By Max More, PhD

From Cryonics 2nd Quarter 2022

Readers of this piece are used to articles by me that convey an encouraging, hopeful, optimistic view of things. This article is not one of those. I will be pressing a point of view that isn’t comfortable, reassuring, or fun. Many of you will resist it because of that. If you already have cryonics arrangements, I won’t be asking you to do anything different. If you want to live longer and do not have cryonics arrangements, the perspective here makes a major difference—the shift in thinking might even save your life.

Many people speak of cryonics as “plan B,” while relying on life extension within their lifetime. They use cryonics as a backup plan in case something unexpectedly fatal happens. Barring such misfortune, they believe that either (a) within their remaining lifetime control of aging will be achieved; or (b) we will make accelerating progress in extending human lifespans so that they will see a time in which technology extends a person’s life by more than one year for each year they are alive. The second view has become especially popular and goes by the moniker longevity escape velocity (LEV) or actuarial escape velocity, a term coined by David Gobel.

Taking someone of my age as an illustration of LEV, right now I’m 58. If life expectancy expands at an accelerating rate, by the time I’m 65 we may be delaying aging by 4 months each year. Each year that passes, I would age only 8 months. At age 70, I might age 6 months each year. At 75, 3 months per year. At 80, we reach LEV and my life expectancy stops decreasing year by year. From that point on, my life expectancy would keep growing indefinitely apart from limits imposed by accidents, homicide, or suicide.

But wait!

Perhaps the life extension curve does not look like the rising exponential curve of LEV. Prior to 2010, life expectancy in the United States rose fairly steadily for decades. Not long before 2010, life expectancy was increasing by about 0.2 years per year. According to the LEV view, life expectancy should now be rising faster than that.

In reality, progress completely stopped. The decade started promisingly. Between 2010 and 2014, life expectancy increased 0.2 years for the total population (less for men, more for women). But from 2014 to 2017, life expectancy decreased 0.3 years for the total population. From 2017 to 2018 life there was an increase of 0.1 years. For the decade as a whole (and this is not getting into the pandemic years) the result is a wash.

Health, United States 2019 (cdc.gov)
Life expectancy at birth, USA
1860: 39.4
1865: 33.1
1890: 44.05
1900: 47.3 (men 46.3; women 48.3)
1950: 68.2 (men 65.6; women 71.1)
1975: 72.6 (men 68.8; women 76.6)
1980: 73.7 (men 70.0; women 78.8)
2000: 76.8 (mean 74.1; women 79.3)
2010: 78.7 (men 76.2; women 81.0)
2018: 78.7 (men 76.2; women 81.2)

You do see a small increase in life expectancy at later ages after 2010 until the last pre-pandemic year of 2018. The increase is considerably smaller than gain in the 2000-2010 period.

Life expectancy at 65, USA:
1950: 13.9
1975: 16.1
2000: 17.6
2010: 19.1
2018: 19.5

Life expectancy at 75, USA
1980: 10.4
2000: 11.0
2010: 12.1
2018: 12.3

Even if the rise in life expectancy resumes—as I expect it to do—it may not rise exponentially. The rise could be arithmetical, or an S-curve, or a set of fits and starts with periods of no progress interspersed with jumps in lifespan. If you favor the idea that age is caused by the accumulation of damage over time, you might expect gradual progress as we develop ever better and more comprehensive means of halting and reversing that damage. If you believe that aging is primarily programmed into us, perhaps one discovery could lead to a huge boost to lifespan. But when will that boost happen?

Even if we do see exponentially rising lifespans reaching to LEV, how do you know where we are on that curve? In the illustration above, my life expectancy reached LEV at age 80. At that age, what if we are only managing an additional 3 months per year? I might live only a few years longer than you would expect today. In other words, even if progress is exponential, that won’t save you if we are too far to the left on the curve or the curve is flatter than advocates believe.

Inventor, visionary, and Alcor member Ray Kurzweil has described cryonics as his “Plan D”, the plans A through C being “don´t die”. Kurzweil has never been reticent about making forecasts. To his credit, he makes these publicly and mostly somewhat specific, and then reviews them over time. Compared to anyone else I know, his forecasts have generally done well. I´m far more doubtful about his forecasts for LEV and the end of aging.

In his 1999 book, The Age of Spiritual Machines, Kurzweil´s scenario was “Expected lifespan has increased to over 100 by 2019” (p.208). By 2029: “The life expectancy of humans continues to increase and is now around 120 years.” (p.223) Clearly, we did not reach an expected lifespan of 100 three years ago. It also seems exceedingly unlikely that lifespan will stretch to 120 in the next 7 years.

Similarly, in a 2017 article, Peter Diamandis quotes Kurzweil as saying: “I predict it´s likely just another 10 to 12 years before the general public will hit longevity escape velocity.” In 2022, this means 5 to 7 years!” A sneaky way around having to acknowledge the implausibility of the LEV claim would be to argue that such a lifespan had been achieved but we won´t know it for decades. This underlines the difficulty in quickly discovering whether a treatment will extend the maximum human lifespan – or even the average life expectancy – without waiting for many years to find out. [Donaldson; de Wolf]

Consider the possibility that we manage to jump onto the LEV curve several times but one or more interventions have expected side effects that have serious health consequences. Given the politics and regulation of the real world, such events could cause a reaction that again drops us below the LEV curve. Even if this never happens, I will show that the LEV idea is far from new – and early advocates would be disappointed with our current state, that agreement is lacking on the nature of aging, and that numerous promising treatments have failed to live up to their promise.

LEV: The launch has been postponed

When you see the same mistake made repeatedly over time, it´s reasonable to be doubtful about the idea behind the mistake. The concept of a longevity escape velocity has been around longer than most people realize. I´ve been following life extension efforts and advocacy since my teens.

One of my favorite magazines when I was 14 was Future Life. I still have a few copies. In the November 1978 issue, Robert Anton Wilson wrote an article called “Next Stop, Immortality.” He started off by saying that the actuarial tables used by insurance companies were wrong and no one could predict your life expectancy because “Recent advances in gerontology… have led many sober and cautious scientists to believe that human lifespan can be doubled, tripled or even extended indefinitely in this generation.”

Wilson went on to express an idea extremely close to that of LEV:

In short, even if we can only double lifespan in this generation, we will still be around when further breakthroughs will probably triple it, quadruple it or raise it into millenniums. And then some of us will be here when the next quantum jump in lifespan occurs, and the next, until Immortality is achieved.

Expert opinion on longevity has grown steadily more optimistic every time it has been surveyed, because the lab results are better every year. In 1964, a group of scientists was polled on the question and predicted chemical control of aging by the early 21st Century. In 1969, two similar polls found scientific opinion predicting longevity would be achieved between 1993 (low estimate) and 2017 (high estimate.) Dr. Bernard Strehler, one of the nation´s leading researchers on aging, predicted more recently that the breakthrough would occur sometime between 1981 and 2001.

Interestingly, Alcor gets a mention at this point: “At the March 1978 Alcor Life Extension conference in Los Angeles, some of the experimental results justifying such forecasts were presented.” Wilson also tells us that “an October 1975 McGraw-Hill poll found the majority of experts in the field believed cryonic freezing would be perfected and perfectly safe by 2000.”

If there is an LEV curve, it has been shifting away from us for decades, taunting us with our inability to jump onto its upward slope.

Another friend of mine, Jose Cordeiro, mirrors Kurzweil´s incredible timetable. In his book, La Muerte de la Muerte (The Death of Death), Jose says, “By 2029/30, so by the end of this decade we will have reached Longevity Escape Velocity.” Since I will be in my late 60s by then, I really want to be able to believe Ray and Jose and Peter Diamandis and Aubrey de Grey at his most optimistic. But I cannot. To better understand why, let´s take a look back at theories of aging and proposed interventions that seemed promising at the time.

Won´t you just tell me what aging is?

In the late 1970s and through the 1980s, I was one of those expecting major advances in life expectancy in the very near future. As reality failed to track the hopeful predictions I had read, my views gradually changed. Over that time, theories of aging have come and most of them have later gone away.

Why do we age and how can we stop it? There is no agreement on this. Across several talks and a panel discussion at the 2012 Alcor Conference, we heard three diverging views from three very smart, very well-informed people: Aubrey de Grey, Michael Rose, and Josh Mitteldorf. Aubrey favors a seven-factor view of damage as aging; Michael has a genetic view; and Josh favors programmed aging. Some of the past and present theories of aging include:

• Antagonistic pleiotropy theory of aging
• Disposable soma theory of aging
• Free-radical theory
• Glycation theory of aging
• Inflammation theory of aging
• Neuroendocrine theory of aging
• Order to disorder theory of aging
• Rate of living theory
• Reliability theory of aging and longevity
• Somatic mutation theory of aging

Saul Kent provides an admirably thorough overview of the field of life extension in his 1980 book, The Life Extension Revolution. There he lays out more than a dozen other theories of aging with only a little overlap with the previous list.

• Random error theory – breakdowns in the genetic machinery.
• Lysosome deterioration. To be treated with membrane stabilizers to repair lysosomal enzymes, e.g., centrophenoxine, Deanol/DMAE.
• The crosslinking of molecules, especially collagen.
• The free radical theory, proposed by Denham Harman. This led to a plethora of antioxidants as ways to quench the free radicals.
• Roy Walford’s immunologic theory.
• Programmed aging/the aging clock.
• Regulatory dysfunction of the neuroendocrine system.
• Breakdown in hormonal regulation (Caleb Finch).
• Hormonal regulation of enzyme activity.
• The role of the pituitary gland in the neuroendocrine controlled rate of aging.
• The aging clock and “unsculptured” hormones (Paul Segall).
• The juvenile hormone (Carroll Williams), which was never found in humans.
• The death hormone. W. Donner Denckla looked for a pituitary hormone.
• The integrated theory of aging, stated by Bernard Strehler emphasizing reduced capacity for cell division in brain, heart, and muscle.

Along with programmed aging, one of the more popular theories (or characterizations) of aging is Aubrey de Grey’s with its engineering approach to preventing aging. This aims to tackle seven major categories of aging damage:

1. Cell loss, cell atrophy
2. Junk outside cells
3. Crosslinks outside cells
4. Death-resistant cells
5. Mitochondrial mutations
6. Junk inside cells
7. Nuclear mutations

In 2022, then, we are still far from universal agreement on a theory of aging. We are even further from agreement on how to treat aging.

Where is that elixir?

Time and time again people have excitedly proclaimed a new compound or treatment as a major advance in life extension. In the process of writing this article I recalled some of the old candidates for the “elixir of life”, as the alchemists called it. You may remember Gerovital-HC (procaine), an immensely popular treatment since 1951 that was used at least into the 1970s. There was Deanol (DMAE), laetrile therapy for cancer, placental tissue therapy in the Soviet Union, ginseng—which lost popularity as a life extension treatment following a 1970s study in England with a null result, fetal lamb cells and “cellular therapy” in Switzerland, estrogen replacement therapy (not a bad idea but at the time the importance of balancing estrogen with progesterone wasn’t well understood), chelation therapy (EDTA), L-Dopa, lergotrile and other ergot derivatives, blood transfusion (newly popular in the form of parabiosis), and nucleic acid therapy.

Saul Kent’s book details these and other substances popular in the 1980s. You can find a similar list in Durk Pearson and Sandy Shaw’s 1983 book, Life Extension: A Practical Scientific Approach. Pearson and Shaw helpfully provide their own regimen of supplements. It includes numerous vitamins in megadoses (but curiously no vitamin D, which has proved to be one of the most worthwhile vitamin supplements), as well as amino acids, inositol, the food additive BHT, thyroid extract, and drugs such as L-Dopa, bromocriptine, Hydergine, and vasopressin. The years since then have found some of these to be helpful for some people in some ways, but not to extend maximum lifespan and with little if any effect on life expectancy.

New supplements periodically capture people’s attention and excitement. These include Alpha Lipoic Acid, blueberry extract, carnitine, carnosine, CoQ10 (ubiquinol), DHEA, Ginkgo, Green tea, Melatonin, various minerals and vitamins, N-Acetyl Cysteine, pomegranate extract, SAMe, and Silymarin (milk thistle). More recently: metformin, NAD+, Dasatinib, quercetin, resveratrol, and Rapamycin.

Hunger strike against death

You have probably heard the advice “Eat to live, don’t live to eat.” Sound advice. Some life extensionists have gone much further and recommended that you don’t eat to live—or at least eat much less. Perhaps the first paean to caloric restriction was the delightful little book, The Art of Living Long, written by Italian nobleman Luigi Cornaro in 1550. Real research began in the 1930s and 1940s with the work of Clive McCay, an American biochemist, nutritionist, and gerontologist.

Caloric restriction research was furthered by my friend, Dr. Roy Walford, also known for being the physician in the first group to inhabit Biosphere II, along with colleague Richard Weindruch, author of The Retardation of Aging and Disease by Dietary Restriction. Walford set forth his research and recommendations in Maximum Life Span (1985) and The 120 Year Diet (1987). Caloric restriction definitely extends mean and maximum life span in many species, with a dramatic extension seen in shorter lived species. However, research on primates has been disappointing. An NIA study did not find calorie restriction to improve survival in rhesus monkeys (Mattison, et. al. 2012), although another study at the Wisconsin National Primate Research Center (WNPRC) reported improved survival associated with 30% CR initiated in adult rhesus monkeys.

Even in the NIA rhesus monkeys, despite no improvement in survival curves, the CR monkeys showed an improved metabolic profile and may have had less oxidative stress. Recent research into intermittent fasting also finds improvements in various measures of health. These improvements seem unlikely to translate into more than a very modest increase in life span in humans. Indeed, theorists as opposed as Michael Rose and Aubrey de Grey agree on one thing: Caloric restriction produces only very modest extension in life span in humans. The downsides of CR include feeling cold, hungry, lacking sex drive, and less resilience in case of infection or accident due to lower stores of metabolic reserves.

I don’t mean to be too gloomy here. Recent research may be finding some means of helping to extend life expectancy, if not maximum life span. We have definitely moved on from the days of gland grafting and vasoligation. Although there is much unsupported hype in the area of stem cells, embryonic and pluripotent stem cells may yet yield strong results. Senolytics and senomorphics are under investigation for their potential to clear out senescent cells and improve health. Thymus regeneration needs more research but looks very promising as a means of strengthening the immune system in older individuals and thereby greatly reducing the risk of early infection-related death.

Fatal cryocrastination

Here are some examples, real and hypothetical, of people putting off making cryonics arrangements until it’s too late.

Jeremy has said for years that he thinks cryonics has a good chance of working. “I’m definitely going to get around to signing up. I know I’m procrastinating, but I’ll get to it soon.” Jeremy develops an autoimmune disease. When he applies for life insurance funding for cryonics, he discovers that he’s no longer insurable. Lacking other means of funding, Jeremy succumbs to his illness and dies. Permanently.

Joan has been fascinated by cryonics for decades. She’s been putting off cryonics arrangements all that time. At 74 years of age, she finally gets moving. When she gets a quote for life insurance to fund her cryopreservation, she gets a nasty shock. She cannot afford the premium payments, and she lacks the means to pre-pay. “If only I’d signed up years ago. I could have easily afforded it then.”

Carl reads news stories about cryonics with great interest. “That’s a great idea. I think it might actually work,” he thinks. One day he checks out the website of a cryonics organization. “Hmm. I should get on with this soon, while I’m still in good health and can afford it comfortably.” Carl gets distracted and doesn’t follow through by applying for membership. He thinks about it vaguely over the next few months. Before acting, Carl has a fatal heart attack. He is cremated.

Add your own scenario here. There are many ways to die, and only one way to make cryonics arrangements.

More reasons for Plan A

Another consideration supports cryonics as Plan A. Suppose we achieve complete control of aging and we are even able to fully rejuvenate people. This does not mean we achieve physical immortality. It does not mean that you cannot die. It does not mean that cryonics will no longer have a purpose.

You may still be prone to some diseases. You may become biologically immortal in the sense that you will never die of old age. But even a biologically immortal person might still be killed by diseases and pathogens that remain without a reliable cure. New pathogens (perhaps engineered to bypass enhanced immune systems) might still kill you. You may have an enhanced immune system but it will not necessarily be able to protect you against all diseases and pathogens.

A biologically immortal or non-aging person is still prone to accidents. Some of the accidents which are fatal today may not be in the future, but some will still kill you. A biologically immortal person can still die by falling from a tall building, plunging down a mountain, or plummeting from a faulty parachute. You can still die from a severe traffic accident (even if these are far less common), be blown up in a aircraft or spaceship, or killed in a homicide, terrorist attack, or war.

A = B = Stay Healthy

Do your best to stay healthy. This is good advice whether you are on Plan A or Plan B. In Plan B, you are primarily working at staying healthy to improve the odds that you will live long enough to reach LEV. Don’t die this year because next year may bring a new discovery that gives you more time. In Plan A, you will also want to improve your odds, but you don’t think it very likely to make a difference. That leaves you with two other reasons to stay healthy, especially in some specific ways.

One reason is that the cryopreservation process and the capabilities of your cryonics organization may improve over time due to learning and more resources. The other reason is to improve the quality of your cryopreservation. You really want to avoid sudden cardiac arrest, stroke, and aneurysm. These can either directly damage your brain or cause a delay in starting the cryopreservation process. Keeping your vascular system healthy should be a top priority.

Look at your cryonics arrangements as your Plan A. Communicate cryonics to others as Plan A. Don’t let them comfortably reassure themselves that cryonics can be Plan B because life extension research will save them in time. If the person you’re speaking to is convinced and asks: “Okay, then. So which cryonics organization should I sign up with?” The obvious answer for Plan A is: Plan Alcor!

My thanks to Aschwin de Wolf for feedback on a draft of this article.

References

“3 Dangerous Ideas From Ray Kurzweil” By Peter H. Diamandis, MD -Nov 10, 2017 https://singularityhub.com/2017/11/10/3-dangerous-ideas-from-ray-kurzweil/

Anti-Aging Medicine: The History | The Journals of Gerontology: Series A | Oxford Academic (oup.com) https://academic.oup.com/biomedgerontology/article/59/6/B515/662071

Products – Health E Stats – Changes in Life Expectancy at Birth, 2010–2018 (cdc.gov) https://www.cdc.gov/nchs/data/hestat/life-expectancy/life-expectancy-2018.htm

“What if senolytics fail?”, Aschwin de Wolf. Biostasis.com, February 5, 2021. https://www.biostasis.com/what-ifsenolytics-fail/

“Why cryonics will probably help you more than anti-aging,” by Thomas Donaldson. Originally published in Physical Immortality 2(4) (2004), p. 28-29. https://www.biostasis.com/why-cryonics-will-probably-help-you-more-thanantiaging/

Saul Kent, The Life Extension Revolution. 1980.

Ray Kurzweil, The Age of Spiritual Machines. 1999.

Life Expectancy – Our World in Data https://ourworldindata.org/life-expectancy

Mattison, et. al., “Impact of caloric restriction on health and survival in rhesus monkeys: the NIA study.” Nature. 2012 Sep 13; 489(7415): 10.1038/nature11432.

United States: life expectancy 1860-2020 | Statista https://www.statista.com/statistics/1040079/life-expectancy-unitedstates-all-time/

Roy Walford, Maximum Life Span (1985) and The 120 Year Diet (1987).

Richard Weindruch, The Retardation of Aging and Disease by Dietary Restriction.

Robert Anton Wilson, “Next Stop, Immortality,” Future Life, November 1978