins
* Neurons
* Nootropic Agents
* Piperidines
* Synapses
|keywords=* Aging
* Brain-derived neurotrophic factor
* Cognitive deficit
* Minocycline
* Synaptic plasticity
|full-text-url=https://sci-hub.do/10.1016/j.nlm.2015.03.003
}}
{{medline-entry
|title=Replicative senescence is associated with nuclear reorganization and with DNA methylation at specific transcription factor binding sites.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25763115
|abstract=Primary cells enter replicative senescence after a limited number of cell divisions. This process needs to be considered in cell culture experiments, and it is particularly important for regenerative medicine. Replicative senescence is associated with reproducible changes in DNA methylation (DNAm) at specific sites in the genome. The mechanism that drives senescence-associated DNAm changes remains unknown - it may involve stochastic DNAm drift due to imperfect maintenance of epigenetic marks or it is directly regulated at specific sites in the genome. In this study, we analyzed the reorganization of nuclear architecture and DNAm changes during long-term culture of human fibroblasts and mesenchymal stromal cells (MSCs). We demonstrate that telomeres shorten and shift towards the nuclear center at later passages. In addition, DNAm profiles, either analyzed by MethylCap-seq or by 450k IlluminaBeadChip technology, revealed consistent senescence-associated hypermethylation in regions associated with H3K27me3, H3K4me3, and H3K4me1 histone marks, whereas hypomethylation was associated with chromatin containing H3K9me3 and lamina-associated domains (LADs). DNA hypermethylation was significantly enriched in the vicinity of genes that are either up- or downregulated at later passages. Furthermore, specific transcription factor binding motifs (e.g. [[EGR1]], [[TFAP2A]], and ETS1) were significantly enriched in differentially methylated regions and in the promoters of differentially expressed genes. Senescence-associated DNA hypermethylation occurs at specific sites in the genome and reflects functional changes in the course of replicative senescence. These results indicate that tightly regulated epigenetic modifications during long-term culture contribute to changes in nuclear organization and gene expression.

|keywords=* DNA methylation
* Epigenetic
* Lamina
* Long-term culture
* Massively parallel sequencing
* Senescence
* Telomeres
* Transcription factor binding sites
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356053
}}
{{medline-entry
|title=Effects of prenatal cocaine exposure on social development in mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24852757
|abstract=Prenatal cocaine exposure (PCE) in humans and animals has been shown to impair social development. Molecules that mediate synaptic plasticity and learning in the medial prefrontal cortex (mPFC), specifically brain-derived neurotrophic factor ([[BDNF]]) and its downstream signaling molecule, early growth response protein 1 (egr1), have been shown to affect the regulation of social interactions ([[SI]]). In this study we determined the effects of PCE on [[SI]] and the corresponding ultrasonic vocalizations (USVs) in developing mice. Furthermore, we studied the PCE-induced changes in the constitutive expression of [[BDNF]], egr1 and their transcriptional regulators in the mPFC as a possible molecular mechanism mediating the altered [[SI]]. In prenatal cocaine-exposed (PCOC) mice we identified increased [[SI]] and USV production at postnatal day (PD) 25, and increased [[SI]] but not USVs at PD35. By PD45 the expression of both social behaviors normalized in PCOC mice. At the molecular level, we found increased [[BDNF]] exon IV and egr1 mRNA in the mPFC of PCOC mice at PD30 that normalized by PD45. This was concurrent with increased [[EGR1]] protein in the mPFC of PCOC mice at PD30, suggesting a role of egr1 in the enhanced [[SI]] observed in juvenile PCOC mice. Additionally, by measuring the association of acetylation of histone 3 at lysine residues 9 and 14 (acH3K9,14) and MeCP2 at the promoters of [[BDNF]] exons I and IV and egr1, our results provide evidence of promoter-specific alterations in the mPFC of PCOC juvenile mice, with increased association of acH3K9,14 only at the [[BDNF]] exon IV promoter. These results identify a potential PCE-induced molecular alteration as the underlying neurobiological mechanism mediating the altered social development in juvenile mice.
|mesh-terms=* Aging
* Animals
* Brain-Derived Neurotrophic Factor
* Cocaine
* Early Growth Response Protein 1
* Female
* Gene Expression Regulation
* Interpersonal Relations
* Male
* Mice
* Pregnancy
* Prenatal Exposure Delayed Effects
* Social Behavior
* Vocalization, Animal

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125482
}}
{{medline-entry
|title=Impaired [[IGF1]]R signaling in cells expressing longevity-associated human [[IGF1]]R alleles.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21388493
|abstract=Dampening of insulin/insulin-like growth factor-1 ([[IGF1]]) signaling results in the extension of lifespan in invertebrate as well as murine models. The impact of this evolutionarily conserved pathway on the modulation of human lifespan remains unclear. We previously identified two [[IGF1]]R mutations (Ala-37-Thr and Arg-407-His) that are enriched in Ashkenazi Jewish centenarians as compared to younger controls and are associated with the reduced activity of the [[IGF1]] receptor as measured in immortalized lymphocytes. To determine whether these human longevity-associated [[IGF1]]R mutations affect [[IGF1]] signaling, we engineered mouse embryonic fibroblasts (MEFs) expressing the different human [[IGF1]]R variants in a mouse Igf1r null background. The results indicate that MEFs expressing the human longevity-associated [[IGF1]]R mutations attenuated [[IGF1]] signaling, as demonstrated by significant reduction in phosphorylation of both [[IGF1]]R and AKT after [[IGF1]] treatment, in comparison with MEFs expressing the wild-type [[IGF1]]R. The impaired [[IGF1]] signaling caused by the [[IGF1]]R mutations resulted in the reduced induction of the major [[IGF1]]-activated genes in MEFs, including [[EGR1]], mCSF, IL3Rα, and TDAG51. Furthermore, the [[IGF1]]R mutations caused a delay in cell cycle progression after [[IGF1]] treatment, indicating a dysfunctional physiological response to a cell proliferation signal. These results demonstrate that the human longevity-associated [[IGF1]]R variants are reduced-function mutations, implying that dampening of [[IGF1]] signaling may be a longevity mechanism in humans.
|mesh-terms=* Aged, 80 and over
* Alleles
* Animals
* Cell Proliferation
* Down-Regulation
* Early Growth Response Protein 1
* Fibroblasts
* Genotype
* Humans
* Insulin
* Insulin-Like Growth Factor I
* Interleukin-3 Receptor alpha Subunit
* Jews
* Longevity
* Mice
* Mice, Knockout
* Mutation
* Phosphorylation
* Proto-Oncogene Proteins c-akt
* Receptor, IGF Type 1
* Signal Transduction
* Transcription Factors

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3094477
}}