Biological Aging Theories

Theories of biological aging need to explain how aging relates to the evolution process. More specifically, if the evolution process has caused organisms to evolve myriad other ways to survive longer and reproduce more, why does aging still exist? As summarized below, aging theories propose three different answers to this question and are based on three different versions of Darwin's survival of the fittest idea.

Simple Deterioration Theories - Fundamental Limitations - "Wear and Tear"

Many people believe that biological aging is simply the result of universal deteriorative processes such as oxidation, entropy, or wear and tear that cause aging in machinery, exterior paint, and other inanimate objects. These theories are superficially attractive if only human aging is considered but fail if life span characteristics of other species are also examined.

As we learn in biology class, Darwin's "survival of the fittest" idea says that the evolution process causes organisms to acquire inheritable design characteristics or traits that help them survive longer and breed more. Deterioration and death from aging clearly does not help humans to live longer and breed more so why do we age? Wouldn't the evolution process have led to longer and longer lived animals eventually resulting in immortality? Contemporaries actually wrote Darwin and asked this question! The obvious answer is that aging results from fundamental limitations such as laws of physics or chemistry that, by definition, cannot be overcome by the evolution process.

There is no question but that many aspects of aging look like the accumulation of damage. Examples are oxidative damage, mutations, and the protein cross-linkages that cause our collagen to lose flexibility with age. But the essential mystery is why the body is able to avoid these problems for many decades, but then permits the damage to occur in old age. And why do some animals age so much more slowly than other, very similar animals? Why would universal laws of physics or chemistry affect biochemically very similar species so differently. (Mouse-sized naked mole rats live ~30 years, while mice live ~2 years.) These are reasons that aging requires a more complex explanation.

Consequently few bioscientists still believe in simple deterioration or "accumulated damage" theories although deteriorative processes such as oxidation and other molecular damage are part of most aging theories. See longer description of wear and tear theories.

Because they are a logical consequence of Darwin's theory as widely taught, fundamental limitation theories are still widely believed by the general science-aware public.

Medawar's Hypothesis - Evolutionary Value of Survival Declines with Age

Peter Medawar, a famous and eventually Nobel-prize-winning British zoologist, published a modification to Darwin's theory in 1952 that is important to all subsequent evolutionary theories of aging. He suggested that the evolutionary need to live longer decreases following the age at which an organism is first capable of reproducing and also depends on many other internal and external circumstances that are specific to a particular species such as gestation time, mating seasons, predation, and seasonal attrition. Although theorists now disagree regarding details of Medawar's hypothesis everybody agrees that an organism that died of old age prior to reaching puberty would not make logical sense. There would therefore be strong evolutionary force toward avoiding aging until the age at which an organism could complete a first reproduction. Medawar further suggested that there would be no evolutionary benefit from a species evolving ways to overcome internal causes of deterioration (aging) beyond the age at which essentially all of the individuals would have died from external causes. If a thousand mice were born today we could easily imagine that under wild conditions few would survive more than two years and therefore the internal ability to survive longer would not have any evolutionary value. This hypothesis was widely embraced by bioscientists because it provided a good explanation for the gross variation in life spans seen in different, but biochemically similar, species.

Medawar's idea was that under wild conditions, aging did not cause any significant deleterious effect on a species population. Immortality or even just a somewhat longer lifespan would not help a population and therefore did not evolve.

Modern Non-Programmed Aging Theories

Modern non-programmed aging theories are based on Medawar's hypothesis, which holds that organisms can and do evolve myriad complex biological mechanisms directed at achieving a lifespan at least able to complete a first reproduction and that the design of any organism must support surviving for a particular minimum lifespan.

Multiple theorists including G. Williams and T. Kirkwood subsequently attacked Medawar's idea by observing that aging did cause at least some deleterious effect on wild mammal populations contrary to Medawar's zero-disadvantage idea. Wild animal studies confirmed this by showing that wild animal death rates increased with age, which presumably would not happen in an immortal population, or one in which aging caused no disadvantage. These theorists therefore concluded that aging must convey some compensating benefit to offset the declined but still non-zero disadvantage of aging. Some non-programmed theories contend that aging is an unavoidable adverse side-effect of some beneficial function. Because of Medawar's declining value hypothesis, a beneficial function that contributed to an animal's early life in even a minor way could offset even catastrophic disadvantage (e.g. death of old age) in later life. All such theories have to explain why the evolution process was unable to find a way to accomplish the beneficial effect without the adverse side-effect, a significant difficulty and one of the problems with non-programmed theories.

Non-programmed theories compete with each other, have apparent logical flaws, and have difficulty in explaining many observations.

The following articles contain descriptions of each of the main non-programmed (non-adaptive, passive) theories of mammal aging including discussion of their apparent logical flaws:

Mutation accumulation theory (Medawar)
Antagonistic pleiotropy theory (Williams)
Disposable soma theory (Kirkwood)

Developmental (DevAge) or Life-history theories of aging contend that aging is an adverse side-effect of the development or growth process. From an evolutionary viewpoint these are versions of "aging is an unavoidable adverse side-effect of some beneficial function."

Population Benefit Evolution Theories

Beginning in 1962 a series of new modifications to Darwin's survival of the fittest idea appeared to the effect that an organism trait that caused a long-term or population benefit such as decreased probability that a species would become extinct could evolve even if that trait caused some degree of short-term or individual disadvantage such as reduced probability that an individual would produce adult descendants. There are now multiple theories including group selection (benefit to a group can offset individual disadvantage), kin selection (benefit to close relatives can offset individual disadvantage), evolvability theory (traits that increase a population's ability to evolve can offset individual disadvantage), and gene-oriented theories (traits that assist propagation of genes can offset individual disadvantage).

Darwin's evolutionary concept (random mutations occur, natural selection selects those that increase the possessing individual's ability to survive and reproduce) is incompatible with the population benefit theories. However, in the intervening 150+ years enormous advances in our understanding of the biological inheritance process have led to an understanding that the evolution process is actually much more complex than suggested by Darwin. Some of the additional complexities specifically favor the population benefit concepts and there is now an extensive theoretical basis for the idea that the population benefit theories (maybe even all of them) are valid. In addition to aging (see below) the population benefit theories provide explanations for other observations that appear to conflict with Darwin's ideas including animal altruism, sexual reproduction, some mating rituals, and delayed puberty.

Programmed Aging Theories

Programmed aging theories are based on the idea that living too long creates an evolutionary disadvantage and that therefore organisms evolved a suicide mechanism or senescence program that purposely limits the lifespan of the organism beyond a species-specific age. These theories are based on Medawar's idea that the evolutionary benefit of survival declines with age and also the idea that a limited lifespan creates benefit according to one of the population benefit theories. Collectively, these theorists have suggested many ways in which purposely limited lifespan creates population benefit. According to programmed theories the compensating benefit of aging is a direct population benefit instead of a side-effect of some individual benefit.

Programmed theories fit observations better than non-programmed theories. These are the programmed aging theories listed by underlying population benefit theory:

Proponents of non-programmed theories have produced Objections to Programmed Aging Theories.

Living organisms possess extensive maintenance and repair capabilities. These capabilities are central to programmed and non-programmed Maintenance Theories of Aging.

Programmed theories suggest that each organism has an optimum lifespan determined by many internal and external species-specific circumstances. Regulated programmed aging theories suggest that an organism design having the ability to adjust (regulate) an individuals lifespan in response to sensing local or temporary changes in internal or external conditions that affect optimum lifespan such as famine, drought, or reproductive conditions would provide an evolutionary benefit. Regulated mechanisms are common in biology and regulation of lifespan in response to temporary conditions like famine or drought matches observations like experiments showing that caloric restriction increases lifespan.

Aging Theories and Medical Research

Programmed and non-programmed theories of aging lead to very different concepts regarding biological mechanisms of aging, which in turn lead to very different approaches in attempting to prevent and treat age-related diseases. In general, non-programmed theories consider that each manifestation of aging is independent of the others such that attempts to treat or prevent age-related diseases or conditions must be separately devised and applied to each disease or condition. Aging, per se, is an untreatable condition. Historically, the vast majority of medical research and resulting treatments have been based on this idea.

Programmed aging theories suggest that the many different manifestations and conditions are ultimately controlled, at least to some extent, by a suicide mechanism or program, and that therefore medical efforts toward interfering with the program can generally delay aging. Anti-aging medicine is therefore possible. Treatments directed at specific disease mechanisms are still valid but programmed theories suggest additional ways in which diseases of aging could be attacked. Because this is a substantially new approach, we could reasonably expect relatively rapid progress.

See: Medical Implications of Aging Theories.

Current Status of Aging Theories and Associated Medical Research

There is no scientific agreement regarding which of the many current versions of Darwin's survival of the fittest idea is correct; nor is there any agreement regarding the dependent programmed or non-programmed aging theories. Proponents of modern non-programmed theories generally accept Medawar's modification of Darwin's theory but reject all of the subsequent population benefit theories and associated programmed aging theories.

However, major investments are now being made in research based on programmed aging theories: See Google Calico Research Company and NIH Interventions Testing Program. The idea that aging is itself a treatable condition is increasingly accepted. For example, the American Academy of Anti-Aging Medicine claims 26,000 physician and researcher members.

Free Kindle Books on Aging

Aging Theory Resources

www.programmed-aging.org

Revised 2015