Machine aging

Aging theories are generally pessimistic. As we approach our end we can do very little about it. This fatalistic view originates in studies on machine aging.  Wear and tear cause machines to break down and engineers  attempt to predict its deterioration rate. Reliability theory was designed to estimate machine survival. The longer a machine exists (survives), the more errors it accumulates until it stops functioning.  Poisson like distributions are therefore applied for modeling machine survival.

The organism is a complex machine

Machine statistics are applied also to estimate human survival. Actuaries calculate insurance premiums, and  epidemiologists derive their conclusions from machine statistics.  As long as these methods remain descriptive no major harm is done . However when interfering with therapy, they may have serious consequences, known as Iatrogenesis. Machine statistics are applied  by Evidence based Medicine to define the normal and the pathological, and determine what requires treatment (repair).  Now a days hardly anybody is normal, since his risk to become ill continually increases.

Damage  accumulation

No wonder that most aging theories are pessimistic. Most  regard aging as an accumulation of damage. Medawar proposed that aging was caused by accumulation of random mutations causing adverse aging characteristics. The modern culprit is known as Reactive Oxygen Species,  which are forms of oxygen that are potentially destructive to tissues. Our body carries its own destructive molecule which is brought about by oxygen.

Hayflick limit

In 1961 Leonard Hayflick and Paul Moorhead  demonstrated that human cells in culture can only divide a limited amount of times. This phenomenon, is called  replicative senescence.  Hayflick's theory  illustrates two pitfalls. He presumed that cells in culture had all that is needed for survival, which may not be so. An undetectable  deficiency of a growth factor may let cells divide only a  limited amount of times. After all most cancer cells can divide in vitro for ever.

The second pitfall is known here as context fallacy,   A phenomenon discovered in a narrow context (petri dish) is applied as such to the  wider context of the organism. Certain cell lines such as hemopoietic cells, bone marrow,  epithelial cells  in the skin and gastrointestinal mucosa, endure many more population doublings in vivo than they do in vitro. Hayflick limit is a laboratory artifact which does not apply to the organism.

Telomeres are the latest incarnation of 'replicative senescense'. They are the tips of chromosomes and get shorter at each division. Short telomeres cause growth arrest and the cell dies. 

True, death is inevitable, yet aging may be pleasant. Our aim here is to slow down aging an postpone death.

A simple model

What we perceive as aging is defined here as  disease indicator (DI), and we are concerned here with what drives it? In order to simplify the forthcoming arguments we shall assume that aging is  driven by a gradual loss of cells due to ionizing radiation from outer space, rocks, and the soil. Ionizing radiation produces several changes that are comparable to those observed during normal aging. It decreases life expectancy. After radiation of a young population, the observed death rate corresponds to the death rate of an older group. Following radiation, there is a reduction in the number of viable cells in many tissues.

Use it or lose it

The cell number in a tissue depends on the birth and death rates of its cells which is controlled by WOB. When the demand rises WOB increases birth rate (+), reduces death rate (-) and the cell number increases, and vice versa. WOB may be instructed by the mind to produce more cells, like during exercise. When we (the mind) decide to join a fitness club, we raise the demand on our muscles. WOB raises the birth rate and muscle mass increases. In other words our will can force WOB to produce more cells. The relationship between the mind and WOB is summarized by "Use it or lose it". If the mind decides to "use it" we may slow down aging. Yet as aging progresses, the capability of WOB to respond to external demands declines. This capacity is defined also as tolerance.

The following image illustrates that a machine does not generate new components (no birth rate). From the time of its production its parts gradually deteriorate and die. It can not slow down its aging. In order to improve machine reliability it may be provided with extra parts which later replace the damaged ones. Such a redundancy prolongs machine survival.

Unlike machine, WOB continually produces new cells  and is capable of slowing down aging. This model indicates that human aging  is more than an ongoing accumulation of errors, some errors are removed by dying cells and are replaced with intact new cells. Despite this, death rate always slightly exceeds birth rate.

Apoptosis or programmed death

The cell contents of the body   depends on  cell birth and death rates . When  demand for cells  is high,  birth rate rises, death rate declines, and  cell number rises, and vice versa. Cell production and destruction are controlled by WOB and so is aging. Since organism maintains homeorhesis (homeostasis)  each dead cell is replaced with a new one, and birth rate = death rate. Aging proceeds from  one homeorhesis state to another. We ought to distinguish between two causes of cell death: 1. Independent, driven by radiation, and  2. WOB controlled death, or apoptosis. WOB can reduce death rate and thus prolong cell survival.

Although programmed death is observed in cells, it is proposed by some scientists that it determines survival of the organism (yet another context fallacy). Accordingly  the organism is programmed to die at a certain time, and programmed death is stored in the genes.

Solution

WOB controls all processes and adjusts them to meet the demand of the organism, constrained by environment and mind. When it gets cold WOB turns the heat  on, and vice versa.  WOB responds  also to the mind, which receives signals and directives from society (culture). The adjustment of  processes at any instant is called WOB solution.  It is always the most optimal solution in circumstances.

Aging proceeds in an optimal fashion

This optimality principle underlies also the evolution of  aging. At any instance WOB adjusts processes so as to make the organism  optimal. What may appear to the observer as a change to the worse  is an evolution of optimal solutions.  It is plausible that radiation causes aging however other factors also contribute to it, yet only WOB knows what really drives aging  and  adjusts its solutions accordingly. We may therefore ignore what drives aging,  and focus on WOB solutions.  Replacement  of lost cells is the only drive for cell birth.

Aging is an ongoing cell depletion. It proceeds through three phases:

1. Full compensation: Linear decline of performance (linear aging). Patient feels healthy.
2. Decompensation,   Gradual deepening of ischemia. Accelerated  decline of performance. Patient  suffers from secondary manifestations due to ischemia (accelerated aging).
3. Total  decompensation, or excessive cell loss (pancytopenia) and weakness.

Anti aging

From birth to adulthood organism grows, accumulates cells, and cell birth rate > death rate. Tissues are made of units, each nourished by a long-lived stem cell which breeds  short-lived transitional cells.   During growth tissues get new units, and since each is nourished by a stem cell, the  number of stem cells in the body increases.  Despite being exposed to radiation the cell content of the growing body rises.  Cell birth rate exceeds death rate. Since aging is regarded here as an ongoing cell loss, aging actually starts at adulthood, and growth has an anti aging effect.

In this sense bacterial population does not  age. When a microbe divides, one progeny replaces the dividing parent, and the other is added to the population (birth rate > death rate). Individual bacteria may age and some even die, but the bacterial population as a whole, which is regarded here as an organism, does not age.

Anti aging reserve (stem cell redundancy)

The more stem cells (units) a young adult gets the better is he equipped  for aging. Like machines which survive longer with redundant  parts. Malnutrition, infections,  and other diseases, retard growth, and the adult comes up with a smaller stem cell pool. 

Full compensation

When  radiation kills transitional cells they  are swiftly regenerated by their parent stem cells. However death of stem cells results in the loss of tissue units (atrophy) which  regenerate extremely slowly.  In other words, when a tissue unit is hit, and radiation kills only transitional cells, the unit regenerates (per primam). When stem cells die, the entire unit is lost (atrophy).  Stem cells are undifferentiated and resist radiation better than transitional cells. Aging thus results from stem cell loss.

Decline of 'physiological' functions

From the age of twenty and on, WOB adjusts processes so as to make up for the loss of tissue units. It sends the mind the message: "Take it easy and do not rush!", and all the so called physiological functions, e.g.,  breathing capacity, muscular mass, bone density, hormonal activity, decline  linearly.  When activity declines more than WOB requires,  it dismantles also inactive units, as it does to astronauts in space. We may distinguish between two kinds of cell loss:1. Stem cell depletion (hypoplasia), caused by radiation, and 2. Transitional cell depletion (unit hypotrophy) which results from disuse. While unit loss is generally irreversible, unit hypotrophy is not. It can be reversed by forceful activity.

Decompensation

Decompensation starts when blood supply to tissues declines. Capillaries are very sensitive to radiation. When endothelial cells are killed,  capillaries  get clogged, and blood supply to tissues declines. Capillaries supply also blood to the walls of blood vessels, like arteries and veins (vasa vasorum). When they clog blood vessels become arteriosclerotic. Deepening ischemia destroys entire tissue units, and depletes stem and transitional cells. The so called age related diseases, e.g., myocardial and cerebral infarctions (heart attack and stroke), senile cataract, senile dementia, osteoporosis , and arthritis, are the outcome of ischemia. 

During compensation WOB task is to  maintain adequate function  in spite of deepening pancytopenia.  During decompensation WOB has to handle also the ensuing diseases, as described in the chapters on diabetes mellitus, and Parkinson's disease

Even when most functions decline and it appears as if the body deteriorates, WOB solutions are the best in the circumstances.

Physician's role

During compensation phase WOB is silent and patient feels healthy;  she starts suffering  when decompensation ensues. The physician's role is to slow down the decline of physiological functions (linear aging), and so delay the onset of decompensation (accelerated aging). WOB solves  the immediate requirements of the organism and  is not concerned with what happens next. Its attitude might be summarized by "carpe diem" (reap now).  The future ought to concern the physician, and the future means to maintain adequate activity.

Exercise

The next image depicts how exercise keeps us fit. When a tissue unit dies, the neighboring units elongate (hypertrophy) and perform its tasks. This process is driven by activity. When experiencing tissue damage WOB signals the mind fatigue, as if saying:"take it easy, I lost some resources and cannot assist you as before."  If mind yields to WOB urge, tissue units will shrink. On the other hand if mind decides to exercise they enlarge.

Mind aging

Aging is also a disease of the mind. Mind receives signals from society and conveys them to WOB. Yesterday it retired from work and feels rejected. It sends WOB a message like: "why bother? "and WOB starts dismantling units like in astronaut disease. Mind aging accelerates linear aging and  drives the patient into decompensation. Meditation is an effective way to reduce mind aging.

Hormone replacement therapy (HRT)

Medicine spreads the myth that hormone treatment slows down aging, while the opposite is true. The chapter on Parkinson's disease  illustrates why.  During menopause, WOB  reduces estrogen production since this is  best for the organism. Most of the hormone is produced by the adrenal. When external estrogen is supplied estrogen level rises above an optimal level, and  WOB  dismantles estrogen producing units, until the  optimal estrogen level has been restored. Cell birth rate declines and death rate rises.  Since cell death rate rises, aging is accelerated.  

Testosterone

Anabolic steroids are synthetic substances related to  male sex hormones (androgens). They promote the growth of skeletal muscle (anabolic effects) and the development of male sexual characteristics (androgenic effects). They  control muscle metabolism , and  have some grave side effects. Like  estrogen, they impede production of internal testosterone. Since muscles require testosterone, one may raise its level by training.  Exercise raises testosterone production in a natural way.  One wonders  what might raise estrogen production?  Since muscle building does not raise estrogen, what else might raise it?

Raising the level of sex hormones slows down linear aging

Which may be achieved by sexual activity. Yet there are other ways to raise the hormone level, suitable for individuals which cannot engage themselves in sexual activity. Here we rely on two powerfully instincts: imitation and imagination. When watching erotic movies, the mind identifies itself with the episode inducing WOB to activate processes engaged in sexual activity which raise also the hormone levels. (v. experiments on empathy).

Active interest in the opposite gender also activates sexual processes. Like watching the breasts of an attractive female, and imagining them being caressed and so on.

WOB in old age

Medicine regards the aged organism as decayed and helpless. Actually as  one gets older WOB becomes more experienced, and wiser. An elderly does not get childhood disease, since his WOB knows how to handle invading bugs. Some changes in the appearance of old people reflect a more optimal design which is more pronounced  during  linear aging, and less during decompensation. Any decompensation is still the most optimal WOB solution in circumstances.

Even cancer is handled better in old age. This may come as a surprise since in old age cancer is more prevalent. Tumor formation is a response to stem cell depletion, and since aging is an ongoing pancytopenia, tumor incidence rises. However in old age tumors grow slower than in young.  Medicine attributes it to the decaying organism which lacks resources to adequately nourish tumors. Actually tumor grows slower since WOB learned how to control it better. Every elderly carries the secret of a Cancer-Yogi.

Age limit

Outside the organism stem cells may proliferate rapidly, and for ever, and  in  the body this capacity is lost. In the body each cell is innervated. Besides serving as action potential carriers, nerves control target cell metabolism, which is known as trophic effect .  A denervated stem cell dies. Like in peripheral diabetic neuropathy, which deprives cells from the trophic control.  Leg tissues become atrophic, and the outcome is an ulcer.

Radiation kills also nerve cells, which regenerate extremely slowly. When a stem cell is killed, the availability of innervation will determine the rate of stem cell replacement (birth rate).  The ultimate rate of aging is set by the CNS, and since it is particularly sensitive to ischemia, brain aging accelerates decompensation.

Life is action, and adequate activity slows down aging. WOB is not concerned with slowing down aging. It aims to  maintain life at minimal cost (optimality). WOB will oppose any unnecessary activity, and has to be forced by the mind to do so. Which is the essence of free will.

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