The fountain of youth
Throughout human history, ageing – and its inescapable companion, death – has fascinated mankind. From the very moment we are able to comprehend we are alive, we are simultaneously faced with the fact that our destiny is to age and die…
Is that a bit too dark for the opening of my first official post? Maybe I should have opened with a joke…ummm,
The Bartender says “we don’t serve time travellers here”.
A time traveller walks into a bar
At least you’re
laughing hysterically smiling politely while your body is decaying now. So let’s continue…
The philosopher’s stone, the fountain of youth, ambrosia and the Norse golden apple. Mythology from all cultures make reference to objects that may grant those who wield them immortality. These objects are generally shrouded in reverence, a testament to humanities enduring fascination with ageing and their desire to slow, or even stop, the ageing process.
Though ageing and death are the great unifiers among all the members of our species, we still know relatively little about why we die. Weird right? We’ve been doing it for hundreds of thousands of years you would think we would know more about our ultimate destination by now. I know many of us were distracted trying to figure out the ending of Lost for a while but that only accounts for about half of those hundreds of thousands of years.
Growing old is getting old
When you think of ageing you probably immediately think grey hair, wrinkles and the sweet sweet bliss of doing and saying whatever the hell you want. But at its core, the fundamental reason for ageing occurs at the level of cell, specifically your DNA. DNA is nature’s flash drive (albeit a far more elegant and beautiful storage device – just look at that double helix). Using just 4 chemical “letters”, DNA is equipped to carry the blueprint for the endless forms most beautiful of all life on Earth (and potentially beyond) from the humble yeast in beer all the way to you, the instructions for building these organisms come from the limitless combination of these 4 letters. However, the process of DNA replication is not fool proof and is prone to error. Our cells contain mechanisms to prevent and detect these errors, but the accumulation of mutations over time limit the cell’s ability to maintain error-free DNA. Additionally, DNA is susceptible to things termed mutagens – physical or chemical insults that can damage DNA such as UV radiation and reactive chemicals created by our very own cells (more on these guys later). Often these mutagens cause damage in areas of DNA that are involved in detecting mutation or replication errors leading to a vicious cycle that makes the cell even more vulnerable to damage.
This is our first stop on the road to old age. Wear and tear due to natural replication errors and encountering mutagens over our entire lives that build up and lead to DNA instability. While genetic damage can be considered the baseline of age determination, a number of other factors actively contribute to how long a cell can survive before succumbing to old age, or senescence.
Look down at your shoes, you see those plastic things on the ends of your laces? What? your shoes don’t have laces? Well go grab a pair that do. We can wait.
Okay. see the little plastic things? These are called aglets. These aglets aren’t there just because they’re pretty, they actually serve a purpose. Protecting the lace and extending the duration you can use them with your favourite shoe. Have you ever had a pair of shoes lose one (or *shudder gasp* both) of these? The lace starts to fray, and eventually becomes useless.
DNA can be thought of as a shoelace (albeit a slightly more complex one) and they too have their own protective caps at the ends. These protective caps are called telomeres. Telomeres are found at the tips of all animal and plant chromosomes (chromosomes are the name given to the structures that house DNA in the cell) and are composed of a variety of proteins as well as around 10,000 of the chemical letters we talked about before. This 10,000 letter stretch of DNA does not actually contain any coding information. Their main role is to act as a kind of buffer keeping the important parts of DNA that actually code for necessary cellular functions safe. Unfortunately, due to the nature of how our cells replicate DNA, we are unable to replicate the ends of chromosomes completely. This results in the loss of a small piece of DNA every time the cell divides i.e. our telomeres get gradually shorter every time the DNA is copied.
A famous experiment in the 60’s showed that cells growing in a petri dish could only divide a set number of times, around 50, before they stopped and eventually died. This was termed they Hayflick limit after the scientist who made the observation. It was later found out that the Hayflick limit is reached after the telomere length reaches a critical limit. One this limit is reached, cell division and DNA replication cut into actual coding genes.
In a sense, telomeres can be thought of as a sort of biological clock. “Our lives are only as long as our telomeres” as my boss likes to say.
“But Seamus, couldn’t we just find a way to replenish or extend or telomeres and live forever?”
I like your thinking, but don’t go running to the patent office just yet. Like most things, life has found a way and beaten us to the punch. There is an enzyme that occurs in nature called telomerase and the main role of this enzyme is to actually grow back telomeres!!! Unfortunately, telomerase is not actively expressed in most cells of our body, so apart from a few rapidly dividing cells, white blood cells for instance, the cells of our body are left to hear the ticking inevitability of telomere shortening as we grow old.
Another genetic component known to be involved in ageing is the mitochondria. Mitochondria are fascinating little structures (or organelles) of the cell. They are often nicknamed “The powerhouse of the cell” and that nickname is well earned as they are the site of production of all the energy our cells use. After a variety of other processes, the food we eat is broken down into its component molecules and then absorbed by the cell. The mitochondria take these molecules and together with oxygen break them down into energy (termed ATP) for the cell to use to carry out functions. Another interesting thing about mitochondria is that they have their own DNA. This is because they used to be bacteria that merged with an animal cell to create the happy partnership they share today. This is referred to as symbiosis…like Venom in Spider-Man, but with less bloodshed.
Anyway, the conversion of food to energy – or respiration – is a necessary process for us to go on living however it does come at a cost. A by-product of respiration is the creation of a highly reactive environment. The DNA in the mitochondria is very close to this volatile environment and also lacks the protective mechanisms of the DNA in the cells (i.e. telomeres, error checking mechanisms). This leads to mitochondrial DNA being a target for mutation and dysfunction. As you can imagine, dysfunction at the site of energy production is not ideal and it is thought that damage to the mitochondria contributes greatly to cellular ageing.
There are a variety of other physiological factors involved in ageing such as:
- Epigenetic changes (I will try to explore what Epigenetics is in a later post)
- Running out of stem cells
- Loss of communication (like in divorce, but with cells)
And a lot more known and unknown factors. Like I said it at the start, it is a fascinating field and a wealth of knowledge is yet to be discovered about this vital process. The study of how and why we age is extremely important, not only because it’s fascinating, but also because something as common as old age is the number one risk factor for so many diseases. You may have heard of the disease progeria. This awful disorder leads to full body premature ageing resulting in a life expectancy of around just 16 years. Discovering the exact cellular processes that lead to these devastating diseases may be the first step in preventing or reversing them and as the population ages this is of great importance.
I know you weren’t reading this just to get depressed about your inevitable fate. You want to know if we can reverse the ageing process? Extend those telomeres, replace those mitochondria and stay young and beautiful (or average in my case) forever.
- Short answer: No
- Long Answer: Maybe, but not at the minute
- Optimistic Answer: OF COURSE! Meet me at the pub in 652 years to celebrate
While it is not uncommon for humans to live to 100+ these days, beyond that is a bit less likely. Though there are animals that have attained increased longevity and even immortality.
Lobsters: Remember telomerase? The enzyme that is able to extend telomeres but which we don’t actually produce as adults? Well lobsters have an incredible relative longevity which may be due to the fact they express telomeres throughout their entire lives. They just keep growing and growing, remaining healthy and fertile with age. Eventually this is hindered by the moulting process and formation of new exoskeleton, but they are still an incredible species.
Hydra: (hail hydra) Hydra are microscopic aquatic animals with the remarkable feature that they do not age. Their cells never undergo senescence and can divide indefinitely, free of the Hayflick limit.
The Immortal Jellyfish: (scientific name: Turritopsis dohrnii) is basically immortal. While most jellyfish share the linear life cycle; fertilized egg -> polyp (child) -> medusa (adult) eventually ending in old age and death. The Immortal Jellyfish has the unique ability to actually return to the polyp stage when under stress (i.e. starvation, physical insult, getting fired from his job etc). It then simply starts growing up again until it reaches maturity, gets in a sticky situation and BAM! Child again. It is thought that these species can undergo this process infinitely, effectively becoming immortal
Cancer: Cancer is a devastating disorder that shares many similarities with ageing. Sort of like a twisted bizzaro cousin. Through a variety of processes cancer cells are effectively immortal, meaning that they can divide free of the Hayflick limit. Often among the first thing a cancer cell does is switch on the gene for telomerase allowing them to divide indefinitely. For a fascinating read check out the book “The Immortal Life of Henrietta Lacks” it tells the story of cancer cells isolated from the tumour of woman named Henrietta Lacks in 1951 that are still alive and dividing and used for research in labs all over the world even to this day.
We are a long way off immortality in humans, but these examples show increased longevity is possible in nature and many scientists around the world are working on translating these processes to humans. Noted scientist Aubrey de Gray even thinks the first person to reach 1000 years old is already alive today.
Until we harvest the awesome power of the jellyfish what can you do to increase your longevity? Keep your internal environment as healthy as possible by eating healthily (not jellyfish necessarily) and exercising regularly, minimizing the oxidative environment and protecting your DNA.
Until next time,
- Lopez-Otin, The hallmarks of aginf. Cell 153, 2013
- Sfier, Telomeres at a glance, Cell Science 125, 2012
- The Immortalists (highly recommended documentary)
- My research involves telomeres and mitochondria as markers for age related disease, feel free to ask any questions