Aging Research Half a Lifetime Ago: the Lost Decades of the 20th Century

We roughly know the recent history of longevity science, starting in the 1990s in a period in which the small scientific community interested in aging was defensive and self-policing, uninterested in any talk of treating aging as a medical condition. Young researchers were discouraged from thinking about intervention in the mechanisms of aging, or any hope of lengthening healthy human life span. Pushing that sort of viewpoint openly was career suicide. Established researchers in the field saw themselves as under siege by a tidal wave of pervasive and damaging nonsense generated by the anti-aging community of pills, potions, and outright lies, harming the prospects for building publicly funded research institutions to tackle specific age-related conditions, such as Alzheimer's disease.

Then came the work showing that single gene mutations could lengthen life in short-lived species. A rediscovery of the plasticity of longevity in response to environmental stress in worms, flies, and mice progressed from there onward. In particular there was ever greater interest and funding for calorie restriction research, mining the biochemistry of the mammalian response to low calorie intake, a part of the field put away and largely lost since the 1930s. Then the SENS rejuvenation research movement emerged just after 2000, and the thaw of a frozen research community started in earnest. Nothing proceeds rapidly in the sciences, even cultural change, and it was the late 2000s by the time that younger researchers could comfortably talk in public and publish papers about treating aging as a medical condition without career consequences. Nonetheless, that came to pass, and matters sped forward from there. Today, senolytic therapies capable of clearing senescent cells, one of the causes of aging, are under commercial development, and there is considerable excitement in the research community for this mode of intervention in the aging process. The thaw has completed, and the research community now confidently holds its own, unafraid of the anti-aging marketplace - which is just as full of nonsense and lies as it was thirty years ago.

What happened between the 1930s and the 1990s, however? Why was calorie restriction research abandoned? How did the understanding of aging progress over the 20th century? Looking back at history, we see so much of the past interest in aging and longevity as brief flashes, a few individuals undertaking it as a part of their broader research interests. Little in the way of a coherent whole emerges until our time; it is a collection of individuals, not a community. It is hard to understand the culture of the time from these few points of reference, the degree to which intervention in aging was or was not on the table as a point of interest for any particular group. Even the science fiction of the mid-20th century, usually illuminating as to the edges of scientific consideration, is unhelpful on this topic. The only assembled historical resource that I know of is Ilia Stambler's "A History of Life-Extensionism In The Twentieth Century", which actually provides much more information on a number of individuals who were at their peak of interest on the topic of aging in the late 1800s, versus what was going on between 1930 and 1950.

We can look back at a series of individual inquiries into aging across the span of very rapid technological progress in the decades to either side of 1900, leading up to, for example, the studies showing calorie restriction to slow aging and prolong healthy life in rats carried out in the 1930s. It all seems a logical progression of understanding and growth, leading somewhere. Yet after this, within the scientific community, it appears that the study of aging became ever more disconnected from practical thoughts of extending life. The closer researchers came to understanding the causes of aging, the more distanced they were from considering intervention in any organized way - the field turned to the treatment of age-related conditions, drawing an entirely artificial dividing line between aging and disease. I have no grasp on why this came to pass, at least in the first decades following the 1930s; after that, however, it is possible to draw connections and conclusions.

With the exception of the early establishment of amyloid aggregation by Alois Alzheimer, the causes of aging outlined in the SENS rejuvenation research proposals were all discovered, and those discoveries refined, in the thirty years between 1955 and 1985. The period between the 1960s and 1990s also encompasses the growth and success of the anti-aging marketplace outside the scientific community, probably spurred by the early scientific discoveries, but taking on a life of its own as people realized just how much profit could be made in this modern and more sophisticated incarnation of the old hoaxes regarding elixirs of life. For every group that approached anti-aging seriously, another ten were cheerfully selling nostrums and misrepresenting scientific discoveries - a trend that continues today.

Life extension was one of the tenets of the 1960s and 1970s culture propagated by people such as Timothy Leary, who wrote optimistically about scientific methods to dramatically extend human life span. There are probably people in the audience old enough and Californian enough to recall SMI2LE - Space Migration, Intelligence Increase, and Life Extension. The Age of Aquarius had its technological counterpart - now an overly optimistic retrofuture, only portions of which were attainable in the time span envisaged. But this movement was in no way a part of the small scientific community that studied aging, and the members of that research community rejected all of it, baby along with bathwater.

Thus to a very crude approximation, aging research in the latter half of the 20th century looks to have been steered by competing dynamics of commercially co-opted popular enthusiasm versus ivory tower rejection of that enthusiasm as a threat. There were never large numbers of thought leaders involved on either side, and the sums of money involved were never truly enormous, but this all happened in a period of growth and foundation and potential on either side of the fence. Could it have been different, and come to a better outcome for longevity science? Were those decades lost in terms of progress that could have occurred towards working healthy life extension technologies?

Everything boils down to economics in the end. It is reasonable to consider that progress only picked up in the frozen scientific community of the early 1990s because biotechnology had improved rapidly following the start of the computing revolution. Falling costs and greater capacity to generate results per unit expenditure mean fewer people must be asked for permission to perform any particular study. More exploration takes place by those with heretical views and useful curiosity. Nonetheless, we can imagine a very different world, one in which the institutional space race of the 1950s and on was instead a focus on biotechnology and aging. How much further might we be today, given massive investment on that front? It is hard to say. Could something like the Human Genome Project, for example, have been conducted at any price in the 1970s? Or any analogous feat of understanding? Drug discovery and cellular assessment were painfully slow and expensive processes back then; would it have been possible to uncover senolytic pharmaceuticals with any reliability?

But that is the root of any answer to the question of the degree to which the latter half of the 20th century was a series of lost decades in the matter of aging. We know that the scientific community retreated from engagement with the goal of extending human life, leaving that to the anti-aging marketplace, a community that did little of any great use for human longevity considering all of the effort expended, and generated much in the way of fraud, lies, and mistaken expectations along the way. A generation passed before the opportunity arose to change that state of affairs, but it is quite possible that the practical outcome might not have been all that different had it happened otherwise.

Comments

Great read. Ive often asked myself what if:

(A) the steam engine were invented by the greeks around 2000 years ago instead of 1769, which there are evidence there were some works on but it didn't proceed since slaves were plentiful. When there weren't possible to get slaves greek economy collapsed and the power center moved to Rome.

(B) What if the printing press were invented only a century before?

(C) The bicycle were invented around the same time, in greece or rome instead of 200 years ago. Remember its an easy invention.

(D) What if the light bulb were invented in early 1800 instead of 1880?

(E) What if WW1 and WW2 were prevented? Europe and the world would not have felt back decades in development.

Think about how muck social suffering these things could have prevented. I always teach to young how important STEM education is.

Posted by: Norse at January 2nd, 2018 1:36 PM

I agree that the 20th century was a lost century for gerontology. It was also a lost century for europe (1914-1991)

Posted by: Norse at January 2nd, 2018 2:07 PM

Another field that has moved slow is cryoprotectants of organs and tissues and maybe also in the more distant future of whole bodies. I think this is also a field that had a lost century or at least decades.

Posted by: Norse at January 2nd, 2018 2:22 PM

This roller-coaster reminded me of the writing style of Brian Alexander:

Like that earlier book, this one is told in a present-tense style that privileges roller-coaster participation over dispassionate context. You know early on that there will be entertainment in the details. As Leary is transferred from one prison to another in the opening pages, we pan over all that he carries with him: "two packs of Bugler roll-your-own cigarette tobacco, two ballpoint pens, and rubber shower shoes that are a goodbye present from a murderer he met in another state facility."

Posted by: Norse at January 2nd, 2018 4:53 PM

@Norse - most of those inventions had concepts that where thought about decades or centuries beforehand, but required other enabling technologies.

Printing press with cheap movable type - required better metal alloy technology (hence why the inventor guttenberg was a goldsmith by trade).

Bicycle - Some guy invented this two centuries earlier than when they become popular in the 19th century. But the ride on wooden wheels was horrible as rubber tires had not yet been invented.

Steam engine - the ancient greeks didn't have the metal alloy technology, or the smooth boring technology to build a practical steam engine. Smooth boring technology was developed in Europe to make better cannons due to near constant war.

Posted by: Jim at January 2nd, 2018 9:00 PM

Not sure it could have happened any other way, or any faster.

Aubrey's great contribution was to find anti-aging intervention points that don't require a complete understanding of metabolisms. Before him the only viable intervention point was perhaps telomeres/telomerase, but again that needed an effective delivery system, which wasn't available back in the 90s. Stem Cell interventions were a similar story; they are only just becoming effective now, mainly because they weren't using the right type of stem cells, or didn't know how create the right systemic environment for them to flourish. Before that all that could be done was calorie restriction, and most research since then has been to find better ways of doing that.

We are at a turning point now though - whether or not the public sees it yet.

Posted by: Mark at January 3rd, 2018 3:17 AM

You actually had quite a lot of useful findings in those middle years that led to actionable knowledge:

- "cross-age" transplantation studies of the 1940's,
- the core of the regenerative biology era,
- original cloning experiments in the early 1950's,
- the emergence of cybernetics as a scientific discipline to explore the integrated dynamics of controlling complex regulatory systems
etc.

The bigger problem was the over all move of the broader industry towards more and more reductionist thinking as far as pharmaco-therapeutic interventions

Posted by: Ira S. Pastor at January 3rd, 2018 9:04 AM

Hi there, just a 2 cent.

I believe, now, the obstacle, besides funds, for SENS, is the conveying part, staying part, not forgetting part, and people wanting it/finding use to it part (or else 'sleep' like every other invention that is forgotten as soon as its made because the public 'does not need it/does not like it/sees no use/gimmick' and between you and me - SENS is tagged with all of these problems since so many people think 'there is Nothing you can do about aging' and they WANT to die before 122; even some want to die with Good Health - Still, want to die...how exactly do you change people's minds - when other inventions failed miserably to do so and ended collecting dust for thousand of years; only to be 'revived' later and have a 'short run'. SENS is not immune to this possibility. It's a 'new invention that comes', it's great, it Never Picks Up, Nobody Cares and Goes to Sleep For Eons - and in the mean time you die...because it's too long before it'S Adopted and Accepted by the public (as useful/wanted...etc)))). The numerous inventions were dormant for so long (such as the steam inventions in ancient Greece 2000 years ago; they might not have had all the necessary Tools/technologies to make them happen...but it was largely dormant and then when it 'happened' in 18-19th century it was short-lived. At least, we can get our hopes up with the printing invention/paper writing with Guttenberg; it had a solid run of at least 500 years and it still useful (we still make use of 'paper books' and writing on paper; but digitalization and 'Reduction of Tree-Cutting for paper production to save planet' hindered that strongly).

Likewise for the 20th century 'genetic', 'biogerontological and medical advancement/inventions. Some were adopted and used immediately, others not so much.

That is what I fear a bit about SENS and other antiaging stuff- it could suffer the 'it's a fad thing' and go to dodo pretty soon; just like most Other Anti-Aging stuff. And because the Public is So Against Life Preservation and So Fatalist Loving - do you think this is a recipe for SENS being 'adopted' by the mass; I doubt it - only the 'luminaries' (us, that is) in micro numbers will make it be known; but overall that'S not enough 'to change the world' - you need ALL on board or else the ship sinks and goes to sleep (just like many inventions/gimmicks/advancements that are 'THE BEST THING EVER' only...no one wants it....)

Just a 2 cent,.

Posted by: CANanonymity at January 3rd, 2018 3:50 PM

In the 1970s there were news reports backed by growing scientific understanding that human biologic destiny is not solely governed by inherited genetic factors, based upon the realization that people emigrating from Japan were living a shortened lifespan, evidence of an environmental influence which was later recognized as epigenetics. Insurance Actuaries were briefed of an expectation of 250-year lifespans which is documented in a report entitled Longevity And Genetic Engineering public in the Record of Society of Actuaries (Volume 5, No. 1, 1979). The life insurance industry exerted influence to throw all this science back into the research closet as it was realized no one would buy life insurance if they were to live that long.

The possibility of a significantly lengthened lifespan had already been posed by Clive McCay of Cornell University who conducted experiments published in 1934 that a limited calorie diet could double the lifespan of laboratory animals.

It took until 2003 for David Sinclair of Harvard and Leonard Guarantee of MIT to identify niacin as a ubiquitous dietary signal that silenced the Sirtuin1 survival gene, while calorie restriction (CR) expressed Sirtuin1 and resveratrol molecularly mimicked a CR diet, all which corroborated with the fact the wine-drinking French were experiencing unusual longevity and a mortality rate from coronary artery disease of 90 per 100,000 versus 240 per 100,000 in North America at that time. The French were eating a diet higher fat calories and cholesterol. This phenomenon became known as the French Paradox.

But subsequent experiments found resveratrol prolonged the life of laboratory animals fed a high-fat diet (60% fat calories) but not on a standard-calorie diet (30-35% fat calories). However, a combination of polyphenols similar to that provided in red wine was found to activate 9-fold more longevity genes than plain resveratrol and switch 82% of the genes in the same direction as life-long calorie restriction in just 12 weeks in the animal lab, but that discovery, while published, has been ignored.

The fact such an anti-aging pill would supplant over 20 prescription drugs as David Sinclair at Harvard indicated, explains why Big Pharma bought out of developmental resveratrol drug company(Sirtris Pharmaceuticals) for $725 million and later put it out of business. Dr. Sinclair says the science his laboratory produced still stands and can be put into practice any day society chooses to do so.

Synthetic resveratrol-like molecules were then introduced in place of resveratrol, but almost amusingly, it was found liver metabolism knocked off their molecular tails and they reverted to resveratrol.

Now, knowing there is a groundswell demand for a pill that might delay aging by 7 years and save the impending bankruptcy of Medicare (the so-called longevity dividend posed by S. Jay Olshansky), modern medicine posits forward metformin, a drug that is only likely to add 8% to the human lifespan and keep doctors and drug companies in control of such pills rather than direct consumer access to resveratrol as a dietary supplement.

Then MIT breaks the mold, introduces its NAD vitamin B3 derivative Nicotinamide Riboside as an anti-aging agent that is sold as a dietary supplement. So we now have high-science backing a pill that would be sold as a nutraceutical. Public adoption of these pills still remain relatively low compared to their promise. The pursuit of an anti-aging pill is an ongoing story.

Posted by: Bill Sardi at January 7th, 2018 5:42 PM

I think advances are driven by scientists making advances through hard work and free thinking/creativity.

The general public will be against anything that is different, so I think this blog more reaches out to people who are open minded and believe in the power of science and technology to make real progress. Large institutional organizations will take the conservative path. Probably they need to be ran this way, and within the institutions people have to think about their careers which basically means never take risks.

However once you get a revolutionary new product that delivers benefits to people, the public changes their tune and is throwing money at you. Eg.. something that can make their skin look 10 years younger, and they don't have to do anything except give you money and take some pills.

And once you have money coming in, you can hire legions of science degree holding and careerist people, most of whom are not free thinkers, but all the same they are smart, work hard, know their profession, and they can be put to work under the direction of visionary thinkers.

At some point it comes down to those free thinking people having to sit down and do the high level science themselves to push it into a new frontier.

Posted by: aa3 at January 8th, 2018 1:55 AM

Post a comment; thoughtful, considered opinions are valued. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.