The Current Paradigm and Age-Associated Disorders

THE CURRENT PARADIGM AND AGE-ASSOCIATED DISORDERS

“The science of today is the technology of tomorrow.”

Edward Teller

The first of Thomas Kuhn’s three prerequisites for paradigm shift is dissatisfaction with the prevailing paradigm. A number of essays in this website discuss how the current aging paradigm is simply not an accurate depiction of reality. Other essays discuss why the current paradigm not only isn’t an accurate depiction of reality but, why, since it is inconsistent with the principles of natural selection, it’s impossible for it to be consistent with reality. Since a paradigm is the set of preconceptions that is assumed to represent reality, the fact that the current paradigm is inconsistent with reality is sufficient cause to be dissatisfied with it.

This essay will address reasons for dissatisfaction with the current paradigm from a practical standpoint. A significant real world problem confronting aging science is age-associated physiological disorders, including the age-associated degenerative diseases, such as osteoporosis, most cardiovascular disorders and dementia. Scientists are at a loss to explain what causes those diseases. These diseases are recognized as clinical events when an organ or system becomes critically dysfunctional. The relatively recent scientific “breakthrough” was the realization that age-associated degenerative diseases, like the other infirmities associated with chronological aging, are the result of decades of accumulation of intrinsic damage. That doesn’t advance the ball at all, because scientists lack the knowledge of what causes that damage to accumulate. Under the current paradigm, damage accumulation is assumed to be an integral part of a natural and inevitable aging process. As a result, the flawed preconceptions in the current paradigm have rendered it impossible for the medical community to develop a coherent approach to the problem of age-associated degenerative disease.

Life sciences technology is constantly advancing, just like technology in all other areas. But without the scientific knowledge of what causes aging-associated degenerative diseases, advances in technology can provide only limited results. Pharmaceutical interventions can ameliorate some symptoms of these diseases and advancing medical technology can keep terminally ill patients alive for a longer period of time, but the identifying characteristic of a chronic degenerative disease is that it cannot be prevented or cured. Until science can identify the cause of the disorders, i.e., what causes the damage to accumulate, improved technologies alone won’t be able to solve the problem.

In the absence of a means to address the cause of the diseases, the approach to the age-associated degenerative diseases is much like the approach to infectious diseases prior to the acceptance of the Germ Theory. Identify risk factors based on statistical correlations and try to control those factors. But the identified risk factors (e.g., smoking, stress, obesity) typically act on the damage side of the equation by accelerating the rate at which damage is inflicted. Even if all such factors are controlled, intrinsic damage slowly accumulates over time, and ultimately some organ or system fails. Lacking the knowledge of why the damage accumulates (and assuming that that accumulation is natural), the medical establishment can treat only the symptoms rather than the underlying cause of the disorders.

Infectious Disease Approach

Infectious diseases are disorders caused by organisms — such as bacteria, viruses, fungi or parasites. Many organisms live in and on our bodies. Most such organisms are normally harmless or even helpful, but under certain conditions, some organisms may cause disease. Some infectious diseases can be passed from person to person. Some are transmitted by bites from insects or animals. And others are acquired by ingesting contaminated food or water or being exposed to organisms in the environment.

Until relatively recently in human history, the majority of humans that survived childbirth and were not killed in wars or accidents died from infectious diseases. Thus infectious diseases were the primary focus of medical care. Prior to the acceptance of the Germ Theory of Disease late in the 19th century, there was no generally accepted theory that explained what caused infectious diseases. In the absence of scientific knowledge, infectious diseases were treated much like age-associated degenerative diseases are treated today. Efforts were made to control risk factors, such as unclean water, but once a subject came down with an infectious disease, all the medical establishment could do was treat symptoms.

The Germ Theory has enabled the development of medical technology that is remarkably adept at dealing with infectious diseases. The standard approach is to determine what the invading pathogen is, and then introduce a pharmaceutical intervention that assists the body in either warding off (vaccines) or neutralizing (antibiotics) the pathogen.

The infectious disease approach has been remarkably successful in eradicating many infectious diseases, such as smallpox, and in prescribing effective treatments for other infectious diseases. Success in preventing and curing infectious diseases has greatly lengthened life expectancy, especially in developed countries. With that success and greater life expectancy the age-associated degenerative diseases have emerged as the major health problem.

For a variety of reasons, the infectious disease approach is ineffective when the disorder is an age-associated degenerative disorder. Since these disorders are not caused by a specific pathogen, none of the conclusions that can be derived from identifying that pathogen are available. There is no pathogen to be neutralized, so a traditional infectious disease “cure” is not possible.

Typically with an infectious disease, an intervention that has the effect of interfering with some process that is essential for the survival of the causative organism is sufficient to initiate a cure. The intervention doesn’t necessarily kill off the organism. The purpose of most interventions is to help the body’s immune system carry out its function of neutralizing invading organisms so that the body can then recover on its own. With degenerative diseases, a statement such as “Alzheimer’s disease is attacking the brain” is inaccurate. The primary symptom of all age-associated degenerative disorders is that an organ or system is not functioning as well as it should, with that dysfunction being the result of years of physiological deterioration. No organism is causing that deterioration, so there is nothing attacking the body and nothing to neutralize. Moreover, since the deterioration is the result of the failure of the maintenance system to prevent damage from accumulating, the concept of interfering with some process to allow the body to recover has no meaning.

Although using the infectious disease approach for age-associated degenerative diseases is misguided from a scientific standpoint, the approach has proven to be remarkably lucrative for the pharmaceutical industry. The pharmaceutical industry’s approach to developing pharmaceutical interventions intended to target age-associated degenerative diseases is discussed in the essay entitled “Pharmaceutical Interventions for Age-Associated Diseases.”

Another reason the infectious disease approach is inappropriate for chronic degenerative disorders is that a person generally either has or doesn’t have an infectious disease. FDS is defined as any deviation from our genetically programmed optimal phenotype. Thus, almost every adult human on the planet suffers from FDS to some degree, and most people evidence a noticeable decrease in function over multiple modalities by their third or fourth decade. But the medical profession does not tend to recognize FDS as a medical problem until there is some potentially life-threatening event (such as a stroke or heart attack) many years or decades later.

In a world where everyone suffers from FDS, and there are no known interventions that would prevent the progression of the disorder, the failure of medical science to recognize that FDS is itself a significant health problem may not initially appear to pose a major problem. However, it is problematic for many reasons. One example arises from the fact that so much of the information that doctors rely upon is based upon statistical analyses of large groups of people. This information is obtained from people who are suffering from FDS – a disorder that significantly impacts the data.

Another problem with the infectious disease approach is the practice of labeling a disease based primarily on a set of symptoms. That works for infectious diseases such as mumps or measles or COVID. The symptoms help identify the underlying causative organism, and much useful information can be derived from that identification. But for noninfectious diseases, a similar set of symptoms can have a number of different causative factors.

For example, there are cases of heart disease that are caused by pathogens. An infectious disease approach would be appropriate for these cases. Other heart malfunctions may be caused by genetic defects. Attempting to identify and correct those defects might be appropriate for these cases. But the great majority of age-associated degenerative diseases are characterized by the slow physiological deterioration of an organ or system over time, or FDS.

Risk Factors

In the absence of an identifiable actual cause for age-associated degenerative diseases, the concept of “risk factor” has been substituted. The indiscriminate use of that term, and the practice of equating risk factor to cause, has had unfortunate consequences. When dealing with infectious diseases, inherent in the concept of “cause” is the understanding that if the cause of the disease (the pertinent pathogen) is eliminated, the disease will either be prevented or cured. Most of the recognized environmental risk factors for age-associated degenerative diseases are factors that accelerate the rate at which intrinsic damage is inflicted upon the subject. Examples include smoking, excessive alcohol consumption, stress, obesity, etc. But we know that none of these factors are the root cause of age-associated degenerative diseases, because even if a subject neutralized or eliminated all such factors, there can be no assurance that the subject will be immune from those disorders.

Generally speaking, a risk factor for a particular ailment merely means that there is a statistical correlation between the factor and the ailment. The risk factor could be strongly connected to a cause of the ailment. For example, impure drinking water is a risk factor for a host of infectious diseases. That’s because the organisms that cause those diseases breed in and are transmitted to humans through the impure water. Thus eliminating that risk factor by purifying drinking water has a significant positive effect on preventing infectious diseases. Similarly, in the United States, reducing smoking and air pollution has had a positive effect on the incidence of a number of aging-associated degenerative diseases. Those risk factors are not necessarily the root cause of the degenerative diseases (because even one who is not exposed to those risk factors can develop the same disease), but the risk factors accelerate the rate at which the diseases manifest themselves.

On the other hand, numerous risk factors that have been identified as being associated with chronic degenerative diseases have little or nothing to do with cause. A risk factor may be nothing more than an early symptom of a disease. For example, high blood pressure is often cited as a risk factor for cardiovascular disease, when in fact it is a symptom of a cardiovascular disorder. A risk factor could show a predilection for a disease. For example one could have a genetic predisposition for a particular disorder. Similarly, certain diseases may occur more frequently in people of a certain sex, sexual preference, race, etc. But none of these risk factors is the cause of an age-associated degenerative disease. If the subject were not suffering from acute FDS, these predilections would not result in any clinical disorder.

Attacking “Aging” as an Approach to Age-Associated Degenerative Disease

There is a growing recognition in the scientific community that all age-associated degenerative diseases have the same root cause. That root cause is FDS. Since scientists assume that FDS is a core trait of a monolithic aging process, they label the cause “aging.” However, since it has proven impossible to develop a theory that explains aging, that recognition doesn’t advance the ball all that far.

The term “Longevity Dividend” was coined by Professor S. Jay Olshansky and a group of scientists and academicians to describe “the economic and health benefits that would accrue to individuals and societies if we extend healthy life by slowing the biological processes of aging… [T]he idea is to slow the aging of our bodies such that 1 year of clock time is matched by less than 1 year of biological time. This approach would allow people to retain their youthful vigor for a longer time period and, if delayed-aging interventions work the way researchers hope they do, compress the infirmities of old age into a shorter time frame at the end of life.”¹

Although Professor Olshansky expressly rejects the proposition that humans are programmed with aging or death genes that are designed to kill us at some point, his use of the term “longevity” reinforces the misconception that FDS is part of a monolithic process that is inextricably linked to mortality. It also reinforces the misconception that longevity is the only applicable metric, which inevitably means that experiments can only be conducted on short-lived surrogates (i.e., organisms with extremely rudimentary maintenance systems).

Genetic manipulation and extreme caloric reduction are typically mentioned as the most likely approaches. But existing genetic programming already provides a mechanism – the maintenance system – which is designed to prevent FDS. Altering our genetic programming to try to address FDS would be like altering our genetic programming to address scurvy. It’s a lot simpler to just take Vitamin C supplements. The New Paradigm suggests that once science has identified the environmental agent that is interfering with the effective functioning of the maintenance system, correcting for that factor would be far simpler than altering our genetic programming.

Extreme caloric reduction has been shown to have a life extending effect on mice. However, one cannot simply assume that an intervention that is successful on mice is going to work on humans.² There is also no reason to believe that something that extends the lifespan of a mouse is necessarily going to reverse cellular and tissue damage in young human adults. Caloric reduction slows the metabolism of mice, thus slowing the rate at which damage accumulates. The damage side of the equation is far more significant to a mouse than it is to a human. A mouse that has doubled its lifespan still lives only a few years. That’s because a mouse’s maintenance system is not nearly as sophisticated as a human’s. If humans were designed to live only a few years, then a radical slowing of metabolism might have an appreciable effect on longevity. But that’s not the case. Humans live much longer than mice (or apes for that matter) because humans have a much more well developed maintenance system.

The SENS Research Foundationi has a different approach to solving the problem. The SENS Research Foundation’s strategy is to prevent and reverse age-related ill health by applying the principles of regenerative medicine. According to its website, it is developing regenerative therapies that remove, repair, replace, or render harmless the cellular and molecular damage that accumulates in human tissues over time.³

To some extent, the Foundation’s strategy is similar to that of the Institute. The difference is that the SENS Research Foundation is attempting to recreate the human maintenance system in the laboratory. The Institute advocates the much simpler process of correcting whatever environmental factor is interfering with the proper functioning of the maintenance system. If that interference is neutralized, the maintenance system itself will, in the words of the Foundation, “remove, repair, replace, or render harmless the cellular and molecular damage that accumulates in human tissues over time.”

The Institute’s approach is much more consistent with the way that successful medical interventions typically work. A successful medical intervention is one that provides a little bit of a nudge to the body’s own processes and then lets those processes do the heavy lifting. For example, vaccines don’t typically directly kill off pathogens. They enable the body’s immune system to carry out its function of neutralizing invading organisms so that the body can ward off the pathogens on its own. Doctors don’t repair broken bones. They set the bones in place and let the healing process do the work. If one is suffering from scurvy, one can remedy the disorder by providing vitamin C. But the vitamin C doesn’t repair anything. It merely allows the body’s own maintenance processes to resume their natural function of removing and replacing damaged components.

Age-associated degenerative diseases are manifestations of acute FDS. FDS is the result of an environmental agent preventing the maintenance system from functioning in an optimal manner. Ineffective maintenance processes allow intrinsic damage to accumulate. Years of accumulated damage result in an organ or system malfunctioning, which is then recognized as an aging-associated degenerative disease. A prevention or cure for age-associated degenerative disease would involve identifying and neutralizing that agent, thus allowing the maintenance system to remove and replace the damaged and dead components that have accumulated.

Olshansky SJ, Articulating the case for the longevity dividend, Cold Spring Harbor Perspectives in Medicine (2016).
Where the disorder is caused by a pathogen invading the organism, it’s not unreasonable to assume that a pharmaceutical intervention that counteracts the pathogen in a lab rat is also likely to counteract the same pathogen in a human. However, when the disorder (FDS) is caused by an external factor interfering with the optimal functioning of the human maintenance system, assuming that an intervention that slows the rate at which intrinsic damage is inflicted upon lab rats will necessarily benefit humans is nonsensical.
The SENS Research Foundation’s website is located at www.sens.org.

The next essay in this Section is “Pharmaceutical Interventions for Age-Associated Disorders.”