Thermodynamics and symmetry of Human Catabiosis- the present understanding Running title: Thermodynamics of Human Catabiosis Abhijit Dutta [First Author] Department of Mechanical Engineering MCKV Institute of Engineering Howrah 711204, India Email: abhijit_me2005@yahoo.co.in Himadri Chattopadhyay [Second Author] Department of Mechanical Engineering Jadavpur University Kolkata 700032, India Email: chimadri@gmail.com Jale Çatak [Third Author] Department of Nutrition and Dietetics Faculty of Health Sciences Istanbul Sabahattin Zaim University Istanbul, Turkey Email: jalecatak@gmail.com ORCID ID: 0000-0002-2718-0967 Thermodynamics and symmetry of Human Catabiosis- the present understanding Abstract: In this paper, human catabiosis has been observed from the vantage of thermodynamics. The nature of human catabiosis, its origin and future evolution are addressed. Research works on human catabiosis based on non-equilibrium thermodynamics are summarized. The origin of the human species, reproduction, growth and ageing are reviewed from the perspective of thermodynamics, and finally, the future trend of catabiosis is discussed. Works of the literature suggest that in the human body, thermodynamic entropy generation increases with the increase in age. It is valid for organs as well. Human catabiosis can be thought of as a continuous degradation of Gibbs free energy, which brings to the thermodynamic equilibrium i.e. death. The choice of dietary patterns and geographical locations also influences the ageing process. The low-calorie diet delayed human ageing. However, literature exhibits that the colder region on the earth (Oceania, Europe and North America) extend life expectancy. The future trend of longevity depends on how the entropy production will be compensated with introduction of futuristic medical aids. Keywords: Catabiosis, evolution, thermodynamics, growth and ageing 1 Introduction Ageing is an inevitable part of life. Normally we accept the fact that ageing comes with the age (time) and we called it ‘growing old’. There are few signs of ageing which include white and thin hair, loss of fertility, low bone density, gastronomically poor, malfunction of the brain, hearing loss, dull skin, poor vision and so on. Human ageing, a journey from birth to death, has been examined through different perspectives. There exist several established theories of ageing from the biological front as well as the non-biological front of observations. The biological theories include Telomere Theory, Reproductive – Cell Cycle Theory, Wear and Tear Theory, Somatic Mutation Theory, Error Accumulation Theory, Viral Theory of Aging, Accumulative – Waste Theory, Autoimmune Theory, Clock Theory, Cross Linkage Theory, Free Radical Theory, Reliability Theory of Ageing and Misrepair Accumulation Theory [1]. Most of the biological theories rely on the genetic alteration of a specific gene, responsible for ageing. On the other hand, Disengagement Theory, Activity Theory, Selectivity Theory, Continuity Theory and Entropy Theory of Ageing [2] are belonging to rather a non-biological point of view. In this paper, we shall discuss the ageing process basically from the perspective of thermodynamics. The connection between thermodynamics and life has always intrigued researchers [3]. Biological systems are considered as an open system which allows to passing mass and energy through the boundary. Biomolecules are highly ordered in nature and they tend to maintain the same over a period of time. Thus biological systems are capable of maintaining lower entropy production. Living systems try to belong in a non-equilibrium state over a while to minimize the decay toward the equilibrium which eventually brings ‘death’ [4-5]. During this time, the system matures, reproduce and fulfil biological requirements for its sustainability. The average period of a particular species under ideal condition can be termed as ‘longevity’ which can vary from hours to centuries depending upon the type of species [6]. As The maintenance of non-equilibrium state throughout life is achieved by self-organising mechanism and has been examined through recent ideas like Constructal theory [7-10]. From the thermodynamic vantage catabiosis is an intrinsic property of a biological system. Age actually means more than the interval of time (extrinsic) [11]. The applications of thermodynamics to human physiological systems have been discussed by [12]. While the first law of thermodynamics is basically the principle of energy conservation, the second law points out to the qualitative aspect of energy and postulates that the total entropy of the system and surrounding always increases which is discernible by the experience of reducing order in daily lives, in contrast to which the living systems exhibit high levels of organization and self-organising mechanism which lead to the coinage of the term ‘Negentropy’. The concept was first coined by Schrodinger in 1944 in his book ‘What is life?’ The relationship between life and entropy production is depicted in Fig. 1. [Fig. 1 Relation between entropy and life] Death is designated as a very close to the thermodynamic equilibrium state where a biological system attains almost maximum entropy production (), though the maximum entropy can be achieved after decomposing the dead body. A biological system sustains over a time period (life) by supplying negentropy to the system. The entropy production of a biological system can be expressed as stated in Eq. (1) [13]. Where, represents entropy generation over a time period and represents the negentropy part. During the life span of a living entity, is always positive and at death . Where entropy denotes degree of randomness of the elements of a system, negentropy can be associated with the degree of certainty. Diseases can be described as a faster rate of entropy production within the system that could lead to attain [14]. The disease can be reduced by the supply of negentropy in the system which certainly suppress the randomness and organise the elements of the system that’s leads to cure [15]. Some literatures are available on the thermodynamic analysis and computation of the performance of biological systems specifically different organs and systems [16-23]. In this paper we strive to present a perspective from thermodynamics on the way humans originated on the earth, live their life to. 2 Origin of life ‘Abiogenesis’ is a biological term that refers to the origin of life and that comes from non-living organic compounds [24]. J.B.S. Halden’s Primordial soup theory suggests that a set of conditions (prebiotic process) favour abiogenesis [25]. Physicist Jeremy England thinks [26] that an inanimate system retains under isothermal condition for a long time, possibly developed a living (animate) system. It happens because of the self-replication process fuelled by entropy production as well as the dissipation of energy. Under certain condition, prolong period of energy dissipation, a system required to reorganise its molecular structures which inevitably acquires characteristics that associated with life. Many researchers believe that the abiogenesis observed on the Archean (4,000 million years ago) sea surface under the influence of solar radiation and thermodynamic dissipation of energy [27-28]. Thus, from one cell to many cells came into being existence. Due to different energy dissipation mechanism, different body plan has been developed on the earth and gradually classified into diverse type of species. The two main pillars of life are metabolism and genetics those control molecular reorganisation, structure development and evolution of a living system far away from the thermodynamic equilibrium [29]. Biological dissipative structures originated mainly in the cellular level due to the biochemical processes [30]. At higher level, population of cell dynamics and dissipative structures appears in the form of special molecular arrangements that influences linear evolution law. A viewpoint from thermodynamic perspective on the development of highly complex lifeform especially evolution of the human species is yet to be offered though seems plausible. 2.1 The reproduction process Reproduction is an important biological process for all species, including human on earth which ensure the existence of life. Human reproduction is reportedly viewed as a thermodynamics process by Maargulis and Sagan [31]. The reproduction process is basically an open system involving mass exchange with a significant dissipation of energy. From the biological standpoint, reproduction modes can broadly be classified into two categories like sexual and asexual. For a particular species selection of a particular mode is determined by the minimum time required for free energy consumption with its surroundings [32]. A significant heat evolution is observed during human sperm-egg interaction. However, elevated oxygen consumption is observed during fertilization process [33]. It is noteworthy that complex organisms experience a longer lifespan than simple organism. They execute several functions as member of the ecosystems, among them fast mobility and hunting for food are on the top of the list. This can be viewed as consumption very high free energy from the surrounding. Due to biological complexities as well as the other physical activities, the complex organisms dissipate more entropy from the body. The frication of energy spent for reproduction purpose is insignificant in contrast to than that of simple organism. Hence, sexual reproduction is favourable for its minimum entropy production within the body as well as dissipation of lower entropy to the surrounding. It also noted that the population of complex organisms are far less than the simple organisms due to the higher entropy production rate. The lower organisms display few simpler functions which lead to less entropy production in their body. Therefore, asexual reproduction is best suited for the dispersion of a low amount of entropy from the body. Thus, their reproduction is fast, rapid and less time consuming. Despite different biological drawbacks in sexual reproduction system, it has a most significant characteristic. Due to low available free energy for the sexual reproduction process genetic alteration creates diverse characteristics within the species. This ensures survival of the species on the earth. The functionalities of several aspects in sexual reproduction of human from the thermodynamic viewpoint are yet too revealed. Authors of this article believes that the effect of surrounding temperature on the human reproductive mechanism possibly have some thermodynamic impact which was evident in the ‘ectothermic’ species [34]. 3 Growths and Ageing The development of human (or any species) anatomically as well as behaviourally is termed as ‘ontogenesis’. The process involves minimum energy dissipation at fastest time which depends on type of species. Thus, different body plan and behaviour is observed in nature. This view point is known as ‘Phenomenological theory of Ontogenesis’ coined by Zotin et al. (1997) [35]. Thermodynamic theory of growth and ageing is a part of a general theory that supports origin of life as well as the evolution. In 1978, Russian scientist G. P. Gladyshev introduced a new concept of thermodynamics called ‘hierarchical thermodynamics’ [36]. As per Gladyshev, Gibbs free energy change equation has its own limitation as it cannot predict the value during the formation of supramolecular structure [37]. The accuracy of a thermodynamic model is depending on strong inequalities of the following Eq. (2 and 3) (2) is the average lifespan of the structure j of the lower level, whereas, represents average lifespan of the structure j+1 at the hierarchical level. For a particular type of species above inequality can be expressed as (3) Where, sm is the supramolecular structure. Eq. (3) exhibits for a specific species (i.e human) the average life span of metabolites is far less than the supramolecular structure. It can be also observed from the inequality relation holds good for that the average lifespan of a smaller element is less than that of larger one [38]. This was agreed by the Wicken (1985) [39]. A number of works have been carried out to understand ageing from the classical thermodynamic perspective. These are now discussing sequentially. Ilya Romanovich Prigogine (1917-2003) introduced ‘Dissipative structure theory’ [40] which stated that the biological systems are continuously import energy while exporting entropy (see Fig.2) [Fig.2 Humans are eliminating entropy to sustain life] Exporting entropy potential not only helps to grow a biological system over time but also lowering entropy accumulation within the body which eventually bring death due to attaining thermodynamic equilibrium. The literature suggests that the major part (around 98.6%) of the net entropy generation within the physiological system is due to the metabolic activities [41]. It is noted by the authors of this work that capability of entropy elimination from the body of different species are different thus the average life span of a healthy human (79 years) is much higher than a giraffe (26 years) but far less than Galapagos giant tortoise (more than 100 years) (see Fig.3). [Fig. 3 Effect of average body temperature on the lifespan] It is noteworthy that the species that has higher average body temperature are poor in entropy elimination from the body. Hence, those who have higher body temperature attain maximum entropy (Smax) in lesser time (lifespan) [42]. The avian groups are the exception for this theory. The average body temperature of parrots (including all sub species) is higher than that of human and their lifespan is almost equal or greater than the humans. The exception is also not so uncommon within the same species. In case of human beings, women live longer than men despite of having higher core body temperature [43]. Heat dissipation is not necessarily a primary requisite for minimization of entropy production in a biological system. Self-organization of the functional components also leads to entropy minimization within the system [44-45]. Ageing is a complex thermodynamic phenomenon which represents irreversible changes of thermodynamic states as well as biological parameters. Hayflick [46-49] conceptualised his theory of ‘Heyflick limit’, which states that every cell within the body is programmed to finite number of cell divisions. The connection between Heyflick limit and entropy production was also examined by him. Human body entropy production also depends on the age. It has been noticed that at the earlier stages (up to 20 years) of life the rate of entropy generation is rapid and later it declines till death [50]. In accordance with the Rahmans’ philosophy, Toussaint et al. [51-55] agreed that entropy generation of cells decreases with the age, as it loses its metabolic efficiency. On the other hand, ageing can be slow down (extend longevity) by restriction of food intake which also helps to maintain healthy and vitality [56-58]. Low calories intake results in shifting metabolic process such a way that helps to reduce heat production rate and entropy as well [59-60]. This phenomenon is also observed in the primates [61-62]. In another study conducted by Silva and Annamalai, [63], it has been observed that low calorie diet increases the lifespan of an individual. This work also recommends human life can be extended at an average of 3.3 years by keeping minimum recommended protein content in the daily diet. Ongel et al., [64] suggested in their work that the women are expected to live longer than men due to different reasons. The primary reason is that the telomere length declines faster in men than women this leads to more entropy production. The lifespan entropy can be estimated as Eq. (4). Where, is the entropy production of the chemical reaction (metabolic reaction). referred as energy efficiency factor. In Eq. (4) time stated the age. Secondary cause is the telomere length is regulated through the diet allocation. The dietary choice of the human being is based on geographical locations since ancient times. Hence different types of cuisine have been developed due to the wide verities of cultures. Several kinds of literature attempted to explain traditional dietary patterns might be associated with the extended lifespan [65-68]. The centenarians have been great examples of consuming an energy-restricted diet throughout their lifetime. In addition, they tended to have a high consumption of plant-based foods and lower consumption of animal food products. Consuming energy-dense foods can lead to a shorter lifespan [69]. The dietary habits of Japanese, Mediterranean and Vegetarian Diet share several common strong anti-ageing features [70] which include whole grains, omega-3 and unsaturated reached foods, fish, extensive use of medicinal, aromatic plants, spices, very low or no use of alcohol, meats and saturated fats. These mentioned food products are associated with the reduction in telomere length over time, therefore, increasing lifespan. Furthermore, whole grains, vegetables, and fruits help to reduce the risks of all natural causes of mortality. Table 1 shows a comparison between five different dietary patterns. [Table 1 Comparison between different dietary patterns [71]] Furthermore, restricted intake of carbohydrates and protein exhibits different results in men and women. A comparatively shorter lifespan was estimated for the women taking the Mediterranean diet and for the men with a ketogenic diet. Both men and women can experience longer lifespans after considering a vegetarian diet. A study was reported by Patel and Rajput [72] about the effect of the food habits of Indians on the thermodynamic lifecycle assessment. The study exhibits that the lifespan of the Indians is ranging between 66–79 years. The people who live in Haryana have an average life expectancy of 66 years and for Tamil Nādu the average life expectancy is around 79 years. From the comprehensive review of literature on human ageing due to dietary patterns, it is evident that the exergy of a particular pattern of food is different from the other. The metabolism of these food nutrients (carbohydrate, protein, fat etc.) leads to different entropy generation in the body because of variations in the percentage of nutrients. Higher lifespan entropy generation leads to lesser longevity. Hence, the dietary pattern that produces lower entropy production during metabolism needs to select for an extended lifespan. As it is confirmed, that diet is an important factor in ageing, and it depends on the geographical location. So it is rather implied that geographical location is another important factor that influences lifespan. A study within a relatively narrow geophysical zone, within Turkey, was conducted by Kuddusi in 2015 [60]. He could indicate the lifespan of seven different regions is as follows; Eastern Anatolia < Southeast Anatolia < Black Sea < Mediterranean < Marmara < Aegean < Central Anatolia. The average human lifespan on different continents is depicted in Fig. 4. [Fig. 4 Average life expectancy in different continents] Fig. 4 illustrates that the life expectancy of a new-born male and female in Oceania, Europe and North America is around 75 years and 80 years respectively. In Asia and Latin America, it is around 70 for males and 77 for women. In Africa, life expectancy is significantly low for both gender in comparison to other continents. Entropy production of men is 11% greater than women due to more physical activity and body weight. It is observed that entropy generation is at minimum when body temperature is 36℃.The tolerable range of human within the temperature limits of 28℃ to 42℃, beyond which human face death. Entropy generation over the lifespan of a healthy individual has been estimated around 11,404 kJ/kg K of body mass [73]. It has been shown that the possible lifespan of a male is 73.78 years and for a female is 81.61 years, through the analysis of thermodynamic entropy generation. On the other hand, it is not only the core body temperature that influences the lifespan but also the size of the body plays an important role [74]. Longevity is inversely proportional to the body size. On that note, larger body consisted with more number of cells, which contribute in higher rate of entropy production. This entropy surplus promotes towards thermodynamic equilibrium. Entropy stress on individual organs of human body was examined by the same authors [75] with the help of allometric law. They predicted that human heart will fail first followed by Kidney, Brain, and Liver and so on during rest condition. Life span entropy generation theory suggests that organism (here human) have limited capacity of entropy generation throughout its lifespan. In this context Catak et al., [76] showed that the entropy generation of Masseter muscles of an obese person produce more entropy than a normal person. Hence it reaches its limiting value five years prior to the normal person. Mitochondria are the important part within a cell. It stores energy in the form of ATP (Adenosine triphosphate) for cellular as well as for the lifting (work done) purpose. The capacity of storing ATP in the mitochondria deteriorates with age. It is observed that the balance between energy metabolism and reactive oxygen species hampered in the mitochondria with the progression of age and disease [77]. In another paper Catak et al., [78] reported that the muscular work efficiency decreases with the ageing. This happens because metabolic energy conversion rate decreases with time hence it contributes in more exergy destruction. Thus, second law efficiency of the human skeletal muscle decreases with the progression of age. Gibbs free energy utilization from the oxidative glucose remains same throughout the lifespan and its magnitude is around 5.5×105 kJ/ kg of glucose per year [79]. The factor which influences human brain function with age is the loss of energy stored by the mitochondria and work done for the warned-out ion pumps. 4 Future evolutions All spontaneous and non-spontaneous changes of natural evolving systems are accompanied by the continuous change in Gibbs free energy. The modern human evolved from the Homo Erectus 117,000–108,000 years back [80]. During this long time, thermodynamic behaviours also evolved in such a fashion that it can maintain its order for entropy minimization. The average lifespan of human increased significantly [81] from the past centuries. This might be strong evidence that modern humans can better eliminate entropy from the body than their predecessors. So far as evolution is concerned ageing is not an exception. Ageing also evolved in its way from the past. In USA, Social Security Administration (SSA) and Census Bureau (CB) independently makes forecasts that the life expectancy of USA male and female combinedly increase in between 3.1 to 7.9 years by the year 2050 [82]. The Gini index which is an indirect measure of statistical entropy, significantly dropping over the century of global population. A report suggests that the Gini index for Indian populations has declined from 0.32 to 0.19 for men and 0.31 to 0.22 for women in the year between 1981 to 2011 [83]. We the humans are gradually adapting to the ambient condition over time to reduce entropy production within the body as well as on the surroundings. The future evolution will depend on the way irreversibility has been generated since the past. It must be borne in mind that the delayed ageing does not guarantee us a good quality of life. It is also possible that in future evolution shall face new diseases which may lead to poor life quality, reproduction and disability in one or more than that limitation in activities. On that note delaying ageing might not be meaningful rather painful from the present scenario. One of the key factors of delaying aging is the evolution of medicine, surgery and testing procedure. These are also evolved with time and contribute to minimize local entropy production (disease) side by side. Physical disability also creates some unpleasant dissipative structures that can be rectify or minimise with the evolution of biomedical aids. The future progress of medicine, surgery and testing procedure might tackle more critical diseases in comparison with the present. Society has a great influence on the process of evolution and naturally on ageing too. It is already mentioned that while biological system always tries to maintain order. The man made inanimate systems produce high level of entropy which is transported through the physiological systems and creates local entropy production. The interaction between living systems and inanimate surroundings is again an important factor on which little is understood and therefore how these inanimate systems will influence the catabiosis of human race is yet to be studied. 5 Concluding Remarks This study aims to survey the thermodynamics of the catabiosis of the human race. The origin of human, ageing (catabiosis) and its evolution is reviewed from the thermodynamics perspective. Works of the literature suggest that thermodynamic entropy generation increases with the increase in age for the body and organs as well. The elimination of this entropy from the body also follows the same pattern. Human catabiosis can be thought of as a continuous degradation of Gibbs free energy, which brings to the thermodynamic equilibrium i.e. the deceased state of death. The hierarchical thermodynamics suggested that catabiosis is a consequence of the change in Gibbs energy within a predefined limit. The possibility of a thermodynamic interpretation of natural selection is yet to be explored. The choice of dietary patterns and geographical locations also influences the ageing process. The low-calorie ketogenic diet delayed human catabiosis. However, literature exhibits that the colder region on the earth (Oceania, Europe and North America) extend life expectancy. On the other side people who live in the African continent can expect the shortest lifespan around 61 years and 64 years for men and women respectively. The future trend of longevity depends on how the entropy production will be compensated with introduction of futuristic medical aids. The impact of adaptation of futuristic lifestyles and its effects on the catabiosis is an important concern of investigation. The laws of thermodynamics are found to govern all-natural and artificial phenomena. Using these laws as tools, many natural and complex phenomena can be described and identified. It is an emerging area of research. A few numbers of literature are available which support thermodynamic analysis of the ageing process. No such literature is found that can describe the past and the future of catabiosis from the viewpoint of predictable thermodynamics [84]. The effect of chronic diseases on the ageing process from the thermodynamic point of view also needs to be investigated. References: 1. Jin, K.; Modern Biological Theories of Aging. Aging Dis. 2010, 1(2), 72–74. 2. Hershey, D.; Entropy Theory of Aging Systems, Humans, Corporations and the Universe. Imperial College Press. World Scientific Publishing Company. 2009, ISBN 9781908978653. 3. 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List of Table: Table 1 Comparison between different dietary patterns [70] Components Vegetarian Japanese Okinawan Mediterranean Nordic Vegetables Extensive Extensive Extensive Extensive Extensive Whole Grains Extensive Extensive Extensive Extensive Extensive Legumes Extensive Extensive Extensive Extensive Extensive Nuts and Seeds Extensive Extensive Extensive Extensive Extensive Fresh Fruit Extensive Extensive Extensive Extensive Extensive Fish - Extensive Extensive Extensive Extensive Red/Processed Meat - Low Low Low Low Poultry - Low Low Low Low Dairy Extensive Low Low Moderate Moderate Cooking oil vegetable oils rapeseed/canola oil rapeseed/canola oil extra virgin olive oil rapeseed/canola oil Alcohol - - - Moderate - Herbs and Spices Extensive Extensive Extensive Extensive Extensive List of Figures: Fig. 1 Relation between entropy and life Fig. 2 Humans are eliminating entropy to sustain life Fig. 3 Effect of average body temperature on the lifespan Fig. 4 Average life expectancy in different continents Fig. 1 Relation between entropy and life Fig.2 Humans are eliminating entropy to sustain life Fig. 3 Effect of average body temperature on the lifespan Fig. 4 Average life expectancy in different continents Male Female Male Female Male Female Male Female Male Female Male Female Ocenia Europe North America Asia La tin America Africa 76 81 75 81 74 80 71 76 70 77 61 64 Continents Life expectancy in years image1.png image2.png image3.png