How Stress Affects Aging, Longevity and Reproduction: Expert Discussion.

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welcome to the cing healthcare research I'm your host ephra riveros Dr Efrain today I have the honor of uh discussing a very important topic about hormesis with one of the experts in in this area Dr mariio kirzis he's a gerontologist and researcher of the national gerontology Center in larnaka Cyprus H welcome Dr k Hello nice to be with you thank you so we will base our discussion on a paper that was published in the journal of clinical medicine in 2023 the title of the paper is the impact of hormesis neuronal stress response and reproduction upon clinical aging and narrative review and uh this this paper is very pertinent as as we delve into the the different aspects related to AG in and it called my attention particularly because you have a unique approach to to low levels of stress and hormesis and how you relate the the central nervous system to the reproductive system and we are going to talk about this but uh but before we we dig deeper into the paper my first question to Dr kiriasis is um what brought you to to analyze hormesis as as part of your research

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part of your research line uh well I'm a gerontologist and I have an interest in the biology of Aging among other things clinical aspects as well but particularly with the the biology um I came to realize that the the process of Aging will not be affected significantly by the current approach so I was thinking of examining different approaches and um the process of hormesis um was something ideal to be applied in this respect coris is a Greek word who which means um in Greek is ores but it's based on another Greek saying which says everything in moderation so if we do everything in moderation um it's going to be good for us but hormesis analyzes this in scientific terms goes into a very long process of investigation and um when we start talking about heresis I will explain some of the basics of it but as I said before it affects the process of aging and how we see a aging and how we can interfere with it among other things in our life I see and uh and I think it's very useful to start with a common ground when we discuss aging and I like the definition that you gave in your paper ER you describe the aging process as a Time related dysfunction and um you explained that as you age you start losing some H ability to to adapt to a change environment can you elaborate

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change environment can you elaborate more on that please uh yes there are many definitions of Aging depending on the researcher who is defining it there are statistical definitions biological definitions I am trying to give it a clinical everyday um definition of Aging so basically with the passage of time due to different damages and the different processes that that happens that that happen in our organism we become unable to function properly in our everyday life either due to disease which is related to aging or to other processes that are related to aging so it's dysfunction that is related to time dysfunction of of the human organism we are talking about humans mainly here not other animals and this is um relevant in aging because many people may have illnesses or conditions or they may be totally healthy but it doesn't matter what matters is their function whether they can live their everyday life do what they want within reason and um enjoy their life and be productive and creative if they cannot have that which is due to to the dysfunction of Aging then we have a problem and that that's that's the main reason that's the main um problems that are related to aging the the lack of function in in our environment as humans exactly and uh and you mentioned the environment because we obviously don't live in isolation and that interaction with the environment carries some stress and uh and it's important that you have the

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and it's important that you have the ability to respond to that stress and that probably is a good segue to to start discussing the concept of hormesis er as it relates to to the interactions with the environment so let's talk about hormesis what is the definition and what is a good way to understand it everybody's thinking that stress is bad for you but uh there are two kinds of stress one one is positive stress and the other one is the negative stress positive stress is hormesis hormesis is when we have um a mild stimulation of any kind we can discuss the different kinds of stimulation so we have a mild stimulation which forces the organism to start repairing the damage caused by this mild stimulation so in the process of repairs the organis become stronger and any age related damage that happens to be around is also repaired and this is used um by applying a mild stimulation not too much and not too little or none at at all uh stimulation can be um for example nutritional stimulation when we do calorie restriction or when we do an age defying diet as we call it we put our organism under under mild stress and uh the body tries to overcome this stress by activating the stress response different biological mechanisms that aim to repair the the damage CA by this mild stress so it is up to a certain limit we can repair ourselves

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certain limit we can repair ourselves and be stronger if it's over a certain limit then it's what we call negative stress which causes damage and if it's under a certain limit then it doesn't do anything it doesn't stimulate the organism and we stay as we are basically that that is what hormesis is is a dose response phenomenon to is not good modate stimulation is good and too much is again not good that's yeah it's like like training our system with the low doses of of stress right and um and I understand that uh behind all these H types of stress ER there is inflammation and a low degree of inflammation that leads to repair is what hormesis is about but I assume that as inflammation becomes overwhelming that's when it becomes problematic and um and there is a concept here that um that is um Central and unique we all have heard that homeostasis is is important and the body always tends to maintain all the physiological variables within a narrow range of values but you mention something different that is the homeo damic space that is is more encompassing and it relates to other aspects related to hor mes can you tell us a little bit more about this this is just exciting and mindblowing I want to hear directly from you yeah well this is a concept that was first described by suratan another colleague of mine who is a bio gerontologist and it aims to become to be a more encompassing definition of

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be a more encompassing definition of normality of the organism because um this is a range of physiological states that um we can stimulate and the organism can cope with the stimulation or it can be damaged if it is over a certain limit that's why is a space So within the space there is Health everything works all right everything is um within normal limits if it is outside the space this theoretical space then we have disease and dysfunction and it is um a bit different from from the concept of homeostasis homeostasis the second part is stasis which means no activity at all in Greek um may not be appropriate to talk about homeostasis because the organism is too complicated um it can have a range of f functions a range of activities biological activities and is not static it's always active working that's why we we talk about Dynamic space is dynamic always changing um reacting with the environment get getting feedback so that's what the aim is to stay within the homeodynamic space um and and this is can be achieved through hormesis stimulation of of a certain moderate degree so it is more like a theoretical aspect this um is more to study the biology of of hormesis but

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study the biology of of hormesis but with in in our everyday life we can um just talk about hormesis in other words my stimulation including every aspect of life uh for example I mentioned the stimulation through nutrition but perhaps a more appropriate example is exercise physical exercise when we exercise we put our muscles under my stress and uh during that exercise our muscles become better functioning everything works better in the muscles all the damage is repaired if we don't exercise at all or if we exercise too much then it's both situations are damaging and this is a typical example of hormesis which keeps our organism within this homeodynamic space you know always everything is working as it should be yeah and it's it's interesting the way you you describe it so the homeodynamic space could be understood as um as some leeway that you have to move within the environment no matter how much the environment changes you can adapt right and you start losing that ability as uh is that correct yes that's right we lose the ability to to counteract any external and internal insults the homeodynamic space becomes less and less with aging and um we cannot be flexible if we are in front of certain problem or certain stimulation or certain illness then we are not able to counteract it because our leway within the space is restricted and this

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within the space is restricted and this is the main problem of Aging seeing from a clinical point of view yeah and this is definitely clinically relevant and applicable as you mention to everyday life and um when we go deeper into hormesis which is a a critical factor for you to try to maintain that homeodynamic space you mentioned that one of the mechanisms behind this hormesis is Auto and how you can clear proteins and stuff when you try to repair tissue and on the side you start also clearing some aging related proteins that may be defective and stuff so H what is the the role of autophagy autophagy is a process where um damaged cells get uh dissolved and and eliminated from the body um and this is a process that is found in aging and in many other situations um and through use of stimulation of hormetic stimulation there is um possibility that autophagy is activated and then all damaged cells get eliminated that's what I said earlier our repair mechanisms get stimulated one of those repair mechanisms is autophagy and it um eliminates cells leave space for new cells to be formed and we have repair everything is back to normal so to say um yeah and that's use that's achieved through use of hormesis yeah it's it's a very exciting mechanism to understand and um and it's

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mechanism to understand and um and it's interesting how you can affect that mechanism you already mentioned a caloric restriction and intermittent fasting and also exercise you also mention exposure to hot and cold and this is something that I bring about because it's becoming um common practice for people to to use the SAA for instance finish SAA or use cold plunges so those are are two ways to to influence the the hormetic processes right yes there are different ways of stimulating ourself and um exposure to Hot througha For example or cold um it can be seen as a stimulation as a physical stimulation of the body there is research showing that this exposure to hot or cold activates different um biological aspect ects different proteins the different stress response Pathways in an attempt to to counteract this mild damage that is our bodies um exposed to the hold and the cold in other words um it's the same mechanism as the exercise as intermitted fting and other um stimulation modalities it activates several aspects of our repair mechanisms one of those is the heat shock protein activation and this can be done through through other ways some some ways are experimental some can be applicable in real life for example um centrifugal force like the one we see in fairs you go in a in

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one we see in fairs you go in a like a barel and the barrel goes around and creates centrifugal force which keeps you on the side of the barel I don't know if you have that in mind or if you try it sometime yeah I used to try those things now I nowadays I get quizy so yeah it's called hyper hypergravity and it is a way another way of stimulating the organism and mhm and it's bit more experimental and there are some others as well but it is possible to to stimulate our organism through that way or medic way and there are also some substances right called um I don't know how to say it horines hortin or hor depending I call them hormetins horting have substances which stimulate hormesis so they are basically mild poisons not not with the way that we mean poisons they are natural supplements which in nature in small qu small quantities can be considered poisons because the plant tries to protect itself and creates these substances and um turmeric for example is is a an example Ginger and um some others roola Rosa which is um another plant supplement and in small doses even arsenic or hydrogen D sulfite which are consider poisons in small doses um create a positive stress response is small appropriate doses so

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response is small appropriate doses so everything dep depends on the moderation that I said earlier too much is not good but this hor hor meting in in a lower to stimulate heres which means that they stimulate all the different mechanisms that we mentioned phagy and H of proteins and many others and this leaves at the end result leaves the organism in a better State than before that's that's what it is I think simple ye yes and even caffeine right yes in small doses there is a lot of research proving that caffeine chocolate um and other things that we consider B too much wine for example um it's better to to use those than not to use them at all if you don't use them at all you don't get stimulated so you don't have hores if we use them in in a low dose we get stimulated and we have hormesis if we use too much 20 glasses of wine a day it's too much so it's damaging that's absolutely that's the general idea yeah and it's um it's nice to see it that way and um I want to use caffeine as an example because he cognitive enhancer and uh that allows me to go into the next section of your paper that has to do with neuronal stress response so now we are going to focus on hormesis of the central nervous system in particular and uh and there are many things that happen in the central nervous system that um when it is subjected to stress low doses of stress and um in that regard you mentioned the that in the digital era there is more

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that in the digital era there is more stimulation to the nervous system and uh some stress responses can you elaborate more about that it's really intriguing yes we need to see what's happening in our life for example now I'm talking to you you're talking to me but we are talking digitally the information we exchange is digital which means is immediate and it force it comes to my brain whatever you are saying to me comes to my brain immediately and I have to give you an immediate reply this puts my brain my neurons under some kind of stress hormetic stress because I have to give you a reply it's not that something that is irrelevant to me you your information is forces me to act so by by um assimilating the information you are sending me and forcing me to digest it and give you a reply this is considered as the hormetic stress of the brain again within reason not too much if I had to do 10 conversations at the same time it's too much if I didn't have at all to do a conversation it's too little one conversation like the example now talking to you is consider hor hormesis because my puts my brain under mild positive stress U and this biologically has different different um consequences on the the neuron stimulates the uron the neuron the EUR neuron has to create other substances which aim to repair the the

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substances which aim to repair the request of information that it has to to digest and um we found that it creates certain other substances which have an effect on the germ line which is another aspect of my discussion which perhaps we talk about later because there are different interconnected aspects of this particular paper yeah and uh and we are and I think that's actually part of the substance of the paper the those interactions that we will discuss in a minute and uh as you say the the brain is uh is subject to that low dose of stress that forces you to act and uh that's a different kind of stress that a muscle can have but it's still stress and um but what what intrigues me the most is that you make a connection you mention something that is a tradeoff so as you respond to the stress of the nervous system that comes at a cost and that cost is going to be paid by the germline cells so there is a connection between the the neurons and the germline cells please tell us a little bit about that connection and how that tradeoff between the two cell lines ER Works basically nature wants survive sural what towards life the germline cells which are cells of the sperm in man and the ovom in the woman um are cells that repair themselves effectively in order to pass the DNA to the Next Generation and ensure the survival of the species there are biological mechanisms which aim to keep repairing The Germ line this type of cells the genetic

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cells the genetic cells from from Aging in order to have a very good DNA and pass it to the next generation and for life to continue um and this has been the case until now because we used to live our life have children life continues through our children nature didn't care so so to speak about who leads as long as life continues through our children and we die because we don't have good repairs we die through aging uh but for nature is the same there is life but now because of technology and the exchange of relevant information have to stress is relevant information that makes the brain think harder um the neurons let's see it as a common sense approach if you are exposed to information your neuron has to assimilate that information digest create a response all of that requires energy and requires the neuron to be in a very good condition um we are forcing our brain we are forcing our urans through exposure of techn to technology to keep working all the time to repair itself to be positive to not to have any damage and um this Alters the balance between survival of the children and survival of ourselves our brain needs to survive wants to survive so all of the energy resources that nature has given to the

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resources that nature has given to the germ line to to the genetic line of cells now we see that slowly is being reversed and going back to the neurons request constant energy and nature has to give it to them by taking it from the genetic um system and this has an an impact on Aging in other words if our neurons work fully and healthily then we live healthy as well we don't have damage or any damage is repaired because of this positive stress of this repair mechanisms but we talked about earlier uh and if we live longer if if the brain lives longer we live longer as well and that means there is less repair energy available to the genetic line so we have less children but again nature doesn't care because life continues we don't have so many children but we live longer we ourselves live longer and this means that life continues and uh this is one one of the main aspects of my theory saying that um we live longer ourselves but without having children um this is something that has been proven in many species species of any animals that live longer have less children and those who have a lot of children proen say um don't live longer think about ants or mice mice have a lot of uh uh babies but they don't live longer an elephant has less babies but

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longer an elephant has less babies but lives longer this is a mathematical aspect of uh survival in nature and then new avenues open from here because if if this theory is correct it means that we we see in the human population that the more we stress our brain through technology through this exchange of information the less children we have and then we see uh countries that are westernized like Germany um or United States or Japan the more they live the more technology they have the less children they have for example in Japan 40% of couble decide not to have children imagine that 40% of young couples don't have children and will never have children this is um because nature senses that the mechanism is being reversed from the genetic line is going back to the nervous system and uh it it somehow doesn't have so much pressure on people to have children because they can survive them themselves and not through their children we can discuss this in some more details if you want because there are many different aspects of it which at first glance they may seem not related but everything is related yeah and there is actually empirical evidence of of what you say because there the the demographics of sociey is you know is changing and that is

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you know is changing and that is definitely related to the fact that you mentioned that young couples are f are having more access to to information and their brains are stressed or all the time right and that may have to do as you mentioned um with the reduction of natality rate and and all these population changes and and it's really interesting how you are able to conect conect the two aspects through through things that are happening in the central nervous system I I think this is a a theory that um that has you actually touch on different aspects um er demonstrating the intimate relationship between their germline cells and the neurons that can create those connections for for this Theory to to be sound and to have um a lot of ground behind it and um yeah well there is there there are biological Pathways that connect the neuron and the germline cells the genetic cells and and the more we investigate this we more the more we find that it's um either one or the other is they are a constant war between them um they want each one wants the repair Energy repair resource es for themselves The Germ line takes as much as possible of the repair resources to repair itself and and the DNA goes passes to the Next Generation and hand but now with technology this is the new thing we have this technology which uh forces us to exchange information quickly um and this makes the brain cell say stop I want repair resources now for

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say stop I want repair resources now for myself don't send it to the germ line and they take it back and this I'm talking I'm not talking about individual people I'm talking about Humanity as a whole it's not I don't want people to think that I didn't have any children that means I will live longer no I'm talking about Humanity as a whole you see that Yeah the more technology is increasing in in countries the less children they have and some of the mechanisms um may appear unrelated for example they may be due to environmental pollution or to the effect of of WiFi the radiation through the Wii which destroys the male sperm we see that um the quality of the male sperm has been decreasing over the the past several decades cancer of the prostate is increasing cancer of the ovaries of the reproductive cells are increasing generally and this is because nature in is sensing that there is no need to maintain the genetic aspect of the organism anymore because the brain aspect is taking over I don't know if this is clear but it is it's either one or the other for nature and now going from the one to the other instead of germ line we have the the neuron and this is due to the exchange of of hormetic information that stimulates the neuron yeah it's interesting and it's very clear the way you you present it so the hormesis is at the center to channel resources to the

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center to channel resources to the tissues that needed the most in this case the central nervous system and that's at the expense of The Germ line so it's like a like uh privileging the individual over the collective right because the resources are going more to the somatic way rather than to the germline way yes so we live longer our body lives longer um and this is a way to So-Cal defeat aging because if we have repairs of the damage that means the Aging it doesn't affect us so we live longer um but as as a society as Humanity not individual people not 10 people who use internet are going to live longer but the others are not as Humanity generally millions and billions of people who put brain under constant suitable hormetic stress um slowly slowly their biology is going to change and uh uh their are process of having children is going to diminish but they are going to live longer themselves so from the point of view of nature it makes sense because life continues not through the children but through us so this is taken care of and we have evidence that this is happening if we keep looking in some detail we'll see that this is now happening I mentioned the example of of genetic can of um cancers of the ovaries of the prostate of the testicles all of these cancers are increasing um homosexuality is increasing what what what's the meaning of increasing homosexuality or um other

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of increasing homosexuality or um other aspects of non procreative sexual preferences why do we have you know many countries we have increased homosexuality is because nature is sensing that having children is not absolutely necessary anymore and through different mechanisms social biological or rather no mechanisms is releasing the pressure from from a man and a woman to have sex and have children and allows other sexual preferences um which don't lead to the production of a baby so that's that's one explanation why we have um an increase in homosexuality in in many countries it's a natural aspect of this process yeah and and it's interesting because there is then the you know the mechanisms go beyond the individual and and start becoming like a societal driver right that start changing other things and it's a there is a connection between what is happening at the individual level and what is happening to the collective and uh and your theory is definitely something to to consider because it explains several changes ER at the societal level and I appreciate you sharing all this with us and um and it's been a very deep narrative review that is shedding light on different aspects both as I mentioned the individual level and also at the community level I I want to thank you Dr kiris for for being here with us today and sharing all this information with us yes thank you for giving me the opportunity it was great and uh

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opportunity it was great and uh for our audience you will find the the link to the paper that we discussed in the description of the video and uh stay tuned for the next episode