Modern longevity is crowded with promises, but the useful conversations stay close to biology. This discussion on mitochondria and mental health points to a steadier truth: healthspan is shaped by the signals we repeat, the capacity we preserve, and the recovery we protect.
Full transcript with timestamped links back to the original YouTube conversation.
welcome back to metabolic mind nonprofit initiative of bazooki group where we focus on the intersection of metabolic health and mental health today we're going to talk about mitochondria all things mitochondria the PowerHouse of the cell but it's so much more than that so my guest is Dr Martin Bard who really is one of the worldwide experts on mitochondria now now Dr Bard um has a PHD in mitochondrial biology from Mill University and he's an associate professor of Behavioral Medicine in Psychiatry and neurology at Columbia where he runs the mitochondria psychobiology lab and you know hearing Dr Bard talk about mitochondria is really in inspiring like he cares so much about it and he's so passionate about it you can tell if you go to his Twitter profile um which is mitos psychobio his picture is a huge mitochondria drawn in the sand which just shows like how how passionate he is about mitochondria and he talks about it so well and we start with the basics because a lot of people really don't know what mitochondria are you can't you know see them with your naked eye you can't touch them you you know they're hard to sort of conceptualize so we talk about what they are how involved in our bodies they are how they're on every cell and how they're involved in so many disease processes but also how they're involved with health so it's not just all about disease it's also about promoting health and what can we do to improve mitochondrial function and mitochondrial health so we go through this whole journey um in this interview with Dr perard talking about mitochondria so if you're wondering about mitochondria you're wondering about their role in health specifically mental health and mental illness but really any any organ system disease process mitochondria have a role this is the podcast Dr perard is the guy for you to listen to um because he not only does he know it well and research it but he's so good about communicating about mitochondria so I hope you enjoy this interview about mitochondria as much as I did with Dr Martin Bard but before the interview please remember our channel is for informational purposes only we're not providing individual group Healthcare or medical advice we're not providing a doctor patient relationship any you know any things we discuss could
any you know any things we discuss could be potentially harmful have done on your own without clinical supervision so never change any of your medications or your lifestyle to treat a medical condition without consulting your healthc care provider first all right so let's get on with the interview with Dr Martin peard well Dr Bard thank you so much for joining me on metabolic mind so we can really sort of dig into and better understand what are mitochondria so thank you so much for joining me today yeah my pleasure yeah so I want to start with a little funny story so um I'm helping my son this was a little while ago a few months ago I was helping my 10-year - old son prepare for this little science competition and one of the things he had to learn about were all the different organel in the cells so we're looking at you know GGI bodies and endoplasmic reticulum and of course mitochondria and like any 10-year - old he says why do I have to learn this this is so stupid like I these These are so tiny little things what are they and I said hold on and I ran and I got Chris Palmer's book and I told him about mitochondria in the book and I told him about the work you're doing and you know his eyes glazed over and he didn't really care but I felt good that I had some like concrete example to explain to him why he had to learn about mitochondria now you study mitochondria you research mitochondria but I think a lot of people still don't really understand like what are mitochondria and why are they so important and why are you devoting your you know your research to mitochondria so if we can take a step back can you give us like the brief 101 about mitochondria sure yes um and thank you for sharing your story we have a book at home called cell biology for babies and there's a page there on on you know my and I've started this early also with my son no knows about mitochondria um yeah so mitochondria are this this beautiful little part of of our cells they're called organel right there some way that the body is made of different organs that do different things you know we have a brain we have a liver a heart and and each organ you know has a different role in sustaining function and health of the whole body so mitochondria is one of the organs of the cell um and maybe the best
organs of the cell um and maybe the best analogy there is you know the brain and then uh and the way that mitochondria are involved in transforming energy but also in processing a lot of information uh so historically mitochondri have been known as the PowerHouse of the cell I think that's a misnomer and uh you know sure they they they're Central to you know transforming energy from the oxygen that we breathe in the food that we eat right and the mitochondria those two things the oxygen we breathe the food we the sorry the oxygen we breathe the food we consume they Converge on in mitochondria and that's where the the magic happens where you have you know incredibly complex processes of like ripping off electrons and the electron transport chain for people who've heard about this and then there mitochondria become charged so there's an electric charge literally inside every one of the hundreds to thousands of mitochondria that populate our cells so then mitochondria become charger like little batteries and they're they actually behave and exist as a network and something very similar to a social network inside every cell where you have mitochondria that can fuse together to form longer filaments or you know tubules of mitochondria longer mitochondria can undergo fision or fragment into smaller bits they have a life cycle old mitochondria actually die out and then new mitochondria are born so there's a beautiful cycle there they they exchange information the same way that we talk with each other with you know language and sound mitochondria have all of these different ways of talking to each other through chemicals and hormones and and ions and um and other other mechanisms so there's there's this social life of these small little you know Bean to um to tubule shaped organel in inside the cell so um and there's a whole history about how they came to be and why they're you know at the origin of life that we can get into if that's are interest yeah it's so
into if that's are interest yeah it's so interesting to think about them as having social interactions with other mitochondria and and that it's beyond them just sitting there producing energy but at their core production of energy is sort of the one of the main features and that's why they're known for that and when we talk about you know disorders uh in human health whether it's um whether it's mental illness or whether it's other disorders we're we're starting to see it as a um disorder of energy production which can then be sort of boil down to the mitochondria so you said you know mitochondria take in oxygen and they take in the food and then they create energy that's where the magic happens to to create energy now I think what also is a little confusing though is this happens everywhere right like it's in your muscles it's in your liver it's in your heart it's in your brain so our mitochondria really just everywhere in our body yes they're they're everywhere there's only one cell type that uh you know the body is made of a few hundred cell types there's one cell type that does not have mitochondria which is the one cell type that actually carries the oxygen right to towards the because the purpose of breathing is to bring in oxygen to your lungs and then oxygen from your lungs diffuses into your blood and then the blood circulates and touches literally every cell in the body right um and there's one cell type in that is a reason why blood is red because of the red blood cells right uh their red blood cells their their life purpose is to carry oxygen towards you know their the destination every other cell in the body where mitochondria ultimately or the the oxygen consumer so red blood cells don't have mitochondria probably because otherwise that would you know the the mitochondria there would consume the oxygen that they're actually meant to transport but otherwise every cell in the body every neuron every GLE cell in the brain every Beating Heart cell every liver cell every skin cell have you know hundreds
every skin cell have you know hundreds to thousands of mitochondria per cell uh and the beautiful thing that we're just starting to uncover now is that mitochondria are not all created the same and different cell types in the body actually have different types of mitochondria so we think of those as mitotypes the same way that they're different cell types or different mitochondria types um so the the brain mitochondria actually quite different than the the heart mitoch than the liver mitochondria so there's this beautiful diversity um of mitochondria and and that makes us think of of the of of them as more of a a family of of related organel and not just kind of a a single thing that's uh you passively transforming energy there's there's a diversity of different types of mitochondria that actually talk to each other so the mitochondria and in your adrenal glands for example where cortisol is made talk to mitochondria and the brain and so there it's a the organism you can see if if you think about this the organism as a um as an ecosystem where you have cells and and energetic system that talk to each other mitochondria is a key part of this and um and if you look at this from a MIT entric perspective uh you know you can think of the whole um um ecosystem of mitochondria as an energy transformation system uh mitochondria transform energy they don't create you know energy per se they they take the energy from the food and the oxygen and then as they combine they can extract energy from this so they can transform chemical energy from the food and oxygen into electrical energy inside the in the membrane potential that's called and then take the membrane potential this other form of energy and then turn this into a different kind of energy like ATP maybe some people have have heard about and then that is what
have heard about and then that is what powers you know the beautiful diversity of of human function and human experiences and eventually Consciousness and it all comes down to this transformation of energy inside mitochondria yeah I like how you said if you look at it from a MIT entric standpoint like coming from like the M mitochondria as the center but I think that's a hard thing for a lot of people to do because you can't see mitochondria you can't you know you don't get a blood test for mitochondria right you get a blood test for your hemoglobin levels and and your your kidney function and your liver function but you don't measure mitochondria so um it's sort of like a leap for people to say for some people to understand how widespread mitochondrial function and dysfunction impact our health but is it safe to say that they're kind of involved with I mean just about any health or or disease process at its core could be related to mitochondrial function yes uh certainly we try to you know review this um and I should you know take a step back and say we think of mitochondria and you know that organel as as you know a potential cause first a source of health and life then a cause of potential diseases that's a scientific model right it's a hypothesis that we're you know invested and and rigorously testing and um so you need to you know do this carefully but what the evidence that's there if you go into PubMed or into Google and you look for studies I have looked at some mitochondrial impairment mitochondrial have many functions right so alterations and some mitochondrial function including energy transformation but also mitochondrial signaling and any disease you can think of there is likely a scientific study that has investigated and identified you know a connection and then the question is are impairments and mitochondrial biology driving those
mitochondrial biology driving those diseases and I think the answer is likely yes uh and and why is that I think it's likely because energy is such a central part of of what we are and you know of who we are to to some extent um so I think that's why you know mitochondria have been implicated in our you know there's growing interest in in understanding the connection between mitochondrial biology and and health and and different disorders is because energy is is Central to to what we are and you know how we function and if we think about the brain if you want to convince yourself and make this real because you're right we can't see mitochondria and we have the chance here you know to have cool microscopes and you can put living cells and make the mitochondria fluorescent and then you look down the eyepiece and you see them move and like fuse and so you you can see them if you have the right equipment but our day-to - day experience is you know is is that of you know is our objective experience and the kind of the the reality of the body and how we feed it and so on we're not aware of our mitochondria which is probably for the better but if you want to convince yourself how Central Energy is if you just you know block blood flow to the brain right if you olude the blood going to you you know perusing your brain for just a few seconds you're out Consciousness is gone right and the reason Consciousness disappears if you don't have have blood flow to your brain or if your heart stops is because you're not feeding your mitochondria anymore right you're not bringing them oxygen you're not bringing them food substrates and that you know shuts down everything um so that's I think a very real example of uh you know how energy just sustains you know human life and human consciousness uh so anything we do as as you know you've uh discussed uh you know with many scientists and Clinic ions uh the way we
scientists and Clinic ions uh the way we feed our body is the kind of energy we put into the system can actually influence right how the system works uh the brain and and the whole organism yeah so let's talk about that for a second because you know one of the things we focus on at metabolic mind is the connection between metabolic and mental health so when there's metabolic dysfunction that can impact um mental health and contribute to mental illness and at its core presumably mitochondria are involved in in that so how does metabolic dysfunction and insulin resistance and you know with some things that are so prevalent in today's society how does that impact mitochondria so yeah metabolic dysfunction is an umbrella term right for that in my view reflects um impaired energy flow right so the what sustains life is the you know blood flow that you know the beating heart is like a clear sign of life because by moving blood you move energy you move oxygen you move uh you know Ketone bodies and fatty acids and and glucose and proteins and so on so and these are energy forms so the disorders of of energy or metabolic dysfunction can be reflected and insulin resistance as which is reflected or which represents the inability of you know cells to take in food sub when that's needed um so there can be metabolic dysfunction at the whole organism level right which can um you know cause or materialize in obesity for example then there's kind of uh systems level metabolic dysfunction inulin resistance would be a feature of this at the cellular level there it can be you know metabolic dysfunction there and then if we go inside the cell there can be mitochondrial uh energy transformation transformation defect or you know impairments which of
defect or you know impairments which of course ripples out if the mitochondria are not functioning properly that can impair how cells function how the tissue function and how the whole organism functions so mitochondria are kind of a such a metabolic Hub that their um inability to transform energy properly or misregulation of you know mitochondria getting turned on and making a lot of ATP or you know being dialed down and making less ATP can really affect other levels of of biological and physiological complexity yeah yeah and I I think it's clear there are a lot of things that can impact mitochondrial function and but when it comes to mental illness and psychiatric conditions in general there's been a lot of talk about genetic predispositions so are there genetic predispositions to mitochondrial dysfunction as well as environmental factors of just how we live our life that impact it but what what do they genetics say about it yes that's a great question um so yes and I'm not a clinician but I spend half a day a week in the clinic with my close colleague neurologist mijo hirano uh where I see patients who have uh rare genetic mitochondrial disorders so um some people may know mitochondria you know those small living life forms inside every cell they have their own DNA and that's you know related to their um uh to their past life as bacteria you know when they were Incorporated so they have a circular little piece of DNA like bacteria um which have a few genes that are involved in energy transformation and some people are born uh with a defect a mutation or uh they lose a chunk of mitochondrial DNA a portion of of the the mitochondrial DNA sequence so those are called mitochondrial DNA deletions uh and that causes primary genetic mitochondrial diseases uh so they're these are rare you know
so they're these are rare you know genetic conditions and but I think they're incredibly illustrative illustrative of what impaired mitochondrial biology can can do to the whole body and and to to the whole mind and uh there these people suffer from multi-stem disease right so often they have cardiac involvement digestive issues renal issues and endocrine issues immune uh alterations in some ways and many of them uh have you know cognitive and and psychiatric manifestations uh so there's there's a lot of uh comorbidity between primary you know mitochondrial diseases that have historically been the domain of Neurology and and psychiatric conditions and this is an area that you know we're interested to understand more but that has been you know under studied so I think that's one of the good evidence that if something's wrong with the mitochondria and here we have like a primary genetic defect in mitochondria this leads to uh impaired brain function and and psychiatric um conditions yeah that is very clear evidence about that connection but then as I alluded to it certainly doesn't have to be a genetic reason there are unfortunately plenty of Lifestyle things we can do to ourselves to to uh decrease our mitochondrial function and decrease our mitochondrial health and the big ones that seem to get a lot of attention are of course nutrition and then sort of poor sleep and toxins and the so I mean how do you see the the main um the main detractors from mitochondrial Health that unfortunately we do in our society yes so you're pointing to what I just described were uh inherited you know mitochondrial disorders and then their acquired mitochondrial disorders so all of the acquired you know result from our exposures and you know kind of internal
exposures and you know kind of internal exposures we're studying how psychological States and exposure to chronic stress or early life adversity and or the uh kind of the the disorders that we can create ourselves either psychologically or through you know nutrition and and other things uh and how they can influence mitochondria so this is all part of the acquired you know mitochondrial um impairments or dysfunctions um so there's a number of things there that Converge on on mitochondria including diet which is a very big one everything we put in her mouth ultimately converges either directly on mitochondria or you know around the the metabolic pathways that mitochondria are involved in regulating uh so that's you know a very big one uh there's a lot of good research on um you know insecticides and pesticides and uh some of those that were used you know back in the days were we use in the laboratory as poisons for mitochondria if you want to know you know how a mitochondrial impairment will change a gene expression right some genes that are turned on or turned off in a Cell you can do experiments in Dish where you have living human cells with their mitochondria which you can image and then you can perur mitochondria right experimentally and then you ask oh what does that do to the signals that the cell will secrete or to the the process of cell division or the effect on a stem cell or things like that and some of the tools we use there or former formerly used you know poisons or in insecticides um that that are direct you know poisons to to mitochondria so there are many things that you know um that we've used or you know that are around our ecosystems um that can you know adversely affect mitochondrial biology yeah that's really disturbing that you don't have to come up with some specialized mitochondrial poison it can just be something that the run-of - the-mill pesticides that's been
run-of - the-mill pesticides that's been used before and and that's a a potent mitochondrial toxin it's a little little disturbing um it but I like how you also mentioned about you know psychological States and how that can affect your mitochondria and so how does our psychological State influence our bodies that's like a big question that you're researching and and you know the the whole brain Body Connection kind of goes both ways right the um it uh dysfunction in the body can affect the brain and I don't know if you want to call it dysfunction in the brain or but but brain experiences psychological experiences can can affect the body and it seems like mitochondria are the connector there I mean that's the common variable is that right yes you know every so the brain is part of the body it let's remind ourselves right but it's there's there's many reasons why we think of you know brain and body and I think it's useful to think of you know brain body or mind body processes right that drive The Human Experience and uh you know as you know there is good evidence for example that the gut microbiome sends uh signals to the brain and then that actually influence mood and affect and you know might contribute to um to some you know to to mental health uh so there's there's clear kind of uh body to brain signals right and the Brain can experience and and respond to the metabolic state of the body and then they're of course a very important uh drivers you know top down brain body uh signals where the brain actually regulates uh blood glucose for example and you know you can psychological stress will can trigger hyperglycemia especially in in susceptible individuals right say you see a stressful email or you know you have a stressful you know interaction and then you secrete cortisol that come from the adrenal glands uh and then cortisol goes and to the liver and says release
and to the liver and says release glucose into the blood and then will'll go to the muscle the the cortisol go to the muscle and causes insulin resistance so then that drives hyperglycemia so a simple psychological State can drive a change in in peripheral you know glucose level so um so there's metabolic influence on the brain and the Brain can influence systemic energy metabolism but every little process we think of when we think of like brain body interactions um a stressful thought will accelerate heart rate within seconds right while the heart beating faster cost energy right every time the heart beats there's energy consumed that need to come from mitochondria and if you're having an experience this changes gene expression you know inside a cell or you create produce or release a hormone well turning on a gene right turning DNA into RNA cost energy then taking the RNA making a protein cost energy and then taking that protein that hormone let's say and then folding it and then packaging it and then releasing it all of this cost energy so um every little bit of communication between in the body is energetically demanding and is is an energetic uh process you know by Nature so I I think you we think that's why energetic processes and then mitochondrial biology being a central part of this is is a an important driver or if you want the fabric right of brain Body Connection is an energetic uh the brain Body Connection is an energetic connection and and therefore energetic perturbations in the mitochondria can you know likely uh you know perturb that system yeah it is fascinating how the the two-way street between the brain and the body is is constant and there's such a such an impact both ways that we need to be aware of in so many variables um but now to bring it back to psychiatry and and symptoms of whether
psychiatry and and symptoms of whether it's bipolar disorder schizophrenia major depression um what about medications because you know if that is a if those diseases have a mitochondrial basis and then medications are used to treat them can medications also further mitochondrial dysfunction or there some that can improve mitochondrial function what what have you learned from a medication standpoint yeah there's there's recent interest in in this and so people have studied this um in fairly rigorous studies in vitro with cultured human cells or in in Vivo in animals and so you can give cells or animals different you know classes of um of psychotropic medication and ask does this change the ability of mitochondria to you know transport the electrons to charge the membrane to make ATP so different domains of mitochondrial biology and the answer yet is yes certainly uh there's uh specific classes of of medication um that impair mitochondrial energy transformation pretty pretty significantly uh which is not widely known and certainly uh psychiatrists don't learn about this and and there is so it's it's not you know well well known but in the last you know 10 years there's been quite a bit of research on this as we uncover you know are starting to understand the role of mitochondria the role of energetic processes in neurotransmitter release neurotransmitter reuptake and uh you know neuronal firing and neuron to gal cell communication all of these processes are energetic in nature so as this becomes better understood and the connection with with uh mental health and psychiatric conditions is is better understood there's been a rising interest to connect you know those treatments like you're saying to to mitochondrial biology and there's a Clear Connection there and that's not my area I don't know the details um but there's there's certainly some you know
there's there's certainly some you know classes of medication that have a direct effect on on the core machinery for energy transformation which is a little scary because um you know playing with the chemistry without really understanding how this chemistry gives rise to human experiences and to mental health is is a little dicey and I think that's you there's a lot of medications in Psychiatry you know lithium being an example we don't know how lithium works we have no idea you know the underlying biology but there's a clear effect of lithium on mitochondrial biology and uh so there's some people you know believe that um parts of of you know the of our of The Human Experience and um the function of brain circuitry and brain networks is actually driven by mitochondrial biology um so maybe the the reason leum Works in some cases is because of its effect on mitochondria mitochondria could be the target for lithium I think based on the evidence out there that's that's a possibility yeah I think it's so interesting though the way you describe that there are certain medication subclasses that that are going to impact mitochondrial function and you know we're going to learn a lot more about this I think as research focuses on it but does that you know separate medications into maybe short-term beneficial medications but long-term harmful medications like maybe they're doing something in the shortterm but for the long term if they're degrading mitochondrial function then they're going to lose their effectiveness and maybe that's why a number of psychiatric medications you know worsen cardiometabolic Health uh could mitochondria be a reason for that I mean certainly certainly plausible yeah and there's you know you mentioned acutely versus chronically you know that we have a hard time I think as uh the way humans think and maybe the way you know scientists are forced to do their research uh it's it's hard to keep those two things in mind that what you observe you know
that what you observe you know acutely does that translate chronically and there is there's a lot of of stimuli and um stressors that have a certain effect acutely but chronically the effect is quite different and a lot of you know medications I think sometimes have an acute you know acutely you know can can help and maybe that's where Psychiatry is most useful in terms of you know helping people deal with you know life-threatening you know acute episodes of psychosis for example then chronically we're we're really bad at at helping people and and maybe but all most from what I know of of you know standard uh um um the way we apply pharmacology to treat people with you know severe mental illness those medications are are given without you know the idea that this should be short term and and most of the time I think it's it's given and and patients are told or kind of uh led to believe that they need to continue taking that medication forever um so but we have no idea I think there's no data in humans on the long-term effects of of medications on mitochondrial health and miton biology which which is a little scary to think about yeah so you mentioned you know this long-term use of medications and with without thinking maybe they should be shortterm but also without thinking what else can be done to specifically Target mitochondrial health because maybe if we're using medications and we're doing other things to Target mitochondrial function and you know overall brain health then we can start to potentially taper those medications under professional guidance of course because everything else is improving because we have heard from a number of people that they're treated they get over their acute episode but then they just feel like they can't Thrive they can't get back to their life and it's not until they do other interventions that that allow them to get back to their lives which frequently
get back to their lives which frequently can also then coincide with tapering of medications which of course is a very complicated topic and we have a whole video with um Dr Georgia Eid and Matt bazuki about that but so what it brings us back to those is this question to you is what can we do to improve our mitochondrial function and I know you're not a you know you're not a doctor you're not giving medical advice here you're just talking about you as a someone who knows mitochondria better than anybody you know what can we do to improve our mitochondrial function which then could potentially be seen as adjunctive interventions to medications in certain disease States yes so you make such a good point Brett the the ability to thrive right and to exhibit resilience and robustness like life is made of challenges and I think what we do really well as living organisms not just humans but all living organisms is we think of we take a challenge right and then we bounce through it and um and there there are some things then you know that make us unable to to bounce and and I think that's one way in which I think about you know acute psychiatric episodes where you know you go really deep and then it's hard to you know to come out of it and and sometimes I worry that some of the medication actually promotes this stuckness right and prevents you know this rebound um and if we think about kind of going down and then rebounding and this this thriving uh ability this requires energy right like it requires fundamentally a change in in how the brain operates the brain body system functions and your ability to make meaningful life changes or right changes and and in your Social Circle or like all of this requires energy and I think that's why change just as a general thing in life changes you know are challenging to most people and because change requires energy uh it's like coming out of inertia if you
it's like coming out of inertia if you want to stop something that's moving right if like so fundamentally there's like an antic energetic requirement to to change and and then therefore bouncing back is an energetic process so impairing mitochondria in that situation or if you live with impaired mitochondria I think this can be even more difficult so that being said what can we do to promote you know good or to optimize mitochondrial Health uh energy transformation or you know proper mitochondrial signaling uh there's not a lot of um there's a need for more research on this that's the first thing I want to say um there three things that we know can optimize and improve you know mitochondrial energy transformation capacity based on kind of scattered research over the last maybe two decades one thing we know for sure is moving uh being Physically Active right so I think many people though you exercise is a protective Factor against you know many uh you know mental illnesses um and exercise is a protective factor for pretty much every disease that we know of and if we flip this if we think about health right as not just the absence of exercise but this ability to thrive and and to um and and to you know live a healthy life uh exercise is good for this so moving stimulates and pretty much in every uh organ that people have looked at stimulates the production of more mitochondria so if you move the body feels oh I need more energy how how do I handle this let me make more mitochondria that's called mitochondrial biogenesis um and we know that this this happens you know a lot for example in muscles uh if you go from being completely sedentary uh to training for a marathon you can double the number of mitochondria in your muscles uh so there's quite a bit of plastic itic it there and we've done some
there and we've done some studies and animal studies of chronic stress for example then this changes how many mitochondria how much mitochondria are in different brain regions uh so moving is number one thing we can do to increase a number maybe the quality of the mitochondria number two is not eating too much so being hungry once in a while is healthy and we evolved you know to do this and the reason why being hungry is is not eating too much is as healthy is not too clear maybe it's because it puts you into ketosis uh maybe it because it's because it prevents nutritional or metabolic over Supply or you know overload people have done beautiful studies and in cultured cells where you take cells and then you bombard them with sugar and with fat and so that causes kind of there's too much energy Supply relative to what the cells need and this causes within minutes the frag mentation of mitochondria so you go from having a beautiful network of connected and you know dynamic mitochondria talking to each other to a completely fragmented mitochondrial Network so there's mitochondrial fragmentation that arises uh you very fairly quickly in cultured cells like this uh in response to this metabolic overload over Supply uh so if you eat too much and uh most people are able to you know take the excess glucose excess you know fat and and excess nutrients in the blood and then store this in in subcutaneous atpo tissue right and then we call this obesity or um um you know just yeah ad deposity um but the reason this exists physiologically is because having too much energy substrate too much sugar fats or proteins in your blood is is actually damaging it's damaging to the mitochondria so not eating too much and you know maybe um something like intermittent fasting or just having just a good diet where you're hungry once in
a good diet where you're hungry once in a while and then you have a good meal and then you're hungry then you have a good meal and you know every ancient tradition um has kind of a fasting period built into their culture right and that's probably for a reason because once in a while uh you know being hungry actually stimulates some cellular processes probably mitochondria in a way that is you know helpful and health promoting so the magic question with fasting though is how long and I know it's like impossible to answer with with certainty but you know Tim restricted eating it can help reduce calories maybe you know it can help reduce insulin and improve um insulin sensitivity to some degree you know probably like a minimum of 12 hours maybe has to be 16 maybe has to be 18 do you have any sense when it comes to mitochondria where The Sweet Spot is or it's just clear that some amount of it helps and we still need to learn more about the specifics yeah I think it's it's clear that some amount of it helps I don't know that we have the right evidence to be prescriptive here about how long should you fast and it probably depends if if you're on a ketogenic diet right and and you or you have a you're on a low carb diet maybe you don't need to FAS for as long to to you know derive the benefit than if you're on a a regular you know high carb diet and maybe you know each person's metabolism is is pretty different and it's clear that some people respond a lot better to uh you know nutritional ketosis than some others and so the the benefits are individual specific and I think uh in the same way that each person responds differently to exercise there there are some people for whom exercise is doesn't seem to trigger a lot of health benefits and and it just makes them it puts them into a bad place if if you do too much of it um other people just respond amazingly well to to exercise and it's you know life transforming so I think they individual differences that are poorly understood and most of the
poorly understood and most of the studies we do are based on like group differences you do an RCT and then you look for a mean difference and like 50 people here oh like exercise was good or you know keto diet was good but there are always people that are at the bottom of you know the respond low responders and high responders um so I think the way we do our science the way we kind of approach things as a little narrow sighted doesn't doesn't um you know respect the degree of individual differences or individuality so I have a hard time and I think ultimately we need to move towards a more uh individualized way of doing medicine uh and and you know of promoting health so I I don't know that there's going to be one kind of solution for everyone I think that's a great point about the the translation of the research to the the one individual or the one you know if you being your own person and and how does that relate and you have to start somewhere you have to use the evidence you have but it's not the end all and be all because are the individual variation so that makes a lot of sense yeah all right so we went through moving your body we went through don't eat too much and then we got number three so what's number three on mitochondrial Health list so number three is the most speculative and we have some you know evidence that how you feel and and I'll Focus specifically on positive psychological States might actually drive changes in your mitochondria and um and we did a study a few years ago with Alyssa eel uh UCSF where they uh took about 90 women who um who were asked every morning and every evening how they feel and then you know imagine you wake up in the morning and then you ask how do you feel now right do you feel you know inspired or do you feel you know confident about your day or do you feel worried and you don't know what's G to happen today and that's really stressful to you and then in the evening there was kind of a more elaborate uh questionnaire that asked
elaborate uh questionnaire that asked how much of this did you feel today and then there were kind of items like love closeness and trust and uh you know being inspired and motivated and uplifted and you know connected to others and so on and then some negative things like feeling betrayed and uh you know rejected and feeling sad and depressed and um and I think everyone you know can can imagine some days you feel a lot of positive stuff right like you had a great day with your partner with your colleagues at work or so you felt a lot of positive things and not so much negative things and some other days you feel a lot of negative things because of things that happened because of your you know psychobiological State you know whatever this whatever drives the emergence of those positive negative experiences so they ask those questions so we have kind of reports on how women feel for seven days in a row for a whole week which is beautiful you know daily repeated measures of of someone and then we we uh we were able to have wide blood cells immune cells from these women on measured on the Wednesday so they answered these questions from you know this the Sunday to the Saturday for these seven days and then on Wednesday they came to the clinic gave blood then uh alysa's Team isolated white blood cells and then we assay the mitochondria and then what we measured in the mitochondria there is we call the mitochondrial Health index which is basically how much energy can each mitochondrian transform right so that's kind of a proxy for a simplistic proxy for mitochondrial health so we were able to to relate for the first time how people felt right across that week and and their mitochondria in the middle of that week um and so we asked you know a simple question uh first do people who feel more positive have better mitochondrial Health than people who feel more experienced more negative things right uh and and the answer there was you know yes and it seems like people who experience more positive things have slightly better mitochondrial Health uh but then the
mitochondrial Health uh but then the more interesting question was well we know how uh these women reported feeling for the three days before we took the mitochondria and then for the three days that's after we took the mitochondria so we can ask is it how people feel that predicts right or drives the mitochondrial health or is it the mitochondrial Health that drives and predicts how people feel right um and the what the study showed is that how people felt uh in the morning in the evening uh on the three days before on the Monday the Tuesday the Wednesday actually predicted mitochondrial Health uh but not the other way around so those are mitochondria in the immune cells right remember what we talked about earlier mitochondria are different the brain mitochondria are different and the Heart mitochondria and the immune mitochondria are also different so it seems like how we feel might drive a fair uh a fairly large change in in the biology of the mitochondria and the the energy production capacity of our immune mitochondria and so if that's true we need to replicate this and we're in the process of developing a study to do this you know at scale and over longer periods and with repeated measures of mitochondria and so on um so if that's true right that that implies that feeling more positive um having more positive experiences can actually directly influence the mitochondrial bi biology and and if you can improve the mitochondrial biology and the the ability of mitochondria to transform energy in the immune cells well maybe that happens also in your brain cells and and we have evidence that this is the case and Koln Trump uh who who works in our group uh has amazing data in brain mitochondria so she was able to measure gene expression in the brain of individuals who have um who've passed away but in whom uh or colleagues had collected um data on how socially
collected um data on how socially connected they feel their level of well-being or their level of depression and in isolation before they died right so you have uh the the psychological exposures the psychological state of these people before they die and then you have the brain after they died and then Caroline used some fancy single cell uh gene expression analysis and neurons and astrocytes and microa to ask is there a connection between how people you know they said I'm feeling great I have amazing sense of purpose you know I feel like my life is Meaningful I have great friends and so on well does this person have better functioning mitochondria in their neurons or in their gal cells than someone who says I wake up in the morning I don't really want to be here and and I I don't feel well and I I'm fairly depressed and what she's finding is yes and the mitochondria are different and people who who report more positive experiences than people who who don't uh so this is opening up a new layer of biology that's you know there a direct psychobiological connection between the lived Human Experience and the biology of her mitochondria so then I if we speculate a little bit it it could be that you know choosing to do something that you find meaningful and purposeful right and arranging your life in you know as much as possible in a way that you feel good about it right and and making decisions in terms of what you eat in terms of the people that you surround yourself with in terms of the job you you choose um actually makes a difference on your biology and on the biology of your mitochondria you know this would be amazing and I think that would be consistent with kind of the the growing understanding of the the metabolic nature of of uh and functioning of the brain and and mental health and maybe a path to to mental health is to taking care of your your mitochondria and you can take care of your mitochondria by by moving more by
your mitochondria by by moving more by being hungry once in a while and by you know making choices that make you feel inspired and motivated about life that's so yeah I think that's so interesting and you can tell your you're excitement and your passion just in the way you're you're explaining it which I think is wonderful but you can look at these studies that show people who are more positive and had a better better outlook on life that they they live longer they have fewer health problems and I would always sort of take those with a grain of salt like okay but there's so many confounding variables and it's just an association and you know it's just that they they make better choices in life and and are healthier in other ways but now you're saying well maybe it actually is causitive and there's a mechanism for that causation which is opening up this whole new sort of Realm um which I think is really exciting and and so yeah just just be happy and we'll be and you'll help your mitochondria but there there's more to it so I think that's really exciting and and you know this is I this is a hypothesis right and but there's a number of of converging lines of evidence that uh what we experience actually translates directly into you know real molecular changes energetic changes in our mitochondria so there's a need now for more research understand you know the mechanisms there and whether those links are direct or maybe you know you feel great therefore you sleep better and it's actually the sleep that making your mitochondrial Health you know improved or you know you feel good and therefore you eat you know well and so there's all of these confounders either we see them as confounders or we see them as kind of this network this ecosystem of of you know um of behaviors and you know lifestyle and and you know nutrition and biology and psychological State it's it's all interconnected um so there but I think the the emerging science is you know makes me optimistic that we can uncover and identify you know real connections there that actually end up being empowering right empowering I like
being empowering right empowering I like that important part a lot of how we do medicine now and the the public message around genetic predispositions which I think is has been overhyped because for for many reasons we could talk about if you want this is highly disempowering and and I think is is not justified you know scientifically based on the the evidence uh I think the the alternative framework that is I think a bigger container that respects more kind of the the reality of individualities and um kind of idiosyncratic differences and and how people manifest health and how people manifest you know their their um the expression of their mental illness you know each person's different and we have these diagnostic categories but each individual person is different people like we said earlier respond to therapies you know differently and um and I think that's is more consistent not with a fixed genetic predisposition but you know health is dynamic and for the most part genetic is is fixed right if everything was caused by genes then there would be kind of this chronic trajectory of you would have no no room to be healthy and then be sick and then be healthy again what we know is that mental health and and physical health is highly Dynamic so just just like energetic processes in the body energetic processes are Dynamic and I think there's there's a lot more uh evidence to think that uh the basis of Health you know once you have the structure and you have kind of the basic information laid down in the genome the the basis of of how health manifest over time is energetic in nature and we've lacked tools I think the reason we've been so focused on other things and genes is is we've lacked tools to measure energy we can't see it like you can visualize a genome you can measure sequence the letters and the DNA and then you can say ah now I know something about this person energy is
something about this person energy is much more difficult to to measure and I think by focusing on mitochondria it's giving us a an in or at least you know a tractable scientific model that that we can you know explore the underlying basis for for human health and human disease so this makes me extremely optimistic about uh our ability to you know build a framework that will be empowering for people and that can be transformative yeah I think that's a that's such a great way to wrap it up on that note and and you know we really it's been a wonderful discussion going through just what mitochondria are their role in energy their role in in disease processes and their role in health and empowering the things we can do to improve mitochondrial function so this has been a a wonderful discussion and I really appreciate you taking the time so if there's so much more to learn though especially from you and all the research and the work that you're doing so if people wanted to find out more about what you're doing where can we direct them to go yes thank you yeah there there's a number growing number of research groups worldwide who are interested in mitochondria and mitochondrial psychobiology uh so this makes me you know hopeful that you know together as as a community we'll you know we'll make progress at at a rate that will allow us to accelerate this transition towards sustainable Health Care not disease care but Health Care uh so people can go on our websites for you know or or uh papers that's psychobiology Lab at at Columbia University uh and on on Twitter there um when we publish new articles you know we share them there and and uh are you know I'd be excited to continue interacting with the community of people who are interested in knowing more and understanding the energetic basis of of Health great well we'll link to those in the description so everybody can find them and and thank you again I really appreciate your time my pleasure thank you br
Transcript auto-generated by YouTube. Verbatim — duplicates intentionally preserved.
Mitochondria are often described as power plants, but the better image is a communication network. They sense nutrition, stress, sleep, movement, inflammation, and danger, then help decide how much energy the body can safely spend.
That is why mitochondrial health can show up as stamina, mood, clarity, and resilience. Energy is not only physical. It is systemic.
The brain is metabolically expensive. When energy production is strained, mental health can be affected through inflammation, oxidative stress, neurotransmitter balance, and the nervous system’s threat response.
This does not reduce mental health to metabolism. It expands the map. The mind feels what the body’s energy systems are carrying.
Mitochondria respond to repeated inputs: nutrient density, aerobic work, strength training, circadian rhythm, heat, cold, and rest. None of these has to be dramatic to matter.
The aim is a rhythm the body can trust. Challenge, recover, repeat.
When energy systems become more resilient, the whole person has more room to recover.
Support mitochondrial health with consistent sleep, movement, whole foods, and recovery before chasing complexity.
View low energy, mood changes, and poor resilience as signals worth investigating, not character flaws.
Use hormetic stress carefully: enough challenge to adapt, enough restoration to integrate.
