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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
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.
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)