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It is commonly acknowledged that the root causes of both disease and health involve multiple agencies. The summary figure of the determinants of health provided in Healthy People displays multiple contributing agencies within an interactive matrix formulation Figure 1.

1841 - 1935

Nearly the entirety of the March—April issue of Health Affairs was devoted to the determinants of health and emphasized the social ecology in which health is enmeshed. Deaton lamented the ignorance of the biological determinants that are not revealed by clinical measurements and that are obscured by the long time interval between cause and outcome. I explore these biological determinants of health and provide a new simple conceptual framework for their consideration.

I hope that such a proposition assists in strategic planning that differentiates those determinants that are tractable and those that currently lie outside clinical approach. To establish a conceptual framework for the biological determinants of health, I propose 4 discrete agencies. The metaphor of car health may help establish this scheme. The life of a car depends on 4 elements: design, accidents, maintenance, and aging. These same 4 categories apply to the human organism but are more appropriately designated as 1 genes, 2 external agency, 3 internal agency, and 4 aging.

I propose that these 4 factors account, occurring in innumerable combinations and chronologies, for the totality of the human health experience, both individual and collective. The 30 gene human genome was widely touted as the ultimate determinant of well-being and illness. This conjecture has now largely been displaced by the recognition that genes actually represent only restricted arbiters of health whose repertoire depends on differential cueing. An approach widely used to quantify genetic contribution is to investigate the health history of identical twins.

If genes were ultimately determinative, and the other 3 agencies were only negligible factors, identical twins would die simultaneously of the same disease. This situation is far from the case. Common neurological diseases of older persons have been shown to have low concordance among twins. Throughout recent history, the major threat to human health has been the byproduct of an adverse encounter with a hostile threat.

Pasteur demonstrated that the previously held attribution of sickness to metaphysical punishment motifs was wrong and that a microbe was more properly labeled as the devil. The varieties of health threat that the external world presents are immense in scope and timing. Injury, infection, and malignancy each are huge demerits.


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These threats may diminish the health reserve catastrophically or may conspire through the accumulation of trivial or sequential insults. In my opinion, the conditions involved in external agency are responsible for the development of the majority of the current medical enterprise of hospitals, surgery, technology, and pharmacy. Medical science has gaudy credentials gained by confronting the conditions secondary to faulty external agency. Technical advance has allowed address and redress of countless illness states that were unapproachable just a few decades ago.

In addition, the issue of prevention is presented when considering external agency as a health determinant. Most infection, injury, and malignancy is preventable—and preventing them is a strategy far preferable to curing them cheaper, too. The era of the dominance of external agents as prime determinants of health has been replaced by the reality of disordered internal function as the principal causes of the chronic illness patterns prevalent today.

Conditions caused by faulty internal agency do not feature a dominant external perturbation. These conditions tend to involve the entire system rather than components as in external agency problems. Instead of the environment being a threat to well-being, internal agency connotes an appropriate and constant interplay of the host and environment. The environment becomes the source of organic order, stability, and, therefore, health. This new conceptualization is captured by the term homeodynamics, as specified by Yates.

Homeodynamics is a substantially more effective term than homeostasis, helpfully supplied by Cannon more than 80 years ago. The extraordinary plasticity of all parts of our body is a vivid demonstration of how form follows function and how the body is constantly remodeling in response to the energetic field in which it is immersed.

We become what we do through homeodynamic reshaping at every level. Environmental interfacing with a healthy body has 2 primary expressions: fuel and energy. The role of adequate nutrition in health maintenance has been voluminously documented. Excesses and deficiencies exact certain tolls.

Less well displayed is the health risk posed by inappropriate energetic stimulation. This maladaptation becomes increasingly important as age proceeds. This misapplied energy comes in 2 forms: too much and too little. Too much energetic interfacing is known by the term stress; too little is known as disuse.

Both have vast negative consequences on the afflicted organism, and both are inadequately recognized as basic health threats. Part of the reason for their lack of proximal recognition, diagnosis, and treatment is the long timeline from cause to effect. Selye first elaborated the diverse spectrum of stressors with which organisms are assaulted. The converse of stress is disuse; disuse means too little energetic interchange, usually manifested through a sedentary lifestyle.

Each of these diverse components has discrete, deterministic mechanisms that relate insufficient energetic throughput to the frequently observed disease byproduct. They are not genetic or externally produced, nor are they secondary to aging per se; instead, they are the byproducts of protracted disuse. The most vivid demonstration of disuse occurs in muscle.


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The energy transduction and gene expression details inherent in this remodeling are now known in great detail. A physically fit person exhibits a decline in VO 2 max at the rate of 0. This is not the result of bad genes or extrinsic agency or aging; it is the result of faulty internal agency.

In my opinion, this category—defective internal agency—is the predominant determinant of failing health in older people, particularly because chronic, time-sensitive illnesses are our most common demons. Unfortunately, the competence of the medical enterprise and its curing mission finds only limited success with the conditions attributable to defective internal agency. Heart disease, arthritis, type II diabetes, and strokes are palliated at great cost, but they are not cured.

However, they are preventable through redress of energetic imbalance and nutritional excess. The participation of the process of aging in the human condition has long been the province of playwrights, theologians, and charlatans.

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Only recently has aging been held to rigorous analysis. No longer is it considered a disease susceptible to a curing potion, gland, or surgery. Aging is wear and tear minus repair. In the past 10 years, 2 reports provided a vital, quantitative measure of the basic rate of aging. This figure is thought, therefore, to represent the underlying rate at which health reserves are debited, specifically, because of chronological, entropic age process. The 0. Such declines are commonly ascribed to aging. However, these declines are caused not by aging but by more tractable agencies.

Consideration of the healthy state leads directly to an estimate of the functional capacity of the organism. A wide range of function assessment tools exist, ranging from daily activity rating scales to technical physiological measurements. The recognition that there is a maximum, total capacity is intrinsic to an effort to assess the amount of health an organism possesses.

Health not only exists at the basal resting state but also exhibits substantial reserve. Such reserve relates clearly to the evolutionary need for organisms to withstand environmental perturbation of substantial variety and extent. Food and fluid availability, temperature extremes, elevation, and energetic loads are the major challenges.

For example, a Tour de France cyclist may expend calories per day for a month, which is several times basal energetic turnover. Physical conditioning implies a full expansion of reserve capacities in which linked, but separate, bodily functions scale together. This systemic, morphological, and physiological reaction to an increased load lies, in my view, at the heart of why physical exercise displays such a wide scope of anabolic benefit.

Many other capacities—cardiac reserve, oxygen transport, neurotransmitter levels, muscle power, arterial cross-section, creatinine clearance, liver mass, sensory and cognitive capacities—exhibit similar safety margins. The clustering of serious medical encounters and expenses in a small minority of persons is repeatedly noted. In the real world, health is determined by a summation of the effects of 4 listed agencies.

What is crucial to observe, however, is that only those determinants caused by faulty external and internal agency are susceptible to clinical intervention. Genetic aberration and the process of aging, which, although theoretically approachable, are still remote in their practicability. Redress of disordered external and internal agencies, which quantitatively are the major biological determinants of health, is eminently practicable, and attention to the behavioral causes of these causes appears acutely necessary.

Such active pursuit is the most likely strategy to succeed in fulfilling the goals of Healthy People PMID: Biological Basis of Determinants of Health. Affiliation Walter M. Bortz MD Walter M. CopyRight Peer Reviewed.

📌 Oliver Wendell Holmes, Sr.

Iglehart JK. Old and new make the warp and woof of every moment. There is no thread that is not a twist of these two strands. A great man quotes bravely, and will not draw on his invention when his memory serves him with a word as good. Self-respect is the early form in which greatness appears. And none of us will ever accomplish anything excellent or commanding except when he listens to this whisper which is heard by him alone. If to follow this native bias is the first rule, the second is concentration. It is this: Every man I meet is my master in some point, and in that I learn of him.

As many as our affinities. But to a practical purpose we may reckon a few of these.