newaging

SCIENTIFIC REVOLUTION

 

“The measure of greatness in a scientific idea is the extent to which it stimulates thought and opens up new lines of research.”

paul a.m. dirac

In his 1962 book, The Structure of Scientific Revolutions, Thomas Kuhn used the term “paradigm” to describe the set of preconceptions that is assumed to represent the objective reality of a particular field of science at any given time. Most of the work of scientists is “normal science.” The then-current paradigm provides the conceptual framework for analyzing observations and conducting experiments. Since the type of solution that must be found is well defined and the paradigm sets rigid parameters for the types of experiments to be conducted, Kuhn characterizes scientific research during periods of normal science as “puzzle-solving.”

Kuhn saw the sciences as going through alternating periods of normal science, when an existing model of reality dominates a protracted period of puzzle-solving, and revolution, when the model of reality itself undergoes sudden drastic change following a paradigm shift. The paradigm shift causes scientists to re-examine prior observations and design new experiments from within an improved conceptual framework.
In most fields of science, much of the “puzzle-solving” involves developing scientific theories. A theory is a set of statements or principles devised to explain a group of facts or phenomena. A good theory creates a conceptual framework that explain why the phenomena occur. Stephen Hawking once stated that a theory is a good theory if it “satisfies two requirements: it must accurately describe a large class of observations on the basis of a model that contains only a few arbitrary elements, and it must make definite predictions about the results of future observations.”
All theories are based upon the then-current paradigm. If the paradigm is an accurate depiction of reality, there should be a scientific theory that explains why each of the phenomena that are encompassed within the paradigm are consistent both with objective reality and with other accepted scientific theories. The dominant, universally accepted scientific theory in the life sciences is the theory of evolution by natural selection. As discussed at length in other essays on this website, the flaws in the current aging paradigm preclude the development of scientific theories to explain the assumed phenomena. First, the presumed phenomena – the preconceptions about aging that comprise the paradigm – are themselves inconsistent with objective reality. Second, the fundamental preconception of the current paradigm – that biological aging is a genetically inherited trait – is incompatible with the principles of natural selection.
The second aspect of puzzle-solving within a paradigm is the practical aspect. A life sciences example of a paradigm shift greatly improving practical problem-solving was the acceptance of the germ theory of infectious diseases in the second half of the 19th century. Prior to that, the prevailing paradigm was that infectious diseases were caused by a miasma that arose from contaminated water. There was a statistical correlation between unsanitary water and outbreaks of infectious diseases. Improving sanitation did reduce the risk of infectious disease. But once an individual contracted an infectious disease, only the symptoms could be treated. No medical intervention would cure the disease.
However, once the new paradigm – that infectious diseases are caused by invading pathogens – was accepted as objective reality, effective medical interventions became possible. As a direct result of the paradigm shift resulting from the acceptance of the germ theory, medical technology has become remarkably adept at dealing with infectious diseases. The germ theory does not directly tell us how to create the vaccine that prevents COVID-19 or how to create any particular antibiotic. However, the knowledge that an infectious disease is caused by a pathogen does provide us with a roadmap that has allowed modern medical technology to fabricate the vaccines and other pharmaceutical interventions that enable the human immune system to neutralize most any pathogen.
As is discussed at length in other essays on this website, the fundamental preconception of the current aging paradigm – that biological aging is a genetically inherited trait – precludes scientists from making any headway in the battle against age-associated degenerative diseases. To effectively counteract a disorder, one must attack the root cause of the disorder. The root cause of age-associated degenerative diseases is decades of accumulation of intrinsic damage. Under the current aging paradigm, that accumulation of intrinsic damage is the result of a completely natural, genetically inherited aging process. That means that, until scientists can discover how to alter the human genome to prevent biological aging,i all that medical interventions can hope to accomplish is to ameliorate the symptoms of the disorders.
Other essays on this website address how the acceptance of the New Paradigm will provide a roadmap that will allow researchers to address the root causes of age-associated degenerative disorders. This essay will explore how the acceptance of the New Paradigm will assist researchers in developing hypotheses that will, to paraphrase Steven Hawking, explain classes of aging-associated phenomena and make definite predictions about the results of future observations.

The Maintenance System and Evolution

A fundamental premise of the New Paradigm is that intrinsic damage is an inexorable force that has afflicted every complex organism that has ever existed on the planet. Multi-cellular organisms are possible only because they have maintenance systems that can replace damaged cells as they die off. But simply replacing cells isn’t enough when dealing with complex metazoans. Complex metazoans with specialized cells are possible only because they have sophisticated maintenance systems that can identify, eliminate and replace those specialized cells when they sustain damage or die. In other words, the story of the evolution of animals must go hand in hand with the evolution of maintenance systems.

It’s estimated that life first appeared on the planet about 3.5 or so billion years ago. For the next couple billion years, the only forms of life on earth were simple, single-celled organisms. The first true eukaryotic cells (cells containing a nucleus, mitochondria and other membrane-bound organelles) appeared about 1.5 billion years ago. At some point, cells began working together in clusters, but the first truly multi cellular animals didn’t appear until about 800 million years ago. Although comprised of multiple cells, these organisms were remarkably simple – akin to sponges. Nonetheless, more complex animals did not appear for another 200 or so million years.
Why didn’t these sponges evolve during that 200 million year period? Under the New Paradigm, a possible hypothesis would be that, in the absence of a maintenance process that could identify and replace specialized components, any organism that was more complex than a sponge was impossible. Specialized tissues are useless if they can’t be maintained.
The term “Cambrian Explosion” refers to the appearance and rapid diversification of an abundance of new life forms, some of which were very sophisticated, within an interval of perhaps 20 million years or less. This time is known as the Early Cambrian, and began around 543 million years ago. For millions of years beforehand, there were no complex metazoans and no significant evolution of the simple organisms that did exist. An important unsolved evolutionary mystery is what caused the Cambrian Explosion. A potential hypothesis suggested by the New Paradigm would be that the maintenance system had finally evolved to the point where it could identify and replace specialized components, thus allowing for more complex organisms.

Longevity is a Function of the Capabilities of the Maintenance System

Aging theorists have long noted the fact that the longevity of otherwise similar species can vary remarkably. An obvious example would be rodents. Even under ideal conditions, the lab rat will rarely survive for more than a few years; by contrast, the longevity of the naked mole rat is estimated to be more than three decades. The only explanation for the extreme variances in longevity is that longevity is genetically determined and developed through an evolutionary process in a way similar to the one that determines other species-specific traits.¹

The New Paradigm posits that each species is endowed with a maintenance system that is designed to prevent any diminution in functionality throughout the natural lifespan of the species. If there is no diminution in functionality, then there can be no aging-dependent causes of death. Thus, by definition, the longevity of any species is determined by the capabilities of that species’ maintenance system.

This hypothesis is discussed in greater detail in the essay entitled “Aging in Other Species.”

Evolutionary Choices

With the longevity of any species being determined by the capabilities of that species’ maintenance system, why would there be any limitations on the capabilities of the maintenance systems of any species? Wouldn’t increased longevity always be a desirable trait?
Maintenance systems are no different than other physiological systems – each species has different capabilities resulting from millions of mutations over the eons. Maintenance processes require resources.
Processes that operate at the tissue or organ level require far more resources than those that operate at lower levels of biological organization. All organisms have finite resources that must be allocated among competing traits. Since allocating additional resources to the maintenance system detracts from other survival traits, natural selection had to make choices.
Just because a trait would appear to be desirable doesn’t mean that it would be selected if there is no net evolutionary benefit. For example, humans assume that intelligence is the most advantageous of all traits and is the inevitable result of the evolutionary process. But consider the fact that dinosaurs ruled the planet for hundreds of millions of years, and there is no evidence that any dinosaur ever developed what a modern human would consider to be intelligence. Intelligence is a function of the physiological capabilities of the brain and central nervous system. But only traits that enhance survival and reproductive success are inherited by subsequent generations. If making a dinosaur’s brain larger or devoting additional resources to the central nervous system would so detract from other survival mechanisms that there was no evolutionary net benefit, then natural selection would reject those traits.

Chronological Limitation on the Efficacy of Maintenance Systems

The New Paradigm defines “natural lifespan” of a species to be the period of time before substantially all members of that species would die from non-aging-associated causes (e.g., starvation or predators) in their evolutionary environment. An “effective” maintenance system is one that would be capable of preventing any symptoms of FDS from manifesting during an organism’s natural lifespan.

Evolutionary principles dictate that any mutation that would allow the maintenance system to ensure optimal functionality throughout the natural lifespan of an organism would confer an evolutionary advantage, and thus such a trait would be genetically inherited.²

However, there is no evolutionary benefit conferred by an organism’s maintenance system functioning effectively beyond the natural lifespan of that species. Thus, the capabilities of the maintenance system of each mammalian species has a genetically established chronological limitation that is a function of the natural lifespan of that species. When an animal outlives its natural lifespan (and thus the chronological limitation on the effectiveness of its maintenance system), it begins to show age-related diminutions in functionality.

This hypothesis is discussed in greater detail in the essay entitled “Aging in Other Species.”

Any Disruption of the Maintenance System Will Result in a Degenerative Disorder

Intrinsic damage has been a pervasive challenge to survival for every complex organism that has ever existed on the planet. Thus all complex organisms have maintenance systems that are designed to prevent the accumulation of intrinsic damage. Since no biological process can be perfect, some accumulation of damage is inevitable. Thus longer-lived species, such as humans, have elaborate backup maintenance processes that operate at higher levels of biological organization.
Since intrinsic damage is an inexorable force, any interference with the proper functioning of the maintenance system will result in the accumulation of intrinsic damage. If uncorrected, further accumulation of intrinsic damage will eventually impair the functionality of the affected organs and systems. The New Paradigm contends that substantially all degenerative diseases – diseases that are characterized by the progressive deterioration of the function and structure of an organ or system – are caused by the accumulation of damage resulting from the disruption of one or more maintenance processes.
Once one accepts the notion that intrinsic damage is an inexorable force, the proposition that a degenerative disorder will inevitably result from the uncorrected disruption of the countervailing force – the maintenance system – is almost tautological.

Damage-Based Theories of Aging

As a result of the misconception that maintenance of the human organism should be simple, much of the theoretical work in the area of human aging has focused upon identifying types of intrinsic damage that are inevitable and irreparable.  One well-known such theory is the mitochondrial free radical theory of aging.  Another damage-based aging theory relates to telomere attrition.  New cells are typically created through mitosis, whereby a mother cell divides and produces two new cells that are duplicates of the original.  However, there is a limit to how many times a cell can divide.  Telomeres are special structures at the ends of all chromosomes that prevent chromosomal termini from joining together.  Every time a mother cell divides to produce two daughter cells, the telomere length of the daughter cells is shorter than that of the mother.  This continues until the critical point at which telomeres can no longer be formed.  A typical cell can only divide approximately 50 to 70 times before it reaches the Hayflick Limit, at which point the cell ceases to divide.  They become senescent cells, or “SCs.”

Although they can no longer self-replicate, SCs stay metabolically active. Among other thing, SCs emit distress signals alerting the maintenance system that the damaged cells need to be eliminated.  The inflammaging hypothesis posits that if SCs are not eliminated, they continue to excrete these signaling molecules.  The signaling molecules have an adverse effect on nearby cells, inciting local inflammation (inflammaging).  The inflammaging proponents speculate that in younger humans, the immune system eliminates the SCs, but that the aging process causes the immune system to lose the ability to eliminate SCs.  The accumulation of SCs causes inflammaging, which in turn causes aging. ³

This analysis has an inherent appeal to life scientists because it focuses on the damage side of the equation.  Better yet, it gives the scientists a target.  Scientists have identified “senolytic compounds” that are capable of the selective eradication of SCs. Experiments show that administration of senolytics is associated with a decrease in the number of SCs and thus a decrease of the cytokine secretion (distress signals) in human tissues.  However, although eliminating SCs appears to have beneficial health effects on mice, no one has been able to demonstrate any beneficial health effects on humans.

The Institute agrees that the glut of molecules, including cytokines, chemokines and proteases, secreted by an SC constitute both a distress signal and information regarding the type of cell involved.  But where proponents of the inflammaging hypothesis see those signals as being harmful to the organism, the Institute posits that these chemical signals are further empirical evidence that humans are endowed with a sophisticated maintenance system.  So long as the maintenance system is working optimally, it will respond to these distress signals, remove and replace the defective cells, and there will be no accumulation of SCs  and no resulting decrease in functionality .  

FDS is a Degenerative Disorder

Another critical hypothesis contained within the New Paradigm is that the progressive loss of functionality that results from the physiological deterioration that substantially all humans experience with advancing chronological age (the phenomenon typically labeled “biological aging”) is itself a degenerative disorder. In other words, most of the symptoms of biological aging are neither natural nor inevitable – they result from a preventable and curable disorder that the New Paradigm labels “Functional Decline Syndrome” (FDS).
A corollary of this hypothesis is that, like other degenerative disorders, the cause of FDS is that some extrinsic agent or factor is interfering with the effective functioning of the human maintenance system. As a result of that interference, intrinsic damage accumulates, and the accumulation of that damage leads to the progressive loss of functionality throughout the entire human organism that characterizes FDS.
  1. Goldsmith TC, On the programmed/non-programmed aging controversy, Biochemistry (2012).
  2. In their evolutionary environment, no mammal ever exhibits any symptoms of FDS. Intrinsic damage is an inexorable force that affects all organisms. Thus, other mammals can avoid the symptoms of FDS only if they do have fully effective maintenance systems. In other words, as an empirical fact, all mammals have fully effective maintenance systems.
  3. See, generally, Franceschi, C, et al, Inflammaging: a new immune-metabolic viewpoint for age-related diseases, Nature Reviews Endocrinology (2018).

The next essay in this Section is “Degenerative Disorders.”

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