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 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)