Why we did not evolve to live forever: Unveiling the mystery of why we age

September 15, 2017
Credit: CC0 Public Domain

Researchers at the Institute of Molecular Biology (IMB) in Mainz, Germany, have made a breakthrough in understanding the origin of the ageing process. They have identified that genes belonging to a process called autophagy - one of the cells most critical survival processes - promote health and fitness in young worms but drive the process of ageing later in life. This research published in the journal Genes & Development gives some of the first clear evidence for how the ageing process arises as a quirk of evolution. These findings may also have broader implications for the treatment of neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's disease where autophagy is implicated. The researchers show that by promoting longevity through shutting down autophagy in old worms there is a strong improvement in neuronal and subsequent whole body health.

Getting old, it's something that happens to everyone and nearly every species on this planet, but the question is, should it? In a recent publication in the journal Genes & Development titled "Neuronal inhibition of the nucleation complex extends lifespan in post-reproductive C. elegans," the laboratory of Dr Holger Richly at IMB, has found some of the first genetic evidence that may put this question to rest.

As Charles Darwin explained, natural selection results in the fittest individuals for a given environment surviving to breed and pass on their to the next generation. The more fruitful a trait is at promoting , the stronger the selection for that trait will be. In theory, this should give rise to individuals with traits which prevent ageing as their genes could be passed on nearly continuously. Thus, despite the obvious facts to the contrary, from the point of evolution ageing should never have happened. This evolutionary contradiction has been debated and theorised on since the 1800s. It was only in 1953 with his hypothesis of antagonistic pleiotropy (AP) that George C. Williams gave us a rational explanation for how ageing can arise in a population through evolution. Williams proposed that natural selection enriches genes promoting reproductive success but consequently ignores their negative effects on longevity. Importantly, this is only true when those negative effects occur after the onset of reproduction. Essentially, if a gene mutation results in more offspring but shortens life that's fine. This is because there can be more descendants carrying on the parent's genes in a shorter time to compensate. Accordingly, over time, these pro-fitness, pro-ageing mutations are actively selected for and the becomes hard-wired into our DNA. While this theory has been proven mathematically and its implications demonstrated in the real world, actual evidence for genes behaving in such as fashion has been lacking.

This evidence has now arrived according to the co-lead author of the paper Jonathan Byrne, "The evolutionary theory of ageing just explains everything so nicely but it lacked real evidence that it was happening in nature. Evolution becomes blind to the effects of mutations that promote ageing as long as those effects only kick in after reproduction has started. Really, ageing is an evolutionary oversight." Jonathan continues "These AP genes haven't been found before because it's incredibly difficult to work with already old animals, we were the first to figure out how to do this on a large scale." He explains further "From a relatively small screen, we found a surprisingly large number of genes [30] that seem to operate in an antagonistic fashion." Previous studies had found genes that encourage ageing while still being essential for development, but these 30 genes represent some of the first found promoting ageing specifically only in old . "Considering we tested only 0.05% of all the genes in a worm this suggests there could be many more of these genes out there to find," says Jonathan.

The evidence for ageing driven by evolution was not the only surprise the paper had in store, according to Thomas Wilhelm, the other co-lead author on the paper. "What was most surprising was what processes those genes were involved in." Not content to provide just the missing evidence for a 60-year-old puzzle, Wilhelm and his colleagues went on to describe what a subset of these genes do in C. elegans and how they might be driving the ageing process. "This is where the results really get fascinating," says Dr Holger Richly, the principal investigator of the study. "We found a series of genes involved in regulating autophagy, which accelerate the ageing process." These results are surprising indeed, the process of autophagy is a critical recycling process in the cell, and is usually required to live a normal full lifetime. Autophagy is known to become slower with age and the authors of this paper show that it appears to completely deteriorate in older worms. They demonstrate that shutting down key genes in the initiation of the process allows the worms to live longer compared with leaving it running crippled. "This could force us to rethink our ideas about one of the most fundamental processes that exist in a cell," Holger explains. "Autophagy is nearly always thought of as beneficial even if it's barely working. We instead show that there are severe negative consequences when it breaks down and then you are better off bypassing it all together." "It's classic AP," he continues, "In young worms, autophagy is working properly and is essential to reach maturity but after reproduction, it starts to malfunction causing the worms to age."

In a final revelation, Richly and his team were able to track the source of the pro longevity signals to a specific tissue, namely the neurons. By inactivating autophagy in the neurons of old worms they were not only able to prolong the worms life but they increased the total health of the worms dramatically. "Imagine reaching the halfway point in your life and getting a drug that leaves you as fit and mobile as someone half your age who you then live longer than, that's what it's like for the worms," says Thomas Wilhelm. "We turn autophagy off only in one tissue and the whole animal gets a boost. The neurons are much healthier in the treated worms and we think this is what keeps the muscles and the rest of the body in good shape. The net result is a 50% extension of life."

While the authors do not yet know the exact mechanism causing the neurons to stay healthier for longer, this finding could have real world implications. "There are many neuronal diseases associated with dysfunctional autophagy such as Alzheimer's, Parkinson's, and Huntington's disease, it is possible that these could represent a good way to help preserve neuronal integrity in these cases," elaborates Thomas Wilhelm. While any such a treatment would be a long way off, assuming such findings could be recapitulated in humans, it does offer a tantalising hope; prevent disease and get younger and healthier while doing it.

Explore further: Cells' garbage disposal may hold key to healthier life

More information: Thomas Wilhelm et al, Neuronal inhibition of the autophagy nucleation complex extends life span in post-reproductive C. elegans, Genes & Development (2017). DOI: 10.1101/gad.301648.117

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19 comments

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jimbo92107
5 / 5 (4) Sep 15, 2017
Dang, so you switch off autophagy after reaching sexual maturity, and you get 50 percent more life? That sounds like a good deal. Where's that switch??
IronhorseA
5 / 5 (3) Sep 15, 2017
Dang, so you switch off autophagy after reaching sexual maturity, and you get 50 percent more life? That sounds like a good deal. Where's that switch??


It's behind the door that says 'Authorized Personnel Only'. :)
BubbaNicholson
1 / 5 (3) Sep 15, 2017
No. This is driven by mathematical imperative. Optimal market operation requires novelty's lack of experience.
xponen
not rated yet Sep 16, 2017
I think this result only apply to the brain.

There is a possibility that it only apply to the brain since other studies with autophagy suggest it increase healthspan instead. These studies look at different part of C.Elegans, like its gut.

This is because, our brain has a bias (tendency) toward recycling itself whenever it is damaged, and this is bad because the brain is irreplaceable. For older people it is hoped that we can halt any sort of self-repair or recycling regardless of the damages because the neurons is irreplaceable and if you let our immune system to discard them, then you'd be inflicted with age related impairment and it will hasten your death.
aeschylus
1 / 5 (1) Sep 16, 2017
Evolution should reward those who have done their part in reproduction by extending their lifespan rather than leaving them on to wither and die not long after their contribution.

And what about those who have made no contribution to reproduction at all?
TheGhostofOtto1923
5 / 5 (2) Sep 16, 2017
Evolution should reward those who have done their part in reproduction by extending their lifespan rather than leaving them on to wither and die not long after their contribution
Reproduction IS your reward. And then you should be happy to die and leave space and resources for your offspring.

Your job is to make them and theirs is to replace you.

Does this make you sad?
julianpenrod
1 / 5 (4) Sep 16, 2017
The fact remains that, if death were truly inevitable, as craven and self absorbed as they are presented to be, the rich and powerful would be always catatonic. In fact, they have a way around it. If you are doing what God wants done, He won't remove you. The powerful and craven apparently provide an obstacle course for those who would never even try to advance by overcoming one, or their beleaguering of so many of the public provide a penance for their sins.
Pooua
not rated yet Sep 16, 2017
The research sounds interesting, but the grammar and spelling in this article is horrible; run-on sentences, misspelled words, and this science error: "...natural selection results in the fittest individuals..." Evolution has nothing to do with individuals; it works only on populations.
FernandoFern__ndez
not rated yet Sep 17, 2017
Well, the failure remains to put the focus on the transient organic vessel, rather than focusing research on the essence of being itself, consciousness. Consciousness remains and transcends generations and generations, and their study will unify scientific fields such as neurobiology, subatomic physics (consciousness is the observer), astrophysics ... Maybe is just too early.
TheGhostofOtto1923
not rated yet Sep 17, 2017
If you are doing what God wants done, He won't remove you
Well statistics and the bible prove you wrong. Even Lazarus eventually died.

Maybe you're talking about immortality but your god guarantees that in any case? Only the accommodations differ.

Seriously Julian do you really think you're going to live forever HERE?

You're just as daft as Fernando who thinks he's found a new name for the soul.
OverTheMoon
not rated yet Sep 17, 2017
What would extending lifespans do to the population of the planet?
There are already way too many of us . . . and what would the quality of that life be?
julianpenrod
1 / 5 (1) Sep 17, 2017
Among other things, despite what TheGhostofOtto1923 says, statistics don't prove anything. A million heads in a row doesn't mean that coins have stopped coming up tails. Also, no one has proof that all the people claimed to have died died. Even in the Bible, of all the names mentioned, only a small portion were described as dying.
But, then, again, if you are dong what God wants, He will not remove you. Many refuse to do what God wants. And, remember, which no one wants to address, if they felt death was inevitable, the corrupt powerful would be catatonic.
Incidentally, with respect to OverTheMoon's comment, if mankind became universally so decent that God would remove none of them, He would provide an answer to the issue of limited space or reveal an answer that is already there.
Eikka
not rated yet Sep 17, 2017
statistics don't prove anything. A million heads in a row doesn't mean that coins have stopped coming up tails.


And the sun coming up every morning doesn't prove that it won't dissapear tomorrow.

if they felt death was inevitable, the corrupt powerful would be catatonic.


Why? If anyone felt that death was inevitable, anybody would be catatonic. Nature has provided us with the wonderful property of not really understanding death until it's just about.
julianpenrod
1 / 5 (1) Sep 17, 2017
Eikka declares "Nature has provided us with the wonderful property of not really understanding death until it's just about". Among other things, which of the accepted aspects of death are not already sufficient to be aware of to have the proper distaste for it? You don't have to know exactly how fact you'll be moving when you hit the ground to avoid falling off a cliff. But, too, why would "nature" give that "property"? If "evolution" is being invoked, what survival advantage is provided to withhold a full understanding of death?
Eikka
not rated yet Sep 18, 2017
what survival advantage is provided to withhold a full understanding of death?


The fact that you wouldn't turn catatonic at the prospect of it. To survive long enough to make offspring, we must think, but not too much lest we're paralyzed by thought.

Everybody "knows" they're going to die, but nobody really takes it seriously. It's the same thing as, if Christians took the gospel seriously they'd be all raving mad on the streets or hiding away in caves and monasteries. I mean, this life is nothing compared to the eternal life, and you're going to spend it in heaven or hell - isn't that even more serious than the prospect that you're going to die and then nothing?

You see, there's two serious sins you can commit as a Christian: believing that you're damned anyways, or that you're already saved, that you already have it in the bank. One is giving yourself up to the devil voluntarily, the other is declaring yourself God.



Eikka
not rated yet Sep 18, 2017
which of the accepted aspects of death are not already sufficient to be aware of to have the proper distaste for it?


You can turn that question on its head: why do you want to live forever?

The rich asshole can't be a Christian, not really, because again if they had some serious faith they wouldn't be in the situation in the first place - with all the eye of the needle business and so-on - so obviously they don't have the same considerations as what you'd accept.

Forgetting all the evolution vs god business, why indeed do you want to life forever? You can't have a life that's all perfect, because to even recognize joy you must also experience sorrow. So, however joyful your life is, the eternal life is also eternal sorrow, and why would you want that?
idjyit
not rated yet Sep 18, 2017
live Forever - Black Sabbath - 13

You should listen to the whole album.
TheGhostofOtto1923
5 / 5 (1) Sep 18, 2017
But, then, again, if you are dong what God wants, He will not remove you
The last religionist I remember talking like this was L Ron Hubbard.

You blaspheme julian

" 2 Everyone will die someday. Death comes to godly and sinful people alike. It comes to good and bad people alike. It comes to "clean" and "unclean" people alike. Those who offer sacrifices and those who don't offer them also die." Ecc9

"27 Everyone must die once, and after that be judged by God. 28 In the same manner Christ also was offered in sacrifice once to take away the sins of many." Heb9

-in the most offensive way possible. You deny the resurrection offered to you by your god. He suffered for you so that you could live forever in heaven, not here.

All religionists are filthy sinners. This proves it.
Eikka
not rated yet Sep 20, 2017
All religionists are filthy sinners. This proves it.


It doesn't need proof because it's already stated so in the Bible.

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