Clonal Mutation in Immune Cells Correlates with Epigenetic Age Acceleration

The nuclear DNA encoding near all of the protein machinery necessary to cell function is constantly damaged and constantly repaired. The repair mechanisms are highly efficient, and are backed up by numerous other systems intended to destroy cells that suffer particularly critical DNA damage, mutations that can lead to cancer or severe dysfunction. Nonetheless, damage accumulates. Near all of this damage is irrelevant, as it occurs randomly in single somatic cells with a limited life span, in genes that the cell isn't using. Unfortunately, there are ways for DNA damage to become significant. The first is obviously cancer, a condition arising from particular combinations of mutational damage that allow a cell to replicate aggressively without limit. The second is when damage occurs in a stem cell or progenitor cell that will create large numbers of descendant somatic cells. A mutation can be spread widely throughout a tissue, and the resulting patchwork of mutations is known as somatic mosaicism. It is thought that somatic mosaicism contributes to the general level of dysfunction in aging tissue, but this is hard to prove at the present time: the compelling experiment that isolates only this class of nuclear DNA damage as a factor and links it to specific aspects of aging has yet to be designed and carried out. It is easy to generate nuclear DNA damage in animal models, via radiation or genetic engineering to disable repair mechanisms, and indeed this causes harm, but it...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs

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In this study, we intravenously administrated the young mitochondria into aged mice to evaluate whether energy production increase in aged tissues or age-related behaviors improved after the mitochondrial transplantation. The results showed that heterozygous mitochondrial DNA of both aged and young mouse coexisted in tissues of aged mice after mitochondrial administration, and meanwhile, ATP content in tissues increased while reactive oxygen species (ROS) level reduced. Besides, the mitotherapy significantly improved cognitive and motor performance of aged mice. Our study, at the first report in aged animals, not only prov...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Conclusion A great deal of progress is being made in the matter of treating aging: in advocacy, in funding, in the research and development. It can never be enough, and it can never be fast enough, given the enormous cost in suffering and lost lives. The longevity industry is really only just getting started in the grand scheme of things: it looks vast to those of us who followed the slow, halting progress in aging research that was the state of things a decade or two ago. But it is still tiny compared to the rest of the medical industry, and it remains the case that there is a great deal of work yet to be done at all...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Conclusion A great deal of progress is being made in the matter of treating aging: in advocacy, in funding, in the research and development. It can never be enough, and it can never be fast enough, given the enormous cost in suffering and lost lives. The longevity industry is really only just getting started in the grand scheme of things: it looks vast to those of us who followed the slow, halting progress in aging research that was the state of things a decade or two ago. But it is still tiny compared to the rest of the medical industry, and it remains the case that there is a great deal of work yet to be done at all...
Source: Fight Aging! - Category: Research Authors: Tags: Of Interest Source Type: blogs
This study shows that CA are released from periventricular and subpial regions to the cerebrospinal fluid and are present in the cervical lymph nodes, into which cerebrospinal fluid drains through the meningeal lymphatic system. We also show that CA can be phagocytosed by macrophages. We conclude that CA can act as containers that remove waste products from the brain and may be involved in a mechanism that cleans the brain. Moreover, we postulate that CA may contribute in some autoimmune brain diseases, exporting brain substances that interact with the immune system, and hypothesize that CA may contain brain markers that m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Publication date: Available online 26 November 2019Source: Redox BiologyAuthor(s): Balaraman KalyanaramanAbstractDoxorubicin (DOX), or Adriamycin, an anthracycline antibiotic discovered serendipitously as a chemotherapeutic drug several decades ago, is still one of the most effective drugs for treating various adult and pediatric cancers (breast cancer, Hodgkin's disease, lymphoblastic leukemia). However, one of the major side effects of the continuous use of DOX is dose-dependent, long-term, and potentially lethal cardiovascular toxicity (congestive heart failure and cardiomyopathy) in cancer survivors many years after ce...
Source: Redox Biology - Category: Biology Source Type: research
In this study, researchers studied 438,952 participants in the UK Biobank, who had a total of 24,980 major coronary events - defined as the first occurrence of non-fatal heart attack, ischaemic stroke, or death due to coronary heart disease. They used an approach called Mendelian randomisation, which uses naturally occurring genetic differences to randomly divide the participants into groups, mimicking the effects of running a clinical trial. People with genes associated with lower blood pressure, lower LDL cholesterol, and a combination of both were put into different groups, and compared against those without thes...
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
Ulrik Stervbo1†, Toralf Roch2†, Timm H. Westhoff1, Ludmyla Gayova3, Andrii Kurchenko3, Felix S. Seibert1‡ and Nina Babel1,2*‡ 1Center for Translational Medicine, Medical Department I, Marien Hospital Herne, University Hospitals of the Ruhr-University of Bochum, Herne, Germany 2Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany 3Department of Bioorganic and Biological Chemistry, Bogomolets National M...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
In conclusion, we identified a novel Bcl-2 inhibitor by QSAR screening, which exerted significant cytotoxic activity in breast cancer cells through inducing mitochondria-mediated apoptosis. Introduction Apoptosis is a process of cellular suicide through which unwanted or unhealthy cells are eliminated during organism development or cellular stress (Reed, 2002; Fernald and Kurokawa, 2013). Deregulated apoptosis is a characteristic of cancers (Doi et al., 2012; Roizen, 2012). The B-cell lymphoma-2 (Bcl-2) family is composed of pro- and anti-apoptotic proteins, plays pivotal role in the mitochondrial pathway of apoptosi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions: Bariatric surgery appears to be capable of partially reversing the obesity-related epigenome. The identification of potential epigenetic biomarkers predictive for the success of bariatric surgery may open new doors to personalized therapy for severe obesity. Introduction Obesity is currently a huge healthcare problem, worldwide, and is a risk factor for several diseases such as type 2 diabetes (T2D), cardiovascular disease and cancer (1). As the prevalence of obesity reaches pandemic proportions, this metabolic disease is estimated to become the biggest cause of mortality in the near future (2). In fact,...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
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