Taurine - Fountain of Life | Aging and Mitochondria

all this is Dr moin Sayad from Dr bean.com welcome to one more show cell senance is a state of a cell where it is locked and it is prevented from further replicating or from further Offspring production the benefit of locking a cell in a senent state is so that it does not produce new cells that may have DNA damage and may become cancerous many of our cells especially in the renewable tissues can convert to cense when they are under stress over our age many of our tissues start accumulating senent cells or the cells that are locked in nonrenewable State and we can say that well these cells are sitting there and it is okay they're just sitting there the problem is that senent cells these rather aging quickly aging cells cells that have accelerated aging they release chemical substances Incans proteases proteases are molecules that would break down other proteins so they release chemical substances in their local environment and modify that environment causing tissue damage so senent cells are not just to be looked at to say it's okay they are cells that have become accelerated old just let them sit there and it is good that they're sitting there it is good they're not renewing it is good they're locked because they're not going to cause any further uh Generations Offspring production progeny production and hopefully we will not develop cancer so it's a protective mechanism however these gripy little senent cells are sitting there causing micro environment to become changed causing Dam to the tissue so then the question becomes is there an understanding of how the cells become senent can we block their cense can we keep them from damaging the environment around them these gripy cells can we protect them can we stop them from damaging the local environment that is the area of study where a lot of research is going on this research then uh correlates with aging with health in advancer age and Longevity so this is one part of the Fountain of Youth and Fountain of Life search I would take this series from here the mitochondria and aging I would discuss some more mechanisms and then I'm going to take you towards torine and other molecules that we are talking about nowadays that help with reducing the Aging progress and keeping us healthy so this is really a a foundation setting for toine discussion okay so let's start so here this is Dr bean.com if you would like to have more lectures please go to Dr bean.com and get access we have hundreds of more medical lectures here this is the study this is a Harvard um article about the study I'm going to discuss this is the study apoptotic stress causes mitochondrial DNA release during sense and drives the sasp we'll talk about this in a second then there are some uh support in evidences and other studies so let's go to my drawings and please realize this study itself is pretty thorough comprehensive and detailed it is a mouse or mice study so as you can see here quite a detailed study I cannot go in this introductory dis discussion throughout the whole study so I'm going to go over highlights of the study and then in the coming days we will go more in depth so let's start so it's a mice study and sometimes my mouse just stops working so my apologies so give me one second I'll have to just restart this um this program so that it could stop doing what it is doing so one second I'll be with you this and perfect so we got it and let's start again okay so here's a study apoptotic stress apoptotic stress is a stress on a cell that empowers the cell encourages the internal mechanisms of the cell to kill itself so the difference of epop epopt Tois versus a normal cell death is that in apoptotic death because the cell is killing itself because of all the stresses on it the inflammatory mediators are not released by the cell so the cell would die but would not activate the immune system so that no inflammatory war starts so that is apoptosis so the takeaway here should be that a cell that is under stress could kill itself without further causing more Flames around without activating the immune system so apop apoptotic stress causes mitochondrial DNA release during cense and drives the sasp so let's look at this first of all instead of the Fountain of Life The Fountain Of Death what is that so this is the F most important concept to capture in a cell that is under stress think of any cell a cell that is in the area of inflammation a cell that is in a tissue where there is less oxygen a cell that is in a tissue where there is less nutrition reaching a cell that is in a physical crushing State a cell that is in an acidic environment a cell that is under energy or light that is damaging to it a cell that is in the presence of bacteria virus and other such pathogens so there a cell that is in the presence of a poison these cells are under stress when these cells are under stress the mitochondria so I have made this mitochondria over here in a very comic way so in mitochondria in such cells can become permeable what does that mean imagine in your mind that mro mitochondria is a bean is a tiny Bean shaped structure there are thousands of bean shaped structures within a cell these mitochondria are producing energy and giving it to the whole cell they have an integrate integral membrane system they have their own membranes mitochondria and within those membranes there are two membranes they have within those membranes are various assemblies to make uh energy in a stress the outer membrane of the mitochondria develops pores in them develops holes in them those holes will allow the products from within the mitochondria to start leaking out this is the Fountain of death and if we can reduce this Behavior then that becomes the Fountain of Life so if you see over here chronic senance Associated secretory phenotypes or sasp so my request is please St start becoming familiar with these terms sasp are the products that are released from a senent cell as I said before these can be Incans these can be proteases these can be other damaging pro-inflammatory molecules released from a senent cell these are called collectively sasps these SAS SPS are the one that cause local tissue damage and why are these sasp released it is the mitochondria that is releasing products from within which would then encourage the cell to release sasp so at the heart of it is mitochondria what are the kind of sasps that cell will release in the environment inter chemokines various growth factors various secreted proteases proteases means they would break down proteins around them secret secreted insoluble proteins extracellular metrics lots of such things so basically if I improve this diagram I'll put a cell outside of this and the cell is releasing sasps which are also a fountain of death for the environment around within the cell there is a fountain of death going on and that is the mitochondrial permeable membrane releasing mitochondrial components within the cell does this make sense now senent cells in our bodies accumulate during aging and chronic diseases imagine that if I am going to live for let's give it a number let's say 80 years from my birth till the 80 years of age my cells would slowly become aged and my tissues collectively would Age till that age whatever that is however if I am exposed to inflammatory States then some cells that are exposed to the inflammation they will age faster they will become senent faster they will become the age of 80 years while I am 50 and they would accumulate there and as I said they would cause pathologies because they are releasing sasps so senent cells will release sasp that would cause local tissue damage can we stop that can we reduce that and we'll become younger and healthier and we would have stalling we would St all our age okay now during apoptosis apoptosis as I said before a cell under stress is trying to kill itself during apoptosis widespread mitochondrial outer membrane permeability occurs so this is a little mitochondria I have made over here it is quite sad here what it is doing is it has these little holes in it pores that have formed here these pores pores are causing its membrane outer membrane to become permeable allowing the things from inside the mitochondria to spill out so these holes these permeabilities these little um pores are called mitochondrial outer membrane permeability or M so when you look at the literature and stud is for anti-aging and Better Health look for the components substances herbs drugs that would help reduce M mitochondrial outer membrane permeability good now how does this happen why does a cell under stress has its mitochondria develop these permeability and what happens what is the result of developing that permeability so let's look at the result then we'll see how this happen so this is the same mitochondria once again this whole cell is under stress for whatever reason let's say this is inflammation mitochondria has developed holes we'll discuss in a second how but now what is happening is from within the mitochondria the nucleus DNA of the mitochondria is spilling out so if you see here the Top Line backs and back macro pores in mitochondria are formed so these mitochondrial pores are called backs and back proteins what is that imagine I'm sitting in this room and this room is a mitochondria and imagine all the windows and doors are shut off they're closed then all of a sudden somebody outside produces a pipe like structure they go to Home Depot and they buy some products and they create a pipe and and then they shove that pipe into the wall of this room and there will be a hole created so first thing to remember that hole is not a puncture in the membrane that automatically appears what happens is outside of the mitochondria that is inside the cell but outside the mitochondria so this is the inside the cell but outside the mitochondria in this space let me actually show you that uh structure for a second here let's look at this for a second this is a stressed out cell when that cell is stressed out within the cell's cytoplasm there are proteins that are called back and backs proteins that become activated under stress when they become activated they join together they coales together they conjugate together and they make pip like or hole like structures those hoik structures then get stuck to the mitochondrial outer membrane and they become the holes in the membrane of the mitochondria so if somebody said how will the mitochondria become permeable your answer is going to be when a cell is under stress it would cause the back and backs proteins to become activated the stress that would cause the these proteins to then active proteins to bind with each other to make tiny hole like structures or pipe like structures then those pipel likee structures will get shoved into the outer membrane of the mitochondria becoming the holes in the mitochondria so let's go back to where we were here once those holes are produced backs and back micro pores or macro pores then the mitochondrial DNA or empty DNA mitochondrial DNA is released in the cytool of the cell that causes the DNA present in the Cell from the mitochondria causes in the cell another pathway of molecules of proteins to become activated that pathway is called SE gas sting pathway that pathway when it becomes activated that causes activation of release of chemical substances as I discussed before inin chemokines proteases Etc so let's see if you can if you can recall it cell is under stress factor number one when the cell is under stress that causes within this Cell Activation of backs and back proteins when these proteins become active they started coaling with each other they start they start to join with each other and they make these pipik structures once those pipik structures are formed these structures are going to get shoved into the mitochondrial outer membrane and now the outer membrane has permeability then from the these holes these pores the mitochondrial DNA starts spilling out into the cell the presence of mitochondrial DNA into the cell would cause the cellular damage patterns to become activated and what they will do is they would cause another pathway to become activated which is called C gas sting pathway when the SE gas sting pathway becomes active that causes the release of sasp proteins incin chemokines proteases extracellular Matrix Etc damaging proteins would come out of the cell so you put stress on a cell the cell would release damaging proteins internal Machinery is in front of you good so now this is an important point when when a lot of mitochondria there are thousands of mitochondria in a in one cell when a majority of the mitochondria become permeable and start releasing their DNA in the cell then the cell would commit epopt posis and cell would die the way Harvard article put it they said when majority of mitochondria burst inside a cell the cell would die but here was a curiosity the Curiosity was what will happen if not a lot of mitochondria are damaged what would happen maybe out of thousands maybe a few hundred are damaged now what will happen to the cell and they found out that is this study they found out that if only a few mitochondria so here let's say this mitochondria is damaged other are happy one that are smiley faces they are happy they're okay but some are damaged when a cell has some mitochondria are damaged they are permeable they have started releasing dnas this cell would have senent Pathways activated and this cell would be locked into senent state it is not dying but it is not living either it has been made old the Fountain of death started on it it is shal it is senent it is stuck in that state it is aged but it would take its revenge it would release asps in the environment and it would cause the other cells healthy cells around it to become sick to become damaged so my minority M this is called minor minority M what is minority a smaller amount of mitochondria and M is mitochondrial outer membrane permeabil permeability so minority M results in cell cense so somebody said from today's talk what is your takeaway there are two takeaways the cell stress causes the mitochondria to become permeable if majority of the mitochondria become permeable the cell would die if minority of the mitochondria become permeable that cell would become senent that senent cell is now going to take a revenge on its brothers and sisters around it and release chemical substances to damage them clear so now this study some more important things of course the the other takeaway that I want to have this is a huge study I'm not going in detail for all of that I'm I'm presenting to you the core of the study in this study they did something that is very interesting what they did was they found a therapeutic product which could inhibit the poe formation so those proteins backs and back they were able to block those proteins from becoming active and they saw that the the senent cell production reduced those cells that were even senent their sence was cleared away the cells stopped killing things around them this cell stopped releasing sasps and the tissues became healthy so here in this study they say we find that inhibition of M in Vivo and this is a mouse study so in Vivo here means Mouse decrease inflammatory markers and improves Health Span in aged mice I see a comment here from Jessel that is saying autophagy in a senent Cell autophagy and mitophagy both get arrested as well and do not occur or become dysfunctional so the cell is just trapped in a sick State and sto and stuck there now now the researchers say our results reveal that apoptosis and senin are regulated by similar mitochondrial dependent mechanisms the mechanism that we just discussed the permeability if all majority of the mitochondria have that the cell would die so that is apoptosis if some of them some of the mitochondria developed this problem then senance would occur and that sublethal mitochondrial epop totic stress is a major driver of the sasp so this sublethal that is the cell has not died it is living got stuck in cence that causes the cell to release sasps which cause the tissue damage we provide proof of concept that inhibition of my mom induced inflammation may be a my mom induced inflammation may be the therapeutic route to improve health span they actually used the back inhibitor molecules to inhibit these macropore formations and they cleared the cense and they made this the mice healthier so here they say in another part of their study cellular cense refers to the irreversible growth rest that occurs as a response to different stressors senent cells secrete multiple factors collectively known as the sasps senent cells accumulate during aging and chronic disease we are all accumulating them over time disease or not and then if we have chronic diseases inflammatory diseases are mostly chronic then we are going to get more senent cells senent cells accumulate during aging and chronic disease and clearance of the senent cells alleviate several age related pathogen pathologies in mice these cells therefore represent promising therapeutic targets to prevent age Related Disorders the reason I'm discussing this is I'm building your foundations to understand mitochondria's role in aging senin and in inflammatory States so that we can talk about toine and some other molecules now this is another study talking about back and backs back and backs are members of the bcl2 family that is a type of proteins family and core Regulators of intrinsic pathway of apoptosis these two proteins that would become a pipe and get shoved into the micro mitochondria's outer membrane and create holes these are actually part of apoptotic protein struct U class their job is to actually cause internal damage which would then cause the cell to die upon apoptotic stimuli when a cell is under stress and the cell is being told by the signals of its own that hey we are in under really lots of stress we should just die upon apoptotic stimuli the they are activated who they back and backs and oligomerize oligomerize mean many molecules of these combined together and oligomerize at the mitochondrial oligomerize is one molecule polymerizes many molecules oligomerize the mitochondrial outer membrane to mediate its permeabilization which is considered a key step in apoptosis now I have skipped over the whole mechanisms about various parts of this uh pathway that I showed I want to show you how they treated it so in their study they say inhibiting m improves Health span we next assessed whether mitochondrial DNA release and the sasp could be suppressed using pharmacological inhibitor of M we investigated this small molecule backs inhibitor or B A1 so remember there was backs and back so they brought in a molecule that might become a drug tomorrow that can block backs which inhibits confirmational events in back's activation preventing back's mitochondrial translocation and oligomerization so confirmational change mean A protein that changes itself because of some um electrochemical influences on it and the activation is of course activation of the molecule and then oligomerization becomes you know stuck to the mitochondrial membrane aligning with published data back's inhibitor treatment had a protective effect against bh3 mimic induced cell death in back knockout cells but not in back knockout cells consistent with the back specific inhibitory effect we next so essentially they it helped we next investigated whether ba i1 impacted cense so one it was helpful now they wanted to see can it help against cense ba i1 was effective at preventing mitochondrial DNA release back activation and the sasp in mrc5 and imr90 secrete senent human fibroblasts so yes it was able to reduce the mitochondrial release that means it was able to reduce the membrane permeability and of course that would help senent cells treated with B1 were also more resistant to ab2 63 induced cell death so they were healthier plus they resisted cell death death further supporting that anti-inflammatory effect of bi1 in cense was due to back inhibition we found that inflammation induced by transection with hering test DNA in human fiber blast occurred independently of backs and blast so no worries finally treatment of cense fibroblast with alomo eloma and FDA approved drug that directly inhibits backs through a different mechanism from by was also effec Ive at suppressing the expression of several sasp factors in senent FB blasts so they had a backs inhibitor molecule and that worked and they had an FDA approved drug the elom bag bag ELR elram eltrombopag which was also helpful these results prompted us to investigate forac olcal inhibition of myom as a therapeutic approach targeting senent cells during aging we treated aged 20 months old mice with B1 for 3 months we found that treatment with B1 ameliorated age related decline in neuromuscular coordination as demonstrated by a significant increase in rotaro latency and improved performance in the pole test in which ba1 treated as animals were able to maintain balance for a significant longer duration of raised Rod B1 treatment improved four Lim grip strength in Old mice and delayed the progression of age Associated Frailty symptoms notably ba1 treatment improved the health span of AG mice without affecting the lifespan so then if you go to the study I I have it till here but if you go to the study you would see that they looked at the osteoporosis of the bone that was reduced by this inhibition they looked at the strength of the bone so the bone breakability had reduced they looked at the neurological tissue and that and the um health of that tissue and that had improved so they had done various tests let me just very quickly go there so here I showed you this part and this part but if you see here then they looked at musculoskeletal system they looked at femur and cortical bones they looked at inflammatory factors in whole brains Etc so they did a lot of further research to figure out what was going on so we found that pharmacological inhibition of my mom through back inhibition inhibits the SA SP and improves various parameters of Health span although Inhibitors have potential of Target effects we found that genetic inhibition of my mop also inhibits the sasp in Vivo so we are done I'm just going to give a quick summary and then we close down and please make sure that you share this with others and like as well and maybe put a comment YouTube El go like these things and I'll earn some pennies from that so A Cell under stress healthy cell under stress activate signals within itself which are called apoptotic signals those signals cause activation not all of them only cause this there are many Pathways within the cell that start but one of the pathway is that back and back proteins become activated these protein when they become activated they are like little pipes and they would migrate towards the mitochondria and get stuck in their membranes this causes permeability of the outer membrane of mitochondria the result is even if the mitochondria is healthy mitochondria did not want this but their but their outer environment is under stress so now the mitochondrial DNA will start spilling out in the cell cytoplasm cell cytoplasm has sensors that will detect this mitochondrial DNA to be present outside it should not be here and they would start the sea gas sting pathway another path way of proteins will become activated because of this foreign DNA present in the cell foreign coming from mitochondria this pathway would cause the cell to start releasing sasp in the environment outer environment so outer environment put the stress on the cell the cell started releasing chemicals in the environment chemokines interlukin proteases extracellular matrices these things that these molecules that are released would start causing damage plus would cause inflammation this may be a situation where if this cell had died of apoptosis it would have been better because it would not sit around and cause damage to others but because this was a minority mitochondria damage the cell got senent and is now bitter and now is releasing things that are causing local environmental damage now that damage caused by sasp is depends upon what tissue the damage is occurring in but it would cause tissue dysfunction and that causes various pathologies in this study they were able to find Two drugs or two molecules that were a those two molecules were able to block the activation of these proteins and production of permeability of mitochondria in a stressed cell and they saw that the cell became clear of cence and the tissue became healthy so that is the discussion we will continue on this path for some more lectures because I want to discuss toine I know there are so many other videos about toin but I want to set up our grounds before we understand how toine helps us so with this thank you very much please like subscribe and share there are links in the description you can get access to Dr Bean if you like these kind of works and you can support these here as well so thank you very much have a nice weekend I'll see you next week bye for now

Channel: Drbeen Medical Lectures

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Length: 37min 49sec (2269 seconds)

Published: Sat Jan 20 2024