The Lifespan of Flies Has Been Extended By Promoting Mitochondrial Replication
I came across a fun article recently published in Nature Communications titled "Promoting Drp1-mediated mitochondrial fission in midlife prolongs healthy lifespan of Drosophila melanogaster." Here the authors were utilizing a model organism of fruit flies (Drosophila melanogaster) inorder to study an aspect of the aging process that many of us might not even know about, the functionality of our mitochondria. I think this is a pretty interesting paper and it will allow us to have a nice discussion about aging (perhaps even from a unique perspective for you). So lets dive in!
** Disclaimer: THERE IS A TON OF DATA IN THIS PUBLICATION, we will only discuss a subset of that data here. Please refer to the above linked article for more if you are interested in a deeper dive **
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This article is centered around this group of researchers interest in the relationship between aging and mitochondria that are not functioning properly. This is a concept that has been studied in some detail in the past, where researchers have identified that these dysfunctional mitochondria are linked to a variety of diseases that are associated with getting old (examples being: diabetes, heart disease, and metabolic syndrome). [2], [3], [4].
In fact there are a whole host of other diseases that also have links to less than functional mitochondria, which perhaps shouldn't be all that surprising considering this cellular organelle is the source of its energy (ATP) processing machinery.
A second concept they were exploring was the involvement of autophagy, the process that cells use to take out cellular garbage (break down broken components), in removing mitochondria that are not working properly.
They were interested in this as the rate of mitophagy (autophagy of mitochondria!) has been reported to decrease as we age. [6].
So, we know that mitochondria are linked to age related diseases, and the recycling process used to get rid of malfunctioning mitochondria slows as we age. These are two compelling reasons to think that aging and mitochondria might have a relationship.
Perhaps even one where the aging process can be slowed down by stimulating those very mitochondria?
Dynamin-related protein 1
The process of breaking down the old mitochondria is related to the inverse, mitochondrial growth processes as well. Mitochondria can replicate through a process called fission in which a single mitochondria splits into two (it requires replication of the mitochondrial genome... yes they have their own genomes).
This fission process requires a protein called Dynamin-related protein 1 or DRP1. Interestingly DRP1 is also required for the breakdown mitophagy process. [7]
The authors postulate that these findings are indicative that the splitting of mitochondria in the fission process, may be required to sequester away dysfunctional mitochondria, and allow for their destruction in the cellular garbage disposal...eer mitophagy process.
Enough Background Get To The Data
Okay.
Here the authors were studying mitochondrial fission in some flies. They wanted to see whether or not stimulating this fission process could lead to an extended fly lifespan. So they turned to the DRP1 protein, which is essential to the mitochondrial fission process and they cranked up the expression levels of this protein in the flies.
What they found is fascinating!
In the figure above section (d), the authors increased the DRP1 expression in some young flies at times between 0 and 30 days in age (after 30 days they stopped the excess expression), when they did this (black dotted circles) there was no observable difference in how long the flies lived. HOWEVER, when the DRP1 expression in middle aged flies (so it was turned on after 30 days and left on) was increased (e) they found that the flies with the extra DRP1 lived quite a bit longer! You can see this as the black circles (where the protein was expressed) show a longer survival time then the open circles (where it was not expressed). They then confirmed that it was expression in the midlife period specifically that caused this effect.
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So here we can see that the flies had the protein expression increased only from days 30 - 37 (mid life), however as a result of this the flies that had the protein expressed (circles with a black dot in them) lived longer then did the flies who never had the DRP1 overexpressed (circles with no black dot in the center).
This means that there is a time dependent component on when mitochondrial recycling is most important, and can extend lifespan. It also means that its a SPECIFIC time, as the protein expression doesn't need to remain on, the effect happens and remains even after the protein expression levels are back to normal.
What Else Was Going On With These Flies? Did Anything Else Change Which Aided Them In Developing This Increased Lifespan?
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The authors explored some other aspects about the flies, for instance how often/how much they fed. Looking at the image to the right (a) you can see that the flies that had the DRP1 expressed more highly (red) did not eat more then the flies that did not have it expressed (blue), however in (b) you can see that the DRP expressed flies (again, red) were much more active.
The authors tested when this activity occurred and found that it was only during the day. So the flies were more active when they were awake but not restless at night.
More DRP1 Keeps Mitochondria Looking Young
So here what we are looking at are some red stained muscle cells and some green stained mitochondria. What you can see is that as time goes on the mitochondria in regular flies get much more elongated and stretched out, but in the right most box after 37 days and with extra expression of DRP1 the mitochondria look like those from much younger flies. Compare the size of the green mitochondria to the 37 day untreated sample directly to its left. Strikingly different!
The authors also discussed that expression of more DRP1 not only corrected the structure of the mitochondria but also restored them to more youthful function levels
Other Reported Findings
Increased expression of DRP1 was observed to:
- increase mitochondrial enzymatic levels
- reduce radical oxygen species levels. (Low levels are necessary, but levels too high are known to cause cellular damage)
- reduce levels of protein aggregation (clumping together into non functional blobs) in the mitochondria
- lower the amounts of mitochondrial DNA present in muscle tissue (hypothesized due to increased destruction of non functional mitochondria)
- Found that the autophagy process (how the broken mitochondria are degraded) is necessary for the added longevity that extra DRP1 caused
A ton of interesting information in this paper!
Brief Conclusions
In this article the authors explored a protein called Dynamin-related protein 1 (DRP1) which is necessary for both mitochondrial replication/splitting (fission) as well as the recycling process where broken old mitochondria get destroyed (mitophagy). They report that increasing the expression of this protein in flies that are middle aged, is able to pretty drastically extend the lifespan of those flies. Indicating that ability of mitochondria to be recycled is essential to longevity.
The results are so fascinating that I hope to read more papers looking into whether this phenomenon is possible in other model organisms as well. Can we extend the lifespan of a mouse through increasing the expression of the mouse variant of this enzyme when they are middle aged? If so, is this a potential avenue for improving the quality of our own lives? Quite fastinating stuff.
What do you think about all of this? Would you want to live a longer life if it required stimulating the expression of this mitochondrial growth/recycling protein? I think I would.
Sources
Text Sources
- https://www.nature.com/articles/s41467-017-00525-4
- https://www.ncbi.nlm.nih.gov/pubmed/23746838
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566449/
- https://www.ncbi.nlm.nih.gov/pubmed/17243117
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990190/
- https://www.ncbi.nlm.nih.gov/pubmed/26549682
- http://cshperspectives.cshlp.org/content/5/6/a011072.full
Image Sources
All Non Cited Images Are From Pixabay.com, Flickr.com, Pexels.com, or Wikipedia.com And Are Available For Reuse Under Creative Commons Licenses
Any Gifs Are From Giphy.com and Are Also Available for Use Under Creative Commons Licences
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Great Post. I know a ton of age longevity work has been done in C. elegans. Some of the work is really cool, but a lot of it boils down to a lab discovering that overexpressing/deleting a gene increase lifespan followed by 10 years of chasing that one phenotype.
Indeed, at least with flies the organismal complexity is a bit higher. I just find the work fascinating. The real way to test this stuff is just to try the overexpressions in other models, and if they don't yield similar effects, move on. Rather than getting bogged down chasing a ghost.
This kind of Mitochondrial editing, when incorporated into human cells, will it also prolong lifespan of humans? More like "Mitochondrial Engineering"
It's a good question, and one which there is no scientific evidence for yet.
Does mitochondrial fission occur using DRP1 in humans as with the flies that were experimented on in this study, or is there an analogous protein that has a similar role in humans? Even so, this is a very exciting study, and something which I would not have come across if it weren't for your simple breakdown of a very complex study.
Thank you very much.
Humans have DRP1 and its functionality should be similar. Now keep in mind that in this study with the flies, they showed that the timing for expression of DRP1 was important. Who knows when or how that would come into play for humans. Biology is very complex, especially with regards to regulation, and the interplay of proteins and cells.
justtryme90, awesome information and analysis. I love the way you take some very technical information and make it understandable to the non-scientist or tech. This topic fits well the research done by Harvard and University of Singopore that looked at the NAD Protein and prolonging life of mice. NAD Protein apparently helps both Mitochondrial and Nuclear DNA repair. Seems indeed getting the Mitocondrial refreshed helps with longevity and energy. While I personal do not know how to increase NAD in my body, I al least research the food that increases NAD in the blood stream. I joke daily with my wife about being on the NAD's diet that day. Let see if this works. Seems that you article supports the body of evidence on this topic. Upvoted and resteemed.
Its definitely an interesting avenue for further research. I will be waiting to see this attempted in additional (higher order) model systems. I think seeing similar work done in a mouse would be extremely interesting. This could lead to a whole host of therapies in the future if it shows promise in mice.
http://news.harvard.edu/gazette/story/2017/03/harvard-scientists-pinpoint-critical-step-in-dna-repair-cellular-aging/
Something to track.. for now advocados, red wine, and blueberries are food that become NADs in the blood stream. I also found a practice in San Diego of 4 doctors specializing in NAD injections for 15+ years, however not for the novice. Also, suppressed by NIH, since there is not a "pill involved". They were relegated to just doing in the state of California and cross border would have resulted in "prosecution" of junk science.
The NIH doesn't give two shits about whether or not something is in pill form. Neither does the FDA. They do care about whether or not something works.
This, sounds like a bunch of hot air.
Likely because what they are doing IS junk science.
At least the Harvard team are validating this protein NAD and Mitochondrial Health in longevity studies. For now "Junk science" indeed. My approach is always natural and wholelistic first. Just my preference. Now my brother is a practicing physician, so he always keep me healthy indeed if I go far afield.
Yep, more research is badly needed in this area.
My statements on this are more to do with the implementation with out necessary research to back it up. Perhaps more of a "junk treatment" then is the actual scientific basis being junk.
Time and more research will tell us the answers :)
agreed, Looking forward to reading more of your posts and ideas.
Fantastic post! Can't wait to see what the data shows with DRP1 in mice. New word of the day for me...mitophagy!
Thanks! Yeah, mitophagy, not a word that I use every day that's for sure!
this just gave me.an insight in my research - could this be the reason why lobsters live near infinity? living infinity is one thing but how the organs continue to function normally is a sruprise. me being a researcher in eye - have been working how the sight is preserved even after hundreds of years? will definately look at it. Also the impact of telomerase has a crucial role. Maybe this will be of some interest for your future research.
I do not know the answer to your question with regards to the lobsters. They are an interesting organism thats for sure.
Nice article ! Really informative !!
Great initiation of #steemstem project !!
Thank you. We are working very hard with the project to support good science on steemit. :)
Thank you so much ! Best of luck for your project !!
Just discovered you after a month in the platform... what a treat!!
loved your post on time restricted eating... I know it's an insane amount of work but it'd be great to summarize four/five studies around a specific topic... have you look into cold thermogenesis? it looks very promising!
I have not read on the subject before. I generally write about articles that I read as I peruse the literature. If I come across an article discussing thermogenesis I will for certain talk about it.
I typically try to break down a new piece of work, rather than discuss a topic in detail, though I'm not against the idea of a summary article where I break down a topic using the work of a few articles. The challenge in that case is finding open access materials that allow me to reproduce their figures so I can try to explain them in simpler terms. It's not so bad with one article, but more than one and it's trickier. This is why I try to have a bit of a background section to start the post.
Serendipity, take me along! :)
I was asking because I remember reading cold thermogenesis affects mitophagy and mitogenesis in the same way as sauna does (no surprise since they both activate HSPs)
If it is helpful in humans aging process, that will a great discovery. Humans always try to find out the ways for anti aging and it has been always a secret how to achieve it. We have always been fascinated by it.
Much more work will need to be done to determine whether or not this carries over into humans. We will have to see :)
It's interesting regardless :D
Alert! Alien invasion!
I'm quite interested in life-extension, so please do!
More money should be poured into this kind of research: since most diseases are age-related, so many diseases would be cured/delayed by default if aging is cured/delayed.
Great to see the inauguration of @foundation 's gif!
Is the mitochondria the alien, or are our own eukaryotic cells the aliens who gobbled up this ancient now symbiotic organelle back when it was its own organism?
What is an alien anyway? The POTUS has me convinced they come from mexico. /s
We should build a membrane to keep them out!