Tag Archives: gerontology

Mammal Aging is Controlled by an Evolvability-Based Adaptive Program

Posted on by
Reply

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

Posted on by
Reply

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.

Non-Science Factors Influence Aging Theory Consensus

Posted on by
2

Aging TheoriesWHY is it that despite more than 150 years of effort there is still no scientific agreement on even the nature of human aging?  Is aging the result of fundamental limitations that could not be overcome by the evolution process, or a consequence of the lack of an evolutionary need for our ancestors to live longer, or the result of our possessing an aging program or biological suicide mechanism because populations of our ancestors received an evolutionary benefit from limiting individual lifespan? Many non-science factors act to bias thinking about aging and aging theories, mainly toward fundamental limitation theories or more recent non-programmed aging theories even though empirical evidence favors programmed aging theories. This is one of the reasons that no wide scientific agreement on even the nature of aging (much less details) exists today or is likely in the near future.

Education and Training

Most people are trained to believe Darwin’s individual-oriented evolutionary mechanics concept, which does not support more recent population-oriented evolutionary mechanics concepts and dependent modern programmed and non-programmed aging theories. Therefore they are, in effect, trained to believe in fundamental limitation theories. This logically leads to the idea that altering human aging is impossible. Very few of these people go on to obtain training in modern evolutionary mechanics concepts and dependent aging theories. Although modern non-programmed aging theories also conflict with traditional evolution theory, they do not present the gross and diametrically opposed conflict associated with programmed theories. The public is also accustomed to extravagant claims regarding discoveries and developments in medicine.

People who think that altering aging is impossible would logically be against funding research into anti-aging medicine or possibly even in studying aging on the basis that funds and other resources would be wasted. This situation also decreases motivation into studying age-related diseases and conditions. If aging is the result of fundamental limitations isn’t our ability to treat highly age-related diseases likely to be severely limited? Try comparing government funding of research on aging and age-related diseases to the defense budget. Now compare the death rates from age-related diseases to those resulting from enemy attack! We could ask the following question: Would funding for research into aging and age-related diseases increase if it was widely thought that aging, per se, was a treatable condition?

Anti-Science Influences

There are substantial anti-science influences at work in biology and medicine. Possibly the largest single anti-science effort currently extant is religious attacks against evolution theory. This effort strives to show that evolution theory cannot explain various observations without the intervention of supernatural intelligence and publishes pseudoscience articles to that effect. They then cite the pseudoscience in efforts to push teaching of anti-evolution religious concepts like creationism and intelligent design especially in introductory venues. This effort has been so successful that as of 2005 a Harris poll showed that the majority of Americans did not believe in evolution theory. Evolution is extremely central to the nature-of-aging issue and the anti-evolution situation leads to non-science biases toward fundamental limitation theories and non-programmed aging theories:

  • Proponents of fundamental limitation and non-programmed theories have, until recently, been able to dismiss programmed aging theories as non-scientific (and similar to anti-science proposals about evolution such as creationism and intelligent design) because of the conflict with traditional evolutionary mechanics.
  • Efforts to teach evolution, especially in more introductory venues like K-12 biology classes, would like to avoid any indication that there is any scientific disagreement regarding evolution theory and thus avoid giving support to the anti-science effort. This contributes to avoiding any mention of scientific disagreements about evolutionary mechanics or specific modern evolutionary mechanics theories.

The Zero-Sum Game

Funding for medical research tends to be rather flat (after inflation) on a year-to-year basis. Consequently, funding for new areas of research (like programmed aging or anti-aging medicine) must come from reducing funding to existing research avenues. Those researchers can be expected to fight fiercely against the new activities.

Scientific Inertia

Some senior bioscientists have a major public and long-term, even career, commitment to the older non-programmed theories. Such a person might well suspect that they are now betting on the wrong horse. However, for such a person to switch now would in many cases be like an Episcopal Bishop deciding to start over as an entry-level Methodist minister – possible but extremely unlikely.

Ethics and Health Policy Issues with Aging Theories

The fact that humans only live for a certain period is one of the most central and seemingly unalterable aspects of human existence and has profound ethical and policy implications. What happens to annuities, health insurance, pensions, social security, and Medicare if people start living significantly longer? What about the need for term limits for elected and life-time-appointed government officials? How do we increase retirement age? Would wealth imbalance increase?

Many have ethical concerns with altering aspects of human design that are “normal.” Most people would consider it unethical to genetically engineer humans to be taller, stronger, or more intelligent. It is certainly acceptable to the vast majority to attempt to treat or even cure cancer, heart disease, or other massively age-related disease because these conditions are not “normal” in that they do not occur in everybody. A very small part of the population does consider trying to treat cancer or other serious disease as interfering with God’s will and therefore sinful.

However, the more or less universal aspects of aging are certainly “normal” including “dying of old age.” Would it therefore be ethical to try to treat aging, per se? Worse yet, programmed aging theories suggest that humans possess an evolved suicide mechanism that limits their lifespans and that they are consequently designed to age. Aging is a feature of an organism’s design (like height) and not a defect (like a disease or injury).

On the other hand, just as it is obvious that different species age at very different rates, it is widely agreed that the aggressiveness of senescence, per se, varies substantially between individual humans. Therefore if a person inherited relatively aggressive senescence, should that person be able to seek medical aid to delay his senescence in such a way as to be able to enjoy a “normal” lifespan? Extending this idea, should we all be able to ethically enjoy the internally-determined lifespan seen by the longest-lived humans?

Many are concerned with medical advances that might extend the “nursing home stage” of life and favor advances that increase the “healthy” stage and decrease the nursing home stage.

Because they are concerned with the policy, ethics, and religious issues, some are against development of medical technology that would “extend normal lifespan” and are consequently against research in directions that might support lifespan extension – including programmed aging research, and even possibly including research as to the nature of aging such as initiatives specifically designed to determine if aging is programmed or not programmed. Some consider that because aging is a natural and normal aspect of human existence it is not a proper subject for medical research and medicine should be confined to treating dysfunction.

My conversations with thoughtful members of the general public indicate that there is substantial concern over these issues. Informal polling suggests that more than half of the U.S. population has at least some ethics, moral, or policy issues with research into lifespan extension or altering aging.

There is no doubt that senescence is surrounded by serious health policy, ethical, and religious issues. However, in my opinion it does not make logical sense to spend billions on research into treating massively age-related diseases without understanding aging and that doing so amounts to a “fool’s errand.” How can we hope to understand and best treat such a disease without understanding aging? If the majority of deaths due to highly age-related diseases (even in 40-year-olds) are caused by aging, how can we ignore aging in devising treatments for these diseases? Senescence is what it is. Ignoring scientific evidence pointing toward a certain conclusion regarding aging mechanisms is like ignoring global warming or ignoring all the evidence that the Earth orbits the sun.

Average human lifespans have substantially increased in the last century and few would really like to return to a much earlier age. Is it likely that there is going to be such a sudden and large increase in human lifespan that there would be huge social upheaval as a result?

Conclusion: A substantial portion of the U.S. population has issues with research into interfering with human biological aging mechanisms because they think such interference is impossible or because of ethical, religious, or policy issues. These attitudes obviously impact funding and support for research into aging and age-related diseases.

Aging Theories Articles Index

 

Anti-Aging Medicine

Posted on by
2

Aging TheoriesMedicine is largely an exercise in cause and effect. Because senescence has such a diffuse and multi-symptom nature and also is of such a long-term nature, it is probably the most difficult area of medicine in which to establish cause-and-effect relationships. This is one reason that theories of aging that suggest research directions are so critical to the development of treatments for age-related diseases and conditions.

The term anti-aging medicine means different things to different people. Many see “anti-aging medicine” as essentially a cosmetic or esthetics effort. We can delay the appearance of aging with tummy-tucks, face lifts, and Botox.

Another view is towards “healthy aging,” or “better aging.” We can work to extend the healthy and happy portion of our lives and decrease the length of the nursing-home-stage but not necessarily live much longer. Life-style modification including exercise and diet are frequently part of this approach. Lifestyle protocols are not very controversial; most physicians favor less obesity, healthy diet, more exercise, a generally more active life, and avoiding dangerous behaviors like smoking, alcoholism and drug abuse. There is wide respect for a “use it or lose it” concept in which exercise and activity are beneficial. Even exercising a person’s mind is thought to delay age-related mental deficits.

Finally, some are looking toward essentially treating aging, per se, and delaying the age at which manifestations of aging would otherwise appear in a particular individual. Some consider that such manifestations are reversible and that regenerative medicine could reverse or reduce some symptoms of aging including age-related diseases. Average and maximum human lifespan could be extended. Since there is little actual clinical evidence of pharmaceutically extending maximum human lifespan and this idea is unpopular in the general public and the medical community, most practitioners are careful not to make extravagant claims in this area. Treating aging, per se, might be expected to have more obvious effects on older people.

In a twist to this idea, it is widely agreed that senescence is largely an inherited characteristic and varies between individuals. The old saw goes: “If you want to live a long life, choose long-lived parents.” An anti-aging practitioner might say “Your hormone levels are not typical for a person your age and need to be adjusted. Of course, if that is a valid approach, the patient might say: “I would like to have my hormone levels adjusted to those of a typical 110-year-old or whatever levels the 110-year-old had when they were my age!” See more on hormones below.

Anti-Aging Agents

The thousands of prescription drugs are tested and certified for use in treating a particular disease or condition. However, a physician can prescribe most prescription drugs “off book” for other uses. In addition there are thousands of over-the-counter non-prescription drugs thought to be beneficial in treating some disease or condition as well as thousands of foods and substances sold by vitamin and health food stores also thought to have beneficial effects. Hard evidence of effectiveness such as double-blind clinical trials is usually much less available on the non-prescription substances.

Programmed aging theories suggest that aging is substantially the result of a biological mechanism and therefore that agents can be found that affect this mechanism just as they can be found for treating the disease and condition-specific mechanisms. As programmed aging theories become more popular we can expect to see many substances suspected of having anti-aging properties. Because it is progressively harder to establish cause and effect for anti-aging agents in longer-lived organisms such as humans a lot of the evidence will be coming from experiments with shorter-lived organisms such a mice (~2.5 years), some short-lived fish species (8 weeks), even worms and flies that may or may not be directly applicable to humans. Agents can also be evaluated by measuring their effect on senescence indicators such as telomere length, hormone levels, etc.

Non-programmed theories suggest that anti-damage agents such as anti-oxidants or anti-inflammatory agents might be effective.

The US National Institutes of Health (NIH) National Institute on Aging (NIA) is operating a search for anti-aging agents that they call the Interventions Testing Program. Oral agents are tested in mice and evaluated for effects on lifespan. This program can only evaluate a few agents per year and does not deal with injected agents or experiments that require special handling such as exercise regimens.

Human testing in elderly subjects might provide relatively rapid results depending on the nature of the aging mechanism. For example if aging is reversible, such testing may provide measurable results in a short period.

Suspected anti-aging agents include: rapamycin, metformin, resveratrol, vitamin D3, Cycloastragenol, and deprenyl.

Because some suspected anti-aging agents apparently have few side-effects large scale human trials are possible.

Blood Factors and Aging Mechanisms

Programmed aging theories suggest that aging is the result of a biological program that purposely causes or allows manifestations of aging to appear on a species-specific schedule. If this program is similar to other biological programs such as the ones involved in reproduction, or glucose metabolism, or circadian rhythms, or stress responses, then it is likely that some part of our body determines when to apply the aging function and sends signals to other parts to implement the function. These signals can be nervous or chemical (hormonal) in nature and hormone signals are typically distributed in blood plasma. Therefore, if aging is programmed we could logically expect to see “age” or “don’t age” signals (or both) in blood plasma. Indeed, many human hormones are observed to either decrease or increase with age.

Experiments have been performed in which tissue from older animals is exposed to plasma from young animals. Senescence markers were observed to change in response.

Heterochronic plasma exchange (HPE), or infusion of young plasma into old patients (or infusion of old plasma into young animals) is being explored as a way to study anti-aging effects of blood factors. The advantage of this approach is that is not necessary to understand which hormones are involved or exactly how they work in order to demonstrate an anti-aging effect. HPE trials could also result in near-term anti-aging treatments. See Young Blood Institute and Ambrosia Company.

Therapeutic plasma infusion is a recognized technique used in treatment of various diseases. However, the trials and prospects for treatments are highly controversial, at least partly because of attitudes described in companion articles.

Any signaling scheme must have means for both asserting and removing the signal. Hormone concentrations naturally decay. Some hormones are cancelled by other associated hormones and endocrinology is a complex subject. It is therefore somewhat unclear if plasma therapy would have beneficial effects for long enough to be practical. The importance of this issue depends on which hormones are actually important in aging.

American Academy of Anti-Aging Medicine

At least in the U.S. anti-aging medicine is an established medical specialty. The American Academy of Anti-Aging Medicine (A4M) is a medical specialty association like the American Podiatric Medical Association, or those supporting any other branch of medicine. From A4M literature:

“The American Academy of Anti-Aging Medicine (A4M) is dedicated to the advancement of tools, technology, and transformations in healthcare that can detect, treat, and prevent diseases associated with aging. A4M further promotes the research of practices and protocols that have the potential to optimize the human aging process.

The organization is also dedicated to educating healthcare professionals and practitioners, scientists, and members of the public on biomedical sciences, breakthrough technologies, and medical protocols through our advanced education entity: Metabolic Medical Institute (MMI).

A4M is a U.S. federally registered 501(c)(3) non-profit organization comprised of over 26,000 members across the globe, including physicians (85%), scientists and researchers (12%) , and governmental officials, media, and general public (3%), all of whom collectively represent over 120 nations.

A4M is focused on spreading awareness about innovative, cutting-edge science and research, in addition to treatment modalities designed to prolong the human life span.

The core of the NEW medicine is based on scientific principles of comprehensive medical care, which encompass many other specialties within healthcare.

A4M Provides continuing medical education (CME) and training to over 65,000 physicians and health practitioners at multiple live conferences worldwide, as well as online CME education in the functional, metabolic, and regenerative medical sciences. A4M supports advanced education, conferences, certifications, fellowships, online courses, and graduate programs.”

A4M practitioners include those supporting all of the treatment viewpoints described earlier. Many practitioners have expanded existing physician practices in some other specialty to include anti-aging medicine. With regard to pharmaceutically delaying aging there are currently (2018) two major initiatives in the A4M community:

Telomerase Activators

Telomeres are the “end caps” on chromosome molecules that tend to shorten with age. Since the 1960s age-related telomere shortening has been suspected as part of an aging mechanism. Telomerase is a naturally occurring enzyme that repairs (lengthens) telomeres. “Telomerase activators” that stimulate production of telomerase and therefore increase telomere length are in use by some anti-aging practitioners. Clinical trials show that these oral medications do increase telomere length but actual lifespan extension is much harder to demonstrate.

From Wikipedia: “The NASDAQ listed company Geron has developed a telomerase activator TAT0002, which is the saponin cycloastragenol in Chinese herb Astragalus propinquus. Geron has granted a license to Telomerase Activation Sciences to sell TA-65, the telomerase activator agent also derived from astragalus. In October 2010 Intertek/AAC Labs, an ISO 17025 internationally recognized lab, found the largest component of TA-65 to be Cycloastragenol.”

Bio-identical Hormone Replacement Therapy (BHRT)

Age-related changes in hormones are specifically suggested by programmed theories as parts of a programmed aging mechanism. Since many human hormones decrease with age and some increase with age enhancing concentrations of the former and interfering with the latter are obvious possibilities for an anti-aging treatment. However, hormone replacement (estrogen, testosterone, “steroids”) has been historically associated with significant adverse side-effects. BHRT practitioners suggest that this problem has been reduced or eliminated by using a different “bio-identical” form of the hormone(s) and using reduced dosage relative to the earlier treatments.

Conclusion: It is possible that therapies and agents that already exist have some effect in treating aging, per se, and therefore produce lifespan extension. However the extreme difficulty in establishing definitive cause and effect evidence and current unpopularity of this idea (see companion articles index) suggest that no definite medical conclusions can be expected in the near future. Plausibility of such result depends heavily on which of the many aging theories one accepts. Trials of therapies and agents that have a reasonable demonstration of safety in relatively elderly patients appear to have the best prospects for demonstrating effectiveness in this area.

Aging Theories Articles Index

 

Medical Implications of Aging Theories

Posted on by
Reply

Aging TheoriesAs can be seen from the figure (U.S. mortality data), human death rates from all causes in developed countries increase exponentially starting at about age 30 and doubling approximately every ten years. We can define age-related disease or condition as one where the incidence and severity drastically increase with age to the point where aging is by far the main cause. Massively age-related diseases include heart disease, stroke, cancer, arthritis, cataracts and other vision deterioration, hearing loss, and loss of strength and balance. Alzheimer’s disease is essentially unknown in young people. Death rates for 40-year-olds are approximately twice the rates for 30-year-olds so we can consider that nominally half of deaths in 40-year-olds are caused by aging along with three-quarters of deaths of 50-year-olds and so forth. Aging and age-related diseases cause about three-quarters of all deaths in developed countries and represent more than half of medical research and health-care costs.

There is wide agreement that there are different immediate or direct causes associated with each age-related disease and condition. The immediate causes of heart disease are not the same as the causes of cancer or the causes of arthritis, etc. Western medicine is largely based on the idea that we need to find different treatments and pharmaceutical agents to treat different diseases and conditions. This approach has obviously been substantially successful in treating age-related diseases.

The current trillion-dollar question is whether or not aging, per se, although obviously the main cause of the age-related diseases is itself a treatable condition. If so, treatment of aging could be used in parallel with the existing medical paradigm in our efforts to treat age-related diseases and conditions. As described below, different aging theories suggest drastically different answers to this question.

Fundamental limitation theories, wear and tear, stochastic, etc. strongly suggest that aging is an untreatable condition. We can find treatments for individual symptoms such as cancer and heart disease but we cannot find ways to treat aging, per se, as it is the result of fundamental limitations that could not be overcome by the evolution process and are very unlikely to be overcome by medical advances.

Modern non-programmed aging theories suggest that aging is not the result of fundamental limitations but rather the result of a large number of different independent factors as explained by George Williams in 1957. Unlike inanimate objects, living organisms obviously have many biological mechanisms for repairing or preventing damage. Wounds heal; dead cells are replaced; immunity is acquired, and so forth. Therefore humans and other organisms reasonably would have developed biological mechanisms to delay the appearance of cancer, other methods for dealing with the different damage mechanisms associated with heart disease, and myriad other mechanisms for delaying the occurrence of other age-related diseases and conditions.

This concept explains why different mammals have such different internally determined lifespans while having very similar biochemistry and similar symptoms of aging. This idea assumes that all of the different maintenance and repair mechanisms each presumably independently evolved and retained just the effectiveness needed to deliver the minimum necessary species-specific internally-determined lifespan called for by modern non-programmed theories based on Medawar’s evolutionary mechanics ideas.

These concepts support the accepted idea that we can find different ways to treat each specific age-related disease. However, these concepts suggest that there is some ultimate age beyond which further progress in extending human lifespan would cease because eventually every aging symptom would appear at catastrophic levels. They further suggest that there is no treatable common factor behind age-related diseases and conditions. These theories therefore support the current medical paradigm of ever-increasing specialization by disease, disease sub-type, and even personal disease variety.

Modern programmed aging theories suggest that a second path toward combating age-related diseases and conditions exists. These theories propose that the age-related diseases and conditions are coordinated by a biological aging program that stages the appearance of aging symptoms to result in a particular optimum lifespan for each species population. In addition to finding better ways to combat each particular disease we can look for ways to interfere with the aging program and therefore generally delay or reduce the severity of age-related diseases especially in older individuals. If valid, this is an exciting development because two different approaches can be used against age-related diseases. Because the anti-aging approach is new, we could reasonably expect “low hanging fruit” and rapid progress.

The effectiveness of an attempt to interfere with the aging program depends on one’s concept of the nature of that program and specifically the degree to which the program is common to the many age-related diseases and conditions and the extent to which the common program can control each symptom. For example, if senescence is controlled by a program similar to the one that controls mammal reproduction, and aging is a genetically programmed phase of life, then we could expect rather dramatic results. If we wanted to delay or advance puberty that would certainly be possible. There is considerable theoretical thinking and empirical evidence suggesting that, like reproduction, aging is controlled by a complex common program involving signaling (hormones).

There is fairly wide sentiment to the effect that aging can be generally delayed by exercise and perhaps by caloric restriction. This idea conflicts with non-programmed “damage” theories because exercise and caloric restriction would be expected to increase, not decrease, damage. Many other observations support programmed aging.

For more discussion of the nature of the aging program and supporting evidence see:

Externally Regulated Programmed Aging and the Effects of Population Stress on Mammal Lifespan

Aging Theories Articles Index