Reduced Expression Of Myc Increases Longevity And Enhances Healthspan Pdf

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A team of scientists based at Brown University has found that reducing expression of a fundamentally important gene called Myc significantly increased the healthy lifespan of laboratory mice, the first such finding regarding this gene in a mammalian species. Myc is found in the genomes of all animals, ranging from ancestral single-celled organisms to humans.

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Centenarians

The gene desert upstream of the MYC oncogene on chromosome 8q24 contains susceptibility loci for several major forms of human cancer. The region shows high conservation between human and mouse and contains multiple MYC enhancers that are activated in tumor cells. However, the role of this region in normal development has not been addressed. The mice are viable and show no overt phenotype. However, they are resistant to tumorigenesis, and most normal cells isolated from them grow slowly in culture. These results reveal that only cells whose MYC activity is increased by serum or oncogenic driver mutations depend on the 8q24 super-enhancer region, and indicate that targeting the activity of this element is a promising strategy of cancer chemoprevention and therapy. Our cells each contain close to 20, genes, which provide the instructions needed to build our bodies and keep us alive.

Address correspondence to Haim Y. E-mail: Haim. Cohen biu. The extension in human lifespan in the last century results in a significant increase in incidence of age related diseases. It is therefore crucial to identify key factors that control elderly healthspan. However, it is as yet unknown whether SIRT6 also affects various healthspan parameters.

Oncotarget a primarily oncology-focused, peer-reviewed, open access, biweekly journal aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Its scope is unique. The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. The term was introduced in the inaugural Editorial , Introducing OncoTarget. Sponsored Conferences.

Reducing Myc gene increases lifespan of mice by 15% on average

So far, several longevity mouse models have been developed containing mutations related to growth signaling deficiency by targeting growth hormone GH , IGF1, IGF1 receptor, insulin receptor, and insulin receptor substrate. In addition, p70 ribosomal protein S6 kinase 1 S6K1 knockout leads to lifespan extension. S6K1 encodes an important kinase in the regulation of cell growth. S6K1 is regulated by mechanistic target of rapamycin mTOR complex 1. The v-myc myelocytomatosis viral oncogene homolog MYC -deficient mice also exhibits a longevity phenotype. The gene expression profiles of these mice models have been measured to identify their longevity mechanisms. Here, we summarize our knowledge of long-lived mouse models related to growth and discuss phenotypic characteristics, including organ-specific gene expression patterns.

Reducing Myc gene increases lifespan of mice by 15% on average

Address correspondence to Haim Y. E-mail: Haim. Cohen biu. The extension in human lifespan in the last century results in a significant increase in incidence of age related diseases. It is therefore crucial to identify key factors that control elderly healthspan.

Loss of gut integrity is linked to various human diseases including inflammatory bowel disease. However, the mechanisms that lead to loss of barrier function remain poorly understood. Using D. Reduction of dMyc in enterocytes induced cell death, which leads to increased gut permeability and reduced lifespan upon DR. Genetic mosaic and epistasis analyses suggest that cell competition, whereby neighboring cells eliminate unfit cells by apoptosis, mediates cell death in enterocytes with reduced levels of dMyc.

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This state-of-the-art review on longevity focuses on centenarians, studied as a model of positive biology. The extraordinary rise in the elderly population in developed countries underscores the importance of studies on ageing and longevity in order to decrease the medical, economic and social problems associated with the increased number of non-autonomous individuals affected by invalidating pathologies. Centenarians have reached the extreme limits of human life span. Those in relatively good health, who are able to perform their routine daily tasks, are the best examples of extreme longevity, representing selected individuals in which the appearance of major age-related diseases — including cancer and cardiovascular diseases — has been consistently delayed or avoided.

MYC is a highly pleiotropic transcription factor whose deregulation promotes cancer. They show resistance to several age-associated pathologies, including osteoporosis, cardiac fibrosis and immunosenescence. They also appear to be more active, with a higher metabolic rate and healthier lipid metabolism. Transcriptomic analysis reveals a gene expression signature enriched for metabolic and immune processes. The ancestral role of MYC as a regulator of ribosome biogenesis is reflected in reduced protein translation, which is inversely correlated with longevity. Our findings indicate that MYC activity has a significant impact on longevity and multiple aspects of mammalian healthspan. Myc is a helix-loop-helix leucine zipper transcription factor that is highly conserved among metazoans Meyer and Penn,

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Article. Reduced Expression of MYC Increases Longevity and Enhances Healthspan. Jeffrey W. Hofmann,1,7 Xiaoai Zhao,1,7 Marco De Cecco.


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