 Understanding aging and talking about healthy old age is a very important issue because this is the question of life and death for all of us. Aging leads to death and that is what we are going to talk about today here. When we talk about aging, there are always sociological and psychological factors because when does society tell you that you are old? That's a very important issue. And when does your own psychology tell you that you are old? When do you tell yourself that you are old? But even more important to that is when does our biology tell us that we become old? And today I would like to talk about the biological basis of aging. Why do our bodies become old in the first place? And why we can or cannot live forever? Why our lifespan is limited? Because the first thing in aging research is that in nature there is nothing immortal. Every individual dies sooner or later. The lifespan can be very short or very long. That depends upon the species. But there is nothing immortal. Nothing lives forever. Why? That is the starting question for a biogenetologist. That why no living system can live forever? We are generally familiar with the two kinds of lifespans. The lifespan is short, but then we talk about average lifespans in the population. Right now, for example, in Denmark, there is average life expectancy of about 80, 85 years. This is very important to know because this is the data which is the basis of deciding many social decisions. What should be the retirement age? What are the future perspectives? Then we also know about maximum lifespan. That who has lived longest so far? And the human record so far is 122 years, which was set in 1997 by this French lady. So it has been 15 years that somebody set that record. Will anybody break it? Will anybody live beyond it? We don't know, but there is nothing special about it. Somebody will cross it. The oldest person living today is 116 years old. So we have to wait for at least six years before we know can anybody live longer than that. These two kinds of lifespan we all know. But then there is a third kind of lifespan that how much lifespan should be there? From nature's point of view, from evolution's point of view. And that is the question of the purpose of life. What is the purpose of life in evolutionary terms? Not in sociological terms or psychological terms, but in evolutionary terms. The purpose of life is what Darwinian theory tells us. Reproduction and continuation of generations. So that lifespan is called essential lifespan. How much lifespan a species should have so that it can give birth to the next generation and continue to carry on with its genes? In the case of human beings, and like all other species also, it's generally very short. And it's not a very good news to look at, that essential lifespan is not more than 40 to 45 years. This is what nature wants us for, to continue Homo sapiens, to continue our species. What happens after that, that is not evolution's concern. And that is a very, very important issue. Because through our own success, through our biomedical achievements, we can expect to live double or triple than that lifespan. And that is what is the start of bio gerontological research. That why our lifespan is so short and when does aging happen? That is also the definition for aging. That if we live longer than our essential lifespan, aging will set in. So beyond the age of 40 and 45, that is one in biological terms we say aging starts. Aging does not start from birth. Although we use the word, how old is the child, but it's not aging. That's growth, maturation, development. Biological aging starts after the age of 40. And that is when we deal with the process of mechanisms, another thing. So, but aging and lifespan, how long a single person will live or how he will become old depend upon many things, many factors affected. And of course, genes are the basis of that. Genes determine or contribute about 25% to our aging and lifespan. There are nice researches done on that. That means that 70% of the lifespan is determined by our lifestyle. So if your parents and grandparents had longer life, you also have some chances to have a bit longer life than the rest of the population. But that contribution is generally about 25%. 75% contribution will come from nutrition and physical activity, level of education, social network and how you look at your own health. These are very, very important factors which determine what kind of old age we will have. Like it has been shown that social network is a very, very important issue whether somebody is living alone or living with a partner or family and friends whether one is physically and mentally active. Higher education is generally related with the longer life spans. Well, we don't know the exact mechanisms behind it. And even your own feeling about your own health, that has to do something with your survival and your quality of life. So these two things together, a little bit from the genes what you inherited from your parents but mostly from your own lifestyle, you live healthy or sick life. And we want to learn a little bit about that. How can we have better quality of life? How can we have healthy old age? So what happens during aging? This is what aging research is all about at the biological level. In the last 50 years, people like us in our labs in Ohus and all around the world, we have described what happens when individuals become old, when the systems in the body become old well cells become old, when even the molecules become old, DNA, RNA, protein. Depending upon the technology available, depending upon the priorities of scientific research we have determined or described almost everything in the field of aging. And that takes a long, long time if I want to describe what happens in brain and what happens in bone and all that. So the carry home message from these 50 years of biological research is that everything ages. This is just an example of showing that in our own labs in Ohus University we work on human cells in culture, that if we grow human cells, like these are skin cells in the laboratory condition, this is what happens to them in about one year's time that when they are young or middle aged and old, whereas in the body it might take almost 100 years so you cannot do experiments with that. But this is a fascinating experimental system which we have also used and lots of other scientists use to understand why this change happens and can we do something about this change. Now what we know from all this research is that everything in the body ages at the biological level, and ages basically mean functionally becoming less able is not improving with age in biological terms. If we want to talk about improvement with age, that's again a sociological and psychological issue that yes we need to celebrate aging, we need to respect old age but we also have to accept the fact that biologically everything will show changes towards dysfunction. The examples are here like the young bone and the old bone. The skin aging, the young brain, old brain with Alzheimer, cells aging, chromosomes changing, DNA changing. So everything ages but the interesting thing is very differently. No two people become old in the same way, not even Monozygotic twins. No two individuals become old in the same way, no two parts in the body become old in the same way. So that's why there are not any common mechanisms. There is not a simple solution to the problem of aging because everything ages differently and that increases the challenge. That makes life more challenging for researchers but it also gives more possibilities of intervention. Then a very, very important question in the field of aging research is are we programmed to age? Are there any timers, clocks or genes which are there with the purpose of killing us with the purpose of making us old? Because earlier people used to think that just like everything else in the body is controlled by genes our old age and death is also controlled but last 20, 30 years of research shows no. There are no genes which evolution has made with the purpose of killing. The body does not have any enemy inside itself to kill itself. Evolution works on life processes and these are very good news because there is no mechanism which is trying to kill you but the fact is that yes we still become old and we will die and that is what opens up the possibility of doing something about it. There are no gerontogenes. Genes affect our quality of life, our basic survival, our basic biochemistry, our basic whether we get diseases or we don't get diseases but genes do not determine how long I will live or what will be the time of my death but then how to understand why I age and die? We have to understand why we live. In order to understand old age and death we have to understand why we live and life is a paradox in itself. Look at these three things. The basis of life, oxygen, food, basic biochemistry, that is exactly what causes all the problems in the body. Most of the damages happening in the body or in the cells are due to oxygen, are due to components in the food, are due to the basic mistakes in the biochemical processes but in a living system in the body we have then very complex processes of maintenance and repair, the biological defenses, right from the level of DNA maintenance which is the fundamental survival molecule to proteins, antioxidants, cells, tissues, thermoregulation. These are all mechanisms which protect the cells and body. If they were not working we can't live even for a second. This is the balance between these two things which we call a kind of survival ability. We call it homeodynamic space, our ability to live and survive. A child is born with normal healthy survival ability which can be improved during growth, development, maturation and then it grows up into a healthy young person who is ready to fulfill the reproduction part of evolution. So this is what keeps us alive. There is a danger zone, a vulnerability zone. Things can go wrong at any age but that's relatively small because the body has its own defense mechanisms. It will take care of itself. But what is then aging? Our way of looking at aging, aging is the progressive shrinkage of the homeodynamic space. This ability to live, this ability to tolerate, this ability to adapt, to change is becoming lesser and lesser and this is the main sign of aging which then leads to the emergence of one or more diseases which finally kill us. So all these diseases have a common cause which is the process of aging. Of course we can either work with one disease at a time which is the normal or the popular procedure in biomedical research that you want to treat one disease or you can prevent these diseases by doing something about the aging process. So aim of aging research is to modulate, to intervene in the process so that these diseases are either delayed or they never come because once they come that requires the traditional biomedical intervention. So in the case of aging researchers the driving force for us is basically this in the ideal that we would like to modulate aging process so that we can extend health span. We do not work on the extension of life span life span has its own complex nature but improving the health span so that we do not have suffering and diseases in the last 10-15 years of life. This can be done by aging and a lot of scientists are working on different aspects of that. Most common are temporary remedies where we take hormone therapies and antioxidants and stem cells and they try to fix what is going wrong one at a time. Sometime these things work most of the time these things don't work as say prevention. If there is very serious deficiency of a molecule yes, some antioxidants can help some hormones can help but in a normal healthy person these things generally do not work and they are just piecemeal therapies but that's where most of the research is also done. But then there is a more promising and successful strategy is the prevention. How can we prevent that shrinkage of the homeodynamics? This is becoming more and more sensitive to disturbances. And this is where I would like to introduce the concept of two sides of stress. We all know that chronic constant long-term stress is very harmful for the body. There is no doubt about it but there is the other side of stress that stress at a lower level generally actually improves your living ability because this is the property of the living system when there is stress it tries to counteract it and it tries to match that stress and then you can get benefits. This we call, this phenomenon is called hormesis. Hormesis is the phenomenon where you can challenge the body challenge the cells with a little bit of stress and it will try to increase its own defense mechanisms and you can get benefits out of it. And the conditions which cause this kind of hormesis, which is the phenomenon are called Hormitins and there are three types of Hormitins which we identify. The first one is Hormitin P or physical Hormitins. We all know about exercise. Exercise is a physical Hormitin which actually causes stress and damage in the body and you are able to get benefits after the exercise. And in our own laboratory we have worked a lot with temperature and radiations and other things which can induce stress and get benefits. The second type of stress or the Hormitins are Hormitin M, mental, the brain activity and there are some research data showing that even meditation induces little bit of stress. That is why you get benefits. But most promising area right now is what we call Hormitin N, nutritional Hormitins because a lot of things which we eat in our food, we don't eat due to its nutritional value but due to something else like spices, ginger, garlic, onion, chilies, pepper. They have very little nutritional value but they have hermetic value. They are good for the body because they cause a little bit of stress. They cause a damage. So using this combination is very, very important to attain healthy life. So Hormesis can be a very powerful holistic tool combining physical Hormitins, mental Hormitins and nutritional Hormitins taking variability in food, having challenges, choosing your stress. Stress of choice can be a very, very powerful strategy to achieve healthy aging and increase health span and have a better quality of life.