The Link Between Cancer and Aging
Exploring biological processes and related treatment.
Cancer is one of the most common diseases, as sad as it is. But, want to know something that is even more common? Aging.
Well, that’s obvious. I mean, we all age.
At some point in our lives we begin to “suffer” from age and some of us are effected further by developing chronic diseases, like cancer. And yes, I just called cancer one of the effects of aging (minus the outlier of leukemia), because as age increases the risk of cancer increases exponentially.
Wait, that isn’t the only relationship between cancer and aging. What if I told you there were actual biological processes that provide evidence of a connection between aging and cancer?
Is your interest peaked? Let’s learn more.
Cancer’s Biology
Before we start linking the two, let’s get a grasp of how cancer happens.
In short, cancer happens when some of the body’s cells begin to divide without stopping and spread into surrounding tissues.
The typical process in our bodies is that human cells grow and divide to form new cells as the body needs them. When cells grow old or become damaged, they die, and new cells take their place.
But, cancer is not so typical and this process changes.
As cells continue to divide, they start wearing off and become not-so perfect. Just like using a sharpened pencil, after each use the tip becomes duller and doesn’t work as well as it did. The same happens with cells, with each divide the cell become less and less optimal. (I’ll explain this in more detail in the Aging’s Biology section).
Now because of these built up imperfections in our cells, the old or damaged cells survive when they should die, and new cells form when they are not needed. These extra cells start to divide without stopping and form masses of unneeded cells called tumours.
These tumours, cancerous tumours are malignant. This means the tumours can spread into or invade other nearby tissues. These cancer cells can even break off and begin its invasion in other parts of the body.
In other words, cancer cells are like weeds. Once one of them pop up, they keep rapidly multiplying and once you think you have pulled them all out, another magically appears the next day.
How do the cells grow out of control?
Another question has popped up. Now we know why cancer happens but how is uncontrollable cell division possible?
Genetics.
Cancer is a genetic disease which means it is caused by changes in genes that control the way our cells function, particularly how they grow and divide. Since, cancer is a genetic disease these changes can be inherited from parents right from the get-go.
On the flip-side, genetic changes can also arise during a person’s lifetime due to errors that occur as cells divide or because of damage to DNA caused by specific environmental exposures (smoking, radiation etc.).
Overall, cancer cells have more genetic changes, like mutations in DNA, than regular cells. Some of these changes might not even have anything to do with cancer as they may be the result of the cancer, rather than its cause.
And guess what, the frequency of these DNA changes increases drastically as we age. Looks like a potential link, right?
Science Behind Aging
There is no one defining mechanism of aging, and we are not nearly close to knowing them all. There are a variety of hallmarks of aging that contribute to aging which scientists do know about though.
9 Known hallmarks Aging
- Genomic instability: Chromosomes become less stable as cells continue aging. When repair mechanisms fail to correct DNA damage, mutations accumulate and lead to aging and disease.
- Telomere attrition: As cells divide, the ends of chromosomes known as telomeres get shorter. Eventually, the enzyme that restores telomeres (telomerase) gets silenced and the telomeres are too short for cells to divide.
- Epigenetic alterations: When cells are exposed to environmental factors, they are subject to changes in their genome through epigenetic (external) mechanisms. These changes build up over time and have been related to the decline observed in aging cells.
- Loss of proteostasis: As environmental stresses add up, mechanisms responsible for maintaining proper protein composition start to decline. Proteins lose their stability, autophagic processes (cleaning out old cells to regenerate new, healthy ones) start to fail, and misfolded proteins accumulate.
- Deregulated nutrient sensing: Metabolic activities can put stress on our cells. Too much activity paired with changes in nutrient availability and composition cause cells to age faster.
- Mitochondrial dysfunction: Aging cells start to lose their mitochondria integrity due to the build-up of oxidative stress (imbalance between production and accumulation of oxygen reactive species). As a result, apoptosis — a process of programmed cell death — is increased, that correlates with aging.
- Cellular senescence: The point at which our cells stop dividing and growing due to damage or lack of necessary components. As cells age, they lose their ability to actively divide and start to undergo senescence.
- Stem cell exhaustion: Our stem cells eventually lose their ability to divide, because of aging. We are then unable to replace the stem cells that have migrated, differentiated, or died. As a result, we show outward symbols of aging, like grey hair or wrinkles.
- Altered intercellular communication: Cells, as they age, show an increase in self-preserving signals that result in damage somewhere else instead. Changed intercellular communication with aging contributes to decline in tissue health.
We’re going to be taking a closer look at genomic instability which is essentially the cause of the cell’s build-up of imperfections during cell division.
Linking the Two
Finally, the meaty part.
Cancer and aging are more alike than you might have thought, they share multiple processes which can be taken into consideration when developing cancer treatments.
Let’s take a look!
Genomic Instability
In both aging and cancer genomic instability is increased.
Human DNA is vulnerable to things called mutagens which are chemical compounds or forms of radiation, and we are exposed to these constantly over our lifetimes. Our cells go through cell division billions of times where the DNA is replicated each time, along with the risk of introducing or suffering mutational events.
Most of these mutations are relatively harmless and can be repaired by the DNA repair system in our cells. However, these small mutations accumulate and create damage eventually.
Genomic instability in key regulator functions is the most relevant “enabling hallmark” that leads cancer cells to gain many of the driving cancer traits, like self sufficiency in growth signals and increased metastatic potential (spread of cancer cells).
The longer we live, the more errors our genes accumulate. Over time, these mutations can lead to cancer.
Beyond these cellular changes, other bodily processes become less effective with age. For example, the body’s immune system becomes less protective and resilient, and is less efficient in detecting and fighting infections and diseases, including cancer.
There is a strong positive correlation between age and risk of cancer.
However, in a way cancer and aging can actually be considered rivalling processes.
When we are young, we have high levels of cell cycle gatekeeper proteins like p53. High levels result in senescence (loss of cell function) and apoptosis (cell death) in order to protect us from harmful mutations which leads to cancer. However, in doing this, you age. Higher senescence and apoptosis leads to aging. Now, when we are old, the levels of cell cycle gatekeeping proteins decrease, because they have been worn out from age. These low levels now allow cells with genetic mutations to propagate and promote cancer.
Genomic instability reflects the wear and tear on cells over time, leading to controlled cell death and loss of tissue in aging. Yet, it also represents the variable risk of accumulating changes that influence uncontrolled cell division and expansion in cancer.
It’s like a game of tug of war, but no side wins. Ever.
When we are young, functions are set in stone to make us age, but prevent cancer. Now that we have aged, these functions wear down, making us prone to cancer.
How can we even win?
Winning this Endless Tug of War
While evaluating the causes of cancer through an aging scope, many treatments can be developed for both aging and cancer.
Calorie restriction slows down aging. Anything that slows aging (ex. calorie restriction and genetic manipulations) also postpones cancer. This predicts that drugs that slow down the aging process will delay or prevent cancer.
Two Birds, One Stone
It was discovered that our two birds, cancer and aging can be tackled with one stone, senolytic drugs.
One such study was conducted at the Institute of Oncology Research which revealed the role of aging cells in the formation of secondary tumours (metastases) and identified a drug capable of blocking them.
The researchers identified a specific gene called TIMP1 which pushes senescent cancer cells to play an active role in the formation of metastases. If this gene is lost or inactivated, the composition is reprogrammed making the tumour more aggressive and invasive.
“Genetic factors of the patient can in fact determine whether senescence has positive effect on tumour growth or a negative effect in stimulating the formation of metastases.”
Professor Andrea Alimonti
Based on this discovery an attempt was made to incorporate senolytic (senescent cell killing) drugs in order to stop this process.
They discovered that TIMP1 was the key gene that determined the type of senescence in prostate cancer and that the formation of metastases could be blocked by eliminating those senescent cells that favoured this process.
This study paves the way at the clinical level for the use of senolytic drugs — which are typically used as “anti-aging” drugs — to fight cancer, and more specifically the risk of metastasis formation.
Aging and cancer are tightly interconnected and many of the same strategies and drugs may be used to target both. Cancer can be considered an aging disease, though the shared mechanisms underpinning the two processes remain unclear. Better understanding of the shared and divergent pathways of aging and cancer is needed.
Aging is the biggest risk increasing factor for not only cancer, but countless degenerative diseases as well. It sounds unreal, but what if we could decrease this risk for every disease by simply delaying age?
We can. However, only with a deeper understanding of the driving functions behind aging.
Further Reading
- Aging and Cancer Research
- Cell Senescence in Drugs
- Aging Treatment through Protein Inhibition
- Senolytic Drugs
- Restrict Cellular Senescence Without Increasing the Risk of Cancer
Let’s Connect
If you found this interesting and want to learn more, let’s connect and talk!
Check out my video on this topic!
