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Bioenergetics and the epigenome: Interface between the environment and genes in common diseases.
Extensive efforts have been directed at using genome-wide association studies (GWAS) to identify the genes responsible for common metabolic and degenerative diseases, cancer, and aging, but with limited success. While environmental factors have been evoked to explain this conundrum, the nature of these environmental factors remains unexplained. The availability of and demands for energy constitute one of the most important aspects of the environment. The flow of energy through the cell is primarily mediated by the mitochondrion, which oxidizes reducing equivalents from hydrocarbons via acetyl-CoA, NADH + H(+), and FADH(2) to generate ATP through oxidative phosphorylation (OXPHOS). The mitochondrial genome encompasses hundreds of nuclear DNA (nDNA)-encoded genes plus 37 mitochondrial DNA (mtDNA)-encoded genes. Although the mtDNA has a high mutation rate, only milder, potentially adaptive mutations are introduced into the population through female oocytes. In contrast, nDNA-encoded bioenergetic genes have a low mutation rate. However, their expression is modulated by histone phosphorylation and acetylation using mitochondrially-generated ATP and acetyl-CoA, which permits increased gene expression, growth, and reproduction when calories are abundant. Phosphorylation, acetylaton, and cellular redox state also regulate most signal transduction pathways and activities of multiple transcription factors. Thus, mtDNA mutations provide heritable and stable adaptation to regional differences while mitochondrially-mediated changes in the epigenome permit reversible modulation of gene expression in response to fluctuations in the energy environment. The most common genomic changes that interface with the environment and cause complex disease must, therefore, be mitochondrial and epigenomic in origin. (c) 2010 Wiley-Liss, Inc. Dev Disabil Res Rev 2010;16:114-119.
Wallace DC. Dev Disabil Res Rev. 2010 Jun;16(2):114-9. The Department of Pathology and Laboratory Medicine, Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania.
Over the years many people have come to see me because of their anxiety regarding taking tests or exams. This is included people who have anxiety regarding performance-based testing, such as taking a driver's test, or a failed multiple attempts to pass a rule state license exam. Indeed, because of the consequences of failure, the stress related to exam taking can be significant. Yet, after one 90 minute session I cannot think of anyone you has failed their test.
My approach is not very much different than that used by many different coaches and clinical hypnotherapists. One cliché that I...
According to be American psychiatric Association, a major depressive disorder is diagnosed when five or more specific symptoms exist for at least two weeks. The symptoms include constant sadness, irritability, hopelessness, feeling worthless or guilty for no reason, trouble sleeping, low energy or fatigue, and significantly change. As depression is widely considered more of a mental than physical problem generally there are no medical tests such as checking a patient's blood. However, recent revelations neurology may soon reveal physiological or genetic problems that are associated with...
When someone has high blood pressure or hypertension there is increased stress on the walls of their arteries. This can result in increased risk that a person can develop heart disease, kidney disease, hardening of the arteries, eye damage, and even stroke. Even though many people with hypertension may not know it, they may also suffer from insomnia, dizziness, or different types of headaches. Medical authorities say the best way to check for hypertension is to have your blood pressure checked. However, this normally happens only during a medical exam. This means that people should receive...