The Role of Mitochondria in Aging and Disease - David Sinclair

[Music] so one of the big questions in biology is why don't we live forever maybe one day we will but until we understand why we grow old and get diseases such as Alzheimer's diabetes cancer cardiovascular disease we will not have a chance to greatly extend our lifespan one of the main reasons for this is that currently we address one disease at a time and even though we have breakthroughs in say cardiovascular disease other diseases such as Alzheimer's are rather a calcitriol very difficult to right now to prevent and cure and so what happens is that we have the decline one disease and another disease accelerates in its in its frequency and we're not living much longer than we did ten thousand years ago unfortunately so really what we're trying to do as a field in us biologists who study aging is to understand what's at the root cause of this decline that we all go through unless we're unlucky enough to be to die early so one of the major theories that's been around really since the 1940s 1950s is the idea that aging is caused by a decline in mitochondrial function so what a mitochondria well these as many of you will have known from high school biology are the bags within our cells that generate chemical energy they do other things they process fat and also allow us to to make other molecules that allow for cells to grow but really for this topic what we want to talk about is their role in making chemical energy called ATP and I draw this like a bag with my hands it's really just a double membrane the inner membrane is ruffled and there are lots of proteins within that bag that carry out these chemical reactions to make ATP and energy now what's really interesting about mitochondria is that they're actually another organism living within each of our cells and unlike the textbooks there isn't just one or two mitochondria per cell there's hundreds encased some cases thousands of these and they're not just single bags they're actually networks in there we're learning that they they divide and then they fuse and then they they can do the cell can destroy the bad ones and improve the healthy ones there are some unfortunate people throughout the world who have mitochondrial diseases and when the mitochondria don't function well from birth patients tend to have a number of neurological disease diseases traits and there are other muscle loss of muscle functions as well so mitochondria are critical for life we know that in fact if you poison the mitochondria say with cyanide you be dead within about 30 seconds so we really need to understand not just how mitochondrial function but how to keep them healthy throughout our life and one of the main theories of aging is that over time well we start out young and there's lots of mitochondria in the healthier and they know how to function they make lots of energy we feel great we've got energy we can run we can fight off diseases our brain functions well we can remember and we don't get diabetes we don't have dysfunctional muscles for example but over time let's say people like me who are now midlife we are starting to lose our mitochondrial function that's a fact and then by the time we're in our 60s and 70s it's even worse and in 80 to 90 year old we'll have much much lower mitochondrial function and they'll have less ATP and this is a problem and we scientists think that one of the major causes of diseases during aging is caused by this loss of the ability of ourselves to make energy now as I mentioned mitochondria are free living organisms in our cells they joined ourselves about two billion years ago they were originally what are called alpha proteobacteria we find these free living bacteria right now in the world but they're genetically related and functionally related to our own mitochondria and what's important is that these mitochondria have their own DNA they brought their own genome with them when they joined ourselves to make eukaryotes and today they still have many of those genes in their genome the other genes that used to be in in that genome it's a circular genome have been transferred to the nucleus and so we're really just a mishmash of two species living together and the genomes exist separately but they need to communicate very well together to maintain their coexistence and be healthy and later I'll tell you that one of the problems with aging might be that these two genomes within ourselves lose the ability to communicate but first I want to tell you about an older theory of aging that still holds some weight what we're starting to think is that this is more of a later stage of Aging so back in the 1940s and 50s I was telling you that the mitochondrial theory of aging was born and that's the idea that during metabolism there's a lot of free radicals or we call these reactive oxygen species that can damage macromolecules the idea is that as the mitochondria when we're young are functioning they're producing these radical free radicals that damage the enzymes and particularly the DNA within the mitochondria and over time we start to lose the code that's in our mitochondrial DNA we get mutations we get big deletions so for example if we took my DNA from pretty much any cell except perhaps my germ cells in my testes these cells would have a large number of mutations and deletions already which is rather disturbing and the idea is that if we could slow down this damage to our DNA we would have a way to delay aging we could prevent these mutations and we would actually be healthier to into long and have a longer life now this theory still had has some merit you can find these mutations in it in anybody even newborns have some mutations already which is a scary thought one of the problems with their theory has been that the ability to extend lifespan by slowing down these mutations has been rather a difficult battle we haven't really had success feeding antioxidants to mice for example or other organisms hasn't had a big impact on their lives and in fact one of the the new theories is that free radicals might be somewhat beneficial and can extend the lifespan if you take a little worm for example and give it antioxidants they can actually have a negative impact on its long life so it's not as simple as we once thought where the field is settling now is that the damage to mitochondrial does occur it seems to be important but it might be most important for the later stages in life let's say after your 50 60 70 but what's going on in someone like me who's 40 what's why am I already experiencing a decline in my mitochondrial function well it may not be to do with mutations and the reason is that we have found just recently studying Meissen and human cells is that if you catch aging early enough and the mitochondrial dysfunction early enough it's actually reversible one of the the new leading theories in aging and mitochondria is that the communication between the nucleus and the mitochondria breaks down early during aging and let's call that stage one of aging now what what carries out this communication is that so if we have the nucleus here in the mitochondria here there are proteins that are made in the nucleus by our main chromosomes and those proteins travel across the cytoplasm into the mitochondria and they help the mitochondria be healthy they make it make just the right amount of energy to match what the cell needs and what we found is that during aging in the early stages this communication these proteins that move across to the new from the nucleus to the mitochondrion they start to lose their activity and you don't have as much made anymore in the cells now the good news now is that if we could restore that communication we might have a chance of reversing aspect of aging if we catch it early enough now the analogy that I like to make is that the nucleus and the mitochondrial genomes these two genomes are like a married couple when they move in together early though they're in love they communicate well they talk they share ideas and that's what our souls are like when were young but over time they don't they don't talk as much they develop different interests and what happens is they stop talking over time and we know that that's the worst thing that can happen for a marriage and we think the same thing happens for the marriage of these two organisms these two genomes in ourselves and what our job is now is to test what happens if you can restore that communication again and that get them talking again and just in December of 2013 our lab published an interesting paper that showed the following it showed that one of the main causes of miscommunication is that the nucleus doesn't think it's getting enough energy anymore and it doesn't it doesn't send the signals to the mitochondrion to make them produce the energy anymore we track this down to the loss of a small molecule called called nad we think nad is critical for cells health and their ability to maintain this healthy communication so what we did was we simply raised the nad levels back up in a mouse to their youthful levels so a mouse when it's young has let's say this amount of nad over time the nad levels drop by half and we found well first of all we ask the question if we raise these levels back up to youthful levels of nad what happens can we restore this communication and we did that that the way you do that actually is quite simple you inject the mouse with a molecule that the animal turns into nad you can buy this from a chemical company you inject it for a week and we ask does this have a benefit restoring the communication and the answer was yes now after one week of raising nad the nucleus was now re-establishing communications to the mitochondria they were talking again and then we could ask does this improve health does it restore the energy of the cell which we think is a cause of Aging and the answer was quite remarkably yes the mice when we looked at their muscle and their heart they had a restoration of youth the mitochondria were revved up again after just a week and they were making energy and as far as we could tell looking at all these functional assays of the mitochondrial activity their ability to make energy their genomes activity the amount of DNA they had they went straight back to being young again so we actually couldn't tell the difference between a two-year-old mouse and a six-month-old now so what that really is like is saying we could take a 50 60 year-old human muscle and make it like a 30 year old again now I mean that would be great if it's true in humans we only know in mice so far but we are gearing up to test this in humans we think that if we could give this molecule that raises nad in a pill or an injection we think that we within a week if we're right then we could reverse aspects of Aging in humans and that would be something really quite spectacular and if we can do that there's a possibility that we could actually not just see people get old and an experience diseases and slow down one disease at a time with with two traditional medicines we might be able to actually if we catch the dis event early we could reverse mitochondrial aging and if everything turns out to be correct that I've said then what we expect is that humans will not develop diabetes even cancer heart disease Alzheimer's until much later maybe into their 90's hundreds or further and so that we're looking at a future where we might be able to restore youthful energetics in cells prevent mitochondrial aging keep this organism within our bodies healthy and live much longer healthier lives [Music] [Music]

Channel: Serious Science

Views: 182,788

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Keywords: science, lecture, Serious Science, biology, aging, molecular biology

Id: v3ncUYKme4k

Length: 13min 28sec (808 seconds)

Published: Thu Mar 06 2014