telomerase – BioQuakes

Have you ever wondered why humans age? Why we can’t stay alive forever? Or is it even possible to? According to a recent article from Scientific American, scientists are actively researching what lifestyle choices and diets can lead to a longer life.

Firstly, before we dive into that, let me explain why the article says we age and what causes cells to lose their ability to regenerate. The article says that cells are constantly being damaged in our body, from UV rays to poor nutrition, which causes them to regenerate to become healthy again. Regenerating cells divide into new healthy ones by making copies of their chromosomes, which contain DNA. But this is where the aging process begins. Each time a cell divides, the end or caps of the chromosome, called telomeres, shrink, and when they become too short, the cells cannot divide further. This cell state is called senescence. This state of the cell is dangerous, so we secrete chemicals to activate our immune system and eliminate them, but when our body does not destroy them, they cause neighboring cells to go into this state as well. If the senescence cells keep spreading to their neighbors, the body and brain work slower, causing our body to deteriorate, become susceptible to disease, and die.

This is where the scientists come in! According to the article, experts often believe in the popular disposable soma theory. This theory indicates that our bodies have limited lifetime energy and that humans use a good amount of it to do reproductive functions. So, if you choose not to reproduce, you could live a longer life. Is that not a hard choice? Children or a longer life? I know I wish there could be a happy medium! But, according to experts, if people try to reach a compromise, they risk mutations and major issues in decedents. Therefore, it is hard to combat the aging of humans from this perspective, not only for ethical reasons but also on the subject of time. In an article by Antonello Lorenzini, he states that time and environmental pressures cause constraints for us to repair damaged cells and reproduce in the limited window we have. Therefore, we as humans must maximize the time and energy we have as it is imperative for our aging process not to slow down at an earlier stage of our lives.

Since this approach did not work, researchers in the article looked at the perspective of targeting short telomeres and preventing cells from entering senescence. Yet, there is a problem in both of these ideas as well. People with long telomeres have more telomerase, which is the enzyme that keeps telomeres long; the problem with this is that cancer cells can use this telomerase to multiply unchecked. As well as this, people with longer telomeres tend to have a more likely chance of getting cancer and brain tumors as well. Is a longer life worth a higher chance of getting cancer? Personally, I do not think so. So researchers also tried to prevent cells from going into a senescent state, but they had a similar problem. The cells researchers need to target are the ones that induce aging, but they must avoid the cells benefitting the body, or else it will cause more catastrophe for human cells.

Next, researchers looked at ideas for extending our lifespan through caloric restriction. A study from Nature displayed that people who ate 15% fewer calories had less body aging. This is also shown in the research from AARP, which said researchers at the National Institutes of Health found that adults who had 12% less caloric intake over two years opened biological pathways associated with healthy aging. But, back to the original article from Scientific American, it says this must be done carefully. Caloric restriction may extend life span but also may cause side effects, such as decreasing gray matter in the brain. So, as researchers try to find a solution that does not cause any harm to us as a species beyond a balanced diet and exercise, aging will not stop anytime soon. (Very sad, I know.)

Lastly, I want to connect this to something we learned in AP Biology this year. In this unit, we discuss cell division and the cell cycle. This relates to the topic of anti-aging/aging because of the cell reproduction rate and the ability of the cell to replicate. As said above, as the cells are damaged, they must replicate. This process starts with interphase, where the cell will go through the G1, S, and G2 phases or the growing and replicating phases. The cell has normal functions, copies DNA, and doubles its organelles in preparation for mitosis. Next, it will move into mitosis, where it will divide the nucleus through kinetochore and nonkinetochore, and finally go into the stage of cytokinesis, where the cytoplasm is split. This can further relate to the topic through the telomeres and the telomerase. As said above, people with more telomerase can have a higher chance of getting cancer because the cancer can multiply unchecked. They can multiply unchecked because most cancer cells use telomerase to divide indefinitely, as it will continue to replicate and not die, which causes tumors to form. So, suppose our normal cells start to use telomerase. In that case, our cells will act similarly in replication to cancer, and our bodies will not be able to tell the difference.

Most cells only divide when given a chemical signal, but cancer cells do not obey this. They will divide even though they did not receive a chemical signal. In AP Bio, we learned that cancer cells also do not have the signal to stop replicating, which is where the telomerase comes in. Since cancer cells do not receive the signal to stop copying and they have long and reconstructing telomerase that allows them to do this, they will never die.

As well as this, we can link the idea from the senescent state – the cells researchers need to target are the ones that induce aging, but they must avoid the cells benefitting the body, or else it will cause more catastrophe for human cells – to this as well. If genes are damaged when they are targeting aging cells, this can cause oncogenes to form. Oncogenes will cause the cells to divide when no signal is sent. This would lead to tumors because of the rapid cell replication. Similarly, suppose a mutation damages the tumor suppressor in the cell. In that case, there will be nothing stopping the oncogenes from replicating, allowing them to do what cancer does and replicate non-stop. Therefore, the process of anti-aging and cancer remarkably coincide as the very thing that we want to use for anti-aging is something that causes cancer to be able to divide indefinitely. That is pretty amazing and crazy to me! How can something in our bodies allow that to happen? What do you think?

Telomerase. They know what it is. They know what it does. They know it is involved with the formation of malignant tumors. Yet for years, cancer researchers could not figure out a way to curb telomerase activity. Not until recently, when a group of researchers at the University of California, Santa Cruz discovered an important structural component of telomerase that could lead to the development of new and more efficient cancer treatment medications.

But first things first: what even is telomerase? To understand the role of telomerase, we must first understand what a telomere is. Analogous to the “plastic tips of shoelaces”, telomeres are located at the tips of chromosomes to keep the ends of DNA from “fraying”, consisting of the repetition of the same nitrogenous base sequence over and over again. In humans, this base sequence is TTAGGG.

(Source: https://en.wikipedia.org/wiki/Telomere#/media/File:Telomere.png)

The sequence can be up to 15,000 base pairs long; however, each time a cell divides, the telomeres get shorter and shorter until they become they become too small to divide again. That is when the telomerase comes in; it adds nucelotides to the telomere to prevent it from becoming senescent, or at least prolong the cell’s life span.

Sounds like a good thing, right? Not when the telomerase gets out of control and does not allow for cells to die, causing a huge growth of cells that eventually evolve into malignant tumors.

What makes it hard for scientists to combat excessive telomerase activity is due to the enzyme’s unique and complex structure. In addition to its sophisticated quaternary structure, telomerase also has an RNA template that allows the telomerase to make the DNA bases (TTAGGG) for the telomere.

(Source: https://vi.wikipedia.org/wiki/Telomerase#/media/File:Telomerase_illustration.jpg)

Researchers at UC Santa Cruz determined the structure of the RNA binding domain of telomerase and how the template border is dependent on how the protein and RNA components interact with each other. Understanding this interaction can help scientists develop cancer medications that more specifically inhibit telomerase. This is the first major advancement in telomerase research since November of 2010 when biochemists at UCLA created an unprecedented 3D model of telomerase’s RNA structure.

While this discovery is a major step forward in cancer treatment research, some experts have their reservations against finding methods of inhibiting telomerase altogether.

However, regardless of the controversy surrounding telomerase inhibition in cancer treatment, this discovery will be useful in coming up with tactics to prevent aging, and improve treatments in other medical fields, such as burns, bone marrow transplants, and heart disease.

What do you think? Leave a comment below!

Original Article

BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: telomerase

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