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.

Non-Aging Species – Negligible Senescence

Are there species that do not age? Some species apparently lack any internal limitation on their lifespans. What implications does this have for aging theories and dependent medical research on aging and age-related diseases?

Observed Long-Lived Species

We can use the term internal immortality to refer to the absence of any internal limitation on how long members of a species can live. Of course such a species would still be subject to death from external causes such as predators, intra-species warfare, starvation, lack of suitable habitat, and infectious diseases. A number of animal and plant species live extremely long lives and might be internally immortal.

It is infeasible to prove that any such species is or is not internally immortal. For example, we could keep a statistically large number of individuals under zoo conditions for 300 years and see if any survived. Such an experiment would probably require multiple zoos in multiple locations to prevent the entire zoo population from being wiped out by fire, earthquake, or epidemic, would take 300 years to perform, and would only show that a lifespan of 300 years was possible.

Some species have internal indicators of age like tree rings or similar markings on fish scales or internal bones so we can determine the age of a captured wild individual by dissection. Because wild species are subject to myriad external threats a very large number of such examinations would be necessary to demonstrate an even very long lifespan much less demonstrate the presence or absence of internal immortality.

Rougheye Rockfish - Maximum measured lifespan 140 years

Rougheye Rockfish – Maximum measured lifespan 140 years

 

Giant Sequoia – maximum measured lifespan >3000 years

Giant Sequoia – maximum measured lifespan >3000 years

Negligible Senescence

Another approach to the species senescence issue that avoids the lifespan measurement problem is to measure symptoms of aging. Humans and most other organisms have very obvious multiple senescence symptoms. A negligibly senescent species is one in which no measurable evidence of senescence such as decreased strength, speed, sensory acuity, reproductive ability, or increased incidence of diseases has been observed.

Some have claimed that the mouse-sized naked mole rat (interesting because it is a mammal) is negligibly senescent even though maximum lifespans of about 30 years have so far been observed. Lab mice live about 2.5 years and some mice live less than one year. Naked mole rats have a reproductive scheme similar to colony insects. In any underground colony only one “queen” female reproduces. This behavior and other strange characteristics likely affect their need for lifespan.

Naked Mole Rat – Maximum observed lifespan ~30 years, may be negligibly senescent

Naked Mole Rat – Maximum observed lifespan ~30 years, may be negligibly senescent

Aging Theory Implications of Non-Aging Species

A reader might conclude that trees, fish, and maybe even rats have no significance regarding human aging. However, as explained earlier, modern aging theories attempt to explain why different species have different lifespans and how aging relates to the evolution process and to other characteristics of a particular species.

An individual tree that has lived for more than 3000 years proves that there is not some fundamental limitation on how long an individual living organism can live (at least up to 3000 years). Trees actually share many life processes (such as sexual reproduction) with more complex species such as mammals so this is significant.

Modern non-programmed (non-adaptive) theories assume that each species only has an evolutionary need to live for a certain minimum lifespan but that there is no evolutionary disadvantage from living longer. For example, even if internally immortal, very few wild mice would live as much as three years because of external factors such as predators, starvation and harsh environmental conditions. Therefore having the internal ability to live longer would have very little value for a population of wild mice. This is the logic used by Medawar in 1952 to suggest that each species only needed to evolve the ability to live for a certain species-specific period. Because there is no disadvantage from living longer there is no evolutionary motivation to evolve a suicide mechanism that purposely limits lifespan.

These theories assume that various natural deteriorative processes would limit lifespan beyond the species-specific age at which there was an evolutionary need to live, thus leading to the huge variety of observed lifespans. There is no scientific disagreement that natural deteriorative processes such as oxidation, random mutations, and mechanical wear and tear exist.

However, non-programmed theories make a subtle but important and undefended assumption:  They assume that each increment of lifespan requires a different organism design because living X +1 years is somehow more difficult or otherwise a different task than living X years for any value of X. They further assume that if an organism inherited a longer lifespan than it needed, the natural deteriorative processes would degrade its design to fit its current external world thus resulting in the huge variety of lifespans observed. These assumptions “assume facts not in evidence.” It is not obvious why replacing dead skin cells or hairs would be any more difficult or require a different organism design in an 80-year-old than in an 8-year-old. Similarly why would preventing or repairing the causes of cancer or other age-related condition be more difficult with age?

In addition to this assumption, modern non-programmed theories assume that each species has an evolutionary need to live for a lifespan that is determined by internal design parameters (such as age of puberty) and external conditions (such as predation). Therefore they have the (so far mainly unaddressed) problem of explaining why some apparently non-aging or negligibly senescent species needed to live so long, even possibly indefinitely! Non-programmed proponents typically suggest that apparently non-aging species must actually age. Readers will recognize this as an example of circular logic: It must be true because our theory says it must be true!

Modern programmed (adaptive) aging theories assume that each species has a particular optimum lifespan, similarly determined by internal and external conditions, that living too long creates an evolutionary disadvantage for a population, and that therefore organisms evolved aging mechanisms designed to produce senescence symptoms on a species-specific schedule. Biological programs that stage various life-cycle events are common (e.g. growth, puberty, mating seasons). Programmed aging theories suggest [1] that negligibly senescent species have lost the ability to age and are therefore more likely to become extinct. This could have been caused by mutations that disabled their aging program.

[1] Goldsmith T. The Evolution of Aging 3rd ed. 2014 ISBN 978978870959 Azinet Press

 Aging Theories Articles Index

Why do we age?

Aging TheoriesThis is one of the longest-running and still-unresolved questions in science. There are hundreds of competing biological aging theories and no scientific agreement that any one of them is correct. There is not even any agreement on the fundamental nature of aging. Is aging something that happens to your body as a result of forces of nature or is aging something your body does to itself like growth or puberty? It turns out that the choice of aging theory is almost entirely driven by one’s choice of evolutionary mechanics theories or the theories describing how the evolution process operates.

Observations Concerning Lifespan and Senescence

There are a number of observations that are essential to modern aging theories. Because aging theories are essentially subsets of evolution theory, and because evolution theory applies to all living organisms, scientifically credible aging theories need to consider multi-species observations about aging and internally determined lifespan such as:

  • Lifespans and senescence vary greatly between species. Mammal lifespans vary over more than a 200 to 1 range between some whales (> 200 years) and some mice (< 1 year). Fish lifespans vary over a range of more than 1300 to 1.
  • Symptoms of aging tend to be similar but not identical between related species. Dogs and humans, even though their lifespans differ by about a factor of seven, suffer from very similar symptoms of aging like cancer, heart disease, stroke, arthritis, mobility and sensory deficits, etc.
  • Internally determined lifespan resembles an evolved trait: It varies somewhat between individuals and to a much larger degree between species.

There is extremely good scientific agreement on most aspects of Darwin’s evolution theory as described in Darwin’s book of 1859 and currently taught. However, despite the more than 150 intervening years there is still disagreement regarding arcane evolutionary mechanics details. Specifically, does the evolution process operate to benefit individual members of a species population or does it operate to benefit a population of individual members of a species? This obscure detail might well appear to be trivial and in maybe 99 percent of observations of organism traits makes no difference. This is because evolved inherited organism design characteristics or traits that benefit the ability of an individual to survive and reproduce also benefit the ability of a population of those individuals to avoid extinction and grow. Aging is one of the exceptions as described below.

This obscure detail is crucial to the aging theory issue. A high-school biology student could tell you that Darwin’s theory says that the evolution process causes organisms to acquire traits that cause possessing individuals to live longer and breed more than non-possessing individuals, and further that aging obviously does not cause an aging individual to live longer and breed more than an otherwise identical non-aging individual. On the other side, some theorists have now suggested at least a dozen ways that aging helps a population despite being adverse from an individual’s viewpoint and, so far, there has been no scientific disagreement with any of these ideas. Therefore the population vs individual issue is the controlling issue for aging theories as well as some other observations. The evolutionary mechanics issues have resulted in four classes of aging theories:

Simple Deterioration or Damage Theories

Simple deterioration theories suggest that aging is simply the result of the same sort of processes that cause gradual deterioration in non-living objects and systems. Physical processes include mechanical wear and tear, and micro-injuries. Perhaps aging results from nuclear background radiation. More chemistry-oriented causes might include oxidation, damage from free radicals, telomere shortening, random damage to DNA, etc. These theories are still popular in the general public: “We wear out” (like automobiles or sewing machines or exterior paint). There is little scientific disagreement with the idea that deteriorative processes could be parts of the mechanisms that cause aging.

However, major problems quickly became apparent in the bioscience community:

  • Living organisms obviously possessed many maintenance and repair functions that acted to prevent or reverse damage. Wounds heal, shed hairs are replaced, worn nails and claws regrow, blood and skin cells are continuously replaced.
  • Living organisms were capable of evolving changes in their designs that act to reverse or prevent deterioration.

Obvious question: If aging is the result of simple deterioration processes, why didn’t organisms evolve ways to overcome those processes as they had already demonstrated? This problem led to the fundamental limitation theories.

Fundamental Limitation Theories of Aging

As described above, Darwin’s evolutionary mechanics concept suggests that the force of evolution is toward developing non-senescent species. Individual members of a species that do not possess any internal limitation on their reproductive lifespans would be able to live longer and breed more than competing senescent individuals. Obvious question: Why, given billions of years of evolution, are there still senescent species? Obvious answer: a longer lifespan is physically or chemically impossible because of some law of physics or chemistry. Of course there are books full of laws of physics and chemistry and human aging is a gradual general deteriorative process superficially similar to aging in machinery and exterior paint. The second law of thermodynamics (entropy) is often cited in connection with aging. Today, because of their good fit with Darwin’s mechanics and human aging, fundamental limitation theories are still popular with the general public and some physicians.

However, fundamental limitation theories utterly fail to explain multi-species observations about aging. Why would a 50 Kg dog be seven times as affected by some law of physics or chemistry as a 50 Kg human?  Why would a parrot live six times longer than a crow? Articles about fundamental limitation theories typically ignore non-humans and target people who are mainly interested in human aging.

Aging Theories that Propose a Limit to Lifespan Benefit

In 1952 Nobel-prize-winning biologist Peter Medawar proposed a modification to Darwin’s mechanics to the effect that the evolutionary benefit of living longer and breeding more declined with age in a species-specific and population-specific manner, and further that internally determined lifespans needed by members of a wild species population depended on external circumstances such as predation, food supply, and habitat surrounding the population as well as internal traits such as age-at-puberty and other reproductive behaviors. Evolution is all about competition and “survival of the fittest” under wild conditions. We can easily imagine that there would be a species-specific age at which virtually no individual members of a population would remain alive because of external causes of mortality such as predators, infectious diseases, harsh environment, lack of food, or any of the myriad other causes of death in wild organisms. Consequently there would be little evolutionary motivation to develop the internal ability to live longer than a species-specific age. A population of aging individuals might be essentially as successful as a population of otherwise identical senescing individuals. This led to a family of modern non-programmed aging theories to the effect that each species only needed the internal capability for achieving a particular internally-determined lifespan and therefore only evolved and retained the ability to live that long. These theories provide a much better match to multi-species observations and are currently popular in the gerontology community.

However, subsequent (1957) widely accepted analysis by George C. Williams suggested that the deteriorative effects of aging occurred too early in life to have no negative effect on a population. Deterioration in strength, speed, and sensory acuity would affect an organism’s ability to survive and compete well in advance of the age at which most individuals would be dead from external causes and thus negatively affect survival of the population. Wild animal studies confirmed Williams’ analysis. This led to the conclusion that senescence must create a benefit for a population that offset its negative effects.

There are multiple competing theories that propose different solutions to this problem including the mutation accumulation theory, the antagonistic pleiotropy theory, and the disposable soma theory, and no agreement as to which is correct. Proponents of programmed aging (below) have described many logical and observational issues with each of these theories. Articles about mammal aging theories based on Medawar’s and Williams’ concept typically ignore non-mammals.

Programmed Aging Theories

Programmed aging theories are based on modifications to Darwin’s mechanics (and extensions to Medawar’s ideas) to the effect that aging, although adverse to individuals, benefits populations and that therefore species evolved biological mechanisms that internally limit their lifespans. Aging is an adaptation that serves an evolutionary purpose just as eyes, ears, and toes serve a competitive purpose in a wild population. Although programmed aging was first formally proposed in 1882, it was largely dismissed as obviously scientifically ridiculous because of the gross and direct conflict with Darwin’s mechanics until about 2002. Various analyses of Darwin’s mechanics confirmed that of the student: Darwin’s mechanics concept does not support population benefit or dependent programmed aging theories. The idea that we possess what amounts to an evolved suicide mechanism or “biological self-destruction clock” that limits an individual’s ability to survive and reproduce grossly conflicts with the nature of evolution as most people understand it.

However, a number of developments (and non-developments) have exposed additional issues with Darwin’s mechanics concept that specifically support population benefit and programmed aging:

  • Despite more than 150 years of effort theorists have been unable to produce an aging theory that is fully compatible with Darwin’s mechanics and simultaneously even semi-plausibly explains multi-species aging observations. Modern non-programmed (non-adaptive) aging theories are based on post-1952 modifications to Darwin’s mechanics that are more population-oriented.
  • In addition to senescence, other observations conflict with Darwin’s mechanics. These include sexual reproduction, individually adverse mating rituals and other behavioral observations such as animal altruism, and existence of apparently non-aging species. This led to the post-1962 development of multiple population-oriented mechanics theories including group selection theories and evolvability theories.
  • Genetics discoveries have exposed multiple issues with Darwin’s mechanics and support population-oriented mechanics and programmed aging theories. More generally, genetics discoveries suggest that the evolution process is much more complex than previously thought.
  • Some very explicit and obviously programmed suicide mechanisms have been discovered in non-mammals such as octopus and roundworm. Genetically engineered roundworms have been produced that live ten times as long as the wildtype!

Current Status of Aging Theories

The present situation is that current published science no longer supports the idea that programmed aging is impossible. The academic gerontology community still largely supports non-programmed theories based on Medawar’s/ Williams’ modifications to Darwin’s mechanics because such theories provide a better fit to multi-species observations than the fundamental limitation theories while not being so obviously incompatible with Darwin’s mechanics. Commercial entities (e.g. pharmaceutical companies) have begun to make major investments in research based on programmed aging theories.

Many non-science factors bias public and academic thinking toward non-programmed aging theories. For example, most people are trained in Darwin’s mechanics theory as the only science-based theory. Only a tiny fraction of these people are trained in modern population-oriented theories and dependent programmed aging theories or their supporting evidence and logic.

Because they predict that very different biological mechanisms are responsible for aging, programmed and non-programmed theories suggest very different medical research paths could be employed toward treating massively age-related diseases and conditions.

For more on evolutionary mechanics and the case for population-oriented theories and programmed aging theories see:

Evolvability, population benefit, and the evolution of programmed aging in mammals.

Aging Theories Articles Index