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August 18, 2016 | By:  Sci Bytes
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DNA Damage Causing Aging or Aging Causing DNA Damage?

How will I die?

This is a question most of us have thought about. Have you ever wondered what is it about our bodies that “makes us die”? What is it in our bodies that tells our cells “that’s it folks”? Is it something that happens over time or is it just as simple as flipping a switch?

Cells are the building blocks of our bodies. Each cell has a copy of DNA, which makes the body function properly by making the materials we need. Scientists use cells to study diseases since cells can help those in the research community understand if something is working or not. The accumulation of damaged DNA over time is a principal cause of aging and aging is, of course, one of the main culprits when it comes to death.

DNA is at the center of our life, it is what defines and makes us—well, us. Any changes that occur to the DNA are permanent so proper maintenance and repair are very important; the cell has components that preserve DNA. Let’s consider twins, when they are born they both have the same DNA but they will age differently because they will have different experiences, environments, diseases, etc.
Exposure to sunlight (while living on desert climate), chemicals from smoke and pollution, and some drugs can modify the DNA causing changes on the outside body overtime. (Menck & Munford, 2014) This shows how modifications to the DNA can change the body.

DNA damage comes in multiple forms; there are both endogenous (internal) and exogenous (external) agents that can affect the body. Some of the internal DNA damages occur spontaneously. For example, about 100,000 DNA damages occur spontaneously in every cell, every day. You don’t have to be alarmed by that number, our DNA is composed of over 3 billion base pairs in each cell and we have around 30 trillion cells, so 100,000 damages is only about 0.003% of our DNA per cell. It is important, however, that “naturally” occurring damage gets repaired because over time that small number accumulates and becomes significant, especially if it is happening in every cell. (Martin, 2008)

The human brain consumes about 20% of the oxygen we inhale. One of the principal ways DNA is affected by agents from within our body is by breathing. Yes, the mundane task that is utterly necessary for our body is harmful to our DNA because the oxygen we breathe forms certain molecules (called Reactive Oxygen Species, ROS) that modify the DNA. Because neurons and brain cells do not reproduce like the rest of the cells in our body, the accumulation of these ROS molecules is one of the causes for brain deterioration. (Madabhushi, Pan, & Tsai, 2014) If you wonder why our brains age, one of the answers is because we breathe. One has to wonder why our body does things that damages itself?

Exogenous (outside of the body) agents also contribute to the deterioration of cells and the DNA repair machinery. You might be aware of the most common “outside” source that damages DNA: Sunlight. A day out in the sun can produce up to 100,000 damages in skin cells. One of the ways sunlight damages cells is by making two DNA bases connect to each other forming what is called a cross-link, and cross-links are very hard to repair.

Additionally, a substance called “acrolein,” is a chemical that can damage DNA by also forming cross-links and by adding to DNA bases. Acrolein is found in tobacco smoke and in emissions from burning petroleum-derived fuel; that is, every day many of us around the world drive our gasoline-powered cars and produce vast amounts of acrolein. (Tang et al., 2011)

Properly preserving the DNA and repairing it is complex. When the repair machinery malfunctions, serious consequences, such as cancer or aging, can result. Some studies show that the way the body prevents cancer is by promoting cell death. But, if the cells stay alive they accumulate DNA damage, which results in aging and death. This is one of the main conundrums of DNA study, how do we keep cells alive but without the risk of cancer?

The study of aging in humans is complicated because following people over 70 or 80 years is a difficult task, particularly because scientists age too. Some (unfortunate) diseases mimic aging, which allows scientists to study the effects of aging on the human body. Cockayne syndrome, Xeroderma pigmentosum (XP), and Fanconi anaemia (FA) are a few premature aging diseases. A commonality among these diseases is a malfunction in the DNA repair machinery and leaves unrepaired damaged DNA in cells. In addition to accumulating damaged DNA in a person’s cells, XP and FA can also increase the risk of getting cancer. People who have XP are especially vulnerable because a main symptom is hypersensitivity to sun exposure. Other diseases such as Ataxia telangectasia show signs of premature aging along with neurodegeneration (the breakdown of neurons in someone’s brain) and cancer. (Schumacher, Garinis, & Hoeijmakers, 2008)

There are many ways by which DNA can be damaged and much of that harm accumulates over time, which is why scientists have not yet found the fountain of youth. If something happens to the DNA then that trickles down to the cells of our body and then our bodies cannot properly function. Scientists want to understand how DNA is damaged and repaired so that we can have treatments for patients with premature aging diseases, but also so we continue to learn more about the wonderful machine we call the human body.

References:

Madabhushi, R., Pan, L., & Tsai, L.-H. (2014). DNA Damage and Its Links to Neurodegeneration. Neuron, 83(2), 266-282. doi:10.1016/j.neuron.2014.06.034

Martin, L. J. (2008). DNA Damage and Repair. Relevance to Mechanisms of Neurodegeneration, 67(5), 377-387. doi:10.1097/NEN.0b013e31816ff780

Menck, C. F., & Munford, V. (2014). DNA repair diseases: what do they tell us about cancer and aging? Genetics and Molecular Biology, 37, 220-233.

Schumacher, B., Garinis, G. A., & Hoeijmakers, J. H. J. (2008). Age to survive: DNA damage and aging. Trends in Genetics, 24(2), 77-85. doi:10.1016/j.tig.2007.11.004

Tang, M.-s., Wang, H.-t., Hu, Y., Chen, W.-S., Akao, M., Feng, Z., & Hu, W. (2011). Acrolein induced DNA damage, mutagenicity and effect on DNA repair. Molecular nutrition & food research, 55(9), 1291-1300. doi:10.1002/mnfr.201100148

Images references:

https://ratedrtech.wordpress.com/tag/dna/

http://www.nature.com/nchem/journal/v7/n7/full/nchem.2296.html

http://onlinelibrary.wiley.com/doi/10.1002/anie.201502566/abstract

http://time.com/45301/see-the-dramatic-changes-of-these-identical-twins-over-time/ (With permission of photographer)


May 11, 2016 | By:  Sci Bytes
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Cosmic Travels Inc.: The effect of zero gravity on the human body

By: Noopur Ranganathan

Remember that time you were upside down in a roller coaster and, for exactly one second, your body left contact with your seat? The moment of exhilaration that made waiting in the long queue for that ride completely worthwhile?

That was your moment of zero gravity!

Zero gravity can be defined as a state of weightlessness, a condition when the gravitational force is zero. A state of apparent weightlessness, zero gravity is best experienced in outer space. When a spacecraft orbits the earth, the acceleration of the spacecraft, known as the centrifugal force, counterbalances the earth's gravity and neutralizes the gravitational force. In other words, the gravitational pull felt by the spacecraft becomes equal to the centrifugal force exerted on the spacecraft. This cancels out the effect of both forces and results in a state of zero gravity. Astronauts experience weightlessness at this point and tend to float; the ultimate roller coaster thrill every little child dreams of.

Occasional trips to the amusement park for a gravity-defying ride will not harm anyone. However, it is important to note that extended exposure to zero gravity is dangerous to our health. Without the downward pull of gravity, our body cannot function properly.

The human body tends to relax in a state of weightlessness because it no longer fights the pull of gravity. This lack of the gravitational pull alleviates the mechanical strain otherwise endured by our skeletal system. Although the exact trigger is unknown, scientists believe that the reduced stress on bones may be responsible for progressive bone loss, a condition most commonly seen in patients confined to beds due to long term illnesses or old age. Lack of stress on the bones reduces the formation of bone building cells called osteoblast cells. Fewer bone building cells result in a loss of bone mass. While in space, the amount of weight the bones must support gets reduced to zero. While making any movements, the bones are not subjected to the same level of stress they would have otherwise endured while on earth. This breaks down calcium that is normally stored in bones, and releases it into the bloodstream. Increased levels of calcium in the blood, lead to a higher incidence of renal stones. The high level of calcium in the blood also reflects a high level of bone mass loss which makes the bones weak and increases the risk of fracture.

All organisms on earth have sensory and response systems with which they respond to internal and external stimuli. Besides the five main senses (smell, touch, sight, taste and hearing) we humans possess, there is one more powerful sense called the vestibular sense that enables our body to sense movements and use it to maintain balance. Walking a tightrope, pirouetting in a ballet performance, or twisting while diving, all showcase our vestibular system as it actively keeps track of the position of our arms and legs and enable us to perform these tricks without losing balance. This requires the precise integration of our body's sensory and response systems including visual, vestibular, somatosensory (pressure and stretch receptors in our skin), and auditory. Together, these senses constantly collect and interpret data from all over the body. However, loss of gravity negatively impacts this spatial perception. The dizziness or difficulty in walking we experience after spinning around in a circle, clearly demonstrate what happens when we lose this sense even for a few moments. The vestibular system, which is situated in the ears, is comprised of otolith organs and semicircular canals. We can sense the direction and speed of linear acceleration (speed changes without change in direction) due to the otolith organs while the semicircular canals allow us to sense the direction and speed of angular acceleration (speed changes along with change in direction). The vestibular apparatus in the human ears is designed to work with earth's gravity and provides sensory information about motion, equilibrium, and spatial orientation. Take gravity away and we can no longer figure out where the ground and ceiling are!

Gravity ensures that the blood in our body maintains an optimum blood pressure level. While standing, the blood pressure in our feet is as high as 200 mm Hg (millimeters of mercury). In the brain however, the pressure is only 60 to 80 mmHg. Take gravity away and the blood pressure equalizes around 100 mmHg throughout our body. Our face puffs up with fluid and our legs thin out because the fluid drains out. The shift to higher blood pressure in the head triggers an alarm that the body has too much blood. Increased blood pressure can make the blood vessels bleed. Optic nerves can swell and this can impair the vision. High blood pressure can lead to a stroke that can damage that area in the brain that processes images. Thus, gravity acts as an important force that helps to maintain the correct pressure in the right places in our body.

A living cell exchanges nutrients and wastes from its watery environment through the process of diffusion which is effective only over a specific distance. This limitation impacts the size of the cell. Nutrient absorption is therefore much more effective in smaller sized cells. Cell biologists Marina Feric and Clifford Brangwynne of Princeton University have proven that in order to optimize nutrient absorption in cells, gravity must play a significant role in determining the size of the cell. Their paper, published in the 2013 October issue of Nature Cell Biology, clearly shows how eukaryotic cells are small in diameter (less than 10 microns) due to gravitational forces. When the cell grows bigger than this size, it is subjected to gravitational forces that require scaffolding or support within the cell nuclei to stabilize the internal components. Their research confirms that larger cells have the extra actin mesh (that acts as an additional support), a key component missing in all other smaller sized cells.

Clearly gravity has played a vital role in the evolution of life on earth over billions of years. Studies such as these recognize the importance of gravity and its phenomenal impact on life on earth. However mankind is now poised to explore the universe beyond our planet and a key concern of this ambitious venture is the effect of zero gravity on human life. NASA embarked on this mission through its Twins study project, a novel experiment in the history of mankind that attempted to study the effects of zero gravity on astronaut twins Mark and Scott Kelly.

Scott spent an extended period on the International Space Station and returned back on Earth on March 2, 2016. NASA scientists intend to compare the results of his body vitals with his twin Mark who remained earthbound. The long-term effects will take some years to be known. But the short-term effects are here for us to see. Astronaut Scott Kelly reported loss of bone mass, atrophied muscles, and redistribution of blood within his body that has strained his heart. Thankfully, most of these are reversible through rehabilitation and exercise. Despite physical setbacks and the increased risk of cancer, due to extended exposure to high levels of radiation, Scott Kelly is proud to be a part of this groundbreaking mission and happy to contribute to scientific discovery.

Ever since our planet was born, it has been subjected to a lot of changes. But there is one force that has remained constant all through these years and that is gravity. There is enough evidence that demonstrates how life on earth has been impacted by gravity. All biological processes have evolved under the ever present force of gravity such that even temporary changes in gravity instantly make a noticeable impact. With our sights set on establishing human life beyond Earth's gravitational pull, it becomes imperative to understand the detrimental effects of zero gravity and devise ways to counter those. The day we resolve those concerns, we will successfully pave the way for mankind to venture into deep space.

References

Azvolinsky, Anna. "Gravity plays a role in keeping cells small." princeton.edu. October 24, 2013.

Feitlinger, Sarah Benton. "Scott Kelly's Historic 'Year in Space' Mission Brings Us One Step Closer to Mars." dogonews.com. April 8, 2016.

Howell, Elizabeth. "Weightlessness and Its Effect on Astronauts." space.com. September 30, 2013.

LE, Freed, and Vunjak-Novakovic G. "Spaceflight bioreactor studies of cells and tissues." ncbi.nlm.nih.gov. 2002.

---. "Spaceflight bioreactor studies of cells and tissues." europepmc.org. 2002.

NASA. "Bones in Space." nasa.gov. August 19, 2004.

---. "Human Vestibular System in Space." nasa.gov. February 26, 2004.

---. "Space Bones." science.nasa.gov. 2001.

Wei-Haas, Maya. "What Happens to the Human Body in Space?" Smithsonian.com. March 1, 2016.

Image Credit: NASA (Wikipedia), Robert Markowitz (Wikipedia)


March 11, 2016 | By:  Sci Bytes
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The New Ebola: Zika

By: Noopur Ranganathan

Waiting in the doctor's office with her baby son, Jose, Solange Fereira hoped it was nothing more than a case of malnutrition or perhaps a mild case of juvenile growth disorder. But her world came crashing down when the doctor confirmed her worst fears. Her baby boy, Jose Wesley, had microcephaly, a medical condition where babies are born with abnormally small heads and suffer from neurological disorders and short life expectancy.

Solange Ferreira lived in Brazil, the world's fifth largest country. Well known for its cinematic landscapes, kaleidoscopic culture, powerful music, dazzling festivities, and of course football fever, Brazil is no newcomer to feeling the heat under the spotlight. However, since May 2015, it has taken center stage for a completely different reason and little Jose was paying the price. Brazil is at the epicenter of the global pandemic, Zika.

Discovered in the Zika forest of Uganda in 1947, Zika is a mosquito borne virus that causes neurological disorders and neonatal malformations. However there is no evidence that directly links Zika to microcephaly. Infact there are several other factors that cause microcephaly. But experts at the CDC and various medical research laboratories in Brazil believe there is strong evidence for a connection between Zika and microcephaly. Dr. Maria Angela Rocha from the Oswaldo Cruz hospital in Recife, a state capital in northeast Brazil where the Zika virus has proliferated, stated that the staff has seen 300 cases of microcephaly in the past six months as compared to the average of five cases a year. Two neuropediatricians in Recife, Dr.Vanessa Van der Linden Mota and her mother Dr.Ana van der Linden, suspected something was terribly wrong when they began seeing dozens of microcephaly cases in just a short period of time rather than the occasional case every few months.Their concern intensified when they took on a case of twins where one baby was normal and the other had a serious case of microcephaly. The Zika virus was found in the blood of another baby that died due to microcephaly. The amniotic fluid from two pregnant women revealed genetic material of the Zika virus. Post delivery, their babies were diagnosed with microcephaly. These incidents and the spike in cases of congenital microcephaly, provided enough evidence to alert State Health authorities and state the Zika virus as the possible prime suspect for the rise in cases of microcephaly. In short, Zika virus is the prime cause of fetal microcephaly.

A flavivirus, the Zika virus, belongs to the family of Flaviviridae. It causes severe diseases such as Yellow fever, West Nile, Chikungunya, Japanese encephalitis and Dengue. Vincent Racaniello, Professor of microbiology at Columbia University, states that the genome is enclosed in a capsid and surrounded by a membrane, which contains the envelope glycoprotein. This glycoprotein allows the attachment of the virus particle to the host cell receptor to initiate infection.

The exact manner in which the Zika virus attacks the central nervous system of a fetus is not clear. However many theories abound. According to virologist Katherine Spindler from the University of Michigan, human cytomegalovirus (CMV) has a strong link with many birth defects, one among them being microcephaly, just like they saw in Brazil. The exact relationship between CMV and brain abnormalities hasn't been established as of yet but one report suggests that during early brain development, the stem cells (no details about the exact location of the brain) get attacked by the virus, thereby inhibiting the stem cell's' ability to differentiate into proper cells, resulting in the brain tissue getting destroyed. This early loss of fetal brain tissue may be the reason for the abnormal shape of the fetal brain. Another theory published in BMC Med Genomics attributes the occurrence of autosomal recessive primary microcephaly (MCPH) to the mutation of certain genes such as Microcephalin and WDR62. Due to the lack of deep research, these are only hypotheses that have been published. Since we are in a very early stage, there isn't much data, analysis, or conclusions as a result.

Transmitted by the Aedes aegypti mosquito, Zika has spread to 29 countries and is expected to infect 3 to 4 million people across the Americas. General Margaret Chan, World Health Organization Director, has declared it a public health emergency. Brazil has recorded 4000 cases of microcephaly since 2015. Doctors in Brazil struggle to find words of encouragement as they break the tragic news to infected young women. Devastated mothers try to cope with the sudden realization of the future their precious babies will face.

With very little research done on the Zika virus, we do not know its exact modus operandi. Due to this lack of knowledge, there are no vaccines to prevent it nor any effective treatment options to treat the infection. Herein lies the whole challenge of tackling the Zika virus. Due to the lack of knowledge and research in this area, there have been no data, analyses, or conclusive information that furthers the study of the Zika virus. As a result, we are relying on published hypotheses and suppositions that give the scientific community some direction to performing further in-depth research.

Rather unsophisticated, prevention of the mosquito bite remains our only defense at the moment. CDC has urged people to take precautions while travelling to the infected countries. Use of long sleeved shirts, long pants, socks, boots, insect repellents and mosquito net are some of the precautionary measures recommended. People, especially young women and pregnant women, have been advised against travelling to those countries. Brazil has undertaken measures to eradicate mosquitos through fumigation and supplying insect repellents to pregnant women free of charge.

We are just beginning to get a grasp of the behavior of the Zika virus. And the more we unravel, the more mysterious it becomes. Why only some women infected with the Zika virus have babies with birth defects while some others have normal babies? How does it affect only one baby among a set of twins? Does the virus affect other animals? Does it get transmitted by other species? What is the duration of the virus strain in the body? What are the chances of getting reinfected if one had contracted it before? Besides wrecking the fetal nervous system, does it cause any other damage?

Zika has fast become the most important public health challenge of this decade. There is an urgent need to find a potential cure in the form of a vaccine or a treatment. Tim Tellinghuisen, from Scripps Florida, is working on finding a chemical compound that inhibits the virus. Another group is analyzing the suspected link between Zika and microcephaly. And Seek, a London based biotechnology firm, is working on a very novel and creative solution by targeting the mosquito saliva. The human blood contains a coagulant that prevents us from bleeding to death. On the other hand, the saliva of the mosquito, contains an anti-coagulant that ensures the human blood it sucks, is maintained in its original liquid form for the mosquito to easily digest. Gregory Stoloff and his team of scientists from Seek are working on creating a vaccine against the mosquito saliva. The immune cells of those vaccinated will react with the mosquito's saliva and clump the blood it sucks, thus blocking the transmission of disease to humans and also killing the mosquito in the bargain.

These are just some of the ways in which scientists are trying to combat this menace. Currently, there is no conclusive data-- therein lies the whole challenge of Zika because we are still very early in the stage of research. Through a multi pronged approach, work has begun in earnest to understand, restrain and eventually eradicate this virus. One day, we hope to create that elixir that will set us free. However until then, thousands of babies, just like little Jose Wesley, will continue to suffer from severe mental and physical disabilities before reaching adulthood.

References:

1. Dana, Felipe, Mauricio Savarese, and Peter Prengaman. "Photographer reflects on

‘bucket baby,' Brazil child born with Zika virus-linked

microcephaly." Globalnews.ca. February 4, 2016.

2. Faheem, Muhammad et al. "Molecular Genetics of Human Primary Microcephaly: An Overview."

Ncbi.nlm.nih.gov. January 15, 2015.

3. Johnson, Reed, and Rogerio Jelmayer. "The Brazilian Doctors Who Sounded the

Alarm on Zika and Microcephaly." Wsj.com.January 29, 2016.

4. Lopez, Andres David. "Scripps Florida has Zika team aiming to fight virus."

Palmbeachdailynews.com. February 27, 2016.

5. McNeil Jr., Donald G., Catherine Saint Louis, and Nicholas St. Fleur. "Short

Answers to Hard Questions About Zika Virus." Nytimes.com. February 24, 2016.

6. Racaniello, Vincent. "Zika virus." Virology.ws. January 28, 2016.

7. Shukman, David, ed. "Brazilian city of Recife sees spike in microcephaly cases."

BBC.com. January 28, 2016.

8. Urwin, Rosamund. "Meet London's Zika virus busters who are on the verge of

creating a vaccine." Standard.co.uk. February 26, 2016.

Image Credit: Beth Herlin (Wikipedia), Day Donaldson (flickr.com)

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