DNA Clock Helps To Get Measure Of People’s Lifespans

DNA Clock Helps To Get Measure Of People’s Lifespans

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Scientists have identified a biological clock that provides vital clues about how long a person is likely to live.

Researchers studied chemical changes to DNA that take place over a lifetime, and can help them predict an individual’s age. By comparing individuals’ actual ages with their predicted biological clock age, scientists saw a pattern emerging.

Biological age

People whose biological age was greater than their true age were more likely to die sooner than those whose biological and actual ages were the same.

Four independent studies tracked the lives of almost 5,000 older people for up to 14 years. Each person’s biological age was measured from a blood sample at the outset, and participants were followed up throughout the study.

Researchers found that the link between having a faster-running biological clock and early death held true even after accounting for other factors such as smoking, diabetes and cardiovascular disease.

The same results in four studies indicated a link between the biological clock and deaths from all causes. At present, it is not clear what lifestyle or genetic factors influence a person’s biological age. We have several follow-up projects planned to investigate this in detail.

Dr Riccardo Marioni

Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh

DNA modification

Scientists from the University of Edinburgh, in collaboration with researchers in Australia and the US, measured each person’s biological age by studying a chemical modification to DNA, known as methylation.

The modification does not alter the DNA sequence, but plays an important role in biological processes and can influence how genes are turned off and on. Methylation changes can affect many genes and occur throughout a person’s life.

This new research increases our understanding of longevity and healthy ageing. It is exciting as it has identified a novel indicator of ageing, which improves the prediction of lifespan over and above the contribution of factors such as smoking, diabetes, and cardiovascular disease.

Professor Ian Deary

Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh

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Gold ‘Nano-Drills’ Help With DNA Analysis

Gold ‘Nano-Drills’ Help With DNA Analysis

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Researcher Lennart de Vreede applied a large number of microscopic discs of gold on a surface of silicon dioxide. When heated up for several hours, the gold is moving into the material, perpendicular to the surface, like nanometer-sized spheres. Nine hours of heating gives a tunnel of 800 nanometers in length, for example, and a diameter of 25 nanometer: these results can normally only be acieved by using complex processes. The gold can even fully move through the material. All nanotunnels together then form a sieve. Leaving the tunnel closed at one end, leaves open the possibility of creating molds for nano structures.

Once heated to close to their melting point, the gold discs – diameter one micron -, don’t spread out over the surface, but they form spheres. They push away the siliciumdioxide, causing a circular ‘ridge’, a tiny dam. While moving into the silicondioxide, the ball gets smaller: it evaporates and there is a continuos movement of silicondioxide.

For example in DNA-sequencing applications, De Vreede sees applications for this new fabrication technology. In that case, a DNA-string is pulled through one of these nano-channels, after which the building blocks of DNA, the nucleotides, can be analysed subsequently. Furthermore, De Vreede expects the ‘gold method’ to be applicable to other ceramic materials as well. His recent experiments on silicium nitride indicate that.

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DNA Survives Critical Entry Into Earth’s Atmosphere

DNA Survives Critical Entry Into Earth’s Atmosphere

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The genetic material DNA can survive a flight through space and re-entry into the earth’s atmosphere – and still pass on genetic information. A team of scientists from UZH obtained these astonishing results during an experiment on the TEXUS-49 research rocket mission.

Applied to the outer shell of the payload section of a rocket using pipettes, small, double-stranded DNA molecules flew into space from Earth and back again. After the launch, space flight, re-entry into Earth’s atmosphere and landing, the so-called plasmid DNA molecules were still found on all the application points on the rocket from the TEXUS-49 mission. And this was not the only surprise: For the most part, the DNA salvaged was even still able to transfer genetic information to bacterial and connective tissue cells. “This study provides experimental evidence that the DNA’s genetic information is essentially capable of surviving the extreme conditions of space and the re-entry into Earth’s dense atmosphere,” says study head Professor Oliver Ullrich from the University of Zurich’s Institute of Anatomy.

Spontaneous second mission

The experiment called DARE (DNA atmospheric re-entry experiment) resulted from a spontaneous idea: UZH scientists Dr. Cora Thiel and Professor Ullrich were conducting experiments on the TEXUS-49 mission to study the role of gravity in the regulation of gene expression in human cells using remote-controlled hardware inside the rocket’s payload. During the mission preparations, they began to wonder whether the outer structure of the rocket might also be suitable for stability tests on so-called biosignatures. “Biosignatures are molecules that can prove the existence of past or present extraterrestrial life,” explains Dr. Thiel. And so the two UZH researchers launched a small second mission at the European rocket station Esrange in Kiruna, north of the Arctic Circle.

DNA survives the most extreme conditions

The quickly conceived additional experiment was originally supposed to be a pretest to check the stability of biomarkers during spaceflight and re-entry into the atmosphere. Dr. Thiel did not expect the results it produced: “We were completely surprised to find so much intact and functionally active DNA.” The study reveals that genetic information from the DNA can essentially withstand the most extreme conditions.Various scientists believe that DNA could certainly reach us from outer space as Earth is not insulated: in extraterrestrial material made of dust and meteorites, for instance, around 100 tons of which hits our planet every day.

This extraordinary stability of DNA under space conditions also needs to be factored into the interpretion of results in the search for extraterrestrial life: “The results show that it is by no means unlikely that, despite all the safety precautions, space ships could also carry terrestrial DNA to their landing site. We need to have this under control in the search for extraterrestrial life,” points out Ullrich.

 

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DNA Mostly ‘Junk?’ Only 8.2 Percent Of Human DNA Is ‘Functional’, Study Finds

DNA Mostly ‘Junk?’ Only 8.2 Percent Of Human DNA Is ‘Functional’, Study Finds

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Only 8.2% of human DNA is likely to be doing something important – is ‘functional’ – say Oxford University researchers.

This figure is very different from one given in 2012, when some scientists involved in the ENCODE (Encyclopedia of DNA Elements) project stated that 80% of our genome has some biochemical function.

That claim has been controversial, with many in the field arguing that the biochemical definition of ‘function’ was too broad – that just because an activity on DNA occurs, it does not necessarily have a consequence; for functionality you need to demonstrate that an activity matters.

To reach their figure, the Oxford University group took advantage of the ability of evolution to discern which activities matter and which do not. They identified how much of our genome has avoided accumulating changes over 100 million years of mammalian evolution – a clear indication that this DNA matters, it has some important function that needs to be retained.

‘This is in large part a matter of different definitions of what is “functional” DNA,’ says joint senior author Professor Chris Pointing of the MRC Functional Genomics Unit at Oxford University. ‘We don’t think our figure is actually too different from what you would get looking at ENCODE’s bank of data using the same definition for functional DNA.

‘But this isn’t just an academic argument about the nebulous word “function”. These definitions matter. When sequencing the genomes of patients, if our DNA was largely functional, we’d need to pay attention to every mutation. In contrast, with only 8% being functional, we have to work out the 8% of the mutations detected that might be important. From a medical point of view, this is essential to interpreting the role of human genetic variation in disease.’

The researchers Chris Rands, Stephen Meader, Chris Ponting and Gerton Lunter report their findings in the journal PLOS Genetics. They were funded by the UK Medical Research Council and the Wellcome Trust.

The researchers used a computational approach to compare the complete DNA sequences of various mammals, from mice, guinea pigs and rabbits to dogs, horses and humans.

Dr Gerton Lunter from the Wellcome Trust Centre for Human Genetics at Oxford University, the other joint senior author, explained: ‘Throughout the evolution of these species from their common ancestors, mutations arise in the DNA and natural selection counteracts these changes to keep useful DNA sequences intact.’

The scientists’ idea was to look at where insertions and deletions of chunks of DNA appeared in the mammals’ genomes. These could be expected to fall approximately randomly in the sequence – except where natural selection was acting to preserve functional DNA, where insertions and deletions would then lie further apart.

‘We found that 8.2% of our human genome is functional,’ says Dr Lunter. ‘We cannot tell where every bit of the 8.2% of functional DNA is in our genomes, but our approach is largely free from assumptions or hypotheses. For example, it is not dependent on what we know about the genome or what particular experiments are used to identify biological function.’

The rest of our genome is leftover evolutionary material, parts of the genome that have undergone losses or gains in the DNA code – often called ‘junk’ DNA.

‘We tend to have the expectation that all of our DNA must be doing something. In reality, only a small part of it is,’ says Dr Chris Rands, first author of the study and a former DPhil student in the MRC Functional Genomics Unit at Oxford University.

Not all of the 8.2% is equally important, the researchers explain.

A little over 1% of human DNA accounts for the proteins that carry out almost all of the critical biological processes in the body.

The other 7% is thought to be involved in the switching on and off of genes that encode proteins – at different times, in response to various factors, and in different parts of the body. These are the control and regulation elements, and there are various different types.

‘The proteins produced are virtually the same in every cell in our body from when we are born to when we die,’ says Dr Rands. ‘Which of them are switched on, where in the body and at what point in time, needs to be controlled – and it is the 7% that is doing this job.’

In comparing the genomes of different species, the researchers found that while the protein-coding genes are very well conserved across all mammals, there is a higher turnover of DNA sequence in the regulatory regions as this sequence is lost and gained over time.

Mammals that are more closely related have a greater proportion of their functional DNA in common.

But only 2.2% of human DNA is functional and shared with mice, for example – because of the high turnover in the regulatory DNA regions over the 80 million years of evolutionary separation between the two species.

‘Regulatory DNA evolves much more dynamically that we thought,’ says Dr Lunter, ‘but even so, most of the changes in the genome involve junk DNA and are irrelevant.’

He explains that although there is a lot of functional DNA that isn’t shared between mice and humans, we can’t yet tell what is novel and explains our differences as species, and which is just a different gene-switching system that achieves the same result.

Professor Ponting agrees: ‘There appears to be a lot of redundancy in how our biological processes are controlled and kept in check. It’s like having lots of different switches in a room to turn the lights on. Perhaps you could do without some switches on one wall or another, but it’s still the same electrical circuit.’

He adds: ‘The fact that we only have 2.2% of DNA in common with mice does not show that we are so different. We are not so special. Our fundamental biology is very similar. Every mammal has approximately the same amount of functional DNA, and approximately the same distribution of functional DNA that is highly important and less important. Biologically, humans are pretty ordinary in the scheme of things, I’m afraid.

‘I’m definitely not of the opinion that mice are bad model organisms for animal research. This study really doesn’t address that issue,’ he notes.

 

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New Laser to Watch DNA-Proteins Interactions

New Laser to Watch DNA-Proteins Interactions

Within the framework of the European ATLAS project, a team of researchers in Naples has created a LASER-based prototype that could revolutionize medicine and our knowledge of the human genome.
The project, brainchild of brother and sister Lucia and Carlo Altucci, has brought together two scientific teams from two very different horizons: physicists and biologists.

The idea of the prototype is to use ultrashort UV-laser pulses. Carlo Altucci, a researcher in optics, invented the machine in his lab. The LASER pulses are delivered on the order of the femtosecond, in other words one millionth of one billionth of a second. Aimed at a sample of cells, the pulse forms a permanent cross-link between the cell’s DNA and the proteins interacting with it. These interactions, which are extremely brief, are thus fixated and can be observed.

This prototype represents a major breakthrough in the intricate understanding of cellular mechanisms. Until now, researchers used chemical reactions to determine DNA/protein cross-links. But these reactions typically take one minute or more, largely insufficient for capturing processes much shorter than a second.

Genetic regulation depends on several factors, notably proteins, which influence genetic activity. The applications of this system range from understanding cellular dysfunctions — such as cancer — and determining new therapies, to the mapping of the human genome. Lucia Altucci, an oncologist, is currently testing it on cancer cells in hopes of furthering the fight against breast cancer.

Credit: Youris