We’ve all heard of genes; the root of who and all we are.
Genes are tiny molecular bundles, like libraries filled with all the necessary information required to make you, you. But the conversation is so much more than your curly hair or green eyes. When you start talking about changes at the genetic level, you’re also talking about widespread and long-term changes at a cellular and behavioral level.
Genetics refers to the study of genes and more specifically, how these genes contribute to traits passed down through generations. You know that when someone says you look a lot like your mother, that you can attribute it to the genes she passed down to you hereditarily.
Genomics however, is the study of a person’s entire set of genes, or their genome. Genomics also involves the scientific study of how one’s specific genome interacts with their environment. For example, to see if a smoker is more vulnerable to lung cancer than another smoker simply due to their genetic makeup, that would be a study in genomics.
Genes are an important regulator of whether a cell lives or dies – so you can imagine how that can affect your vital internal systems.
What is gene expression?
You’ll typically hear about genes becoming “expressed,” which is just a scientist’s way of saying genes have been “switched on.”
However, genes don’t just turn on and off by themselves. They are tightly regulated by small compounds called transcription factors, which are regulated by cell signaling pathways (remember those roadmaps for cells?).
Let’s say a cell is undergoing high levels of oxidative stress, and this stress leads to the generation of free radicals, misfolded proteins, and damaged cellular debris. Each of these are considered “danger-associated molecular patterns,” or DAMPs, which, simply translated, means excess material the cell doesn’t need.
These DAMPs are sensed by immune cells responsible for surveying the cellular environment through protein receptors located on their cell surface (or other intracellular mechanisms).
The detection of DAMPs by immune cell receptors triggers several intracellular signaling pathways that activate nuclear factor kappa B (NFκB), which is a transcription factor primarily involved in the expression of genes that control the production of inflammatory proteins.
Now bear with us, this is where things get technical. Normally, NFκB is bound (or attached) to a protein called inhibitor of NFκB (IκBα). When bound to this protein, NFκB transcription factors are not active; but, when those pesky DAMPs begin to accumulate in the cell, IκBα detaches from the original NFκB. Think of it as somewhat of an act of self-preservation.
This normally happens when proteins in signaling pathways attach phosphate groups to the inhibitor IκBα; a common way that cells communicate messages within the cytosol. This phosphorylation of IκBα frees the original protein from inhibition and allows it to move into the nucleus, where it binds sections of DNA that represent genes of various inflammatory proteins. Now you see where we're going with all these gene talk?
In the end, this causes the production and release of inflammatory proteins like cytokines, which in turn communicate with nearby cells to further propagate a local immune response to eliminate cellular waste and restore cellular homeostasis.
We know that’s a lot of acronyms and technical jargon, but that’s the reality of understanding how important regulating cellular homeostasis is, and more importantly, how we can hope to master it.
This is just one of the ways that cellular pathways and genetics interact to regulate cellular health and function, resulting in you feeling better overall.
Gene expression and the regulation of the cellular division
Genes play a key role in many functions of the living cell, one of these functions being the regulation of cellular division. That’s right, genes are an important regulator of whether a cell lives or dies – so you can imagine how that can affect your vital internal systems.
Cellular division is a process necessary for an organism to mature and grow. Without cellular division, for example, humans would never develop into the embryo of a fertilized egg. Life, creating life, is what keeps it all afloat.
The division of cells is a highly controlled process and is tightly regulated by checkpoint genes and intracellular signaling pathways. When cells divide, the genetic information (i.e., DNA) in the original (or parent) cell is copied to form duplicates to be used in the newly formed daughter cell.
Genetic material must be copied in a highly precise manner because if there are errors, the newly formed daughter cell could end up dysfunctional and unable to carry out the duties of a normal cell.
To ensure this does not happen, all cells have checkpoints that guide the division process. On the one hand, if replication of DNA goes according to plan, the signaling checkpoints are activated in a step-by-step manner to allow the cell to completely divide, enabling cellular growth and maturation. Great! That's what we want to see in great cellular health, in turn promoting your body's systems to work effectively and efficiently.
If replication of DNA causes damage to the genetic material, such as an incorrect pairing of nucleoside bases, or if DNA damage is detected prior to replication, signaling checkpoints inform the cell of the error. They do this knowing that this type of damage can be detrimental to the functioning of the fresh, newly formed cell. Nobody wants that!
When a cell does not successfully pass through all checkpoints in the division process, a series of messages are sent along signaling pathways to dictate the fate of the cell. These may involve continuation of cell division if the errors can be fixed, a halt of cell division, or the induction of cell death mechanisms.
In summary, your genes actually determine the fate of a cell in a highly controlled process; and those intricate signaling pathways are essential to the proper functioning of cells.
Gene expression and cellular senescence
Within discrete phases of the cell division process, there is a stage where cells continue to carry out metabolic activity, but do not divide their genetic material. This is called interphase and is essentially a stage within the cell cycle that allows it to function without undergoing the highly demanding process of cell division. Following interphase, the cell goes through a series of phases that involve genetic replication, proofreading of the copied genes, and division.
But, when cell division becomes too stressful for a cell, or genetic replication becomes too prone to errors, it is possible for signaling pathways within the cell to halt the cell cycle entirely. Think of it like a recall when a quality assurance issue is found on a production line -- everything stops until the issue is located and fixed accordingly.
When this happens, the cell transitions to a state known as cellular senescence in which it no longer divides and replicates genetic material but continues metabolic functions like creating proteins and producing energy. You may have read our recent piece on Zombie Cells and cellular senescence; if not, it may be worth your time to really dive into and understand this phenomenon!
Senescence is similar to interphase in the respect that the cell continues metabolic activity, but it is physiologically distinct because it simply cannot divide any more.
This is often the case with cells that have divided several times, which commonly occurs throughout the aging process. Importantly, senescent cells are thought to contribute to various chronic diseases by increasing inflammation in the body.
Known as the senescence-associated secretory phenotype (SASP), senescent cells release inflammatory mediators that signal nearby cells about their senescent status, which often results in causing neighboring cells to become senescent as well.
As are many other cellular processes, the SASP is also governed by gene expression and highly involves the NFκB pathway mentioned earlier. Recall DAMPs—waste floating around in the cell. The thing is, damaged DNA is considered a DAMP known to trigger intracellular signaling pathways that cause the genetic changes responsible for promoting inflammation. Damaged DNA, environmental stress, and genomic instability are all key influencers of the NFκB pathway and thus, contribute to this senescent phenomenon.
So what does this mean for how we feel in our day-to-day life?
Ultimately, as more cells age and become senescent, the collective accumulation of inflammation-producing cells can be a cause of concern in terms of chronic inflammation and disease.
This is one of the reasons that senescent cells are commonly associated with chronic diseases that often present in older aged individuals (i.e., arthritis, osteoporosis, and so on). This also importantly highlights how cell signaling and genetic expression interact to influence the overall reproductive capacity and maturation of cells as we age.
So no, your genes aren't just what you look like, or how fast your metabolism can burn off a delicious double fudge brownie. Your genetic makeup and gene expression actually play a major role in the phases and health of your cells and ultimately, your healthspan over time.
It's pretty amazing what we've learned about these intricate processes as science and technology continues to grow. If you're interested in genetic testing or other related evaluations for your own health, reach out to your healthcare provider and see what options are available for you.