Metabolic functions of the tumor suppressor p53: implications in normal physiology, metabolic disorders, and cancer

Publication date: Available online 18 October 2019Source: Molecular MetabolismAuthor(s): Matthieu Lacroix, Romain Riscal, Giuseppe Arena, Laetitia Karine Linares, Laurent Le CamAbstractBackgroundThe TP53 gene is one of the most commonly inactivated tumor suppressors in human cancers. p53 functions during cancer progression have been linked to a variety of transcriptional and non-transcriptional activities that lead to the tight control of cell proliferation, senescence, DNA repair, and cell death. However, converging evidence indicates that p53 also plays a major role in metabolism in both normal and cancer cells.Scope of reviewWe provide an overview of the current knowledge on the metabolic activities of wild type (WT) p53 and highlight some of the mechanisms by which p53 contributes to whole body energy homeostasis. We will also pinpoint some evidences suggesting that deregulation of p53-associated metabolic activities leads to human pathologies beyond cancer, including obesity, diabetes, liver, and cardiovascular diseases.Major conclusionsp53 is activated when cells are metabolically challenged but the origin, duration, and intensity of these stresses will dictate the outcome of the p53 response. p53 plays pivotal roles both upstream and downstream of several key metabolic regulators and is involved in multiple feedback-loops that ensure proper cellular homeostasis. The physiological roles of p53 in metabolism involve complex mechanisms of regulation implicating both cell ...
Source: Molecular Metabolism - Category: Endocrinology Source Type: research

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Publication date: Available online 31 October 2019Source: Pharmacological ResearchAuthor(s): Jong Hyun Lee, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Omar H.M. Shair, Gautam Sethi, Kwang Seok AhnAbstractEpithelial mesenchymal transition (EMT) refers to a phenomenon through which epithelial cells develop the metastatic and invasive potential, which are closely related to carcinogenesis. Farnesol (FOH) obtained from the oils of diverse plants can exhibit significant therapeutic actions against obesity, diabetes, inflammatory conditions and cancers. Here, we evaluated the potential effects of FOH on growth and metastasi...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
In this study, the enhanced mice live somewhat longer than their unmodified peers, though not as much longer as is the case for the application of telomerase gene therapy. The mice do also exhibit reduced cancer risk, however. The scientists here class telomere shortening as a cause of aging, which is not a point universally agreed upon. Reductions in average telomere length in tissues looks much more like a downstream consequence of reduced stem cell activity than an independent mechanism. Researchers obtain the first mice born with hyper-long telomeres and show that it is possible to extend life without any geneti...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, AT1-AAs were detected in the sera of patients with peripheral arterial disease (PAD) and the positive rate was 44.44% vs. 17.46% in non-PAD volunteers. In addition, analysis showed that AT1-AAs level was positively correlated with PAD. To reveal the causal relationship between AT1-AAs and vascular aging, an AT1-AAs-positive rat model was established by active immunization. The carotid pulse wave velocity was higher, and the aortic endothelium-dependent vasodilatation was attenuated significantly in the immunized rats. Morphological staining showed thickening of the aortic wall. Histological examination showe...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, our findings link the calcification of the vascular tissue with the expression of FGF23 in the vessels and with the elevation of circulating levels this hormone. Permanently Boosting Levels of Natural Killer Cells in Mice to Increase Cancer Resistance https://www.fightaging.org/archives/2019/09/permanently-boosting-levels-of-natural-killer-cells-in-mice-to-increase-cancer-resistance/ Researchers here demonstrate a very interesting approach to immunotherapy: they introduce engineered stem cells in mice that will give rise to additional natural killer T cells, boosting the capability of the ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Discussion of Developmental Effects on Aging Microtubule Function and Longevity in Nematodes Quantifying the Correlation Between Poverty and Faster Pace of Aging Matthew O'Connor Presenting on Underdog Pharmaceuticals at Undoing Aging 2019 https://www.fightaging.org/archives/2019/09/matthew-oconnor-presenting-on-underdog-pharmaceuticals-at-undoing-aging-2019/ Here Matthew O'Connor of the SENS Research Foundation talks about the research that led to founding of Underdog Pharmaceuticals, a biotech startup incubated by the foundation to commercialize a means of targeting 7-ketocholesterol in atheroscleros...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
We examined human lung tissue from COPD patients and normal control subjects, and found a substantial increase in p16-expressing alveolar cells in COPD patients. Using a transgenic mouse deficient for p16, we demonstrated that lungs of mice lacking p16 were structurally and functionally resistant to CS-induced emphysema due to activation of IGF1/Akt regenerative and protective signaling. Fat Tissue Surrounds Skeletal Muscle to Accelerate Atrophy in Aging and Obesity https://www.fightaging.org/archives/2019/09/fat-tissue-surrounds-skeletal-muscle-to-accelerate-atrophy-in-aging-and-obesity/ Researchers her...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
We examined 9293 individuals from the Copenhagen General Population Study using nuclear magnetic resonance spectroscopy measurements of total cholesterol, free- and esterified cholesterol, triglycerides, phospholipids, and particle concentration. Fourteen subclasses of decreasing size and their lipid constituents were analysed: six subclasses were very low-density lipoprotein (VLDL), one intermediate-density lipoprotein (IDL), three low-density lipoprotein (LDL), and four subclasses were high-density lipoprotein (HDL). Remnant lipoproteins were VLDL and IDL combined. Mean nonfasting cholesterol concentration was 72...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, with study of the frailty syndrome still in its infancy, frailty analysis remains a major challenge. It is a challenge that needs to be overcome in order to shed light on the multiple mechanisms involved in the pathogenesis of this syndrome. Although several mechanisms contribute to frailty, immune system alteration seems to play a central role: this syndrome is characterized by increased levels of pro-inflammatory markers and the resulting pro-inflammatory status can have negative effects on various organs. Future studies should aim to better clarify the immune system alteration in frailty, and seek to esta...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study we show, for the first time, significant alterations in cholesterol efflux capacity in adolescents throughout the range of BMI, a relationship between six circulating adipocyte-derived EVs microRNAs targeting ABCA1 and cholesterol efflux capacity, and in vitro alterations of cholesterol efflux in macrophages exposed to visceral adipose tissue adipocyte-derived EVs acquired from human subjects. These results suggest that adipocyte-derived EVs, and their microRNA content, may play a critical role in the early pathological development of ASCVD. Commentary on the Developing UK Government Position on Hea...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, we show here that sEVs are responsible for mediating paracrine senescence and speculate that they could be involved in inducing bystander senescence during therapy-induced senescence or aging. In fact, when compared to soluble factors, sEVs have different biophysical and biochemical properties as they have a longer lifespan than do soluble factors and they are more resistant to protease degradation. The idea that blocking sEV secretion could be a potential therapeutic approach to alleviate senescence "spreading" during chemotherapy-induced senescence or in aging tissues presents itself as a very at...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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