Aristotle on Life and Long Life

Ilia Stambler

The concept of life

The tremendous influence of Aristotle (384–322 BCE) on the development of western philosophy and science is undisputable. Volumes have been written on his philosophical, epistemological, esthetic, cognitive and ethical theories. Yet, in fact, Aristotle’s corpus of treatises mainly concerns zoology and physiology, including: History of Animals; Parts of Animals; Movement of Animals; Progression of Animals; Generation of Animals; On Plants;  On the Soul; On Generation and Corruption; On Breath; Physiognomics; and the various treatises of Parva Naturalia ("the short treatises on nature"), including On Sense and Sensible Objects; On Memory and Recollection; On Sleep and Waking; On Dreams; On Prophecy in Sleep; On Length and Shortness of Life; On Youth and Old Age, Life and Death, and Respiration, etc. However, it is the biological works of Aristotle that are less researched by modern scholars, and their relation to modern findings is underappreciated.1 As the American philosopher Marjorie Grene stated, “biology, like all modern science, really is, and must be, un-Aristotelian.”2 The reason for this relative under-appreciation of Aristotle’s physiology might be that Aristotle’s esthetics and epistemology may have been perceived to be of a more perennial nature, relevant to the present time; whereas his physiological observations and theories came to be considered as largely erroneous and irrelevant to modern biomedical research, and therefore dismissed as undeserving of study. Thus, for example, one of the foremost British Aristotle’s scholars and translators Walter Stanley Hett recurrently spoke of Aristotle’s “errors” and deviations from ”truth,” and made an apology for him, basically saying that if Aristotle had better data he could have done better, but even as it is his theory is pretty impressive and consistent.3 This commentary was published in 1941, and it might be interesting to trace how many physiological theories from the early 1940s are currently cited in the biomedical literature. And yet, it might be reasonable to assume that there might indeed be a succession from Aristotle to the present time, with respect to physiological research, as Aristotle’s corpus was a major part of European university curriculums through the Renaissance,4 and remained on the curriculum well into our time, even though its repute and authority as a valid source of biological knowledge diminished drastically. Therefore, it might be of interest not just to study where Aristotle was “wrong,” but where he might have been “right,” or to put it in more correct terms: in what respects the succession of Aristotle’s physiological theories can be traced through time, or where Aristotle’s formidable power of common sense might coalesce with the sensibilia of later generations of researchers.
 In Aristotle’s physiological corpus, the main issue concerns, no more no less, the essence of life and death. In De Anima (“On the Soul”), an equation is made between the soul and life. In other words, when speaking of the soul, Aristotle in fact speaks of the “vital principle” or the distinct characteristics of living beings in contrast to inanimate matter.5 Aristotle provides definitive answers to the questions ‘What is life?’ and ‘how it can be maintained’ as well as ‘what constitutes death’ and ‘whether it can be avoided.’ The most basic component of vitality (i.e. the soul) is the “nutritive soul,” which is responsible for or characteristic of the organism’s physical maintenance and growth, or what we may now call ‘basic physiology.’6 This faculty is common to all living beings and distinguishes them from inanimate things. Animals differ from plants by having a perceptive faculty, and man differs from animals by having an intellectual faculty, but all share this basic vital principle. While De Anima provides a rather brief definition of the nutritive faculty (most of the treatise deals with the perceptive and cognitive functions), Parva Naturalia examines in detail the physiological processes responsible for maintaining life or causing death. Despite their generality, the operation of these processes in human beings is given a predominant consideration. Within the Parva Naturalia, several short treatises provide a most concise, yet comprehensive account of human physiology: “On length and shortness of life,” “On youth and old age, life and death, and respiration” and “On sleep.” As the titles suggest, these works have a special relevance to the issue of life maintenance and life extension. In this paper, I would like to focus on a possible relation of these works to subsequent biomedical research, though other physiological treatises, such as On the Soul and On the Generation of Animals will be also considered. 
Regarding the essence and the basic operative principles of life, of special interest is Aristotle’s controversy with previous philosophers: Pythagoras of Samos (c. 569-475 BCE), Alcmeon of Crotona (a Pythagorean, who was active about 510-480 BCE), Anaxagoras of Clazomenae (c. 500-428 BCE), Empedocles of Acragas (c. 494-434 BCE), Democritus of Abdera (c. 460-370 BCE), Plato of Athens (427-347 BCE), and others. Aristotle’s dispute with these philosophers, as presented in Aristotle’s own works, is fundamental and may represent an early, perhaps even a ground-laying, instance of the age-old controversy between “mechanism” and “vitalism,” the controversy that reverberated into modernity.7 The first part of On the Soul summarizes previous conceptions of life and Aristotle’s objections to them. According to Aristotle, most former philosophers agree in that the Soul is composed of elements (particles) that have a mechanical motion of their own, i.e. the “Soul moves itself.”8 In other words, the mutual arrangement of elements and their mechanical motion is what constitutes life. Thus, according to Aristotle, Democritus believed that the particles composing the soul (the “smallest” “round” “fiery” elements of “the least corporeal” nature)9 have an intrinsic motility (now we would call it a kinetic particle motion), and the unison and force of this motion is what creates life. Empedocles, on the other hand, placed a greater emphasis on the mutual arrangement, the “ratio” or “harmony” of the elements comprising a living body (or the soul).10 According to Empedocles, Pythagoras and his “students,” and other “traditional theories,”11  the special harmonious organization (which can be expressed by numerical ratios) is what distinguishes the living matter. According to them, these ratios are controlled by forces of attraction/repulsion between the elements.12 Empedocles called the unifying force eros / philia or “love”. It is exactly the same term, in exactly the same sense, that Freud used in describing the synthesis of matter into a living being (Beyond the Pleasure principle, 1920).13 Modern natural sciences (biology, chemistry and physics) usually employ the terms synthesis, anabolism and synergy (Schrödinger, What is Life, 1944).14 But the meaning of these terms is similar to the ancient concept of the harmonious arrangement of elements by the natural forces of attraction and repulsion. Thus the ‘pre-Aristotelian’ philosophers may have laid the grounds for the ‘atomistic-mechanistic’ theory of life, with a special emphasis on the spatial kinetic motion and mutual arrangement of elements.
It is interesting to note that the “atomistic-mechanistic” concept of the soul may have been relevant not only to future scientific theories, but also to “near-scientific” or “meta-scientific” doctrines. Specifically, the idea that the Soul may be composed of a matter of its own, having a motion of its own, reverberated in subsequent “spiritualist” teachings, professing the separate existence and spatial migration of the soul (or “astral body”), and even in the attempts “to weigh” the soul exiting the dying body.15
Aristotle smashes these theories to pieces by ruthless logic. He counters the supposition of earlier philosophers that the soul must be composed of elements in order to be able to perceive the surrounding environment composed of the same elements (i.e. the soul must have a material affinity to the sensible objects). One of his counterarguments is that, from the principle of material affinity, it follows that “there will be nothing in the soul to recognize bone, for instance, or man, unless they too exist in it.”  “This is impossible” – Aristotle argues – “For who could seriously ask whether there is a stone or a man in the soul?”16 In contrast, Aristotle accounts for sensation by the identity of the percipient sense and sensible object’s activity, and not by the identity of their material composition: “The activity of the sensible object and of the sensation is one and the same, though their essence is not the same.”17 He also employs the principle of contradiction in order to counter the mechanistic theory. That is, according to Aristotle, a corporeal soul cannot be in a corporeal body, because then two bodies would occupy the same space.18 More fundamentally, Aristotle undermines the mechanical composition theory of life by saying that the harmony or proportion of elements (that we may now refer to as a “pattern”) cannot account for the movement or change inherent in all living beings.19 Hence, in Aristotle’s account of life, mechanics and material composition are of less importance than the functional state and activity of the living being. In other words, in Aristotle’s view, life is a unity, which cannot be reduced to a combination of material components, but it is rather due to a special force of activity inherent in a living body.20
This definition of life is very close to the vitalist definition, to the idea of a special “life-force” or “spiritum vitae” permeating and animating all living bodies. The vitalist tradition dominated Western scholarship until late Renaissance,21 as it was compatible with the spiritual doctrines of the Church. It might be, at least partly, because of this affinity to the prevailing vitalism that Aristotle’s physiological teachings survived so long as a part of the European university curricula. It might be also this affiliation with vitalism that finally contributed to the demise of Aristotle’s authority, when mechanistic and atomistic worldviews resurfaced in the works of Rene Descartes (1596-1650), Pierre Gassendi (1592-1655), Robert Boyle (1627-1692) and other “mechanists.”22
In describing the properties of life, Aristotle uses a distinct set of terms which are in many respects synonymous. Life is associated with the soul, as the soul is the “source of movement [the generative cause], it is the end [the teleological cause], it is the essence [ontological nature] of the whole living body.”23 Life is also associated with the form (eidos) to distinguish it from the formless matter (hyle). Life is a state of actualization or activation of matter, or the transition from a state of potentiality (dynamis) to a state of actuality (entelechia or energia).24 The latter two terms for the activated/animated state of matter are of special interest. The term entelechia later became synonymous with the notion of the “vital force” (the principal concept of vitalism),25 whereas the term “energia” has been used to the present day to describe an activated state of matter, or the ability to perform work by a system.26 Other key terms are the symphyton pneuma - σύμφυτον πνeυμα (the connatural, innate or inherent spirit) and the symphyton thermon - σύμφυτον θερμόν (the connatural, innate or inherent heat). According to Aristotle, the “connatural heat” is a primary essential attribute of any living body, and it is the alterations of connatural heat that are responsible for all processes of life.27
There appears a striking similarity between Aristotle’s terms of “form” (structure), “activation,” “energy” and “heat,” and the terms used in modern thermodynamics. A similarity can be observed between Aristotelian ‘vitalism’ and thermodynamics in that both emphasize the general state, faculty, property or activation degree of matter, rather than the mechanical and spatial interrelation of its components.  In Aristotle’s On Youth and Old Age, Life and Death, and Respiration, the distinction between the proto-thermodynamic and proto-mechanistic views becomes clear. In this treatise, Aristotle states that respiration is a necessary essential condition for maintaining human life and provides a qualitative explanation for this process. In doing so, Aristotle again cites previous theories. Sometimes, the insight of the preceding philosophers is uncanny. Thus Empedocles describes the respiratory system as a pneumatic device (analogous to the clepsydra, similar in operation to the modern pipette) based on pressure differences.28 Democritus claimed that respiration is due to the relative weights and impetus of elements, describing a process very similar to what we would now term “particle convection” or “diffusion.”29 Moreover Anaxagoras and Diogenes posited that fishes breathe the air dissolved in water – again strikingly similar to modern accounts.30 Aristotle, as usual, wrestles these theories to the ground, and shows by formidable rational arguments that ‘particle convection’ is impossible and that fishes couldn’t possibly breathe.31
However, the physical insights provided by Aristotle himself are no less outstanding. Perhaps the most critical is the equation he makes between the processes of life-maintenance and processes of combustion and heat equilibrium – the association that forms the basis of modern bioenergetics and the thermodynamic theory of metabolism. According to Aristotle, life can only continue for as long as the living body contains a necessary amount of “connatural heat” (now we might term it intrinsic energy), for as long as “life’s fire” is maintained.32 The amount of heat tends to dwindle either by “extinction” or “exhaustion.”33 “Extinction” occurs because of a damping, neutralizing influence of external antagonistic (“opposite”) agents, or because of the  wastes/residues produced during the combustion process that are antagonistic/opposite to the continuation of the burning process.34 “Exhaustion,” on the other hand, takes place because of internal processes, namely because of the depletion of the nutrients that sustain the combustion.35 According to Aristotle, in order to conserve the vital heat and thus prolong life’s existence, the living system needs “cooling” or “refrigeration,” otherwise the vital heat will quickly use up all its nutrient, and the living body will “burn out” and cease living.36 Respiration, accordingly, is a means for such a cooling in terrestrial sanguineous animals (the air is said to “cool” the vital heat), whereas in aquatic animals (such as fishes) cooling is performed by the surrounding water.37
It is now firmly established that “cooling” is a necessary process for the operation of any thermodynamic system or machine. The importance of “refrigeration” is shown in the formula for the thermal efficiency of a heat engine: N=(Q1-Q2)/Q1, where Q1 is the heat input and Q2 is the heat output.38 This formula in fact describes the changes in the heat content and the “cooling” that take place during thermodynamic operation of either a living or inanimate system. It has also become firmly established that “combustion” is the most fundamental and essential process of metabolism. The combustion (or oxidation) of glucose has been shown to provide the energy needed to sustain life. The process is described by the equation: C6H1206+6O2 → 6H20+6CO2 +E(energy).39 In this process, the energy/heat is released that drives all body functions. Yet, the energy content of the carbohydrate (“the nutrient” in Aristotle’s terms) is reduced by the interaction with oxygen (the electron acceptor/or oxidizing agent) supplied from the air by respiration. To describe the process in Aristotle’s tropes: the “air” (oxygen) “cools” the “vital heat” inherent in the “nutrient” and aids in maintaining the “combustion” process or “life’s fire.” Thus, by simple observations and sheer power of imagination, namely by associating life with combustion, Aristotle may have foreshadowed the basic thermodynamic principles of biology.

Aristotle on aging and longevity

In Aristotle’s works, the “proto-thermodynamic” principles are used to account for aging and dying. These principles bear a direct relation to the question of the possibility (or impossibility) of life extension, as well as practical suggestions for its achievement. The treatise On Length and Shortness of Life provides a most concise, yet comprehensive discussion of the physiology of aging. Aristotle carefully investigates the possible causes of longevity and mortality. He compares the life spans of various species of animals, various individuals or sexes of the same species, various life styles, and environmental conditions or animal habitats, and attempts to find a correlation between the various species, life styles or habitats and longevity. His method in doing so is not much different from that of modern comparative gerontology.40 Specifically, he examines the size of animals, whether they are ‘bloodless’ or warm-blooded (‘sanguineous’), whether they reside in a terrestrial or aquatic environment, warm or cold climate, whether they copulate frequently, or whether their life is leisurely or strenuous. He also points out to the difficulty in such a categorization, as exceptions can be found that may contradict the general theory.41 Nevertheless, Aristotle does come up with a set of generalizations concerning the qualities, life style and environment that may be conductive to longevity.
According to Aristotle, terrestrial animals are generally longer lived than aquatic, sanguineous animals live longer than bloodless ones, larger animals live longer than smaller, and animals occupying warm habitats live longer than those who live in a cold climate.42 From these observations, Aristotle proceeds to generalize about the animals’ material and thermal constitution that may favor longevity. Briefly, long lived animals are said to be of a larger size, and have a greater degree of “humidity” and “warmth” in them. Short-lived species or aging animals, on the other hand, are characterized by “dryness” and “coldness.”43 Aristotle’s conclusions sometimes coalesce with and sometimes contradict later findings. And yet, the fields of observation and comparative analysis outlined by Aristotle (viz. the species, life style and habitat) and the theoretical discussions of the  material and thermal basis of animal longevity, have become central themes for a great deal of subsequent gerontological research.
Since Aristotle, the concept of “dryness” has undergone many contextual transformations, and yet the basic proposition that “dryness” (i.e. a deficit of fluid or rigidity) is detrimental to health and longevity, has remained scientifically valid. It has been firmly established that “dryness” in the simple sense of a fluid deficit or desiccation, is incompatible with life – water being the essential solvent necessary for most of the biochemical and bio-energetic processes occurring in the body, and for maintaining its homeostasis (in terms of osmosis and pressure maintenance, substance transport, electric potential, pH balance, etc.).44 In line with Aristotle’s suggestions, restoring the fluid content or fluid balance have become established life-saving therapies.45 According to Aristotle, the body “humidity” must not be “easily dried up,” and “viscous” or “oily” fluids are “not easily dried up.”46 By this theory he accounts for the greater longevity of plants (having more viscous/oily fluids) and the lesser longevity of aquatic animals (with less viscous body fluids). The importance of viscosity in fluid homeostasis has been later confirmed.47 “Dryness” in a broader sense of body “rigidity” or “hardening” has proven to be an even more influential and productive concept in subsequent biomedical research. Tissue sclerosis (or tissue hardening) has become recognized as a major factor in aging and a major cause of death (especially arteriosclerosis).48 Many other pathological processes have been associated with rigidity, such as muscle spasms due to calcium or ATP deficit, and its extreme form, the “rigor mortis” – or complete muscle rigidity upon death.49 The increased tissue rigidity (or loss of elasticity) has become one of the most popular explanations of aging. Specifically, the cross-linking theory of aging accounts for the loss of protein elasticity by glycosylation cross links between proteins.50 At a more fundamental thermodynamic or information-theoretical level, rigidity may be associated with a lower entropy (or rigid order) of a subsystem or organ, and the subsystem’s lower entropy can be in turn associated with pathology, as in the case of Parkinson’s disease and other diseases associated with enhanced regularity.51 Thus again, Aristotle’s common sense, the fairly straightforward association between aging and “dryness,” anticipated much of future research.
Aristotle’s discussion of the thermal properties of life, the association of life with “fire,” “warmth” or “connatural heat” proved to be even more seminal. As mentioned above, Aristotle believed that long lived animals are characterized by a greater degree of “intrinsic heat” and consequently, in order to prolong life’s existence, the body “heat” must be conserved. According to Aristotle, the heat conservation can be achieved by countering the processes of “exhaustion” and “extinction” by “cooling” (so the internal “heat” will not be expended too quickly). The concept of body “connatural heat” can be recognized in the later concepts of body energy or metabolic rates. Among other current detection methods, Metabolic Rates (MR) have been measured simply by temperature changes or by the amount of heat emitted by the body.52
Recently, there has been a fundamental controversy on the correlation between the metabolic rates and longevity. The dominant “Rate of living” school posited that increased metabolic rates (manifested by an increased heat production) are detrimental for longevity, whereas a lower energy expenditure can extend the life span.53 Excessive metabolic rates, contingent on excessive stimulation, were shown to be ‘exhaustive,’ to increase body ‘wear and tear’ and ‘burn it out’ (these are almost precisely Aristotelian terms), leading to an excess of toxic waste products (especially reactive free radicals). On the other hand, it has been suggested that life would be impossible without active exercise, and conditions characterized by slow metabolism, such as obesity and hypothyroidism, are dangerous and often fatal, and therefore increased metabolic rates favor healthy longevity.54 Moreover, the “Uncouple to survive” school professed that higher metabolic rates (accompanied by a higher heat generation) are crucial for survival (which may explain the advantage of warm-blooded animals), and therefore the process of oxidative phosphorylation must be uncoupled (e.g. by tyrosine, or other means)55 in order to achieve greater metabolic rates and heat production. 56 Both these options are covered by Aristotle’s reasoning. Indeed, Aristotle argues, the higher degree of “connatural heat” is essential for health and longevity, because the larger amount of heat means a higher degree of life’s actualization. And yet, the internal heat needs “cooling,” needs “inhibition,” in order to enable nutrient replenishment and heat recovery for further actualizations. In view of this, Aristotle may be considered the father of the homeostatic “balanced” approach to life extension. In particular, Aristotle’s general emphasis on the need to “conserve” the “connatural heat” to achieve longevity, implied the need for moderation in life style, diet in particular – an idea with far-reaching ramifications for aging research, ranging from various attempted life-prolonging “moderate” diets to the experiments on life extension by calorie restriction57 (literally, “heat restriction” as “Calor” is Latin for “heat”).
Aristotle’s provides extensive empirical evidence for his main theoretical claim that the degree of internal heat determines longevity. Notably, he reports that small size, cold climate, strenuous life style, and excessive copulation are all detrimental to longevity, since these conditions contribute to diminishing the internal heat by “exhaustion.”58 These phenomenological observations were based on the most extensive available research of Aristotle’s time, and they have been a subject of scientific debate to the present day, in the framework of the “Rate of living” vs. “Exercise to survive” controversy.59 Aristotle’s conclusion that larger animals possess greater life spans (in order to contain a greater amount of fluid and heat) has been recently corroborated.60 The observation that inhabitants of warmer terrains are longer-lived, might have been especially true at the time of Aristotle, as the warm Mediterranean area served as a cradle of civilization, whereas in colder climates the chances for survival were slimmer.  And yet, there have been found abundant examples to the contrary. Thus, the renowned German hygienist Christoph Wilhelm Hufeland, in Macrobiotics or the Art of Prolonging Human Life (1796), suggested that colder climates are more favorable for health and longevity.61 Also statistical evidence indicated that residents of the colder Scandinavian countries and certain mountainous areas (e.g. the Caucasus, the Alps, and the Himalayas) enjoy relatively good longevity.62 Despite the continuous controversies and conflicting data, the very consideration of those factors as potential determinants of longevity is a pioneering contribution of Aristotle.
 The claim that a strenuous life style or hard labor shorten the human life span, has also been actively debated. Certain studies showed that people leading a leisurely life style or people of sedentary professions live longer (possibly due to a reduced stress and lower energy expenditure).63 On the other side, advocates of active exercise provided extensive evidence for the benefits of physical labor and exercise for life prolongation.64 Sweeping generalizations still appear to be impossible. At the same time, the exact indications for the beneficial or adverse effects of specific rest and activity regimens for specific people or groups of people (the subject of the so-called “precision medicine”) still appear to be uncertain. In any case, recognition is due to Aristotle as one of the initiators of this debate.  
 The debate concerning the life-prolonging effects of sexual moderation proceeded along similar lines. According to Aristotle, men who don’t copulate frequently have a greater longevity (because they don’t expend the vital heat and moisture inherent in the semen). Women, according to Aristotle, have a lesser degree of “vital heat” than men and therefore live less, provided men don’t copulate frequently. If men do waste their semen, then women outlive the men. In the same line of argument, the sterile mules are said to live longer than their fertile sexual parents (the horse and the donkey).65 Agreeing with Aristotle, the idea of life extension through sexual moderation (in other words, by conserving sexual energy) has been a cornerstone of medical science for centuries.  For example, one of the ancient techniques of “Gerocomia” (from the Greek – “treatment of old age”) was the proximity to young healthy individuals, or sexual stimulation without discharge, which was prescribed by Galen and practiced by King David (1 Kings 1:2); this method retained its popularity well into modernity.66  In the eighteenth and nineteenth centuries, much ink was spilled on the dangers of masturbation.67 In recent times, several studies evaluated the costs of reproduction and enhanced copulation for longevity in animals.68 Such costs were indicated for humans as well.69 However, in the past decades, these views have been increasingly challenged by studies professing that sexual activity is “good for health and longevity,” that life span can be positively correlated to sexual activity.70 Nonetheless, the exact thresholds, personal indications and tradeoffs for the benefits vs. drawbacks of increased or decreased sexual activity, for men vs. women, still remain undetermined.
The outcomes of Aristotle’s comparison between the life spans of men and women have also remained disputable, as it has been found that women indeed generally have lower metabolic rates, but commonly live longer than men.71 Still, there can be found numerous contrary showcases, and different population studies often arrive at different gender-longevity correlations.72 In any case, Aristotle’s bringing into consideration the relation between gender (sex) and longevity, or more precisely the consideration of the physiological differences of men and women in relation to their longevity, has become indispensable in gerontological research.
As it can be seen, despite numerous discrepancies and controversies, despite the large number of unaccounted thresholds and factors – the Aristotelian proto-thermodynamic account of aging, the ideas of “vital heat” and its “conservation” and “replenishment” haven’t lost their appeal, and may be still considered as a part or origin of the ongoing physiological discourse. Sometimes Aristotle’s specific deductions on the ways of “heat replenishment” may seem prophetically inspired, given the contemporary state of empirical observations. Thus, according to Aristotle, “viscous” or “oily” bodily fluids “are not easily dried up” and contribute to heat preservation.73 It has become established much later that fat may indeed act as an insulator (and thus prevent heat dissipation), that viscous substances are less easily evaporated (due to adhesion), and that fatty substances have the highest content of energy and are used by the body as long-term nutrient reservoirs.74 
Even more prophetic was Aristotle’s idea that, during the processes of combustion in a living body, “wastes” or “residues” are produced that are antagonistic (“opposite”) to the very process of combustion that generated them, and thus act to “extinguish” the body internal heat.75 This general account closely describes the process of allosteric inhibition or negative biochemical feedback, where the products of a chemical reaction act as inhibitors to the reaction that produced them.76 This formulation generally describes the production and accumulation of toxic metabolites in a living body. It is particularly relevant to the Free Radical theory of aging. In this theory, during the oxidation process in the mitochondria, nutrients are oxidized by oxygen (undergo combustion), with a concomitant production of reactive oxygen species. The reactive oxygen species, in turn, may damage the mitochondria and thus stall the very process of combustion that generated them, thereby contributing to cell damage, energy deficit and aging.77
 Interesting proto-thermodynamic and proto-homeostatic insights can be found in Aristotle’s treatise On Sleep. According to Aristotle’s definition, sleep is a state of sensory deprivation and a form of “cooling” needed for the conservation and replenishment of vital heat, and therefore essential for life preservation.78 In Aristotle’s description of the mechanism of the “sleep-wakefulness” cycle, an excess of heat in the body triggers its “compression” or “condensation” into the “vital center” until the “nutrient” nourishing the combustion process is replenished, thus leading to a new heat “expansion” throughout the body.79 In modern terms, this sequence describes a negative feedback process, relevant for both living systems and thermodynamic machines in general.80 Modern studies of sleep and rest speak of “refractory periods,” “potential recovery,” “energy carriers replenishment,” etc.81 But the principle of negative biofeedback is the same, and the analogy of these processes to those described by Aristotle is apparent. The very critical role of sleep for life preservation generally, and its particular role for the amelioration of degenerative aging processes, has remained a fruitful field of study.82
According to Aristotle, “symphyton pneuma” (or innate spirit) animates the body and serves as the carrier of vital heat. Its movements and alterations in the body – such as expansion, condensation, flow, and changes in heat content – are responsible for body operations. In this regard, the “pneuma” is very similar to steam in a stem engine.83 Presently, the transmission and transformation of vital energy and substance is discussed in terms of blood flow, diffusion, active transport, electro-mechano-chemical coupling, etc.84 – but these modern descriptions seem to involve the same basic intuitions of energy flow and its homeostatic regulation.
According to Aristotle, the heart serves as the center and major “seat” of vital heat. Into that center the heat is condensed during sleep, and it is responsible for the expansion and distribution of heat throughout the body.85 Indeed, also in modern views, the heart is seen as a vital organ, a motor of life, a most metabolically active center, which never ceases activity throughout life, a ‘pump’ supplying the “vital energy” and “vital substance” to the body. Heart’s proper operation is most essential for life maintenance, and heart diseases are primary, widest-spread causes of death.86 Aristotle did not speak of heart action in terms of “circulation,” but rather in terms of “pulsation” and “palpitation.”87 However, the modern recognition of the primary function of the heart in life support, coalesced with Aristotle’s assertions of the central role of the heart as the “seat of the vital principle.”
In Aristotle, the heart has a supreme place in the hierarchy of animal life. It is the central locus and the highest form of life’s actualization. However, according to Aristotle (On the Length and Shortness of Life), in other life forms, such as plants and certain insects, vitality is more uniformly distributed throughout the body and has a higher extent of potentiality. Therefore, if insects are cut to pieces, life continues in these parts for some time (not for long though, as vital organs are missing), and if plants are cut to pieces, each piece can produce a plant identical to the parent.88 These observations may represent rudiments of another vast biological field: namely the study of regeneration, differentiation, asexual reproduction, and even genetics. The idea that certain organs reach a highest irreversible degree of actualization may correspond to the modern concept of differentiation (also a kind of ultimate and usually irreversible degree of development).89 On the other hand, the observation of the ability of plant parts to regenerate the entire plant body (due to a greater degree of potentiality inherent in them) foreshadowed the concept of toti-potency (a key notion in modern research of vegetative reproduction and regeneration, as well as in embryological and stem cell research).90 Moreover, Aristotle scholars noted the apparent similarity of the concept of a vital form (eidos) to genes: both confer structure to a living organism.91 Indeed, concerning gene expression, Aristotle’s terms are very relevant: potentiality corresponds to gene dormancy, while actuality corresponds to gene activation and expression.
This reasoning can be taken a step further. In De Anima, Aristotle claims that even though no body can be preserved in a constant state, it “strives” to preserve itself as something “similar” to its present state.92 This seems to be precisely the function of genes: acting to replicate themselves and the original organism, but never able to produce a precise “replica.” In On the Length and Shortness of Life, these observations are used to account for a generally greater longevity of plants as compared to animals (even though Aristotle recognizes a great number of exceptions from this general rule). According to Aristotle, the vital moisture in plants is not “easily dried up” (due to its greater viscosity), and plants’ “vital heat” is not easily dissipated (due to a lesser nutrient expenditure).93 Another part of the explanation is the above-mentioned uniform distribution of vital heat and a greater degree of potentiality in plants that enable their constant regeneration.94 Combining the proto-thermodynamic and proto-genetic terms, a contemporary-sounding paraphrase of Aristotle’s theory can be obtained: Plants may generally have a greater longevity because their body constitution contains a sufficient amount of potential energy which is uniformly distributed and economically expended, enabling the continuous structure maintenance, self-organization and replication.
In this regard, a seeming contradiction must be noted in Aristotle’s account of life and longevity. It is Aristotle’s strong assertion that the soul or the vital principle is the same in every part of a living organism.95 Yet, the amount of “vital heat” whereby the soul operates in the body or degrees of life “actualization” in various organs or faculties are not homogeneously distributed throughout the body, and in some organisms are more uniform than in others. This apparent contradiction can be reconciled using the modern gene metaphor: a complete set of genes is present in each and every somatic cell of the body, yet their expression varies in different organs and tissues. It can be also reconciled using the thermodynamic metaphor: each body has a single energy function and structural unity. However, the operators of this function and structural components may differ. Whatever the interpretation, Aristotle’s reasoning about the observable properties of living beings is insightful, with both profound theoretical and practical implications.

Aristotle on the possibility of radical life extension and immortality

Among the chief practical implications of Aristotle’s physiological theory is the question of the feasibility of increasing longevity and its limits. In particular, in considering animal longevity, Aristotle raises the crucial question of the possibility of a radical life extension or even immortality. This question has remained a major bone of contention in modern biomedical gerontology.96 Even though Aristotle carefully investigates the causes of longevity and mortality, in order to select environmental and physiological factors that may increase human life span (such as gentle climate, economical heat expenditure, or diet rich in “heat and moisture”) – eventually Aristotle states the impossibility of a significant, not to mention infinite, life extension. Aristotle believes that any physical entity is composed of opposite and conflicting elements. According to Aristotle, any such entity must be in a constant process of change, and therefore cannot be preserved “as is” for a long time. Thus, a living organism is fated for ultimate destruction, for it contains in itself antagonistic forces and elements that mutually annihilate each other, and thus destroy the entire body.97 Moreover, the “vital heat” cannot be preserved indefinitely as it is continuously diminished by “extinction” and “exhaustion.”
These views of the ultimate destructibility of any living body (in other words, the impossibility of its preservation beyond a predetermined limit), have continued through centuries. Among many instances, they resonated in the writings of Avicenna (who also stated an inevitable self-destruction of the body due to opposition of its components)98 and even in recent bio-gerontological views positing an inherent genetically predetermined limit to the life span due to self-destruct programs and processes which, as believed, cannot be overcome by any means (e.g. Hayflick’s school).99 There has been a controversy among Aristotle scholars as to the exact meaning of Aristotle’s term “opposite elements”: some understood it in a more literary sense of opposite kinds of matter or opposite kinds of atoms (e.g. fire vs. water, or earth vs. air); others perceived it as a more general opposition of qualities, forces or states (hot vs. cold, active vs. non-active, etc).100 In modern thermodynamics, the opposition of elements forms the basis for the concept of entropy (or degree of chaos). Systems with a low entropy (a greater degree of orderliness) are composed of elements with a distinct relation or juxtaposition to each other: the more distinct is the opposition of the elements or the less the number of their distinct states – the greater is the system’s orderliness. On the other hand, when the amount of particles’ states increases, or when their opposition or mutual relation becomes less distinct – such a system is more chaotic, with a higher degree of entropy.101 According to the second law of thermodynamics, in any closed system, the entropy increases, and the system tends to reach a state of “heat equilibrium” or “heat death” where there is no distinct opposition between elements and all the elements are distributed chaotically. Thus Aristotle’s ‘pessimistic’ precepts of the inevitable death due to heat dissipation and inevitable reduction in “opposition of elements” may have directly anticipated the thermodynamic concept of an inexorable “heat death” of any closed system.
 Despite the assertion of the inevitability of death, Aristotle’s views on life extension and immortality contain an element of hope. Even under the ultimate verdict of destruction, by conserving and renewing vital heat, life could be extended. Moreover, in Aristotle’s vitalism, there is an indication for the possibility of immortality of the soul or of the “vital principle” which is not subject to the transformation and destruction of the physical body. Aristotle seems to present a border case (also chronologically) between Plato’s idealism devaluing this-worldly existence and projecting the hope of immortality to the ideal world of forms102 and Epicurus’ ‘thick’ materialism resigning to the utter physical and mental annihilation upon death.103 Aristotle’s position may be termed ‘thin’ materialism. As it is seen in De Anima, most faculties of the soul are inseparable from the body, and disappear upon physical death. The “active mind,” however, or the “thought that thinks itself” is given a privileged status, and is said to be divine, “immortal and eternal.”104 However, the relation of the “active mind” to the rest of perceptive and intellectual faculties is obscure, and it is hard to imagine its separate existence, since its ideations are based on previous sensory experiences. The soul in Aristotle is not the ideal Platonic soul. It is associated with or operates through a kind of matter, though an infinitely thin (the “least corporeal”) matter. This “least corporeal” energized matter is symphyton pneuma (σύμφυτον πνeυμα) – the “innate spirit” – analogous to ether, the fifth element, which is not subject to a conflict of elements, and is therefore indestructible. It is the same substance the eternal Sun and higher spheres are made of (cf. Aristotle’s On the Heavens,105 Physics,106 and On the Soul107,108). However, as in the case of the “active mind,” the hardly destructible “pneuma” does not constitute the entirety of human being. Aristotle’s concept of the “pneuma” is complex, with many possible interpretations.109 In one sense, as discussed above, the pneuma serves as the carrier of “vital heat” (and is in many respects similar to steam in a steam engine). However, as previously mentioned, the heat content in the body is subject to change and exhaustion, therefore the constancy and indestructibility of the pneuma becomes questionable. Thus, Aristotle gives us a hope for immortality, but not too much hope. 
 Aristotle was, first and foremost, a great biologist who cherished life in all its forms. This field of Aristotle’s study may have come to be underappreciated by modern scholars. Yet Aristotle’s physiological corpus may not warrant oblivion. Far from being irrelevant to modern biomedical research, Aristotle’s insightful and imaginative writings provide amazing anticipations of modern physiology, bioenergetics and gerontology. In the historicist school, any attempt to seek modern concepts in ancient texts is branded as “anachronism” and considered almost a mortal sin. Yet, there seems to be nothing wrong in trying to search for origins of modern concepts, or for similarity of concepts through history, in trying to understand the voices of great thinkers coming from the past, and not just disregard them as “untrue” or “anachronistic” or “contextually irrelevant.” Aristotle is very inclusive. He may be considered an early anti-longevitist, stating the ultimate futility of attempts to achieve a radical life prolongation. And yet, despite the sense of doom, in many respects he is close to life-extensionism, studying causes of mortality and seeking practical ways for forestalling death. This subject matter can hardly ever become historically irrelevant.110

References and notes

1. Thus, for example, the 400 page long Cambridge Companion to Aristotle (Edited by Jonathan Barnes, Cambridge University Press, 1995), includes only about 10 pages related to Aristotle’s biology.
A basic JSTOR search ( shows that out of tens of thousands of articles mentioning Aristotle, perhaps a few hundreds make any connection between Aristotle and physiology, still less discuss the relevance of Aristotle’s theories to modern findings. No articles on the relation of Aristotle’s teachings to modern bio-gerontology were to be found.
2. Marjorie Grene, “Aristotle and Modern Biology,” Journal of the History of Ideas, 33(3), 395-424, 1972.
According to Grene, Aristotle’s methodology is largely irrelevant to modern research. She perceives some continuity for Aristotle’s fundamental ontological concepts of “telos,” “eidos” and the “being what it is,” but not for the actual physiological processes that Aristotle describes.
3. Walter Stanley Hett, “Introduction to Aristotle’s On the Soul,” in: Aristotle in Twenty-Three Volumes, William Heinemann Ltd., London, 1975, Vol. VIII, p. vii.
4. Edward Grant, “Aristotelianism and the Longevity of the Medieval World View,” History of Science, 16, 93-106, 1978.
5. Aristotle, On the Soul (translated with notes by Walter Stanley Hett), in: Aristotle in Twenty-Three Volumes, William Heinemann Ltd., London, 1975 (hereafter referred to as “On the Soul”, unless a different translation is specified), Book 2, Part 4, 415b9-12, p. 87.
6. On the Soul, Book 2, Part 4.
7. “Vitalism” seemed to be a very “viable” theory at the beginning of the 20th century, as can be seen from the following works:
Hans Driesch, The History and Theory of Vitalism, J.A.Barth, Leipzig, 1905,;
Walter T. Marvin, “Mechanism Versus Vitalism As a Philosophical Issue,” The Philosophical Review, 27(6), 616-627, 1918;
Herbert Spencer Jennings, “Mechanism and Vitalism,” The Philosophical Review, 27(6), 577-596, 1918.
Later, the scholarly prestige of “vitalism” appears to have been drastically decreased. However, “vitalism” continued to be referred to in the biological discourse. Of special interest is the adoption of vitalism in aging theory by the German gerontologist Max Bürger (1885-1966). See: Max Bürger, Altern und Krankheit (Aging and Disease), Zweite Auflage (2nd Edition), Veb Georg Thieme, Leipzig, 1954 (first published in 1947), “Das Altern im Lichte der vitalistischen Autonomielehre” (Aging in the light of the theory of vitalistic autonomy), pp. 39-41.
Aristotle’s affinity with vitalism has been frequently asserted, for example in such works as:
Ernst Mayr, The Growth of Biological Though, Harvard University Press, Cambridge MA, 1982, p. 52;
Richard J. Cameron, Teleology and Contemporary Philosophy of Biology: An Account of the Nature of Life, University of Colorado, 2000, pp. 33-40.
8. On the Soul, 1.2. 405b 12-31, pp. 29-30; 1.5. 409b19- 410a3, p. 55.
9. Ibid. 1.2. 405a6-14, p. 27.
10. Ibid. 1.4. 407b28-32, p. 43; 408a10-28, pp. 45-46.
11. Ibid. 1.4. 407b28, p. 43.
12. Ibid. 1.4. 408a24, p. 45.
13. Sigmund Freud, Beyond the Pleasure Principle (Translated by James Strachey), Liveright, New York, 1976, p. 38.
14. Erwin Schrödinger, What is Life? Cambridge University Press, Cambridge, 1996, p. 67.
15. Len Fisher, Weighing the soul: the evolution of scientific beliefs, Weidenfeld & Nicolson, London, 2004.
16. On the Soul, 1.5. 410a7-14, p. 57.
17. Ibid. 3.2. 425b27-426a2, p. 147.
18. Ibid . 1.5. 409a32-409b4, p. 53.
19. Ibid. 1.4. 407b33-408a9, pp. 43-44.
20. Ibid. 1.5. 411b16-31, p. 65.
21. “Vitalism,” Wikipedia, 2017,;
Hans Driesch, The History and Theory of Vitalism, J.A.Barth, Leipzig, 1905,;
Philip G. Fothergill (Ed.), Mechanism and Vitalism: Philosophical Aspects of Biology, University of Notre Dame Press, Notre Dame Ind., 1962.
22. “Atomism,” Wikipedia, 2017,;
Robert Hugh Kargon, Atomism in England from Hariot to Newton, Clarendon Press, Oxford, 1966;
Joshua C. Gregory, A Short History of Atomism: from Democritus to Bohr, A. & C. Black Ltd., London, 1931.
23. Aristotle, On the Soul (Translated by John Alexander Smith), in: The Complete Works of Aristotle: The Revised Oxford Translation (Edited by Jonathan Barnes), Princeton University Press, Princeton, 1984, Part 2, Ch. 4, 415b9-12, p. 661.
(Smith’s translation of this passage seemed more comprehensive than that of Hett: “The soul is the cause and first principle of the living body.” Except for this single instance, Hett’s translation of On the Soul is referred to throughout this paper.)
24. Walter Stanley Hett, “Introduction to Aristotle’s On the Soul,” in: Aristotle in Twenty-Three Volumes, William Heinemann Ltd., London, 1975, Vol. VIII, pp. xi-xii.
25. See notes 7, 21 and 22.
26. “Thermodynamics,” in: Oxford Dictionary of Science, Oxford University Press, 1999, pp. 784-785.
27. Aristotle, On Youth, Old Age, Life and Death, and Respiration (Translated by George Robert Thomson Ross), in: The Complete Works of Aristotle: The Revised Oxford Translation (Edited by Jonathan Barnes), Princeton University Press, Princeton, 1984, Vol. 1, 14(8). 474a25-27, p. 754 (hereafter referred to as On Youth and Old Age).
28. On Youth and Old Age, 13(7). 473a28-473b8, p. 753.
29. Ibid. 10(4). 471b30-472a17, p. 751.
30. Ibid.  8(2). 470b27-471a5, p. 749-750.
31. Ibid. 13(7). 474a7-23, p. 754; 8(2). 471a6-19, p. 750.
32. Ibid. 14(8). 474a25-27, p. 754.
33. Ibid. 5. 469b21-470a4, p. 748.
34. Ibid. 5. 469b21-470a4, p. 748; 26(20). 479b19-20, p. 761.
35. Ibid. 5. 469b21-470a4, p. 748; 24(18). 479b1-5, p. 761.
36. Ibid. 5. 470a517, p. 748.
37. Ibid. 6. 470a20-470b5, p. 749.
38. “Carnot cycle,” in: Oxford Dictionary of Science, Oxford University Press, 1999, p. 130.
39. Max Fogiel (Ed.), The Biology Problem Solver. A Complete Solution Guide to Any Textbook, Research and Education Association, Piscataway, New Jersey, US, 1990 (republished in 2001), 3.35, p. 117 (hereafter referred to as “Fogiel, The Biology Problem Solver”).
It must be noted that here the references to this rather well known and well disseminated textbook/problem solver, including about 800 topics “for undergraduate and graduate studies,” relating to all areas of biology and physiology, are intended to show the relation and succession with the current commonly taught views (compared to original research that may be considered more partial and potentially controversial, which is nonetheless also quoted). References to other text books, scientific reference books and dictionaries are made with the same purpose in mind to show relevance to the contemporary common knowledge.
40. On the comparative gerontology approach, seeking the differential determinants of aging and longevity, see for example:
Steven N. Austad, Kathleen E. Fischer, "Mammalian aging, metabolism, and ecology: evidence from the bats and marsupials," Journal of Gerontology: Biological Sciences, 46(2), B47-53, 1991;
Steven N. Austad, "Comparative aging and life histories in mammals," Experimental Gerontology, 32(1-2), 23-38, 1997;
Virpi Lummaa, “Early developmental conditions and reproductive success in humans: Downstream effects of prenatal famine, birthweight, and timing of birth,” American Journal of Human Biology, 15(3), 370-379, 2003;
S. Jay Olshansky, Toni Antonucci, Lisa Berkman, Robert H. Binstock, Axel Boersch-Supan, John T. Cacioppo, Bruce A. Carnes, Laura L. Carstensen, Linda P. Fried, Dana P. Goldman, James Jackson, Martin Kohli, John Rother, Yuhui Zheng, John Rowe, “Differences in life expectancy due to race and educational differences are widening, and many may not catch up,” Health Affairs, 31(8), 1803-1813, 2012.
41. Aristotle, On Length and Shortness of Life (Translated by G.R.T. Ross), in: The Complete Works of Aristotle: The Revised Oxford Translation (Edited by Jonathan Barnes), Princeton University Press, Princeton, 1984, Vol. 1 (hereafter referred to as On Length and Shortness of Life), Section 1, 464b20-465a11, p. 740.
42. On Length and Shortness of Life, 4. 466a9-16, p. 742.
43. Ibid. 5. 466a17-31, p. 742.
44. Elie Metchnikoff, Etudes On the Nature of Man (in Russian), The USSR Academy of Sciences Press, Moscow, 1961 (first published in 1903), p. 193 (hereafter referred to as “Metchnikoff, On the Nature of Man”);
Fogiel, The Biology Problem Solver, 1.15, p. 17;
“Water,” Oxford Dictionary of Science, Oxford University Press, 1999, pp. 833-834.
45. Michael N. Sawka, Samuel N. Cheuvront, Robert Carter 3rd, “Human water needs,” Nutrition Reviews, 63(6 Pt 2), S30-S39, 2005;
Michelle P.B. Guppy, Sharon M. Mickan, Chris B. Del Mar, Sarah Thorning, Alexander Rack, “Advising patients to increase fluid intake for treating acute respiratory infections,” Cochrane Database of Systematic Reviews, 2011(2), CD004419, 2011;
Bell T.N., “Diabetes insipidus,” Critical Care Nursing Clinics of North America, 6(4), 675-685, 1994;
Friedrich Manz, Andreas Wentz, “The importance of good hydration for the prevention of chronic diseases,” Nutrition Reviews, 63(6 Pt 2), S2-S5, 2005.
46. On Length and Shortness of Life, 4. 466a17-24, p.742; 6. 467a6-9, p. 743.
47. H.T. Hammel, Whitney M. Schlegel, “Osmosis and solute-solvent drag: fluid transport and fluid exchange in animals and plants,” Cell Biochemistry and Biophysics, 42(3), 277-345, 2005.
48. Metchnikoff, On the Nature of Man, p. 193;
Julie C. Wang, Martin Bennett, "Aging and Atherosclerosis: Mechanisms, Functional Consequences, and Potential Therapeutics for Cellular Senescence," Circulation Research, 111, 245-259, 2012.
49. Burkhard Madea, "Methods for determining time of death," Forensic Science, Medicine, and Pathology, 12 (4), 451-485, 2016;
Fogiel, The Biology Problem Solver, 19.6, pp. 579-581; 14.6, pp. 424-425.
50. Johan Bjorksten, “The Crosslinkage Theory of Aging,” Journal of the American Geriatrics Society, 16(4), 408-427, 1968;
Norman C. Avery, A.J. Bailey, “Enzymic and non-enzymic cross-linking mechanisms in relation to turnover of collagen: relevance to aging and exercise,” Scandinavian Journal of Medicine and Science in Sports, 15(4), 231-40, 2005;
SENS Research Foundation, “A Reimagined Research Strategy for Aging. GlycoSENS: Breaking extracellular crosslinks,” accessed March 2017,;
Richard D. Semba, Emily J. Nicklett, Luigi Ferrucci, “Does Accumulation of Advanced Glycation End Products Contribute to the Aging Phenotype?” The Journal of Gerontology: Series A Biological Sciences Medical Sciences, 65A(9), 963-975, 2010.
51. Lewis A. Lipsitz, Ary L. Goldberger, “Loss of ’complexity’ and aging: potential applications of fractals and chaos theory to senescence,” Journal of the American Medical Association, 267, 1806-1809, 1992;
Molly M. Sturman, David E. Vaillancourt, Daniel M. Corcos, “Effects of aging on the regularity of physiological tremor,” Journal of Neurophysiology, 93(6), 3064-3074, 2005;
Olivier Toussaint, Martine Raes, José Remacle, “Aging as a multi-step process characterized by a lowering of entropy production leading the cell to a sequence of defined stages,” Mechanisms of Ageing and Development, 61(1), 45-64, 1991.
52. John Reginald Brande Lighton, Measuring Metabolic Rates: A Manual for Scientists, Oxford University Press, Oxford, 2008;
Charlene Compher, David Frankenfield, Nancy Keim, Lori Roth-Yousey, Evidence Analysis Working Group, "Best practice methods to apply to measurement of resting metabolic rate in adults: a systematic review," Journal of the American Dietetic Association, 106(6), 881-903, 2006;
Fogiel, The Biology Problem Solver, 3.31, pp. 112-113; 17.4, pp. 510-511.
53. Raymond Pearl, The Rate of Living, University of London Press, London, 1928; 
Denham Harman, “Aging: a theory based on free radical and radiation chemistry,” Journal of Gerontology, 11, 298-300, 1956;
Rajindar S. Sohal, “Role of oxidative stress and protein oxidation in the aging process,” Free Radical Biology and Medicine, 33(1), 37-44, 2002. 
54. J. T. Nicoloff and J. Thomas Dowling, “Estimation of thyroxine distribution in man,” The Journal of Clinical Investigation, 47(1), 26-37, 1968;
Daniel Rudman, Michael H. Kutner, C. Milford Rogers, Michael F. Lubin, G. Alexander Fleming, Raymond P. Bain, “Impaired growth hormone secretion in the adult population: relation to age and adiposity,” The Journal of Clinical Investigation, 67(5), 1361-1369, 1981;
George A. Bray, David S. Gray, “Obesity I: Pathogenesis,” The Western Journal of Medicine, 149(4), 429-441, 1988.
55. Fogiel, The Biology Problem Solver, 3.32, pp.113-114;
Antoine Stier, Pierre Bize, Damien Roussel, Quentin Schull, Sylvie Massemin, François Criscuolo, "Mitochondrial uncoupling as a regulator of life-history trajectories in birds: an experimental study in the zebra finch," Journal of Experimental Biology,  217, 3579-3589, 2014.
56. Martin D. Brand, “Uncoupling to survive? The role of inefficiency in ageing,” Experimental Gerontology, 35, 811-820, 2000;
John R. Speakman, Darren A. Talbot, Colin Selman, Sam Snart, Jane S. McLaren, Paula Redman, Ela Krol, Diane M. Jackson, Maria S. Johnson, Martin D. Brand, “Uncoupled and surviving: individual mice with high metabolism have greater mitochondrial uncoupling and live longer,” Aging Cell, 3(3), 87-95, 2004;
Giuseppina Rose, Paolina Crocco, Francesco De Rango, Alberto Montesanto, Giuseppe Passarino, "Further Support to the Uncoupling-to-Survive Theory: The Genetic Variation of Human UCP Genes Is Associated with Longevity," PLoS One, 6(12), e29650, 2011;
Karine Salin, Sonya K. Auer, Agata M. Rudolf, Graeme J. Anderson, Andrew G. Cairns, William Mullen, Richard C. Hartley, Colin Selman, Neil B. Metcalfe, "Individuals with higher metabolic rates have lower levels of reactive oxygen species in vivo," Biology Letters, 11(9), 20150538, 2015.
57. “Moderation” has been a prevalent mainstay in the history of the pursuit of life extension, throughout the world. In the words of Lao-Tse, the great teacher of Taoist immortalists (China, c. 6th century BCE), “For regulating the human in our constitution and rendering the proper service to the heavenly, there is nothing like moderation.” The passage continues, “It is only by this moderation that there is effected an early return (to man's normal state). That early return is what I call the repeated accumulation of the attributes (of the Tao). With that repeated accumulation of those attributes, there comes the subjugation (of every obstacle to such return). Of this subjugation we know not what shall be the limit; and when one knows not what the limit shall be, he may be the ruler of a state.” (Lao-Tse. The Tao Teh King. The Tao and Its Characteristics, Translated by James Legge, 1880, Section 59.1-2, reprinted in Project Gutenberg,
Also in the Western tradition, agreeing with Aristotle, moderation, particularly moderation in diet, has remained the prevailing life-extensionist consensus for centuries. (See, for example, a brief account: Steven Shapin, Christopher Martyn, “How to live forever: lessons of history,” British Medical Journal, 321, 1580-1582, 2000.) However, it has never been agreed on what exactly a “moderate” measure is. And yet, despite the uncertainties regarding the exact “moderate” measure, the importance of moderation, of consuming less than people usually do, has been emphasized throughout by most researchers of aging, up to the modern period, for example by the life-extensionist hygienists such as Luigi Cornaro (1467-1566, Discorso sulla vita sobria - Discourse on a sober life, 1566), Leonardus Lessius (1554-1623, A Treatise of Health and Long Life - Hygiasticon, 1613), Hufeland (Macrobiotics, 1796), and other authors. (See: A Treatise of Health and Long Life, with the Sure Means of Attaining It. In 2 Books. The first By Leonard Lessius. The Second by Lewis Cornaro, Translated into English by Timothy Smith, London, C. Hitch, 1743.)
The research on life-prolongation by calorie restriction may be one of the ramifications of this tradition. Some of the prominent studies of calorie restriction for life-extension included:
C.M. McCay, W.E. Dilly, M.F. Crowell, “Growth rates of brook trout reared upon purified rations, upon skim milk diets, and upon combinations of cereal grains,” Journal of Nutrition, 1, 233-246, 1929;
Clive McCay, “The Effect of Retarded Growth Upon the Length of Life Span and upon the Ultimate Body Size,” Journal of Nutrition, 10, 63-79, 1935;
Richard Weindruch, Roy L. Walford, The Retardation of Aging and Disease by Dietary Restriction, Charles C. Thomas, Springfield, Illinois, 1988;
Luigi Fontana, Linda Partridge, Valter D. Longo, “Extending Healthy Life Span – From Yeast to Humans,” Science, 328(5976), 321-326, 2010;
Eric Ravussin, Leanne M. Redman, James Rochon, et al., “A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity,” Journal of Gerontology: Medical Sciences, 70(9), 1097-1104, 2015.
Perhaps one of the very few dissenters from this consensus for dietary moderation was the famous French lawyer, physician and gastronome Jean Anthelme Brillat-Savarin (1755-1826). In his Physiologie du goût (The Physiology of Taste, 1825), Brillat-Savarin spoke of the “Longevity of Gourmands” and claimed:
“I am happy, I cannot be more so, to inform my readers that good cheer is far from being injurious, and that all things being equal, gourmands live longer than other people. This was proved by a scientific dissertation recently read at the academy, by Doctor Villermet [the hygienist Louis René Villermé, 1782-1863]. … Those who indulge in good cheer, are rarely, or never sick. … as all portions of their organization are better sustained, nature has more resources, and the body incomparably resists destruction.”
(Jean Anthelme Brillat-Savarin, The Physiology of Taste; or, Transcendental Gastronomy (Translated by Fayette Robinson), Lindsay & Blakiston, Philadelphia, 1854, pp. 194-196, first published in 1825,
Still, even when asserting the value of moderation, it is now often emphasized that the meals need to be “nutritious” – that is, to provide all the necessary substances and sufficient energy. Yet in many cases those “necessities” are not well defined. Thus, the ambiguity exists, since Aristotle, regarding the exact measures of “heat” (energy) that is needed to be expended or “conserved” for life-prolongation.
See also: Ilia Stambler, A History of Life-Extensionism in the Twentieth Century, Longevity History, 2014,
58. On Length and Shortness of Life, 466b8-28, p. 743.
59. Since Aristotle’s times, well until modernity, the concept of “innate heat conservation” had important implications for practical therapy. In the pre-chemotherapeutic era, many techniques employed by physicians/medicine-men for the conservation of the “vital heat” – such as drug-sedation, starving, blood-letting, freezing, purging, and even incantation – were designed to overcome stimulation and quiet the person down. This view was fundamentally opposed to the idea of exercise or internal stimulation as a means to counter the threat of destruction by the environment.
One instance of this controversy was the opposition between the views of the English physician John Brown (1810-1882), the proponent of physiological excitation or exercise, as opposed to the views of the French physician François-Joseph Broussais (1772-1838), the advocate of physiological inhibition as the path to conserving the vital energy and hence increasing longevity.
The French historian of medicine Charles Daremberg poignantly noted the old conflict between the Stimulation and Relaxation schools (1870):
“All of [John] Brown’s patients were destined to become athletes. All of Broussais’s were supposed to be reduced to the state of diaphanous bodies. One left Brown’s care with a ruddy complexion, Broussais’s as a pale and a winding sheet. For Brown stimulation was the remedy, for Broussais irritation was the ill.”
(Charles Daremberg, Histoire des sciences médicales, 1870, quoted in Georges Canguilhem, "John Brown's system: An Example of Medical Ideology," in: Ideology and Rationality in the History of the Life Sciences, translated from French by Arthur Goldhammer, Cambridge MA, The Massachusetts Institute of Technology Press, 1988, article note 11, p. 49. See also William Randall Albury, “Ideas of Life and Death,” in: Companion Encyclopedia of the History of Medicine, Edited by William F. Bynum and Roy Porter, Routledge, London and New York, 2001, pp. 253-254.)
Interestingly, both the stimulatory and inhibitory approaches agree with the vitalist conception of life and longevity. The vitalist perception of the lifespan as determined by a limited amount of “vital force” that can be “exhausted,” even though ostensibly fatalistic, nonetheless offers several theoretical possibilities for life prolongation. A good explanation was provided by the German gerontologist Max Bürger in Altern und Krankheit (Aging and Disease) as recently as 1954, going back to Aristotle’s original concept of entelechy. Basically, the vital force of entelechy could be enhanced by manipulating body structure. First of all, the life force can be conserved by diminishing activity (in line with the inhibitory approach). Yet, on the other hand, the body structure can be reduced – for example, by dissolving structure or by amputation – to “free the room” for a continued action of the “vital force.” In this way, Bürger writes, “the catastrophic end can be postponed either by dissolving structure or by a forced regeneration after amputation.” In this view, during a moderate exercise, some body structures become partly worn out, the life force receives a “new room” to operate and rebuilds the lost structures even stronger than before (that would agree with the stimulatory approach). And thirdly, the immaterial “vital force” could be directly affected by another “immaterial” entity – the mind (an “intellectual faculty” in Aristotle’s terms).
(Max Bürger, Altern und Krankheit (Aging and Disease),  Leipzig, 1954 (1947), “Das Altern im Lichte der vitalistischen Autonomielehre” (Aging in the light of the theory of vitalistic autonomy), pp. 39-41.)
Though Aristotle was not that explicit, he nonetheless pioneered the conceptual and terminological framework for this discussion. In practical terms, the relative merits and specific indications, thresholds and balances of stimulatory exercise vs. inhibitory conservation of life’s energy for life prolongation, still appear to be unclear.
60. William A. Calder, Size, Function, and Life History, Harvard University Press, Cambridge MA, 1984;
Knut Schmidt-Nielsen, Scaling: Why is Animal Size So Important? Cambridge University Press, Cambridge UK, 1984;
João Pedro de Magalhães, “Comparative Biology of Aging,” Senescence Info, 2004,
61. Christoph Wilhelm Hufeland, Makrobiotik; oder, Die Kunst das menschliche Leben zu verlängern, Sechste verbesserte Auflage, A.F. Macklot, Stuttgart, 1826 (Macrobiotics or the art of prolonging human life, the 6th improved edition), first published in 1796 in Jena for Gotthold Ludwig Fiedler, Academische Buchhandlung.
The book is available in several languages, including Russian: Iskusstvo Prodlevat Chelovecheskuyu Zhizn (Macrobiotika), translated by P. Zablotsky, E. Pratz Typography, St. Petersburg, 1852, republished by Leila, St. Petersburg, 1996.
It is also available in English: The Art of Prolonging Life, Edited by Erasmus Wilson, Lindsay & Blakiston, Philadelphia, 1867 (the latter edition is used here, and is hereafter referred to as “Hufeland, Macrobiotics”). The influence of climate on longevity is considered in Hufeland’s book, among other places, in Part 1, Ch. 6, Sections 4-5, p. 99-100.
62. Hufeland, Macrobiotics, Part 1, Ch. 6, Sections 4-5, pp. 99-100;
Zavadovskii A.F., Vavakin Iu.N., Korotaev M.M., “The effect of moderate altitude on the maintenance of a good health status and high physical work capacity in cosmonauts over the course of a long period of time,” Aviakosmicheskaya i Ekologicheskaya Medicina (Aerocosmic and Ecologic Medicine), 26(4), 40-43, 1992 (in Russian);
Alexander Leaf, Youth in Old Age, McGraw-Hill Book Company, NY, 1975;
Dan Buettner, The Blue Zones: Lessons for Living Longer From the People Who've Lived the Longest, National Geographic, Washington DC, 2010;
Bloch K.F., "Why do the very aged become so old?” Acta Biotheoretica, 28(2), 135-144, 1979.
Just by looking at the world map of life-expectancy, it can be seen that countries with colder climates (e.g. the Scandinavian countries and Canada) are generally characterized by a greater life-expectancy than tropical (“hot and humid”) countries (e.g. most of Africa and Latin America). Of course, there are also many other parameters at play.
Though exceptions from those “rules” are obvious, and arguments can be made both for the benefits of a “warm” or “cold” climate. Clearly, an enormous amount of factors are unaccounted for by the temptingly simple “climatic-geographic” theory of longevity. As Hufeland points out as well in the referenced sections, both extreme cold and heat, and the rapid oscillations of cold and heat, are detrimental for longevity. The question still remains regarding the exact definition of “warm” vs. “cold” climate, beyond common intuitive perception. Nonetheless, the assumption of the influence of climate, of the environment, on human and animal lifespan appears to be commonsensical and Aristotle’s contribution to this field of study may have been groundbreaking.
63. Mary Shaw,  Helena Tunstall,  George Davey Smith, “Seeing social position: visualizing class in life and death,” International Journal of Epidemiology, 32(3), 332-335, 2003;
Jong-In Kim, “Longevity and occupation,” Age and Ageing, 31(6), 485-486, 2002.
64. On the benefits of physical exercise for healthy longevity, see for example:
James Rollin Slonaker, “The normal activity of the albino rat from birth to natural death, its rate of growth, and duration of life,” Journal of Animal Behavior, 2, 20-42, 1912;
Alexander Vasilievich Nagorny, “K voprosu o faktorakh, obuslovlivayushikh dlitelnost zhizni” (On the question of factors determining the duration of life), in: Starost. Trudy Konferenzii po Probleme Geneza Starosti I Profilaktiki Prezhdevremennogo Starenia Organisma. Kiev 17-19 Decabria. 1938, Izdatelstvo Akademii Nauk USSR, Kiev, 1939 (Aging. Proceedings of the Conference on the Problem of the Genesis of Aging and Prophylaxis of the Organism’s Untimely Aging, Kiev, December 17-19, 1938, Publication of The Ukrainian Soviet Socialist Republic Academy of Sciences, Kiev, 1939), pp. 156-172;
Blain H., Vuillemin A., Blain A., Jeandel C., “The preventive effects of physical activity in the elderly,” Presse Medicale, 29(22), 1240-1248, 2000;
I-Min Lee, Ralph S. Paffenbarger Jr., “Associations of light, moderate, and vigorous intensity physical activity with longevity. The Harvard Alumni Health Study,” American Journal of Epidemiology, 151(3), 293-299, 2000;
Lee I.M., Paffenbarger R.S., Hennekens C.H., “Physical activity, physical fitness and longevity,” Aging (Milano), 9(1-2), 2-11, 1997;
Matthew M. Robinson, Surendra Dasari, Adam R. Konopka, Matthew L. Johnson, S. Manjunatha, Raul Ruiz Esponda, Rickey E. Carter, Ian R. Lanza, K. Sreekumaran Nair, "Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes in Young and Old Humans," Cell Metabolism, 25 (3), 581-592, 2017.
Generally, physical exercise has been regarded as beneficial for longevity. Yet, there have been conflicting findings.
Thus, it was found that athletes live longer than normal insured men, but shorter than “physically underdeveloped” people. (Louis I. Dublin, “Longevity of college athletes,” Harper’s Monthly Magazine, 157, 229-238, 1928.)
It was also found that athletes live longer in general. (Martti J. Karvonen, “Endurance sports, longevity and health,” Annals of the New York Academy of Sciences, 301, 653-655, 1977.)
And it was also found that athletes live shorter in general. (Peter V. Karpovich, “Longevity and athletics,” Research Quarterly, 12, 451-455, 1941.)
And there were also found no significant differences. (Henry J. Montoye, et al., The Longevity and Morbidity of College Athletes, Indianapolis, 1957.)
The results also varied widely depending on the type of sports, level of athleticism, period of practice, and many other factors. (Anthony P. Polednak (Ed.), The Longevity of Athletes, Charles C. Thomas, Springfield IL, 1979.)
It was also shown that “blue-collar,” physically active workers live shorter than sedentary “white-collar” workers. But this was explained by the assumption that the “white-collar” workers were able to exercise regularly, in a protected environment, and with sufficient rest. (Charles L. Rose and Michel L. Cohen, “Relative importance of physical activity for longevity,” Annals of the New York Academy of Sciences, 301, 671-702, 1977.)
(These works are reviewed in William G. Bailey, Human Longevity from Antiquity to the Modern Lab, Greenwood Press, Westport CN, 1987, “Athleticism and Exercise,” pp. 98-104.)
Further complicating the picture, Howard Friedman and Leslie Martin’s The Longevity Project. Surprising Discoveries for Health and Long Life from the Landmark Eight-Decade Study, Hudson Streen Press, Penguin Group, NY, March 2011, suggests that cheerful and relaxed people tended to live shorter than “prudent and persistent” individuals (p. 9) and that strenuous exercise does not necessarily lead to greater longevity (pp. 105-106).
65. On Length and Shortness of Life, 4. 466b8-17, p. 743.
66. There has been a vast, ancient tradition advising on sexual moderation in order to achieve life-extension, from Aristotle, through Taoist physicians, to the Renaissance and early modern hygienists (Luigi Cornaro, Leonardus Lessius, Christoph Wilhelm Hufeland, and others). Some (rare) more recent examples of this attitude are Edwin Flatto’s Warning: Sex May Be Hazardous to Your Health (1977) or David Pratt’s Sex and Sexuality (2002):
Aristotle, On Length and Shortness of Life, Aristotle, On Youth, Old Age, Life and Death, and Respiration, translated by G.R.T. Ross, in: The Complete Works of Aristotle: The Revised Oxford Translation, Princeton University Press, Princeton, 1984, Vol. 1, pp. 740-744, 745-763;
Aelius/Claudius Galenus (c. 129-217 CE), Galen, De tuenda Sanitate. Gerontocomia (On the Preservation of Health. Gerontocomia), quoted in Sir John Floyer [1649-1734], Medicina gerocomica, or, The Galenic art of preserving old men's healths, J. Isted, London, 1725, p. 107;
Gabriele Zerbi (1445-1505), Gerontocomia, scilicet de senium cura atque victu (“Gerontocomia, or, care and nutrition for old age), Rome, 1489;
Hufeland, Macrobiotics, “Part 2 - Means which Shorten Life, Ch. 2 - Physical excess in youth,” pp. 163-164; “Part 3 - Means which prolong life, Ch. 4 – Abstinence from physical love in youth, and a too early assumption of the married state,” pp. 225-228;
A Treatise of Health and Long Life, with the Sure Means of Attaining It. In 2 Books. The first By Leonard Lessius. The Second by Lewis Cornaro, Translated into English by Timothy Smith, London, C. Hitch, 1743;
Gerald J. Gruman, A History of Ideas about the Prolongation of Life. The Evolution of Prolongevity Hypotheses to 1800, Transactions of the American Philosophical Society, Vol. 56 (9), Philadelphia, 1966, in particular “Taoist prolongevitism in theory,” pp. 28-37, and “Taoist prolongevitism in practice,” pp. 37-49;
Edwin Flatto, Warning: Sex May Be Hazardous to Your Health, 2nd edition, Arco, New York, 1977;
David Pratt, Sex and Sexuality, 3.6. “Pleasure at a Price,” New York, 2002.
67. Hufeland, Macrobiotics, “Part 2 - Means which Shorten Life, Ch. 2 - Physical excess in youth,” pp. 163-164; “Part 3 - Means which prolong life, Ch. 4 – Abstinence from physical love in youth, and a too early assumption of the married state,” pp. 225-228;
Thomas W. Laqueur, Solitary sex: a cultural history of masturbation, Zone Books, New York, 2003.
68. A series of studies showed the costs of reproduction for longevity in animal models, for example:
Jens Rolff, Michael T. Siva-Jothy, “Copulation corrupts immunity: a mechanism for a cost of mating in insects,” Proceedings of the National Academy of Sciences USA, 99(15), 9916-9918, 2002;
Wayne A. Van Voorhies, “Production of sperm reduces nematode lifespan,” Nature, 360, 456-458, 1992;
Casandra L. Rauser, Laurence D. Mueller, Michael R. Rose, “Aging, fertility, and immortality,” Experimental Gerontology, 38(1-2), 27-33, 2003.
More generally, according to the “Disposable Soma” theory of aging, energy expenditures on reproduction come at the cost of energy expenditures on the maintenance of the body:
Tom Kirkwood, Time of Our Lives. The Science of Human Aging, Oxford University Press, Oxford, 1999.
And in the “Phenoptosis” or “programmed aging” theory, sex is considered as a trigger of the ‘self-destruct’ mechanism in animals:
Vladimir P. Skulachev, “Aging is a specific biological function rather than the result of a disorder in complex living systems: biochemical evidence in support of Weismann's hypothesis,” Biochemistry, Moscow, 62(11), 1191-1195, 1997.
69. The indications for the potential life-prolonging effects of sexual moderation or abstinence in humans include the findings of the consistently higher longevity among monks:
Bartosz Jenner, “Changes in average life span of monks and nuns in Poland in the years 1950-2000,”  Przeglad Lekarski, 59(4-5), 225-229, 2002;
de Gouw H.W., Westendorp R.G., Kunst A.E., Mackenbach J.P., Vandenboucke J.P., “Decreased mortality among contemplative monks in The Netherlands,” American Journal of Epidemiology, 141(8), 771-775, 1995;
Marc Luy, “Sex differences in mortality - time to take a second look,” Zeitschrift für Gerontologie und Geriatrie, 35(5), 412-429, 2002; 
Marc Luy, Katrin Gast, "Do Women Live Longer or Do Men Die Earlier? Reflections on the Causes of Sex Differences in Life Expectancy," Gerontology, 60, 143-153, 2014;
Marc Luy, Klosterstudie zur Lebenserwartung von Nonnen und Mönchen (The “Closter” study of life-expectancy in nuns and monks),
There have also been indications about the longer life span of eunuchs:
James B. Hamilton, Gordon E. Mestler, “Mortality and survival: comparison of eunuchs with intact men and women in a mentally retarded population,” Journal of Gerontology, 24(4), 395-411, 1969;
John P. Phelan, Michael R. Rose, “Why dietary restriction substantially increases longevity in animal models but won’t in humans,” Aging Research Reviews, 4(3), 339-350, 2005;
Kyung-Jin Min, Cheol-Koo Lee, Han-Nam Park, “The lifespan of Korean eunuchs,” Current Biology, 22 (18), R792–R793, 2012.
70. Presently, even when discussing the “disposable soma theory,” the “phenoptosis theory” or the “costs of reproduction” – sexual moderation in humans is hardly ever recommended.  Instead, there is a common popular belief that “sex is good for longevity.”
“Sex is good,” for example, according to Dr. Mark Stibich; Dr. Michael Roizen; Dr. Kevin Netto; or the “sensual product designer” Anne Enke; and many more such examples of the popular stance can be added.
A single most widely cited study in this approach is: George Davey Smith, Stephen Frankel, John Yarnell’s  “Sex and death: are they related? Findings from the Caerphilly cohort study,” British Medical Journal, 315, 1641-1644, 1997, which correlated between high sexual activity and lower mortality in a group of aged men.
The majority of authors now heavily emphasize the possibility and desirability of sex for the aged, the benefits of sex with a constant partner, its positive role for the production of stress-reducing hormones, and for the improvement of self-image and connection. See for example:
Normal Aging: Reports from the Duke Longitudinal Study, 1955-1969, edited by Erdman Palmore, Duke University Press, Durham NC, 1970, pp. 266-303;
Nathan W. Shock, et al., Normal Human Aging: The Baltimore Longitudinal Study of Aging, NIH Publication, 1984, pp. 164-165;
Thomas H. Walz, Nancee S. Blum, Sexual Health in Later Life, Lexington Books, Lexington MA, 1987;
Modig K., Talbäck M., Torssander J., Ahlbom A., “Payback time? Influence of having children on mortality in old age,” Journal of Epidemiology & Community Health, pii: jech-2016-207857, March 2017.
In animal models, the longevity benefits of mating were also found, for example:
Alexandra Schrempf, Jürgen Heinze, Sylvia Cremer, “Sexual cooperation: mating increases longevity in ant queens,” Current Biology, 15, 267-270, 2005.
The terms “exhaustion” and “moderation,” that had been prevalent among the earlier hygienists, are now hardly ever present, and at any rate the possibility of a “threshold” or “tradeoff” in sexual activity with reference to human longevity is hardly ever considered.
71. Jose Viña, Consuelo Borrás, Juan Gambini, Juan Sastre, Federico V. Pallardó, “Why females live longer than males? Importance of the upregulation of longevity-associated genes by oestrogenic compounds,” FEBS Letters, 579(12), 2541-2545, 2005;
Marc Luy, Katrin Gast, "Do Women Live Longer or Do Men Die Earlier? Reflections on the Causes of Sex Differences in Life Expectancy," Gerontology, 60, 143-153, 2014.
72. Concerning gender specific longevity, women might have not been always longer lived than men. Female relative life spans were likely shorter in the past (due to higher mortality at childbirth):
Irvine Loudon, “Deaths in childbed from the eighteenth century to 1935,” Medical History, 30(1), 1-41, 1986.
73. On Length and Shortness of Life, 5. 466a20-24; 466b3-8; 466b33-467a5; 6. 467a6-9, pp. 742-743.
74. “Fat,” Oxford Dictionary of Science, Oxford University Press, 1999, p. 302;
Fogiel, The Biology Problem Solver, 17.3, pp. 509-510; 2.31. p. 68.
75. On Length and Shortness of Life, 3. 465b17-21, p. 741; 5. 466b4-8, p. 743;
On Youth and Old Age, 23, 479a14-27, pp. 760-761; 26. 479b18-18, p. 761.
76. “Allosteric Regulation,” Wikipedia, 2017,;
Fogiel, The Biology Problem Solver, 3.19, p. 98; 3.3. p. 82; 24.26, p. 787.
77. Rajindar S. Sohal, “Role of oxidative stress and protein oxidation in the aging process,” Free Radical Biology and Medicine, 33(1), 37-44, 2002;
Rajindar S. Sohal, “Oxidative stress hypothesis of aging,” Free Radical Biology and Medicine, 33(5), 573-574, 2002.
78. Aristotle, On Sleep (Translated by J.I. Beare), in: The Complete Works of Aristotle: The Revised Oxford Translation (Edited by Jonathan Barnes), Vol. 1, Princeton University Press, Princeton, 1984, 1. 453b26-27, p. 721; 454a24-31, p. 722; 454b31-455a3, p.723; 455b20-22, p. 724; 457b1-6, pp. 726-727;  458a-26-32, p. 728 (hereafter referred to as “On Sleep”). 
79. On Sleep, 456b18457b2, pp. 725-726.
80. Alan H. Cromer, Physics for the life sciences, McGraw Hill Inc., New York, 1974, Ch. 6.5. “Feedback and Control,” pp. 118-125 (hereafter referred to as “Cromer, Physics”).
81. Vladimir M. Kovalzon, Tatyana V. Strekalova, “Delta sleep-inducing peptide (DSIP): a still unresolved riddle,” Journal of Neurochemistry, 97(2), 303-309, 2006;
György Buzsáki, Andreas Draguhn, “Neuronal oscillations in cortical networks,” Science, 304, 1926-1929, 2004;
Tarja Porkka-Heiskanen, Robert E. Strecker, Mahesh Thakkar, Alvhild A. Bjørkum, Robert W. Greene, Robert W. McCarley, “Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness,” Science, 276, 1265-1268, 1997.
82. Karine Spiegel, Rachel Leproult, Eve Van Cauter, "Impact of sleep debt on metabolic and endocrine function," The Lancet, 354 (9188), 1435-1439, 1999;
Mark R. Zielinski, Dmitry Gerashchenko, Svetlana A. Karpova, Varun Konanki, Robert W. McCarley, Fayyaz S. Sutterwala, Robert E. Strecker, Radhika Basheer, “The NLRP3 inflammasome modulates sleep and NREM sleep delta power induced by spontaneous wakefulness, sleep deprivation and lipopolysaccharide,” Brain, Behavior, and Immunity, 62, 137-150, 2017.
Tatiana-Danai Dimitriou, Magdalini Tsolaki, "Evaluation of the efficacy of randomized controlled trials of sensory stimulation interventions for sleeping disturbances in patients with dementia: a systematic review," Clinical Interventions in Aging, 12, 543-548, 2017.
83. On Sleep, 457b27-458a9, p. 727.
84. David G. Nicholls, Stuart Ferguson, Bioenergetics (Fourth Edition), Academic Press, London, 2013;
Fogiel, The Biology Problem Solver, Sections 2.29-2.32, pp. 66-69; 15.2, pp. 458-9; 3.6. p. 84.
85. On Sleep, 455b34-456a23, pp. 724-25.
86. Valentín Fuster, “Applied Cardiological Research. Challenges for the New Millennium,” Revista Española de Cardiología (English Edition), 55, 327-332, 2002;
Judith Meadows, Jacqueline Suk Danik, Michelle A. Albert, “Primary prevention of ischemic heart disease,” in: Elliott M. Antman (Ed.), Cardiovascular  Therapeutics:  A  Companion  to Braunwald's Heart Disease, Third edition, Saunders Elsevier, Philadelphia PA, 178-220, 2007;
Roger Yu, Kaveh Navab, Mohamad Navab, “Near term prospects for  ameliorating  cardiovascular  aging,” in: Gregory M. Fahy, Michael D. West, L. Stephen Coles, Steven B. Harris (Eds.), The Future of Aging: Pathways to Human Life Extension, Springer, New York, 2010, pp. 279-306. 
87. On Youth and Old Age, 26. 479b17-480a15, pp. 761-762.
88. On Length and Shortness of Life, 467a12-29, pp.743-744.
89. Oberley L.W., Oberley T.D., Buettner G.R., “Cell differentiation, aging and cancer: the possible roles of superoxide and superoxide dismutases,” Medical Hypotheses, 6(3), 249-268, 1980.
90. Gretchen Vogel, “How does a single somatic cell become a whole plant?” Science, 309 (5731), 86, 2005;
Gretchen Vogel, “How can a skin cell become a nerve cell?” Science, 309 (5731), 85, 2005;
R. John Davenport, “What controls organ regeneration?” Science, 309 (5731), 84, 2005.
91. Thomas C. Vinci, Jason Scott Robert, “Aristotle and Modern Genetics,” Journal of the History of Ideas, 66(2), 201-221, 2005;
Ernst Mayr, This is Biology: The Science of the Living World, Harvard University Press, Cambridge, Massachusetts, 1997, p. 154; 
Ernst Mayr, The Growth of Biological Thought: Diversity, Evolution, and Inheritance, Harvard University Press, Cambridge, Massachusetts, 1982, p. 89.
92. On the Soul (Translated by J.A. Smith), in: The Complete Works of Aristotle: The Revised Oxford Translation (Edited by Jonathan Barnes), Princeton University Press, Princeton, 1984, Vol.1, 416b22-26, p. 663.
93. On Length and Shortness of Life, 6. 467a6-9, p. 743.
94. On Length and Shortness of Life, 467a12, p. 743.
95. On the Soul (translated by W.S. Hett), 1.5. 411b24-31, p. 65.
96. Metchnikoff, On the Nature of Man, pp. 227, 230;
On various concepts of the “limit” to the animal and human lifespan, see: Ilia Stambler, A History of Life-Extensionism in the Twentieth Century, Longevity History, 2014, Chapter 4, Section 10 - Rectifying “Discord” and conserving “Vital Capital,” pp. 198-201, note 876 (on-line edition)/note 873 (print edition), pp. 409-410,
97. On Length and Shortness of Life, 3. 465b1-21, p. 741.
98. Avicenna, “On Causes of Health and Illness and the Inevitability of Death,” in: The Canon of Medical Science, Selected Parts (edited by U.I. Karimov, E.U. Hurshut), FAN Publisher of the Uzbekistan Academy of Sciences, Tashkent, 1994, Part 1, pp. 128-129 (in Russian, translated from Arabic by A. Rasulev, U.I. Karimov).
99. Leonard Hayflick, Paul S. Moorhead, "The serial cultivation of human diploid cell strains," Experimental Cell Research, 25, 585-621, 1961;
Leonard Hayflick, How and Why we Age, Ballantine Books, NY, 1994, “No More Aging: Blessing or Nightmare?” pp. 336-338.
100. Arthur Leslie Peck, “Introduction to Aristotle’s Generation of Animals,” in: Aristotle in Twenty-Three Volumes, William Heinemann Ltd., London, 1975, Vol. XIII, p. L.
101. Cromer, Physics, “Entropy” Section 11.5, pp. 228-229.
102. Plato (427-347 BCE) – or Socrates (469 –399 BCE) in Plato’s corpus – seemed to opt for the afterlife. In the “Allegory of the Cave” (The Republic, Book VII), Plato appeared to employ a perceptual stratagem to bring home the notion of the soul’s immortality: if we believe that we can cast shadows, we can be also made to believe that the pure form, indestructible shadows can cast us, that shadows of the other realm constitute our essence.
(Plato, The Republic, Translated by Paul Shorey, in: The Collected Dialogues of Plato, Including the Letters (Edited by Edith Hamilton and Huntington Cairns), Princeton University Press, Princeton, New Jersey, 1961, Book VII. Allegory of the Cave, 7.514-7.518, pp. 747-750.)
103. In contrast to Plato’s idealism, Epicurus (342-270 BCE) asserted the utter and final disintegration upon death. Epicurus’ resignation to the finality of death is complete, as expressed in his Letter to Menoeceus. According to Epicurus, a person must live in “fullness of pleasure” banishing the fear of death: “The wise man neither seeks to escape life nor fears the cessation of life, for neither does life offend him nor does the absence of life seem to be any evil.” 
(Epicurus, Letter to Menoeceus, Translated by Cyril Bailey, in: The Stoic and Epicurean Philosophers. The Complete Extant Writings of Epicurus, Epictetus, Lucretius, Marcus Aurelius (Edited by Whitney J. Oates), The Modern Library, New York, 1957, pp. 30-31.
104. On the Soul (translated by J.A Smith), 5. 430a10-26.
105. Aristotle, On the Heavens (Translated by J.L. Stocks), in: The Complete Works of Aristotle: The Revised Oxford Translation (Edited by Jonathan Barnes), Princeton University Press, Princeton, 1984, Book 1. Chapters 1, 2, Vol. 1, 184a10-186a3, pp. 315-317.
106. Aristotle, Physics (Translated by R.P. Hardie and R.K. Gaye), in: The Complete Works of Aristotle: The Revised Oxford Translation (Edited by Jonathan Barnes), Princeton University Press, Princeton, 1984, Book 1. Ch. 3, Vol. 1, 270b1-270b25, pp. 450-451.
107. Aristotle, On the Soul (Translated with notes by Walter Stanley Hett), in: Aristotle in Twenty-Three Volumes, William Heinemann Ltd., London, 1975, “Book 1. Ch. 2. Previous Theories as to the Nature of the Soul,” Vol. VIII, pp. 19-31.    
108. Walter Stanley Hett, “Introduction to Aristotle’s On the Soul, in: Aristotle in Twenty-Three Volumes, William Heinemann Ltd., London, 1975, Vol. VIII, pp. vi-vii.
109. Arthur Leslie Peck, “Appendix B to Aristotle’s Generation of Animals,” in: Aristotle in Twenty-Three Volumes, William Heinemann Ltd., London, 1975, Vol. XIII, pp. 578-593.
110. Ilia Stambler, A History of Life-Extensionism in the Twentieth Century, Longevity History, 2014,


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