Mammal Aging is Controlled by an Evolvability-Based Adaptive Program

Evolvability is one of several modifications to traditional (Darwinian) concepts regarding the nature of the evolution process and suggests that the ability to evolve and genetically adapt to external conditions is itself an evolved trait. The subject article shows how a programmed aging concept based on evolvability provides a better fit to observations of mammal aging than other concepts that are also based on the idea that an aging program provides a necessary evolutionary function.

The article also suggests that the aging program is adaptive in the sense that it can non-genetically adjust in response to local or temporary conditions that affect the optimum value for the effects caused by aging.

Programmed aging theories propose that aging is controlled by a complex evolved biological mechanism that evolved because individual aging increases the chance that a population will survive and grow.

The programmed/non-programmed issue is very important to medical research because programmed theories suggest that there is a common treatable cause for most instances of highly age-related diseases like cancer, Alzheimer’s disease, and heart disease. In the same way that we can find ways to treat a disease we can also find ways to delay aging.

The Evolution of Evolvability and Programmed Aging

The evolution concept has two distinct parts. The facts of evolution can be summarized as follows: Humans, and other current species are descended from earlier different species, that in turn were descended from still earlier species, that were ultimately descended from a very simple (single-cell) organism that lived billions of years ago (the universal common ancestor). Our scientific certainty in this part of Darwin’s 1859 idea has steadily increased for more than 160 years and there is currently essentially no scientific disagreement.

The second part concerns the mechanics of evolution or how the evolution process works. Here we have the reverse situation. Darwin’s concept involving mutations and natural selection is very individual-oriented: The evolution process causes organisms to acquire design characteristics that increase a wild individual’s ability to produce descendants. This idea plausibly fits the vast majority of observations concerning organism evolved design characteristics (traits) and Darwin’s ideas were virtually unopposed (scientifically) until the 1950s.

There was a problem: It was immediately obvious that aging in mammals did not fit with Darwin’s concept. Aging did not help an individual produce more descendants despite otherwise strongly appearing to be an evolved trait. Aging, because of the gross reduction in fitness aspects such as strength and sensory acuity clearly reduced the probability that an individual would produce descendants. In many other organisms, internally caused death could be explained by some evolved feature that increased reproduction at the expense of additional lifetime and indeed some species only reproduce once. This idea did not apply to mammals

Despite more than a century of effort no theory has been produced that plausibly explains observed mammal aging while simultaneously maintaining full compliance with Darwin’s individual-oriented mechanics concept.

The idea that we possess an evolved biological mechanism that purposely limits lifespan (essentially a suicide mechanism) certainly directly conflicts with evolutionary mechanics as generally understood despite increasing evidence and theoretical support. In 2022 there is still no wide scientific agreement on a solution to this problem and therefore no agreement on even the general nature of aging. Biology courses still typically state that evolution works entirely on an individual level and fail to mention the substantial disagreements. However, discoveries, especially in genetics, have exposed issues with the Darwinian mechanics concept specifically regarding the individual vs population issue. Multiple concepts now propose that evolution is more population-oriented. As shown in the figure, our collective confidence that we understand the mechanics of evolution has actually declined and the number of different mechanics concepts has increased! All of the more recent concepts are at least somewhat population-oriented. That is, they suggest that evolution is at least partly driven by the success (non-extinction and growth) or failure (extinction) of populations.

Timeline of Evolutionary Mechanics Theories

The most recent and least-known modern mechanics concept is evolvability, which can be defined as a species population’s ability to evolve or more exactly as the rapidity and precision with which a population can genetically adapt to changes in its external world. A population that could adapt more rapidly or comprehensively to changes in their world would have an evolutionary advantage over a similar population with less evolvability. Where Darwin’s concept suggests that the ability to evolve is an inherent property of all living organisms, the evolvability concept suggests that the ability to evolve is itself mainly the result of evolved characteristics that increase evolvability.

Theorists have now suggested multiple ways in which internally limiting lifespan enhances the probability that a population will survive and grow by increasing evolvability. The reason that this is critically important to anti-aging medicine is that these theories support the idea that there exists a treatable common cause of the many different manifestations of aging and therefore the idea that aging can be generally delayed. Further, evolvability theories of aging suggest different biological mechanisms cause aging and therefore suggest different possibilities for treatment approaches relative to aging theories based on other population-oriented concepts.

The need for evolvability can vary greatly between populations. Some clams and trees have apparently existed for millions of years with little change or need for adaptation. Mammals typically occupy a food-chain in which different species force adaptation on other species. A predator could evolve better ways for catching prey. The prey can evolve better ways to evade predators. This observation might explain why some clams and trees have extremely long lifespans while mammals have lifespans that are tightly controlled.

Future posts will describe why aging increases evolvability.

Aging, Treatability, Population Benefit, and Evolutionary Mechanics Theories

A Reply to Алиса’s comment on the book: Anti-Aging Medicine: How We Can Extend Lifespan and Live Longer and Healthier Lives.

There are two main biological aging theories: non-programmed aging and programmed aging.

There is wide agreement among gerontologists that aging has in some way been determined by the evolution process. Aging and internally determined lifespan, like other evolved traits (such as adult height), varies somewhat between individual members of a species and to a much greater extent between species. Consequently, evolutionary mechanics theory, or the theory describing the evolution process, essentially determines aging theories. Although there is wide agreement regarding the existence of Earth-life evolution there is still substantial disagreement regarding the mechanics of evolution.

Everybody also agrees that age-related diseases like cancer and heart disease have a common cause (age) that causes most cases of age-related diseases and the more universal age-related conditions. There is also wide agreement that each age-related disease has a different immediate cause. Cholesterol causes some heart disease, inappropriate cell division causes cancer, etc. The trillion-dollar question for more than 160 years has been: Is there a treatable common cause of age-related diseases and conditions? Is some single upstream biological mechanism regulating the multiple immediate-cause mechanisms resulting in the multi-species aging observations?

Darwin’s evolutionary mechanics concept, as we all learned in high school, is very individual-oriented. An inheritable mutational change occurs in a single individual. If that change causes descendant individuals to produce more adult descendants, it propagates in a population. This idea explains the vast majority of organism traits.

However, there is wide agreement that aging does not help but hurts the ability of individual mammals to produce more descendants leading to an obvious question: Why didn’t evolution produce internally immortal organisms. Unfortunately, despite more than 160 years of effort no one has produced an aging theory that even semi-plausibly explains multi-species aging observations while remaining completely compatible with Darwin’s mechanics.

This eventually led to the development of population-oriented evolutionary mechanics theories in which evolution is driven by the success (survival and growth) or failure (extinction) of populations of a particular species. Genetics discoveries support this view.

Modern Non-programmed aging theories propose that aging only weakly negatively affects populations even though it is catastrophic as seen from an individual’s viewpoint. This is obviously true. Mammals (including humans) have evolved to their current state despite aging. This concept leads to the idea that each of many different maintenance mechanisms that act to prevent each of the many age-related diseases and conditions only evolved the effectiveness needed to produce the lifespan needed by a particular species population. Therefore, there is no treatable common cause of agingmanifestations. This idea fits well with the existing medical paradigm.

More recent programmed aging theories suggest that aging, in addition to having little negative effect, actually produces a net evolutionary benefit for a population and that therefore organisms evolved biological mechanisms that purposely limit their lifespans. We possess what amounts to a biological suicide mechanism, which represents a treatable common cause of the age-related diseases! Anti-aging medicine including generally delaying aging (lifespan extension) is possible.

There is still major disagreement among gerontologists and medical researchers on this issue. As described in the book current science greatly favors programmed aging but non-science factors favor non-programmed aging. As described by Алиса, some gerontologists and many medical people still see programmed aging proponents as lacking “respectability” and interfering with “serious” research. However, serious, substantially funded research efforts based on programmed aging are now underway by organizations such as Alphabet Calico, AbbVie, and NIH. Gerontology journals increasingly accept pro-programmed aging articles and major textbooks on aging include programmed aging concepts. Programmed and non-programmed theories suggest very different biological mechanisms are ultimately behind age-related diseases so this issue is critical to research.

There have been few attempts to disprove any of the multiple population benefits of aging or to disprove the specific supporting evolutionary mechanics theories such as evolvability theory. Objections are usually based on the idea that it is “impossible” that the objector’s chosen evolutionary mechanics theory (incompatible with programmed aging) could be incorrect.

So Алиса if you (or anyone) has specific scientific arguments against the pro-programmed aging arguments summarized in the book (or in the cited literature) please post a summary and links to applicable journal articles.

Aging Theories in the Commercial Medicine World

The situation regarding the programmed vs non-programmed aging controversy in the commercial world (doctors, patients, pharmaceutical companies) is very different from the situation in the academic world. Patients and doctors tend to be relatively unconcerned about obscure nuances in the theoretical basis of a treatment approach and much more concerned with effectiveness and lack of adverse side-effects. Certification of drugs and treatments generally does not involve extensive theoretical discussion but rather demonstration of effectivity and reasonable side effects.

Commercial operations are much more private and internal thinking about the theoretical basis of some treatment development effort can be closely held.

The global pharmaceutical industry (including biopharmaceuticals) is one of the largest in the world (with a current market capitalization of more than a trillion dollars) and can be expected to grow as populations of developed countries continue to age. According to a study published in JAMA (1/2010), in the U.S. “the pharmaceutical industry is the largest contributor towards funding research, funding over 60 percent. The government contributes to about a third of the costs, with foundations, advocacy organizations and individual donors responsible for the remaining investments.”

During the long period during which programmed aging was virtually universally thought to be theoretically impossible, it was entirely reasonable for a pharmaceutical company dealing with age-related diseases to invest all of its resources into research based on non-programmed aging concepts.

However today, an even cursory review of the literature would reveal that programmed aging can no longer be considered to be “impossible.” Consequently, any such company would need to perform a “due diligence” study of the current situation and produce an internal estimate of the probability that programmed theories are correct along with an estimate of the likely nature of the human aging program and the research directions suggested by that estimate. Any such study would need to consider the following:

  • Programmed aging theories suggest new paths toward treating age-related diseases that consequently present the possibility for rapid initial progress or “low hanging fruit.”
  • A programmed aging approach involves interfering with the operation of a biological program, likely to be similar to other programs and involving signaling, hormones, receptors, proteins, etc. This is a relatively familiar problem.
  • Programmed aging theories suggest that aging, per se, is a treatable condition and therefore suggest that treatments can be devised for delaying and potentially reversing at least some aging symptoms and diseases, especially in relatively older patients.
  • Competitors (e.g. Google Calico and AbbVie) are known to be already pursuing programmed aging research.

There is of course no such thing as certainty in any drug development effort. Any such research project is essentially an informed wager based on the available information. Given the foregoing it seems unlikely that any larger pharmaceutical company dealing in age-related diseases and conditions would conclude that they can completely ignore programmed aging concepts in developing their research planning. Programmed aging researchers may go from being semi-pariahs to being in high demand!

Are we likely to see the introduction of drugs that have been clinically tested and FDA approved “to delay human senescence?” This is very unlikely to happen because the claim is too broad, the claim is controversial, and the claim is extremely difficult to prove. We are much more likely to see a drug claim along the lines of: “reduces the adverse effects of macular degeneration in certain elderly patients.” Notice the narrow claim, much easier clinical demonstration, and lack of controversial claims. In addition, for programmatic reasons companies would be likely to want to develop 50 drugs to treat 50 different diseases and conditions of aging as opposed to one or a few drugs to treat senescence.

Conclusion: We can expect to see increasing efforts by pharmaceutical companies to explore drug development based on programmed aging concepts.

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