Homeostasis (biology)

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Referring to animal systems, pioneering 20th century physiologist Walter Cannon,[1] who coined the word homeostasis 1926,[2] defined it as follows:

Walter Bradford Cannon

> The coordinated physiological reactions which maintain most of the steady states in the body are so complex, and are so peculiar to the living organism, that it has been suggested (Cannon, 1929) that a specific designation for these states be employed -- homeostasis.[3]

Cannon recognized that "living being(s)" function as 'open' systems (see Life) -- i.e., not 'closed' or 'isolated' from their surroundings -- having many "relations" with their surroundings -- for example, interchange of materials through airways, gastrointestinal tract and skin. He noted that the surroundings could perturb the system, dislocating the quasi-stable states of activity of its key internal components or subsystems, inducing states of activity outside of their relatively stable and optimal ranges -- the "steady states" he referred to in his definition. A change in outside temperature, for example, might perturb the quasi-stability of internal biochemical processes to the detriment of the organism. If the temperature of the brain exceeds a certain value, for example, it malfunctions globally. The organism reacts to such potentially adverse effects of its surroundings with physiological adjustments that tend to maintain steady-state, i.e., to maintain 'homeostasis'.

> ....homeostasis. The word does not imply something set and immobile, a stagnation. It means a condition -- a condition which may vary, but which is relatively constant.[4]

This article will explore the concept of homeostasis from an early 21st century biological perspective. It will exemplify 'homeostatic' (i.e., homeostasis-maintaining) mechanisms. It will relate homeostasis to metabolism; physiology; cybernetics; hormesis; rheostasis, systems biology; the concepts of cellular and organismic adaptability, robustness, growth, development and reproduction; and, to the extent to which living systems sacrifice homeostasis of particular systems components in the short-term to maintain viability of the system as a whole. We will see that homeostatic mechanisms (vide infra) offer humans the advantage of living in a wide variety of environments, and in environments that change state predictably or unpredictably, and explore the trade-offs of those advantages.

## Contents

* 1 Terminology and examples of usage
* 1.1 Narrow and broad definitions of homeostasis
* 1.1.1 Narrow conceptions of homeostasis
* 1.1.2 Broad conceptions of homeostasis
* 2 Scope of homeostasis
* 3 Mechanisms mediating homeostasis
* 3.1 • Negative feedback
* 3.2 • Positive feedback
* 4 History of concept of homeostasis
* 5 The work of Walter Cannon
* 6 The concept of 'internal environment' or 'internal milieu'
* 7 Living systems as 'homeostatic machines', self-fabricating, autonomous and cognitive
* 8 Homeostasis and longevity
* 9 References
* 9.1 Citations and notes

## Terminology and examples of usage[edit]

Note that Cannon applied the term 'homeostasis' to the "steady states in the body", not specifically to the physiological mechanisms maintaining them. Indeed, he specifically distinguished between "homeostasis" and the mechanisms "preserving" homeostasis"

> It seems not impossible that the means employed by the more highly evolved animals for preserving uniform and stable their internal economy (i.e., for preserving homeostasis) may present some general principles for the establishment, regulation and control of steady states, that would be suggestive for other kinds of organization....[4]

In common physiological usage today, 'homeostasis' refers not only to a living system’s internal stability, but also to the system’s ability or tendency to maintain that stability, or to its process of maintaining that stability. As to the latter, some biologists interpret Walter Cannon as defining 'homeostasis' "....to describe the regulation of [the] internal environment [emphasis added]".[5] Thus the nuances of 'homeostasis' and the vagaries, or flexibility, of language.

Use of the adjectival form, homeostatic, offers the possibility for a modicum of coherence. Typically biologists speak of 'homeostatic mechanisms', namely mechanisms or processes that achieve, or tend to achieve, internal stability (homeostasis) of a particular internal state. For example, the mechanism underpinning the behavior of a thirsty land vertebrate seeking and drinking water qualifies as a 'homeostatic mechanism' adjustive to the organism’s internal state of dehydration. Biologists do not typically speak of homeostatic mechanisms as mechanisms that endow an organism with the ability to make the adjustive physiological changes required to maintain homeostasis -- a subtle but important distinction. To explain the foundation that underpins a living system’s ability to self-regulate its internal environment requires investigation of the foundation that underpins the very activity of living itself, including evolutionary forces enabling self-organization and autonomous self-serving behavior (see Life). (The confusion between homeostasis and homeostatic mechanisms perhaps has resulted in part from a loose reading of Walter Cannon.[6])

### Narrow and broad definitions of homeostasis[edit]

#### Narrow conceptions of homeostasis[edit]

In applying a narrow definition of homeostatic mechanisms in living systems, we can say they operate as built-in autonomous molecular physiological processes, goal-directed to maintain, within an optimal range, the properties, functions or behaviors of the system’s key components (structures, metabolic pathways, networks, or other subsystems) when any vital component deviates from its optimal ‘set-point’, or often more precisely, ‘set-range’. The metrics (volume, concentration, output rate, shape, etc.) of that range depend on the nature of the regulated component.

For a cell, homeostatic mechanisms operate, for example, to maintain its internal concentration (or more precisely, chemical activity) of hydrogen ion within its optimal range, the failure of which would, among other adverse consequences, perturb catalytic activity of enzymes necessary to maintain cell organization for ‘healthy’ living. For a multicellular multi-organ organism like a land vertebrate, homeostatic mechanisms operate, for example, to maintain within optimal ranges the supplies of oxygen to organs, the failure of which could lead to organ dysfunction and cascading deleterious effects on other organs, leading to organ system and organism dysfunction. Sometimes, for want of a nail a kingdom tumbles.

Another key variable that influences cell functionality and viability is the [redox] state of the cell as determined by the relative concentrations of oxidizing agents and reducing agents. When oxidizing agents (aka, oxidants) predominate, their potent ability to strip electrons from cellular macromolecules -- proteins, nucleic acid, lipids -- disrupt their conformational patterns, so impairing their function. Homeostatic mechanisms attempt to restore balance by increasing antioxidizing components (aka, reductants) in the cell.

#### Broad conceptions of homeostasis[edit]

In applying a broad definition of homeostatic mechanisms to living systems, we can say they operate as the totality of those molecular and physiological adjustive processes that maintain the system's dynamic organization in a state that sustains its activity of living. Sustaining viability need not require homeostatic mechanisms to maintain a perturbed set-point or steady-state in every component and subsystem of the organism. If it did a fetus would not develop into an infant, an infant into a child, a child into an adult.

Homeostatic mechanisms operate widely in biological nature, including all living systems, and those biological systems whose parts consist of living systems, e.g., a community of populations of many different species (an ecosystem). The Gaia hypothesis entertains the proposition that homeostatic mechanisms operate in sustaining the biopshere itself.[7]

Living systems have a natural history, growing in time and space in a self-programmed process, behaving 'healthfully' differently in different environments, and sustaining their living processes by manufacturing living things like themselves. Because of that natural history, set-range optimality values do not remain fixed for some system components. Homeostatic mechanisms themselves adjust their goals to accommodate the system’s natural history, indicating their adaptability. Optimality ranges do not remain constant, though remaining optimal, for some systems.

The use of ‘optimal’ here does not intend to imply that organic evolution optimizes living systems and subsystems for anything more, ultimately, than reproductive success. Moreover, when cultural evolution emerged in one species of land vertebrate, Homo sapiens, the determination of ‘optimal’ became individualized, and conscious choice could determine criteria for reproductive success, including the decision to reject reproduction, or to strategize for maximize fecundity.

We can view homeostasis in a somewhat narrow sense of keeping a molecular network in a cell operating within a determined range, or more broadly, of keeping a living system, or a biological system consisting of living systems, thriving, regardless of level of organization. In any case, homeostasis emerges through self-organization.

## Scope of homeostasis[edit]

The idea of homeostasis. at least in the narrow sense, is about preserving the status quo, regulation to achieve viability through resistance to change. However, a broader concept is allostasis, regulation to achieve viability by adjusting to change, not by restoring, but by altering equilibrium settings, adapting to shifts in environmental input.[8]

There are other types of adaptation: for instance, the metamorphosis of insects, amphibians, and some other animals; embryology; and cell differentiation that occurs in both plants and animals, which have to do with dramatic changes of organization generally not included in discussions of homeostasis or allostasis. The cellular and molecular processes involved in developmental anatomy fall under the heading of morphogenesis.[9]

A still broader category is physiological regulation, which includes evolutionary mechanisms that cope even with dramatic changes in environment and in the species itself.[10][11]

## Mechanisms mediating homeostasis[edit]

Several points to remember in considering the adjustive physiological mechanisms that maintain the internal environment approximately stable:[12]

* more than one mechanism may operate to maintain stability even of a single variable, a redundancy that enables finer control;

* the set-point of a variable refers to the value that homeostatic mechanisms target for stability, and may refer to a range of values, the set-point range;

* homeostatic mechanisms that succeed in maintaining the targeted set-point or set-point range establish a steady-state;

* set-point targets for homeostatic mechanisms may change during a day (circadian rhythms) or with other periodicities;

* when a perturbing condition persists or recurs cyclically, the homeostatic adjustive mechanisms may mitigate the set-point deviation but not return it to its original value;

* the term, error signal refers to the difference between the original value of a variable and the value returned by the homeostatic mechanism(s) during a persisting perturbation;

###  • Negative feedback[edit]

In the figure, the state of the system is a result of the combined input of stress from the world and feedback from the system. The terminology of the figure is common in descriptions of homeostasis.[13]

(PD) Diagram: John R. Brews
Negative feedback description of homeostasis

Suppose a change occurs in the stress upon the system from the outside world (say, increased heat). A receptor (say, the skin) responds to the combination of the stress and the organism's feedback. A sensor converts the receptor's status to some signal that is meaningful to the internal mechanisms of the organism (say, indicative of temperature). A controller compares the signal to a desired set-point signal, and issues an error signal if there is a discrepancy. The error is interpreted by an activator, which instructs one or another effector to initiate a response (say, perspiration, or shivering).[14] In this way, the effector produces a counter to the world's stress, and the combined input of stress and feedback is regulated this way so the receptor status remains constant. In other words, information on receptor status generates feedback that keeps its status fixed.

The maintenance of body temperature, homothermal control, is much more complex than this simplification would suggest.[15]

The thermostatic control of house temperature (see Feedback) is a commonly used analogy to a homeostatic negative feedback system.[14]

It might be noted that translation of signals between various forms (such as temperature, chemical signals, electrical signals, mechanical signals) occurs throughout the feedback loop. Also, there are time delays introduced at each step in a feedback loop that affect its success in tracking variations in the world's input.

###  • Positive feedback[edit]

Although uncommon in biological systems, positive feedback is sometimes used. In positive feedback, instead of returning a parameter to a set-point value, the error signal is amplified to move the system further from its set point. An often used example is birth of a baby where contractions are amplified during birthing, rather than opposed.[14][13] Positive feedback increases departure from a set point, and must be interrupted eventually if the system is not to reach unsustainable levels.

## History of concept of homeostasis[edit]

Claude Bernard (1813-1878)

The French physiologist Claude Bernard (1813-1878) introduced the concept of the internal environment of an organism, upon which the concept of homeostasis was built. Claude Bernard was a staunch advocate of experimental verification in physiology, and a prolific experimental physiologist. He postulated, initially blood, as a milieu interieur, or internal environment, surrounding the interior cells of higher animals. He first recognized that mechanisms operated to maintain relatively constant the temperature and glucose concentration of the blood, and the importance of those stabilities to the health of the organism. From those and many other observations, he developed the concept of the fixity or constancy of the internal environment as essential to the vital processes of the body.

Although not the first to have inklings of physiological homeostasis, and not the term's neologist, physiologists would not dispute that the impact of his researches and ideas merit him the title of ‘father of homeostasis’.

In his book on Claude Bernard’s place in the history of ideas, historian and Professor of French Reino Virtanen writes:[16]

> “…there is one basic insight we owe to Bernard which has continued to exert a seminal influence on contemporary science. It is the concept of the milieu intérieur. Yet although he stated it quite early and repeatedly, its full potentialities were not generally realized until decades after his death. The basic significance is suggested by the words of the historian of physiology John F. Fulton:[17] "One can again approach the human body as a single functional entity. The first great step toward this goal was taken in 1878 by Claude Bernard who enunciated the conception..."

And Virtanen writes further to indicate how Claude Bernard’s idea of the fixity of the internal environment help lead physiologists to consider the broader organizational character of the organism, the “coordination of physiological processes”:

> It is with the researches of [respiratory physiologist, Fellow of the Royal Society] J. S. Haldane [1860-1936] and [biochemist and physiologist] Lawrence J. Henderson [1878-1942] that Bernard's teaching really began to show its suggestive value...Henderson himself has more than once acknowledged the impact of Bernard's ideas. In his valuable introduction to H. C. Greene's translation of the Introduction to the Study of Experimental Medicine, Henderson suggests a reason for the tardy recognition of the concept: "The theory of the internal environment . . . we owe almost entirely to Claude Bernard himself. . . . Today with the aid of a physical chemistry unknown to the contemporaries of Claude Bernard, it is fulfilling the promise which he alone could clearly see."…J. S. Haldane’s study of Respiration was another sign of the times. But neither Haldane nor Henderson was content with the verifiable implications of the concept. The inner medium involves the whole question of the coordination of physiological processes. This becomes their springboard into speculations on the philosophy of the organism.

Neuroscientist Charles Gross quotes Bernard directly, from Bernard's Lectures on the Phenomena of Life Common to Animals and Plants.:[18]

> The fixity of the milieu supposes a perfection of the organism such that the external variations are at each instant compensated for and equilibrated .... All of the vital mechanisms, however varied they may be, the uniformity of the conditions of life in the internal environment.... The stability of the internal environment is the condition for the free and independent life…

Many physiologists, and students of physiology, who credit Claude Bernard and Walter Cannon as ‘fathers’ of the concept of homeostasis tend to ignore other scholars who had adumbrations of the concept, some of whom may have known of Claude Bernard's ideas. Walter Cannon did not ignore those forerunners. In his 1932 book Wisdom of the Body,[4] Cannon mentions earlier thinkers:

* Hippocrates (ca. 460 – ca. 377 B.C.E.): Cannon points out that Hippocrates recognized the role of “natures helping hand”, otherwise referred to as the doctrine of vis medicatrix naturae (the healing power of nature).[19]

* Cannon recognized that Hippocrates' healing power of nature “...implies the existence of agencies which are ready to operate correctively when the normal state of the organism is upset.”

* Eduard F. W. Pfluger (1829-1910), German physiologist: Cannon quotes Pfluger as having written in 1877:

* “"The cause of every need of a living being is also the cause of the satisfaction of the need", in the context of natural adjustments maintaining the stability of the organism.

* Leon Fredericq (1851-1935), Belgium physiologist: Cannon quotes Fredericq as having written in 1885:

* “The living being is an agency of such sort that each disturbing influence induces by itself the calling forth of compensatory activity to neutralize or repair the disturbance…[It] tend[s] to free the organism completely from the unfavorable influences and changes occurring in the environment.”

* Charles Richet (1850-1935) French physiologist: Cannon quotes Richet as having written in 1900, remarkably:

* "The living being is stable…"It must be so in order not to be destroyed, dissolved or disintegrated by the colossal forces, often adverse, which surround it. By an apparent contradiction it maintains its stability only if it is excitable and capable of modifying itself according to external stimuli and adjusting its response to the stimulation. In a sense it is stable because it is modifiable -- the slight instability is the necessary condition for the true stability of the organism."

## The work of Walter Cannon[edit]

There is online access to two key works of Walter Cannon that summarize his work and ideas:

* A 1929 extensive review article, "Organization for physiological homeostasis" [3]
* A 1932 famous and influential book, The Wisdom of the Body [4]

It may serve to emphasize the Cannon's concept of 'homeostasis' to quote from the latter work:

> The constant conditions which are maintained in the body might be termed equilibria. That word, however, has come to have fairly exact meaning as applied to relatively simple physico-chemical states, in closed systems, where known forces are balanced. The coordinated physiological processes which maintain most of the steady states in the organism are so complex and so peculiar to living beings -- involving, as they may, the brain and nerves, the heart, lungs, kidneys and spleen, all working cooperatively -- that I have suggested a special designation for these states, homeostasis. The word does not imply something set and immobile, a stagnation. It means a condition -- a condition which may vary, but which is relatively constant.

The quote also serves to indicate Cannon's view that homeostasis does not mean the "conditions of the body" will not vary. Though he sets the limits of variation as "relatively constant", he does not take into consideration the great variations in "conditions of the body" in the organism as it develops, in the case of mammals, from a single fertilized cell to a mature adult.

## The concept of 'internal environment' or 'internal milieu'[edit]

Applying to mammals, Cannon calls attention to the fluid environment of the organic processes occurring in cells and organs, considering that the volume of water alone makes up the bulk of body weight. Cannon considered also the chemical composition of that fluid matrix (or 'internal environment'), as well as its physical characteristics, such as temperature and pressure:

> In the main, stable states for all parts of the organism are achieved by keeping uniform the natural surroundings of these parts, their internal environment or fluid matrix. That is the common intermedium which, as a means of exchange of materials, as a ready carrier of supplies and waste, and as an equalizer of temperature, provides the fundamental conditions which facilitate stabilization in the several parts. This "milieu interne," as Claude Bernard pointed out, is the product of the organism itself.

## Living systems as 'homeostatic machines', self-fabricating, autonomous and cognitive[edit]

We can take an even broader view of homeostasis by relating it to the concept of 'autopoiesis' -- which in its simplest expression refers to autonomous self-fabrication. The concept was introduced in the 1970s by Humberto Maturana (b. 1928) and Francesco Varela (1946-2001),[20] though first enunciated, as pointed out in 2007 by J-H S. Hofmeyr,[21] by the philosopher Immanuel Kant (1724–1804),[22] and adumbrated by twentieth-century biologists before Maturana and Varela.[23]

Microbiologist Harold Frank elaborates on Kant's view:

> In a machine, [the German philosopher, Immanuel] Kant said, the parts exist for each other but not by each other; they work together to accomplish the machine's purpose, but their operation has nothing to do with building the machine. It is quite otherwise with organisms, whose parts not only work together but also produce the organism and all its parts. Each part is at once cause and effect, a means and an end. In consequence, while a machine implies a machine maker, an organism is a self-organizing entity. Unlike machines, which reflect their maker's intentions, organisms are “natural purposes.” Kant's vision was eminently sensible and remains true, but even he was stymied by the next stage: How can we ever discover the cause of that purposeful organization that is the hallmark of organisms?[24]

Any entity we recognize as living we recognize also as a ‘system’, an assemblage of components, interrelated structurally, interacting in a coordinated, dynamic, hierarchical way such as to self-construct an autonomously working organization characterizable as a ‘whole’ or ‘operational unit’ in virtue of a boundary selectively separating it from its environment — a kind of universe unto itself. We can hold that view of living systems regardless of the nature of the components that self-construct it, but on Earth we recognize those components as matter in the form of atoms and molecules, importing, converting, storing, releasing free energy, and actuated by it.

The precise description of the organization of living things differs widely among species. Think of an ant and an anteater. We can, however, specify characteristics of the ‘kind’ of organization that all species share here on Earth. For one thing, we can say a living system’s complexity exceeds current human cognitive ability to comprehend it, even with the aid of a powerful computer exo-cortexes. Arguably, in the future that characteristic of the organization in living things may prove non-constitutive.

We can say also that the organizational state of living systems resembles that of a man-made machine, like a super-jet airplane or a super-computer, though not made by man and not obviously having a purpose except to perpetuate its activity of living. We can think of a living system as a different ‘kind’ of machine than man-made machines. We can see that living machines exhibit a natural, or non-contrived ability to keep many of its internal variables constant, or within narrow bounds — it qualifies as a homeostasis machine.

A living system’s homeostatic ability plays a critical role in defining its uniqueness, as it enables it to homeostatically regulate the most important variable required for its continued living: an organization, whatever its description, that perpetuates its existence as a living system. Through the activity of its organization, the living system produces those components that provide the structural basis for the self-construction of its state as an autonomously working organization. If a living system cannot self-maintain its organization, it cannot produce the structure whose self-constructed coordinated interactions enable it to remain a living machine.

Autopoiesis co-founder Francisco Varela summarizes thus:

> Autopoiesis attempts to define the uniqueness of the emergence that produces life in its fundamental cellular form. It's specific to the cellular level. There's a circular or network process that engenders a paradox: a self-organizing network of biochemical reactions produces molecules, which do something specific and unique: they create a boundary, a membrane, which constrains the network that has produced the constituents of the membrane. This is a logical bootstrap, a loop: a network produces entities that create a boundary, which constrains the network that produced the boundary. This bootstrap is precisely what's unique about cells. A self-distinguishing entity exists when the bootstrap is completed. This entity has produced its own boundary. It doesn't require an external agent to notice it, or to say, "I'm here." It is, by itself, a self- distinction. It bootstraps itself out of a soup of chemistry and physics.”[25]

We can view a living system then as:

* A self-constructed machine organized as a network of interactions that fabricate, cyclically, the components whose self-organized interactions self-construct the system’s self-perpetuating network of interactions.
* A self-constructed machine organized as a network of interactions that can respond to perturbations either by self-correction of its disturbed organization (homeostasis), or by reorganizing itself into a different self-perpetuating network of interactions (adaptability; reproduction).

We can encapsulate that view of living systems preliminarily as ‘self-constructed self-perpetuating homeostatic machines’. Maturana and Varela[20] introduced the term ‘autopoiesis’ and ‘autopoietic organization’ to encapsulate that view of living machines as self-constructed self-perpetuating homeostatic machines as we have characterized them. Bitbol and Luisi expressed the definition of autopoiesis as follows:[26]

> The theory of autopoiesis...captures the essence of cellular life by recognizing that life is a cyclic process that produces the components that in turn self-organize in the process itself, and all within a boundary of its own making.

That view of a living system reveals a special property of homeostasis in living machines: adaptability. A human, to take an example mammal, self-perpetuates a life-sustaining organization despite enormous perturbations of its organization during embryonic and fetal ‘development’. It does it by self-reorganizing — the homeostatic property of adaptability. If we think a fetus or a child an immature adult, we must think of adults as aged fetuses or children. As one individual or identity, fetus and adult represent a single self-constructing self-perpetuating homeostatically adaptable machine.

Ontogeny highlights the living system’s unique property of homeostasis in targeting with highest priority the maintenance of an organization that produces components that self-organize a network of interactions that perpetuates that organization -- including its networks of interactions that retain its homeostatic property of adaptability. Homeostatic reorganization goes on continuously. The living machine maintains networks of interactions that define it as a self-constructing self-sustaining machine.

The self-constructed self-perpetuating homeostatic machine also produces its own boundary, as without that it could not maintain its organization against all the chaos outside.

A man-made, non-living machine yields products other than itself, products for human use. A living machine yields itself as its product, a product in continuous production, no matter how much it must modify itself in the process.

Therein defines the living machine’s autonomy —- it works in its own behalf to construct and sustain itself. So central to a living machine's uniqueness, its homeostatic organizational ability to produce components whose interactions self-organize a self-perpetuating organization, that, before accumulated perturbations of its organization overwhelms its homeostatic ability, the machine self-reproduces.

By this view, neither growth nor reproduction necessarily constitute ‘primary’ abilities of living machines, as both occur, in life on Earth, as the consequence of the homeostatic adaptable activities of the self-constructing organization that fabricates components whose interactions realize that organization, along with its homeostatic adaptability. On other worlds, living systems need not necessarily grow or reproduce, so long as they can, in some way, fabricate the components that can self-organize to construct the organization that can fabricate those components, including the system’s own boundary whose character enables its individuality and access to resources and waste disposal.[27]

Scientists can model and even synthesize experimental living machines that satisfy the basic criteria of a self-constructing self-perpetuating homeostatic machine (see[26]).

Access to resources alone cannot carry the day for a self-constructing homeostatic machine. It must have the ability, as part of its self-constructed organization, to recognize the resources it needs in order to sustain its organization. Recognition, however mediated, implies a type of ‘cognition’. In that case, for living machines to have an organization that produces the components that self-construct their-own component-producing organization, that organization must devote some of its activities to a type of cognition that enables it to recognize resources and import them and dispose of waste.

Those considerations dictate that a full description, or definition, of a living machine include the following:

* An organization of components capable of producing and reproducing, cyclically, the components that self-organize to construct the organization of components that produces those components;

* The components produced self-construct a boundary between the machine and the environment, of a nature that enables the machine to trade with the environment, acquiring the materials and/or energy required to sustain its self-perpetuating organization;

* The components produced self-construct an organization that has the cognitive ability to recognize the resources it needs to import and the wastes it needs to export.

* The components produced self-construct an organization that has the homeostatic ability to ‘correct’/’accommodate’ perturbations of the organization, or to reorganize appropriately to sustain a self-perpetuating organization;[28]

With those conditions realized, we can then ask about the details of the mechanisms or conditions that effect that realization in Earth’s living machines, whose components are molecules that self-construct networks comprising an organization that recursively constructs its components of such nature that the organization they produce can operate autonomously with homeostatic adaptability to sustain or reorganize itself as a cognizing compartmented system capable of escaping thermodynamic equilibrium through repeated self-reproduction.

## Homeostasis and longevity[edit]

Cell homeostasis, tissue homeostasis, and organ homeostasis determine organismic homeostasis [29]. Therefore the 'efficiency' with which cells, tissues and organs in maintain homeostasis would likely influence the longevity of the emergent organism.

To quantify the homeostasis efficiency of a complex system, even one low in hierarchy, like a eukaryotic cell, one might try valuating the degree/promptness of homeostasis of its major subsystems in response to a perturbation spectrum. But that could only quantify efficiency under the environmental conditions of the studies. Each different environmental condition might affect efficiency differently, and variably differently, in the various subsystems. Because an enormous number of environmental conditions test homeostasis-maintaining ability of the organism during a lifespan, one would need to obtain and integrate too much detail of human subsystems’ properties for any valuation of efficiency of homeostasis to have practical value in controlling human lifespan.

The property of 'lifespan' in the human system emerges only when organismic homeostasis fails completely and death results. A model that could predict lifespan long in advance of death, even one that age-modified the prediction, might lend itself to teaching how to treat the system to improve the efficiency of homeostasis of its subsystems.

What form would such a model take? For personal benefit -- a major goal of aging research -- the model would seem to require itself to extensively interrogate the individual human system before running its lifespan-predicting algorithm. And do such interrogation time after time as time goes by. One would want the model’s systems readout, however implemented and interpreted in relation to previous readouts, followed by a prediction of lifespan as well as a prescription of steps to take to reverse damage and improve homeostasis-maintaining ability. A massive-load-capable information-gathering-and-processing method, abstract, computational: a cyber-smart doctor, distributed geographically or miniaturized.

But that ideal model allows control of lifespan for extreme longevity, as opposed to merely extending it substantially beyond present norms. Yet, learning to extend lifespan substantially may crucially underpin any model that permits control of lifespan for extreme longevity. Minimized energy consumption in the form of food extends lifespan in diverse genera. That would seem to have potential for obese humans, but not necessarily for non-obese humans. We do not know whether calorie minimization, ceteris paribus, extends lifespans in non-obese humans. If it did, we might want to revise our quantitative criteria for obesity to retain its connotation of poor health. We have no firm idea what body mass indexes, or percent body fat, however adjusted for other anthropomorphic variables, associate with human lifespans substantially greater than current norms.

Depending on how extreme the possible longevity, achieving it may require the complex task of controlling the entire human environment, the biosphere at minimum. Hopefully, but likely, all humans will require a large core-biosphere-set of common conditions, however geo-regional, for super-efficient organismic homeostasis. In recognizing that, the motivation of individuals for youthful longevity may impel them to interact in ways to achieve that common set of conditions. Sacrifices might involve opposing nature’s algorithmic drive to reproduce. Doing that would step us closer to the question of optimal sustainable population size, and if one can be determined satisfactory, how to achieve that ethically.

The property of lifespan has interest because the desirer of longevity wants a long healthy mental life, a long-lived kingdom of the mind. Why? Because as one’s knowledge increases so do the number of paths for curiosity to pursue -- and a healthy youthful mind dictates the exercise of curiosity. Often one has ambitions and goals that require many prolonged stages. Those who do not believe in ‘afterlife’ feel they should get the greatest possible satisfaction from living before dying. Living longer increases the chances of participating in breakthroughs to extreme longevity.

Though some suggest the possibility that someday supercomputers, perhaps quantum computers, will have the ability to simulate the processes that generate conscious and self-conscious experience in simulated humans living in a simulated biosphere [30]. For all we know, we live as a simulation in a simulated world, as an experiment, perhaps an iterative run of a model program developed by model-building systems scientists beyond our ken.

## References[edit]

#### Citations and notes[edit]

1. ↑ Anonymous. (1963). Walter Bradford Cannon (1871-1945). The Physiologist 6(1): 4. Link to PDF

* A brief biography of physiologist Cannon.
2. ↑ Cannon WB. (1926) Physiological regulation of normal states: some tentative postulates concerning biological homeostatics. In: Jubilee volume to Charles Richet. Paris: Editions Medicales, 1926:91-93. (Cited in Cannon WB 1929: see below)
3. ↑ 3.0 3.1 Cannon WB. (1929) Organization For Physiological Homeostasis. Physiol Rev 9:399-431.

* Note use of word 'organization' (see article 'Life' at [1])
4. ↑ 4.0 4.1 4.2 4.3 Cannon WB. (1932) The Wisdom of the Body. W.W. Norton
5. ↑ Silverthorn DU, Ober WC, Garrison CW, Silverthorn AC, Johnson BR. (2007) Human Physiology: An Integrated Approach. 4th Edition. Page 5. Pearson Benjamin Cummings, San Francisco. ISBN 0-8053-6849-3. “Human Physiology: An Integrated Approach broke ground with its thorough coverage of molecular physiology seamlessly integrated into a traditional homeostasis-based systems approach.”
6. ↑ Ashcroft FM. (2007) The Walter B. Cannon Physiology in Perspective Lecture, 2007. ATP-sensitive K+ channels and disease: from molecule to malady. Am J Physiol Endocrinol.Metab 293:E880-E889. PMID 17652156.

* Note: From the Introduction: "WALTER BRADFORD CANNON (1871-1945) was an eminent American physiologist who pioneered the concept of homeostasis. In his seminal text, The Wisdom of the Body, he described it [homeostasis] as "the coordinated physiological reactions which maintain most of the steady states in the body." Among these steady states...."
* Cannon's words: "The coordinated physiological processes which maintain most of the steady states in the organism are so complex and so peculiar to living beings -involving, as they may, the brain and nerves, the heart, lungs, kidneys and spleen, all working cooperatively- that I have suggested a special designation for these states, homeostasis."
7. ↑ Lovelock J. (2007) [http://encarta.msn.com/sidebar_701616168/Gaia_Theory.html Understanding Gaia Theory] Encarta Encyclopedia.
8. ↑ Michael L Power (2004). “Commentary: Viability as opposed to stability: An evolutionary perspective on physiological regulation”, Jay Schulkin, ed: Allostasis, Homeostasis, and the Costs of Physiological Adaptation. Cambridge University Press, p. 347. ISBN 9780521811415.
9. ↑ Jonathan Bard (1992). Morphogenesis: The cellular and molecular processes of developmental anatomy. Cambridge University Press. ISBN 9780521436120.
10. ↑ Michael J Angilletta, Jr. (2013). “§III.13: Biological and physiological adaption”, David A. Baum et al. eds: The Princeton Guide to Evolution, pp. 282 ff. ISBN 9781400848065.
11. ↑ Michael L Power, Jay Schulkin (2009). The evolution of obesity. John Hopkins University Press. ISBN 978-0801892622.
12. ↑ Biology Online
13. ↑ 13.0 13.1 For example, see David O. Norris, James A. Carr (2013). “A homeostatic reflex model”, Vertebrate Endocrinology, 5th ed. Academic Press, pp. 14 ff. ISBN 9780123964656.
14. ↑ 14.0 14.1 14.2 See, for example, Lauralee Sherwood (2005). Fundamentals of Physiology: A Human Perspective, 3rd ed. Cengage Learning, p. 14. ISBN 9780534466978.
15. ↑ Laura Freberg (2009). “Homeostasis: Regulation of body temperature”, Discovering Biological Psychology, 2nd ed. Cengage Learning, pp. 256 ff. ISBN 9780547177793.
16. ↑ Virtanen R. (1960) Claude Bernard and His Place in the History of Ideas. University of Nebraska Press, Lincoln.
17. ↑ Fulton JH. (1931) Physiology Clio Medica series, no. 5, New York, p. 112.
18. ↑ Gross CG. (1998) Claude Bernard and the Constancy of the Internal Environment The Neuroscientist 4:380-385
19. ↑ Bynum WF. (2001) Nature's helping hand. Nature 414:21 PMID 11689921 Link to Full-Text

* From Bynum’s article: “The Hippocratic physicians identified one potential answer: the healing power of nature. Doctors, they taught, are merely nature's servants. They took their diagnostic and therapeutic cues from what they could observe at the bedside — sick people, especially patients suffering from acute illnesses, often sweat, vomit, have diarrhoea, are pale, flushed or jaundiced, cough up phlegm or blood, lose their appetites, and develop pustules or rashes. The Hippocratics interpreted these signs and symptoms as evidence that the body is a marvellous mechanism with an innate capacity to restore the natural humoral balance that constitutes health. Their ministrations were generally aimed at assisting and encouraging these natural processes.”
20. ↑ 20.0 20.1 Maturana HR, Varela FJ. (1973) Autopoiesis: The Origin of the Living. In: Autopoiesis and Cognition: The Realization of the Living. D. Reidel Publishing Company, Dordrect:Holland. ISBN 90-277-1015-5
21. ↑ Hofmeyr JH (2007) "The biochemical factory that autonomously fabricates itself: A systems biological view of the living cell." In: Boogerd FC, Bruggeman FJ, Hofmeyr JH, and Westerhoff HV (editors). Systems Biology: Philosophical Foundations. Elsevier, Amsterdam. ISBN 13:978-0-444-52085-2 (see page 225)
22. ↑ Immanuel Kant. Kant’s Critique of Judgement, translated with Introduction and Notes by J.H. Bernard (2nd ed. revised) (London: Macmillan, 1914).

* For a body then which is to be judged in itself and its internal possibility as a natural purpose, it is requisite that its parts mutually depend upon each other both as to their form and their combination, and so produce a whole by their own causality; while conversely the concept of the whole may be regarded as its cause according to a principle (in a being possessing a causality according to concepts adequate to such a product). In this case then the connexion of effective causes may be judged as an effect through final causes. In such a product of nature every part not only exists by means of the other parts, but is thought as existing for the sake of the others and the whole, that is as an (organic) instrument. Thus, however, it might be an artificial instrument, and so might be represented only as a purpose that is possible in general; but also its parts are all organs reciprocally producing each other. This can never be the case with artificial instruments, but only with nature which supplies all the material for instruments (even for those of art). Only a product of such a kind can be called a natural purpose, and this because it is an organised and self-organising being. [Emphases added]
23. ↑ Alexander J. (1948) Life: Its Nature and Origin New York: Reinhold Pub. Corp.
24. ↑ Harold FM (2003) The Way of the Cell: Molecules, Organisms, and the Order of Life New York: Oxford University Press. p220.
25. ↑ Varela F. (2001) The Emergent Self. In: The Third Culture, by John Brockman. Chapter 12.
26. ↑ 26.0 26.1 Bitbol M, Luisi PL (2004) Autopoiesis with or without cognition: defining life at its edge. PMID 16849156
27. ↑ Varela FG, Maturana HR, Uribe R (1974) Autopoiesis: the organization of living systems, its characterization and a model. Curr Mod Biol 5:187-96 PMID 4407425

* "We assert that reproduction and evolution are not constitutive features of the living or¬ganization and that the properties of a unity cannot be accounted for only through ac¬counting for the properties of its components. In contrast, we claim that the living organiza¬tion can only be characterized unambiguously by specifying the network of interactions of components which constitute a living system as a whole, that is, as a "unity"."
* "We also claim that all biological phenomenology, including reproduction and evolution, is secondary to the establishment of this unitary organization."
* "Thus, instead of asking "What are the necessary properties of the components that make a living system possible?" we ask "What is the necessary and sufficient organization for a given system to be a living unity?" In other words, instead of asking what makes a living system reproduce, we ask what is the organization reproduced when a living system gives origin to another living unity?"
28. ↑ Note: Taking homeostasis to mean stability of self-construction and self-sustenance, a living machine might achieve that by incorporating the perturbation (e.g., a foreign molecule) into its organization.
29. ↑ Adam and Eve Don't Want to Get Old: New Strategies for Fighting Aging. Annals of the New York Academy of Science, Annals Extra. 8-29-2006
30. ↑ Tipler FJ. (1994) The Physics of Immortality: Modern Cosmology, God and the Resurrection of the Dead. New York: Doubleday