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Extending Lifespan of Mice, Then Human

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Invariably, everyone gets old. However, as a true testament to human stubbornness, research toward a “cure” for aging has never stopped. Over the past few decades, various approaches have allowed scientists to generate animal models with extended lifespans. In recent years, this trend has moved from lower organisms to mammalian model systems. There are now several rodent models with enhanced longevity. Many of these models are directly relevant to human aging. A new study has identified a deletion in exon 3 of human growth hormone receptor (GHR) to be prevalent in naturally long-lived men (1). The presence of two copies of this mutation may allow men to live about ten years longer than they otherwise would. This agrees with many findings from rodent models. Transgenic mice that overexpress GH age rapidly, while knockout mice lacking GHR are long-lived (2,3). In humans and mice, IGF1 signaling is also closely linked to longevity via a signaling pathway overlapping that of GH (4,5). ...

Healing a broken heart

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Introduction: Reduced heart function due to aging and disease is a major health problem. Heart attacks can have devastating impacts, often leading to the death of the patient or chronic morbidity for those that survive. A major reason for the sensitivity of the circulatory system to heart malfunction is that heart muscle cells (cardiomyocytes) of adult mammals generally do not divide. This means that when a cardiomyocyte dies, due to localized loss of blood supply, for example, that dead cell will never be replaced. Normally, heart tissue has a robust, healthy blood supply, but when a heart attack strikes, portions of heart tissue are deprived of blood flow, resulting in rapid cell death in those sections of the heart. Recovering the ability to heal Interestingly, newborn hearts can heal. In 2011, scientists discovered that newborn mice are able to regenerate cardiomyocytes to repair heart damage, but this ability is lost soon after birth (1). More recently, researchers disc...

Your brain is mutating

It has long been known that cells acquire mutations over time. In fact, ongoing random mutation rates are such that no two cells in a human body are identical. Unlike most cell types, which die and are frequently replaced, human neurons can live for decades, carrying on their functions for the entire lifetime of the organism. We know that mutations must accumulate in neurons over their long lifespan, but until now we had no clear picture of the frequency or pattern of neuronal mutations. Using the seemingly impossible approach of sequencing genomes of individual human brain cells, a group of researchers have now shown that the average human neuron carries a whopping 1700 mutations per neuron. These neuroscientists, based at Harvard and MIT, sorted individual neurons from the postmortem brains of three individuals, amplified their genomic DNA, and were able to use whole-genome sequencing to obtain individual cell genome sequences at ~40x coverage. In addition to the sheer number of neur...

CRISPR-based unicellular computer

A major goal of synthetic biology is to design and build digital genetic circuits inside cells, effectively programming cellular functions. Achieved this could allow living cells to be engineered to perform decision-making tasks, similar to computers, but composed of genetic elements rather than electronic components. This technology could be applied to medical therapeutics, molecular detection, diagnostics, tissue engineering, bio-electronic interfaces, and many other science-fictionesque uses. However, genetic elements tend to be less predictable and more “leaky” than electronic components, and this has limited progress. In a brand-new study from the University of Washington, Gander et al. overcame these obstacles by using CRISPR/Cas9 linked to the transcriptional repressor Mxi1 to make genetic circuits in yeast. The group designed and built a library of single-gene NOR gates (which give an output signal only when there are no input signals). Each gate consists of a gRNA-expressing...

Optogenetics: Light-control of genes, pathways, and cells

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Introduction: Optogenenetics refers to a family of techniques which allow modulation of biological processes using light. Over the past 12 years, optogenetics has revolutionized neuroscience and is now expanding to impact many fields of biology. There are now genetic tools which can be used for photo-control of signal transduction, gene expression, apoptosis, histone modification, cytoskeletal dynamics, and many more processes. The incredible power of optogenetics comes from the very high spatial and temporal resolution possible using light, as opposed to chemical or genetic effects. Optogenetics can also be combined with other genetic or chemical approaches to further increase the level of experimental control. For example, optogenetic constructs can be targeted to specific cell types or subcellular locations, or can be engineered to require specific chemical cofactors, further limiting when and where light-induced effects will occur. The key component of an optogenetics ex...

Mouse Models for Multiple Sclerosis

Introduction: For complex diseases like multiple sclerosis (MS), animal models are highly important because they allow researchers to systematically study numerous factors which contribute to the disease in ways that are not possible in human patients. Animal models also serve as testing arenas for potential treatments. However, the disease complexity which makes animal models so necessary also means that animal models are only able to reflect some aspects of human MS. Induced Models Experimental autoimmune encephalomyelitis (EAE) is the oldest model of demyelinating diseases (1), and has led to the discovery of human therapies for MS, but EAE has shortcomings that make it difficult to connect findings from the animal model to the human disease, particularly with respect to drug testing (2). To induce EAE, researchers stimulate a T-cell-mediated immune response against myelin, which leads to an inflammatory response in the CNS, and demyelination. Not only is the pathophysiology o...

The Effects of Invisible Viruses

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Viruses are pseudo-living organisms which inhabit and influence virtually every type of plant and animal cell. In some contexts, viral infection has obvious and profound consequences for the host organism, such as causing disease. However, many viral infections go completely unnoticed, with infections having essentially no phenotype or having an effect only long after the initial infection. Several examples of chronic, unnoticed viral infections affecting human health have been discovered. In several cases these long-term effects have been implicated in major, worldwide health problems. Cytomegalovirus (CMV) is one of the most common human virus, being present in around 75% of adults worldwide. Once acquired, CMV infection persists lifelong in a dormant state. CMV infection is a known risk factor for high blood pressure and has been implicated in atherosclerosis, and people who test positive for human CMV infection are at increased risk of cardiovascular diseases and heart attack ...