Ageing is unavoidable. Ageing is something we try to avoid most.
Beauty products and anti-wrinkle remedies parade their antioxidants, glycans and tocopherol (vitamin E by the way) and we accept this jumble of scientific terminology on a label next to a face glowing with youth as a promise that tomorrow we will wake with one less crease, or maybe the next day, or the next day..
What is quite ironic about these products and their exuberant claims to reverse ageing is that scientists are still unsure as to what is the source of ageing in the first place. Of course there are numerous theories and possible explanations, one of which I will address later in this post, but the fact remains that we don't know. In fact, it is quite possible that ageing may be a result of the contribution of many of the theories, or at least parts of them. This is counter-intuitive. The concept of there not being a simple definitive answer is a concept most of us struggle to accept. The lesson to be learnt here is that this ambiguity is unfortunately also a common occurrence in science.
The mitochondrial free radical theory of ageing.
Free radicals are pretty widely known.
All of our cells respire, it is how we generate oxygen and energy. Respiration takes place in small energy factories in our cells, the mitochondria. Any efficient factory has a production line, in the mitochondria it is known as the electron transport chain or ETC. As in any factory employees get tired and machinery breaks down: things can go wrong. A small blip in the production line could cause a faulty product to be attained at the end. When things go wrong in the ETC we end up with free radicals.
Our bodies are wonderfully complex designs, of course we have a system in place for when the ETC leaks free radicals: Scavengers. But if these are overrun by reactive oxygen species, or they stop working properly, that's when problems may occur.
Free radicals are also known as reactive oxygen species and as their name suggests, there are highly reactive. They are also not particularly fussy. Lipids, proteins and carbohydrates are all potential targets. So, could these reactions be ageing our cells? Probably.
Some research certainly says so. A study carried out in McGill University, Canada showed that when components that make up the ETC are mutated so they work less, the lifespan of worms increased. The idea here is that slowing down the manufacturing pace results in less free radicals, and as the theory states, a higher lifespan.
However, anyone who watched Sir David Attenborough's recent BBC hit Africa will have seen for themselves one of the contradictions to this theory: The naked mole rat. Whilst it does look rather irrelevant to humans don't knock them just yet, the naked mole rat has been hailed as "holding the key to the elixir of life". Why? The average rat life expectancy is two to three years. The naked mole rat can reach its flirty thirties. It also is highly resistant to cancer. So where does this all lie in the context free radicals. Well, if this theory was definitively true then surely we would expect the naked mole rat to have less reactive oxygen species than its bog-standard peers? They do not. In fact, they have more, and here's a paper to prove it.
The paper was published in Nature and the first thing to note is that this paper is not a trivial one, Nature is one of the Holy Grails of journals. The main point of this paper was that the research group who published it managed to sequence the wrinkly fountain of youth's genome. The previous post equipped you with knowledge of sequencing so I won't go into too much more detail about that, more importantly is how exactly did the researchers go about assessing the cause of the animal's incredible lifespan. The basic method was actually quite simple: they compared what genes were expressed in three different naked mole rats, each a different age - newborn, four years old and 20 years old. They were specifically looking in the brains, livers and kidneys of these animals. Something was up. Barely anything was different between the different aged rats; this is a stark contrast to humans where patterns of genes "turned on or off" change as we get older.
As well as genes that didn't change at all there were even some which did change but in the opposite way to how they would in humans. For example, one gene, that codes for a protein called SMAD3 was up-regulated in the naked mole rat brain whereas in humans there is less of it when we get older. In scientific research differences allow conclusions to be made, tentative as they might be. For example. SMAD3 is known to help stop cells dividing. As you probably know, cancer occurs when our cells can't stop dividing - could more SMAD3 be one of the reasons naked mole rats are able to evade cancer so effectively?
So free radicals are bad. But naked mole rats have lots and live longer than normal. Doesn't quite all add up - see what I meant about disharmonious science now?
All of our cells respire, it is how we generate oxygen and energy. Respiration takes place in small energy factories in our cells, the mitochondria. Any efficient factory has a production line, in the mitochondria it is known as the electron transport chain or ETC. As in any factory employees get tired and machinery breaks down: things can go wrong. A small blip in the production line could cause a faulty product to be attained at the end. When things go wrong in the ETC we end up with free radicals.
Our bodies are wonderfully complex designs, of course we have a system in place for when the ETC leaks free radicals: Scavengers. But if these are overrun by reactive oxygen species, or they stop working properly, that's when problems may occur.
Free radicals are also known as reactive oxygen species and as their name suggests, there are highly reactive. They are also not particularly fussy. Lipids, proteins and carbohydrates are all potential targets. So, could these reactions be ageing our cells? Probably.
Some research certainly says so. A study carried out in McGill University, Canada showed that when components that make up the ETC are mutated so they work less, the lifespan of worms increased. The idea here is that slowing down the manufacturing pace results in less free radicals, and as the theory states, a higher lifespan.
However, anyone who watched Sir David Attenborough's recent BBC hit Africa will have seen for themselves one of the contradictions to this theory: The naked mole rat. Whilst it does look rather irrelevant to humans don't knock them just yet, the naked mole rat has been hailed as "holding the key to the elixir of life". Why? The average rat life expectancy is two to three years. The naked mole rat can reach its flirty thirties. It also is highly resistant to cancer. So where does this all lie in the context free radicals. Well, if this theory was definitively true then surely we would expect the naked mole rat to have less reactive oxygen species than its bog-standard peers? They do not. In fact, they have more, and here's a paper to prove it.
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| Don't be fooled by the wrinkles, this creature is the picture of health. (This work is licensed under a Creative Commons Attribution 3.0 Unported License.) |
The paper was published in Nature and the first thing to note is that this paper is not a trivial one, Nature is one of the Holy Grails of journals. The main point of this paper was that the research group who published it managed to sequence the wrinkly fountain of youth's genome. The previous post equipped you with knowledge of sequencing so I won't go into too much more detail about that, more importantly is how exactly did the researchers go about assessing the cause of the animal's incredible lifespan. The basic method was actually quite simple: they compared what genes were expressed in three different naked mole rats, each a different age - newborn, four years old and 20 years old. They were specifically looking in the brains, livers and kidneys of these animals. Something was up. Barely anything was different between the different aged rats; this is a stark contrast to humans where patterns of genes "turned on or off" change as we get older.
As well as genes that didn't change at all there were even some which did change but in the opposite way to how they would in humans. For example, one gene, that codes for a protein called SMAD3 was up-regulated in the naked mole rat brain whereas in humans there is less of it when we get older. In scientific research differences allow conclusions to be made, tentative as they might be. For example. SMAD3 is known to help stop cells dividing. As you probably know, cancer occurs when our cells can't stop dividing - could more SMAD3 be one of the reasons naked mole rats are able to evade cancer so effectively?
So free radicals are bad. But naked mole rats have lots and live longer than normal. Doesn't quite all add up - see what I meant about disharmonious science now?
Why is ageing so hard to study in humans?
Good experiments need control groups. What would be the control group for older than average humans? Dead humans who would've been the same age? It can't be done! Another reason is, shockingly, it takes a long time. It's not really plausible to study a human for their entire life, cost is the obvious factor but also, would you choose to be poked, prodded and examined for the entirety of your life all for the good of science? Didn't think so.
Good experiments need control groups. What would be the control group for older than average humans? Dead humans who would've been the same age? It can't be done! Another reason is, shockingly, it takes a long time. It's not really plausible to study a human for their entire life, cost is the obvious factor but also, would you choose to be poked, prodded and examined for the entirety of your life all for the good of science? Didn't think so.
We are an ageing population.
Should we really be undertaking research to increase lifespan?
Should the real question be: how can we age well?
Please feel free to comment with your own views on the matter, I'd be glad to have provoked them.
What do you think the best theory is for the theory of ageing? Personally I think free radicals are good and antioxidants supplements are unnecessary (or even make us worse!). Our bodies have evolved to deal with free radicals and the stresses they cause, so they actually help us in repair systems.
ReplyDeleteVery interesting post! Love the picture and the caption.
"The concept of there not being a simple definitive answer is a concept most of us struggle to accept." Good point! Guess that's due to advertisement and commercial marketing? Or do you think its actually part of our nature to think that way?
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