Lipofuscin is so toxic that it actually glows. It then occurred to biologists that theoretically, mass graves and graveyards should be glowing from the large proportions of lipofuscin. Upon inspection of mass grave sites in England, biologists came across something extraordinary. Bacteria had evolved and actually consumed the lipofuscin as a source of energy!
Soil bacteria quickly evolves to eat anything,such as oil and pullutates, and turns them into carbon dioxide and water.
The solution for lipofuscin build-up in our lysosomes is to study the soil bacteria that digests it and to discover the enzymes that it uses to degrade the junk; therefore, enabling us to deliver these enzymes into lysosomes.
We won't be able to simply inject the new enzymes, since it would be injected into the blood stream and that could have dangerous repercussions. It would also be difficult to use this enzyme for lysosome build up in the brain (which I shall discuss in my next post) because of the blood-brain barrier, which is a highly effective shield against enzymes.
The key would be to modify or introduce DNA to create the new enzyme through a gene therapy. For example, one could inject the lipofuscin-eating enzyme DNA into mannose 6-phosphate, which lysosomes pick up during their travels.
Thursday, September 15, 2011
Tuesday, September 13, 2011
The Build Up of Lipofuscin In Lysosomes
Lysosomes are the recycling centers of our cells. They are packed with enzymes(proteins which speed up chemical reactions), with each enzyme "trained" to target weak spots in chemical waste. The enzyme latches onto the chemical structure, like a mutated mitochondria for example, and then twists and tears its molecular joints.
Now, Lipofuscin is any waste product that refuses to break down inside the lysosome. The lysosome simply doesn't have to correct enzymes for the job. Therefore, the lipofuscin accumulates inside of the lysosome and takes up a large amount of room, especially in the lysosomes of long-lived cells, like the heart and brain for example. Since the heart cells never divide; therefore, they don't share the lysosome waste between the two offspring cells.
The serious damage occurs like this:
Mutilated Low-Density Lipoprotein, LDL cholesterol,which has been damaged by free radicals, tries to deliver membrane materials(that's what cholesterol does) to cells along the arteries. Since the LDL is damaged, its proteins tend to stick together which other LDL's. This is why high-cholesterol is detrimental, since the more cholesterol in your blood, the more contact it has with free radicals, and the more it clogs up your blood stream. When the LDL is in the blood stream, it tries to slip through the blood vessels and head for the cell that is receiving its new membrane. But alas, the LDL never makes it to the cell since it gets caught in the blood vessel. This stuck LDL begins to attract other LDL's, which in turn get stuck as well.
Once a decent-sized plaque of LDL is formed, the immune system sends a phagocyte, known as macrophages, to clean up the mess. Unfortunately, the lysosomes inside the macrophages do not have the correct enzymes to clean up the LDL, and it turns into lipofuscin. The lipofuscin builds up inside the lysosome until it actually explodes and kills the macrophage, which adds to the already accumulating clot.
When this clot occurs near the heart = heart attack. Near the brain = stroke.
Aside from heart attacks and stoke, the build up of lipofuscin in lysosomes is also responsible for Age-Related Macular Degeneration, or vision loss.
Vision is from energy from the light that is reflected off the object, into the lens of our eyes, and is carried through our optic nerve to our visual cortex(back lobe of the brain). A chemical reaction occurs and our vision is produced. Since vision relies on chemically unstable components, issues will arise. A by-product, known as A2E is formed in our cones and rodes, which cannot be broken down by lysosomes and eventually ruins our retinas.
Now, Lipofuscin is any waste product that refuses to break down inside the lysosome. The lysosome simply doesn't have to correct enzymes for the job. Therefore, the lipofuscin accumulates inside of the lysosome and takes up a large amount of room, especially in the lysosomes of long-lived cells, like the heart and brain for example. Since the heart cells never divide; therefore, they don't share the lysosome waste between the two offspring cells.
The serious damage occurs like this:
Mutilated Low-Density Lipoprotein, LDL cholesterol,which has been damaged by free radicals, tries to deliver membrane materials(that's what cholesterol does) to cells along the arteries. Since the LDL is damaged, its proteins tend to stick together which other LDL's. This is why high-cholesterol is detrimental, since the more cholesterol in your blood, the more contact it has with free radicals, and the more it clogs up your blood stream. When the LDL is in the blood stream, it tries to slip through the blood vessels and head for the cell that is receiving its new membrane. But alas, the LDL never makes it to the cell since it gets caught in the blood vessel. This stuck LDL begins to attract other LDL's, which in turn get stuck as well.
Once a decent-sized plaque of LDL is formed, the immune system sends a phagocyte, known as macrophages, to clean up the mess. Unfortunately, the lysosomes inside the macrophages do not have the correct enzymes to clean up the LDL, and it turns into lipofuscin. The lipofuscin builds up inside the lysosome until it actually explodes and kills the macrophage, which adds to the already accumulating clot.
When this clot occurs near the heart = heart attack. Near the brain = stroke.
Aside from heart attacks and stoke, the build up of lipofuscin in lysosomes is also responsible for Age-Related Macular Degeneration, or vision loss.
Vision is from energy from the light that is reflected off the object, into the lens of our eyes, and is carried through our optic nerve to our visual cortex(back lobe of the brain). A chemical reaction occurs and our vision is produced. Since vision relies on chemically unstable components, issues will arise. A by-product, known as A2E is formed in our cones and rodes, which cannot be broken down by lysosomes and eventually ruins our retinas.
Sunday, September 11, 2011
Aging: Production of Free Radicals by Mitochondria
In each cell, thousands of little "power plants" known as mitochondria are hard at work. These mitochondria produce ATP(Adenosine-5'-triphosphate) which is essentially what powers our bodies. The production of ATP works by stripping electrons from the molecules, which then power the mitochondria's "turbines." Protons are then fed through the turbines and ATP is produced. The electrons are then sent to an oxygen molecule, which removes four electrons at a time. Once in a while, the oxygen molecule may receive an extra electron or two, making it chemically unstable and forming what is known as a free radical. These free radicals cause oxidation and try to steal electrons from other molecules, which leads to a chain reaction of issues. Since the free radicals are produced so close to the mitochondria, the mitochondria's DNA is sometimes mutated, which corrupts the mitochondria. These mutated mitochondria then no longer produce free radicals and are then not signaled for destruction by lysosomes.
This creates the first issue. How do you prevent the oxidation which is occurring by the production of free radicals? Obviously, the first solution that comes to mind are antioxidants. But antioxidants don't work too well since they lead to oxidative stress and can make cancer cells resistant to chemothearpy. Oh, and did I mention that only 1% of mitochondria's are actually mutated? So now you are probably wondering, how can 1% of these randomly occurring events lead to overall aging? The answer is LDL.
LDL(Low-Density Lipoprotein) is a bad type of cholesterol(which I shall discuss later). Cholesterol, is an important aspect of metabolism and is responsible for strengthening a cell's and/or a mitochondria's membrane. While these LDL pass by mutated mitochondria, they are attacked and mutated by free radicals. The LDL cholesterol then travels to the rest of the body, infecting a large amount of area and eventually becomes evenly spread throughout the body. So, how can we prevent all of this?
Well, you can't simply mess with mitochondria since they are a major aspect of metabolism and interfering with the process of metabolism leads to more severe issues. You can't simply destroy the mitochondria since that would destroy muscle fiber and interfere with the bodies skeletal muscle. The best bet? A treatment known as Allotopic Expression.
Allotopic Expression is the inputting of copies of the mitochondria's DNA inside the cell's nucleus. Mitochondria are one of a handful of cells which contain their own individual DNA. Injecting the mitochondria's DNA inside of the cell's nucleus would allow for the mitochondria to be properly rebuilt if it ever became mutated by free radicals. There are two known issues with Allotopic Expression though.
The first issue is that the DNA sequencing of the 13 proteins that make-up the mitrochndria's DNA are a different sequence than the cell's DNA, which is called code disparity. This can easily be fixed by swapping the "A's" to "B's", and the "B's" to "C's."
The second issue is that the 13 proteins that make-up the mitochondria'a DNA are highly hydrophobic and, when introduced to water, they curl up. This makes it impossible to extract them through the TIM/TOM(Tansporter Inner Membrane/Transporter Outer Membrane) of the mitochondria. This can be solved by trying to find other sub-species in which evolution has solved the issue of hydrophobia. Luckily, scientists have found a species of algae which has figured out a way to make 3 of the proteins for its mitochondria's DNA unhydrophobic. We can either search for the last 10 proteins in other sub-species, or we can take matters into our own hands with inteins. Inteins are sequences which tell a protein what to do and could tell the proteins which are hydrophobic to break into two small pieces, and then reassemble once they exit the TIM/TOM. The only issue with this is the inteins could be sequenced wrong and have the protein join back together inside of the TIM/TOM, causing excessive damage to the mitochondria.
Allotopic Expression seems to be the best bet to prevent the excessive damage caused by free radicals. It is estimated by Dr. Aubrey De Grey that Allotopic Expression can increase the human lifespan by 50%.
This creates the first issue. How do you prevent the oxidation which is occurring by the production of free radicals? Obviously, the first solution that comes to mind are antioxidants. But antioxidants don't work too well since they lead to oxidative stress and can make cancer cells resistant to chemothearpy. Oh, and did I mention that only 1% of mitochondria's are actually mutated? So now you are probably wondering, how can 1% of these randomly occurring events lead to overall aging? The answer is LDL.
LDL(Low-Density Lipoprotein) is a bad type of cholesterol(which I shall discuss later). Cholesterol, is an important aspect of metabolism and is responsible for strengthening a cell's and/or a mitochondria's membrane. While these LDL pass by mutated mitochondria, they are attacked and mutated by free radicals. The LDL cholesterol then travels to the rest of the body, infecting a large amount of area and eventually becomes evenly spread throughout the body. So, how can we prevent all of this?
Well, you can't simply mess with mitochondria since they are a major aspect of metabolism and interfering with the process of metabolism leads to more severe issues. You can't simply destroy the mitochondria since that would destroy muscle fiber and interfere with the bodies skeletal muscle. The best bet? A treatment known as Allotopic Expression.
Allotopic Expression is the inputting of copies of the mitochondria's DNA inside the cell's nucleus. Mitochondria are one of a handful of cells which contain their own individual DNA. Injecting the mitochondria's DNA inside of the cell's nucleus would allow for the mitochondria to be properly rebuilt if it ever became mutated by free radicals. There are two known issues with Allotopic Expression though.
The first issue is that the DNA sequencing of the 13 proteins that make-up the mitrochndria's DNA are a different sequence than the cell's DNA, which is called code disparity. This can easily be fixed by swapping the "A's" to "B's", and the "B's" to "C's."
The second issue is that the 13 proteins that make-up the mitochondria'a DNA are highly hydrophobic and, when introduced to water, they curl up. This makes it impossible to extract them through the TIM/TOM(Tansporter Inner Membrane/Transporter Outer Membrane) of the mitochondria. This can be solved by trying to find other sub-species in which evolution has solved the issue of hydrophobia. Luckily, scientists have found a species of algae which has figured out a way to make 3 of the proteins for its mitochondria's DNA unhydrophobic. We can either search for the last 10 proteins in other sub-species, or we can take matters into our own hands with inteins. Inteins are sequences which tell a protein what to do and could tell the proteins which are hydrophobic to break into two small pieces, and then reassemble once they exit the TIM/TOM. The only issue with this is the inteins could be sequenced wrong and have the protein join back together inside of the TIM/TOM, causing excessive damage to the mitochondria.
Allotopic Expression seems to be the best bet to prevent the excessive damage caused by free radicals. It is estimated by Dr. Aubrey De Grey that Allotopic Expression can increase the human lifespan by 50%.
Tuesday, March 1, 2011
March 2, 2011
Wow. It has been exactly a month since my last post. Where has the time gone? I have been fairly busy lately on escapades around the Delaware Valley.
I have submerged myself in Carl Sagan's "Demon Haunted World" which discusses the prevalence of pseudo-science in the 21st century. It is quite humorous how in the year 2011, people still check their daily horoscopes, visit Psychics, and believe in ghosts. In a technological society, such as what we are in, it is dangerous for such pseudo-science to thrive among us. Carl Sagan, in the mid-1990s’ wished to assist in the eradicating of these mental disease, which can even be physical at times.
Let us migrate away from pseudo-science and into a more current and dire situation; Libya.
It appears that after forty years under the rule of Col. Gaddafi, Libya (like much of the Middle-East), is revolting. Col. Gaddafi is ordering his supporters to annihilate those against his rule. How ironic, due to that fact that Gaddafi came into leadership forty years ago through a peaceful Coup. I suppose it is acceptable for him to start a revolution, but not his own people? Due to the fact that Europe gets 80% of Libyan oil, and Libya shut down its oil pumping stations, global oil prices have been on the rise. This simply reinforces the fact that the United States, and the rest of the world for that matter, must find a more reliable source of energy, like the sun or wind.
I have submerged myself in Carl Sagan's "Demon Haunted World" which discusses the prevalence of pseudo-science in the 21st century. It is quite humorous how in the year 2011, people still check their daily horoscopes, visit Psychics, and believe in ghosts. In a technological society, such as what we are in, it is dangerous for such pseudo-science to thrive among us. Carl Sagan, in the mid-1990s’ wished to assist in the eradicating of these mental disease, which can even be physical at times.
Let us migrate away from pseudo-science and into a more current and dire situation; Libya.
It appears that after forty years under the rule of Col. Gaddafi, Libya (like much of the Middle-East), is revolting. Col. Gaddafi is ordering his supporters to annihilate those against his rule. How ironic, due to that fact that Gaddafi came into leadership forty years ago through a peaceful Coup. I suppose it is acceptable for him to start a revolution, but not his own people? Due to the fact that Europe gets 80% of Libyan oil, and Libya shut down its oil pumping stations, global oil prices have been on the rise. This simply reinforces the fact that the United States, and the rest of the world for that matter, must find a more reliable source of energy, like the sun or wind.
Wednesday, February 2, 2011
February 2, 2011
Interesting how riots bring out the true nature of humans. It doesn't matter whether you are in a Third World country, or a First World country; if you are in Los Angeles in the United States of America, Cairo in Egypt, or Darfur in Sudan. All riots possess an uncanny resemblance to one another, even if the cultures are “worlds” apart.
Sunday, January 30, 2011
January 30, 2011
Tired of the constant budget cuts for NASA and other scientific institutions, I decided to e-mail the government to voice my thoughts and opinions. Below is my comment.
"Dear Government of the United States of America,
NASA’s current budget is inadequate to complete their projects. The American government must become much more prudent. Scientists worldwide agree that space exploration is crucial for the survival of the human race. NASA is less than one percent of the federal budget. In comparison, defense and homeland security spend over forty times NASA’s budget each year. The government could easily cut a small percentage of the defense budget and put it towards public education, medical science, and space exploration, without any additional cost to tax payers. This is possible due to the withdraw movement of troops from Iraq. In retrospect, this would be good for Public Relations. Taxpayers would not need to pay additional taxes, education and science funding would increase, and more jobs could be created.
America: The leader in science and space exploration"
Wednesday, January 26, 2011
January 26, 2011
It seems fit to let Mr. Carl Sagan write today's entry-
"The Frontier is Everywhere"
"The Frontier is Everywhere"
We were hunters and foragers. The frontier was everywhere. We were bounded only by the earth, and the ocean, and the sky. The open road still softly calls. Our little terraqueous globe as the madhouse of those hundred thousand millions of worlds. We, who cannot even put our own planetary home in order, riven with rivalries and hatreds; are we to venture out into space?
By the time we are ready to settle even the nearest other planetary systems, we will have changed. The simple passage of so many generations will have changed us; necessity will have changed us. We are... an adaptable species. It will not be we who reach Alpha Centauri and the other nearby stars. It will be a species very like us, but with more of our strengths, and fewer of our weaknesses; more confident, farseeing, capable and prudent.
For all our failings, despite our limitations and fallibilities, we humans are capable of greatness. What new wonders undreamt of in our time, will we have wrought in another generation, and another? How far will our nomadic species have wandered, by the end of the next century, and the next millennium?
Our remote descendants, safely arrayed on many worlds through the solar system, and beyond, will be unified, by their common heritage, by their regard for their home planet, and by the knowledge that, whatever other life may be, the only humans in all the universe, come from Earth. They will gaze up and strain to find the blue dot in their skies. They will marvel at how vulnerable the repository of all our potential once was, how perilous our infancy, how humble our beginnings, how many rivers we had to cross, before we found our way.
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