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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Aging Theories in the Academic Gerontology World

Aging TheoriesThinking about theories of aging in humans and other mammals in the academic gerontology and more general bioscience community now centers around two concepts: Aging (and an organism-design-limited lifespan) is genetically programmed and an adaptation because limiting lifespan created an evolutionary advantage, or, it is not. Opinions in the gerontology community tend to be highly polarized on this issue.

Members of the programmed aging faction tend to think that current published science overwhelmingly supports programmed aging.

Many members of the non-programmed faction consider programmed aging to be scientifically ridiculous because it conflicts with evolution theory as generally understood. Some non-programmed proponents have compared programmed aging to popular but scientifically ridiculous concepts about evolution such as creationism and intelligent design. Non-programmed aging is still more popular in the academic community and general science-aware public but programmed aging provides a better match to empirical evidence.

Life in the academic world is very public; we could say “publish or perish.” The scientific journal system including peer review is widely seen as necessary to maintain scientific integrity, especially for articles describing experimental or observational results and procedures. However, the system is less amenable to theoretical work. The “peer” review process tends to work against publication of new or unpopular ideas and some gerontology journals effectively will not accept articles that favorably describe programmed aging. Gerontology journal editorial boards are usually staffed by senior people who tend to follow older theories, in this case non-programmed theories, and often contain dedicated proponents of and even authors of non-programmed theories. This creates a rather hostile academic work environment for one considering performing research in programmed aging. Publicly declaring a belief in programmed aging could well amount to career suicide if one’s boss or institution thinks that programmed aging is “nuts.” Few researchers can afford to follow such a path.

In addition, the vast majority of the science-aware general public has essentially been trained to believe in non-programmed aging. No institution wants to be seen as performing research that is widely seen as scientifically ridiculous. Funding sources do not want to be seen as funding junk science.

Only a few research institutions publicly support the idea that human aging is genetically programmed because such a design created an evolutionary advantage. One such is Moscow State University.

This creates a situation where some researchers are performing research that does not make any sense under non-programmed theories but scrupulously avoid controversial terminology such as “programmed aging” or worse yet “suicide mechanism.” One sees creative ways of “finessing” this issue such as journal articles with titles along the lines of “Semi-programmed non-programmed aging.”

Nobel-prize-winning physicist Max Planck famously said: “A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die, and a new generation grows up that is familiar with it.”  Younger researchers are more likely to follow programmed aging concepts.

One workaround for the journal problems that has proved successful is for a journal to host a special issue to specifically compare opposing schools of thought, in this case programmed vs. non-programmed aging. Authors for both sides can then be assured that their review is going to be performed by someone who is in their faction and that therefore rejection is not preordained. In addition this creates a useful “shoot out” context where readers can compare multiple pro and con arguments. See example [1]. Note that this requires the journal to concede that programmed aging has attained a level of scientific plausibility that at least justifies serious discussion. Some journals (like Elsevier Medical Hypotheses) are specifically designed to allow reviewed publication of unpopular theories using a modified review process.

Until about 2005 many senior gerontologists dismissed programmed aging as ridiculous and “impossible” without providing any attempt at serious rebuttal or refutation of arguments and claims by programmed aging proponents. However, some senior non-programmed proponents now concede that programmed aging is possible “under certain circumstances’ and are arguing details, a significant change in attitude [2].

NIH PubMed now (Jan 2018) shows 1323 articles in a search for “programmed aging.”

Conclusion: No one would be surprised if the endless academic arguments regarding the programmed vs. non-programmed nature of aging continued for another 150 years! However, venues for publication of programmed aging articles are increasing and the programmed aging faction is growing in size, popularity, and impact. The research environment in the commercial world (e.g. pharmaceutical companies) is much more favorable to programmed aging as will be discussed in a companion article.

[1] Current Aging Science Vol 8 Nr1 Programmed vs. non-programmed aging, 2015, Libertini G. ed. open access

[2] Curr Biol. 2011 Sep 27;21(18):R701-7. Kirkwood TB, Melov S. On the programmed/non-programmed nature of ageing within the life history.

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