Every cell in your body goes through a countless number of divisions. When a division happens, the cell makes a new copy of your DNA.
Sometimes, however, things do not go as planned.
In genomic instability, the division and copying process loses some of its stability. This causes errors to occur in your genetics, and with age, the rate of such errors becomes more prominent.
This can lead to a higher risk of age-related conditions, but many people do not understand how exactly genomic instability affects aging.
In the 12 hallmarks of aging, genomic instability is a particularly important factor that you need to be aware of.
So, why care about genomic instability?
It turns out that instability in genomics plays a very important role in Alzheimer’s disease, arthritis, heart disease, and other age-related conditions.
In this article, you’ll discover what you can do to reduce the rate at which your genome becomes unstable.
What Is Genome Instability?
Before we look at how genome instability contributes to your aging, we should first consider what it is.
Genomic instability simply refers to instabilities that are present within your genome and the process of cellular division. When your cells make a copy of themselves through this division process, there are some cases where errors occur.
There are different types of alterations in the genome that can be considered contributors to instability. For example, mutations may occur when your cells divide.
Sometimes, it’s also related to the deletion or translocation of these cells.
Over time, the rate at which such mutations happen in your body tends to increase. This is why age is the number one factor behind genomic instability.
As you age, your body becomes less capable of implementing its natural DNA repair functions. This makes alterations or mutations in cell division more likely to happen when DNA repair genes do not work properly.
With more errors in cellular division, the severity of your genome’s instability also increases.
When cells have errors, they cannot function at their full capacity. Since the body depends on the function of every cell, this can cause problems with certain processes. Additionally, the instability in the genome can lead to inflammatory triggers and even have an impact on your immune system.
Genome instability has been shown to play a significant role in the risk of developing diseases that are associated with your age.
As genome stability becomes more severe in older age, the risk of conditions like Alzheimer’s disease and arthritis tends to increase too.
Researchers explain that along with genomic instability, these age-related diseases tend to show up as a result of cellular senescence and telomere shortening too.
How Does Genome Instability Contribute To Aging?
Aging is inevitable for every person, and it's something that we constantly experience.
To understand the role of genome instability in aging, it’s also important to know how the cell cycle works. Every cell in your body goes through a process - they grow, divide, and eventually, the cell ends up dying.
The cell cycle plays an important role in maintaining a healthy body. Through this division process, there are enough cells in your body to support various functions, from muscle function to metabolic processes and more.
When there are mutations in your DNA repair genes, or your DNA sequences are damaged, it can cause problems with this natural process where cells grow and divide and then die when they are old.
For example, when there is instability in your genome, it could cause mutations in the copy of a cell during the division process.
As these cells divide, they need to make a copy of a DNA sequence - and when this “copy” is not properly made, it leads to a cell that does not function as it is intended to.
When there are errors in cell division, growth, and death, then it can affect aging.
Errors in cell division, for example, can cause mutations when the cell copies DNA code. These errors can also cause cells to initiate the apoptosis process too early or skip it. If there are errors in cellular growth, then it could result in abnormal growth.
At this point, we also need to consider apoptosis. This is a process by which a cell that is not repairable activates a type of self-destruct mechanism. Once this happens, the cell is marked to be removed from your body through your immune system.
Some of the damaged cells do not properly go through the apoptosis process, leaving them to circulate in your body. Additionally, more of these altered or damaged cells start to accumulate in your body with age.
The accumulation of these cells can cause problems with tissue and organ function, both of which are important for well-being.
Characteristics Of Genome Instability
There are certain key characteristics that researchers associate with genome instability. We’re going to take a closer look at important things to know about the characteristics of genome instability below.
● DNA Mutations: Mutations in DNA, caused by chemical exposure, viral infections, radiation, and DNA replication errors contribute to genome instability. It’s possible for structural changes to occur within the DNA sequence, although sometimes it only affects one nucleotide.
● Telomere shortening: Chromosomes in your body have caps that provide protection to the interior parts of the chromosome. As cells continue to divide, these caps, also known as the telomere, of the chromosomes start to become shorter. In genetic instability, the shortening of the telomere may be too significant. This can cause accelerated aging and increase the risk of age-related diseases.
● Changes in Gene Expression: Genetic instability can also cause alterations to occur in your gene expression. In particular, genes that need to help in repairing damage in your DNA may experience mutations. This can lead to more DNA damage that becomes difficult or even impossible to repair.
● Abnormalities in Chromosomes: As we already discussed, telomere shortening can happen in your chromosomes. There are other abnormalities that sometimes occur in chromosomes too. Sometimes, genome instability causes your body to lose an entire chromosome. These abnormalities can also lead to the abnormal duplication or deletion of chromosomes.
● Changes in Epigenetics: When there is instability in your genome, it can also have an implication on the expression of genes. These epigenetic changes can be caused by a number of factors, such as modifications to histone or your DNA methylation patterns. DNA damage would make it difficult for DNA repair to happen.
Causes Of Genome Instability
Numerous factors affect the stability of your genome, including both internal and external elements.
In the modern day, both environmental and lifestyle factors are considered common contributors to genome instability.
Environmental factors include exposure to radiation and industrial chemicals.
Lifestyle factors generally include poor dietary choices, smoking, and being sedentary.
Genotoxicity is considered an important factor behind genomic instability. The term describes exposure to certain agents or chemicals that can attach themselves to DNA sequences and eventually cause alterations in the cell cycle.
There are many types of toxic substances that we are exposed to on a daily basis that can cause problems in our genome.
Asbestos, benzene, cyclophosphamide, melphalan, nickel compounds, tobacco products, vinyl chloride, cadmium, and cisplatin are only a few examples of agents that may have an impact on your body at a cellular and DNA level.
It is important to also consider the impact of reactive oxygen species, free radicals, and UV radiation. Free radicals can become present in many ways and refer to cells that have mutated. The cells do not function normally and can cause damage to the DNA.
When errors or defects are present in DNA and its repairing process, it can also become contributor to genome instability. As DNA repair functions fail, the instability in the genome continues to grow.
Apart from these factors, age is also considered one of the major causes of genomic instability.
As cells continue to age, mutations in the DNA tend to show up more often. This causes instability in your genome and essentially contributes to age-associated conditions.
What Does Genomic Instability Lead To?
There are many ways that genomic instability can affect you. The specific impact depends on the target site and the particular cells that are affected by the instability.
Cancer is one particular disease that holds a strong connection to genome instability. When your genome is unstable, it can cause cells that are involved in suppressing the growth of tumors to become less effective.
As these cells no longer have the ability to provide efficient protection against tumor growth, cancer can develop.
Other age-related diseases that have also been associated with genetic instability:
● Cardiovascular diseases
● Neurodegenerative diseases
● Immune system disorders
● Musculoskeletal disorders
Genome instability also affects DNA repair. The body has DNA repair genes that naturally act when damage to DNA is detected.
Diagnosis Of Genome Instability
There’s no specific way to diagnose genome instability, but researchers have identified various methods that can help to detect an unstable genome.
Genetic testing is currently considered to have potential, where DNA is assessed from a tissue or blood sample. This type of assessment can often help you identify damage to your DNA or mutations to cells.
If genome instability is identified, researchers can further use certain assays to help them determine how this issue has affected your cells. The assays can help researchers determine how your body’s ability to repair DNA damage has been affected.
When physical complications occur, X-ray imaging tests are useful to see how genome instability has affected your body’s tissues, as well as the organs.
In some cases, fluorescence in Situ Hybridization can be used with Karyotyping in order to identify genome instability. This technique has proven useful in diagnosing multiple myeloma and to assist in follow-up tests.
Genomic Instability Prevention And Treatment
While you can’t escape aging, there are some things you can do to prevent accelerated instability of your genome.
A good starting point is to consider environmental factors that might cause alterations to your DNA, chromosomes, and cells.
Exposure to certain toxic chemicals, for example, can be limited to help reduce the effect they have on your cells.
Giving up on smoking can also be a great choice. Tobacco products have been shown to impact the genome and can cause instability in cellular division.
The effects of tobacco smoking over a long period of time often affect the cells that are responsible for suppressing the growth of tumor tissue. When you give up on smoking, it helps to reduce future mutations in these particular cells.
Studies are still being conducted to better understand how therapeutic approaches could be taken in order to rectify DNA damage and improve the stability of the genome.
One study explains that progress has already been made, especially in the research areas that are related to cancer.
Current investigations are looking at how therapeutic approaches could be used to specifically target the cancerous cells that form a tumor without causing damage or mutations to other healthy cells that might be present in the surrounding tissue.
Frequently Asked Questions
Is genome instability the same as DNA damage?
It’s important not to confuse DNA damage and genome instability. Damage to your DNA could cause instability in your genome, but there are also structural changes in your DNA that could cause genome instability.
Genome stability can also be used to describe a much broader range of abnormalities in your genetics over a period of time.
Can genomic instability be inherited?
There are certain genetic conditions that could carry over from your parents to you. Bloom and Lynch syndrome are two important examples to consider.
In these cases, genome instability can be inherited. Sometimes, mutations in the genes that repair your DNA can also be inherited.
Conclusion
Your cells divide naturally over time, but sometimes, there are mutations in the division process. When this happens, it can cause genomic instability. There are several abnormalities with your genes and your cell cycle that can cause the instability in your genome.
When your genome is unstable, it's often hard for your body to fix DNA damage that happens as a result.
While it’s possible to inherit some traits that contribute to genomic instability from your previous generation, both environmental and lifestyle factors are also at play.
There are some things that you can do to improve the process of cellular division and increase the stability of your genome, as we outlined in this article.
References
Z. Li, Z. Zhang, Y. Ren, et al. Aging and age-related diseases: from mechanisms to therapeutic strategies. Journal of Biogerontology. Published April 2022. https://pubmed.ncbi.nlm.nih.gov/33502634/
J. Vijg, Y. Suh. Genome instability and aging. Annual Review of Physiology. Published 2013. https://pubmed.ncbi.nlm.nih.gov/23398157/
S. Marja. Genotoxic Chemicals. Encyclopaedia of Occupational Health & Safety. Published 28 February 2011. https://www.iloencyclopaedia.org/part-iv-66769/biological-monitoring-65407/item/406-genotoxic-chemicals
C.M. Bielski, B.S. Taylor. Homing in on genomic instability as a therapeutic target in cancer. Nature Communications. Published 16 June 2021. https://www.nature.com/articles/s41467-021-23965-5
Y. Yao, W. Dai. Genomic Instability and Cancer. Journal of Carcinogenesis & Mutagenesis. Published 2014. https://pubmed.ncbi.nlm.nih.gov/25541596/
E.I. Atli, H. Gurkan, H.O. Kirkizlar, et al. Pros and Cons for Fluorescent in Situ Hybridization, Karyotyping and Next Generation Sequencing for Diagnosis and Follow-up of Multiple Myeloma. Balkan Journal of Medical Genetics. Published 23 March 2021. https://pubmed.ncbi.nlm.nih.gov/33816073/
