Living Long Enough to Live Forever
This is the second part of my “Bio-Hacking and Cyborging” series. To read into humanity’s relationship with immortality, see my previous essay. Read on about the only known immortal organisms, the problems modern medicine faces in making us as old as Methuselah, Longevity Escape Velocity, and the dark horse of the endless lifespan.
Contents:
Part I: Beating the 120-Year Lifespan
Is death a consequence of evolution?
The scientific community doesn’t think so. Death by old age seems to be the product of ‘evolutionary neglect’. Running our metabolism for a single day is taxing, let alone for the 30,000 days of the average Westerner’s lifespan, yet there is no ‘shutdown mechanism’ in our genes that kills us after a certain age, our bodies simply ‘damage’ themselves to death.
The expected lifespan for every organism (with very few exceptions) can be calculated when the mortality rate reaches 1 for all members of that species. If you eliminated the bad health associated with Death 1.0 (defined here), every species would still be bound by their vulnerability to Death 2.0. Without preventing the causes of Death 2.0 with medicine, we are almost guaranteed to die within a predictable timeframe.
Humans born before 1800 were 30% likely to die before their 5th birthday, even in the most developed countries. The invention of incubators and modern medicine lead to a sharp fall in this rate, and by 1925 it was around 10%. Even in the modern day, Sudden Infant Death Syndrome (SIDS), extremely premature birth, and infections mean infant mortality still effect the most developed countries, but at around 0.3%.
After our 30th birthday, human mortality rate doubles every 8 years, and most of us can expect to die by natural causes before our 120th birthday. Cancers, inherent in almost every animal (vertebrate or invertebrate – even jellyfish), can develop from an early age, and the thyroid glands will exhibit signs of ‘aging’ when most are in their teenage years; both are side effects of the metabolism and start the clock running until our eventual demise. As we age, our vulnerability to pathological diseases increases, and the median age of death in most developed countries is 82, where 9 out of 10 die by age-related disease.
Figure 1. Life expectancy plotted from birth to death.
While this natural decline in health effects practically any organism with cells, some animals have created so-called “longcuts” on their path to death. If we look at the Terrestrial Kingdom, we can study interesting cases where organisms have slowed, prevented or even reversed relationships with age.
Hydra are small organisms named after the regenerative Lernaean Hydra of Greek myth. Observed over four years, they exhibited no detectable increase in mortality rate. In other words, their metabolisms eliminate Death 2.0 at a constant rate; their generative abilities come from having stem cells exist in a continuous state of renewal. Ultimately, they are only able to do this by substituting a recognisable nervous system with a simplified ‘nerve net’ (a highly simplified nervous system, similar to that of plants). As simple organisms, Hydra have no recognizable brain or true muscles. [1]
Figure 2. Hydra, depicted alongside their nerve net.
Hydra mortality rate seems to stay constant, meaning that the rate of mortality determines the overall lifespan. Though the species does not age, their lives are cut short by Death 1.0, such as periods of starvation or predation.
Humans, unblessed by asymptomatic regeneration, have had to take the opposite approach; we have as a species worked to eliminate our risk of death by taking-on our immediate surroundings. The invention of nuclear warheads lead to a significant decline in military warfare. The development of vaccines and antibiotics have made us impervious to viral and bacterial infections. Now that we live in a society of abundance, we can tackle our metabolic inefficiency.
Part II: Immortality in the Terrestrial World
Other organisms are not as invincible as the Hydra, but some endoliths (rock-dwelling organisms) have extremely long lives and boast 10,000-year generation times. They do this by slowly metabolising. A bacteria named Actinomycetota found in Siberia is estimated to be over half-a-million years old.
This was considered the best contender for immortal life from 2018 until a June 2020 discovery of aerobic microorganisms in the South Pacific Gyre, 68.9 metres beneath the seafloor. These Archea are believed to be about 101.5 million years old, born midway through the Cretacious period when the Argentinosaurus roamed the Earth (which, for reference, had around the same lifespan of modern elephants). These organisms “chose the slow lane of life”, to put it lightly. [2]
Jellyfish typically have at most a year-long lifecycle, with the medusa stage (the recognisable stage with a bell and tentacles) being the last stage of the lifecycle. There are exceptions to this rule; the “immortal jellyfish” (Turritopsis Dohrnii) is capable of returning to the polyp state by the process of stem cell transdifferentiation. In the same way as the Hydra, their mortality rate defines their average life expectancy.
What about organisms which possess recognisable brains?
Small mammals generally evolved to populate when times were good, and few genes are spared for longevity. The oldest rodent is the naked mole rat, living to 28 years, and the oldest bat lived to 41. Termite queens (in laying over a quarter of a billion eggs) live the longest of any insect at around 50 years, but are frequently licked to death long before this. Arachnids typically live longer at 43 years.
In terms of hominids, orangutans have lived to 55 years, and the oldest chimpanzee lived to 80. The largest land mammal, elephants, are 5x less susceptible than humans to cancer, despite weighing up to 11 tonnes; the oldest Asian elephant lived for 89 years. Fascinatingly, humans are the longest living land mammals at 122 years old (though the oldest human ever lived 2.5% longer than anyone else in history).
Only since the later 1990s have humans beaten the oldest birds: the 114-year-old macaw and the 120-year-old cockatoo, and most other species of cetacean. For thoroughness, blue whales, the largest mammals of Earth, grow up to 90ft and over 180 tonnes, with a lifespan of up to 110 years. But bowhead whales, the oldest mammals in the world, can live for over 211 years. The 255-year-old Aldebra giant tortoise is the oldest terrestrial animal on Earth and the Greenland shark lives substantially longer at 512 years, making it the oldest of all vertebrates. [3]
Figure 4. The oldest terrestrial and aquatic vertebrates.
Animals age because it is very energy intensive to slow down genetics. In most every case stated above, these species are the most resistant to Death 1.0. Birds, for example, live very long relative to their size because they can avoid predators far more easily than rodents can. The naked mole rat lives in a protected environment beneath the forest floor and this lifestyle give them an evolutionary pressure to live longer, making their genetics more efficient and robust. This genetic robustness is expressed in their resistance to pathological diseases; there has not been a single case of cancer observed in naked mole rats ever.
To summarise, natural selection has not developed to kill us (unless we shoot our genitals off as part of the mating process). There is no law of nature that makes aging immutable. Rather, we have come to realise in the last 20 years just how plastic aging really is. [4]
Part III: Living Forever
It seems far-fetched to assume that humans would, within the space of a century, transgress the realm of “hypercentenarian” and live indefinitely. But there are scientific grounds supporting this process. To simplify and assume that medical advancements are roughly constant, humans need only repair their bodies until their risk of mortality is no longer climbing. Aging at 1-year-per-year, life expectancy is constant, as in the case of Hydra.
In the fashion of most developing technology, after early breakthroughs against aging, refinements will lead to widespread extensions in the lifespan. Like immortality, the human desire of flight is prehistoric, though it wasn’t until 1903 when man first achieved powered flight. Despite this staggeringly long development phase, transatlantic flights were achieved just 24 years later, commercial jetliners 22 years after that, and supersonic airliners 20 years after that. The fastest form of flight man could hope for was developed in 1966 in the form of the SR-71 Blackbird, capable of flying at 3,500kph, and early manned rockets achieved terrestrial escape velocity in 1961, just 57 years after the first powered flight. [5]
Compared to flight, the first breakthroughs in longevity will buy scientists time to make further advancements that may enable us to stay ahead of the “ticking clock”. With enough of a collective effort and continued growth in technological innovation, we will be able to fix the body faster than it accrues damage. By fixing the causes of death that 200-year-olds face before they reach 200 years old, we can then focus on becoming biologically younger as treatment continues. Aubrey de Grey calls this “Longevity Escape Velocity” or LEV.
Figure 5. Longevity Escape Velocity (LEV) for humans at each age in 2022 (approximation).
And yes, this means that the first 150-year-old may be born only a few years before the first 1000-year-old.
Given, the biological processes associated with longevity are considerably more complex and less understood than the scientific principle of thrust. With powerful machine learning and quantum technology, the problems we can expect to solve in the next fifty years will far surpass in scale what we have achieved in the past. For humanity to achieve this feat would require an enormous amount of collective effort, but it is feasible that many of today’s generation will be able to achieve LEV.
Part IV: The Four Horsemen of Immortality
We are not limited to just one method of achieving LEV. There are many schools of thought when it comes to life-extending remedies, and as with most questions this complex, the solution is unlikely to be binary.
To frame aging in its simplest form, as our metabolism runs (like a spinning vinyl), it accrues damage. Over time, this damage can lead to pathological diseases, caused by depleted physiological reserves in our organs. This damage manifests itself as cardiovascular disease, Alzheimer’s, cancer, dementia, as well as muscle wastage, fragility, and other symptoms of the elderly.
Figure 6. The organic aging process.
4.1. Geriatrics and Gerontology
The field of “Geriatrics” is concerned with the final stage of the life cycle, once pathological diseases have started to show. Geriatric medicines help the body cope with immobility, instability, incontinence, and loss of memory, particularly with onset muscle loss called sarcopenia. As time goes on, multiple onset disorders in the body lead to combinatorial explosion of age-related symptoms, meaning many elderly people must take a daily cocktail of drugs to slow the accumulation of side effects of their metabolism. This accumulating wave of symptoms will eventually overcome us, and even the best medicine in the world cannot prevent our inevitable passing.
This problem makes the field of geriatrics less significant in relation to the longevity problem, though therapies for elderly bodies remain highly important for an aging population.
The “Gerontological” approach to longevity aims to prevent the accumulation of side effects throughout one’s life, in order to keep us young with high quality and satisfaction of life. Many methods hinge around the “Rate of Living Theory”, which suggests that the faster our metabolism is working, the shorter our lifespan is destined to be. An increased metabolic rate may increase cell division, mitochondrial burn and the prevalence of DNA mutations. Without contingency agents and intervention, the body will become more and more inefficient as time goes on.
Humans can reduce their rate of metabolism with a large number of lifestyle changes, particularly to do with diet and exercise. Studies of rodents exposed to a chronic moderate caloric restriction of 30% can lead to a 50% extended lifespan while improving general health, maintaining cognitive performance, and decreasing mortality to age-related diseases. Some labs are looking at developing drugs that will produce the same effect without requiring caloric restriction in the first place. [6]
Equally, cutting out bad habits can lead to a reduced risk of pathological disease in later life.
Sunbathing and other forms of radiation exposure can increase the risk of genetic mutation, causing skin cancer. Strokes are linked to high blood pressure and lack of exercise. By avoiding sunburn, working out, and eating healthily, we can reduce our chances of Death 2.0. These are mitigators; behaviours that support our pursuit of longevity (and generally improve our mobility, energy, and quality of life). Achieving a basal level of exercise, nutrition, and sleep are necessities to maintaining a healthy life. — The War on Death
4.2. The Maintenance Engineering Approach
This approach focuses on the many hypothesis about ‘damage’ and looks to stop the effects of aging by intervening with the natural organic metabolism with surgical treatment and the provision of drugs. The ideal scenario is one where we periodically get scanned and ‘repaired’ in an operation that will improve the metabolic state, extending our lives each time.
We need only repair our cells to the point where pathology does not occur before our next servicing, but Aubrey de Grey insists that “sufficiently comprehensive maintenance on any machine (organic or inorganic) can keep it going just as well as when it was created”.
The three general ‘damage theories’ are the following:
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Wear and Tear Theory, which suggests that aging is the result of vital parts in our cells and tissues wearing out. This links to DNA damage or mutations which prevent cell renewal, which reduce stem cell efficiency, hindering the regeneration and repairing process. It is also linked to the shortening of telomeres, which are the tips of chromosomes. Telomere shortening occurs over time with DNA replication and is believed to hinder the regenerative process.
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Cross-Linking Theory is linked to the intra-and-extracellular build-up of protein ‘junk’, slowing down bodily processes and resulting in reduced metabolic efficiency, which causes aging.
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Free Radicals Theory pertains that as mitochondria burn energy with oxygen, they generate a highly reactive compound which creates damaging oxidative stress that accumulates with age.
Aubrey de Grey classifies seven age-related forms of damage that lead to pathology and these three theories cover all of them. This list, compiled in 2002, has remained unchallenged and appears to be comprehensive, capping the complexity of the aging problem.
Figure 7. All factors causing Death 2.0. [See Appendix]
By repairing our metabolism before pathological diseases are expressed, we can effectively ‘cure’ the diseases that have inevitably appeared in every human who has lived long enough. We can visualise all non-communicable diseases as a product of these factors.
Figure 8. Breakdown of Death 2.0 diseases caused by each factor.
Cancer is defined simply : the over-proliferation of cells. We can aim to eliminate the likelihood of cancerous mutations happening by reinforcing our DNA on a molecular level. This level of technology, rolled out across a large enough population, would make life-threatening cancer cases as infrequent as car crashes. [7]
The same goes for other diseases; 40% of the world dies from cardiovascular disease, which includes coronary and congenital heart disease, angina, heart attack, hypertension, stroke, and vascular dementia. By eliminating heart disease by finding remedies for coronary cell atrophy, intercellular and extracellular junk, and matrix stiffening, we can alleviate this figure until heart disease kills a small fraction of the population. This would extend the average life expectancy by potentially many years.
If we extended the human lifespan just by 7 years we would be halving the incidence of age-related diseases at every single age.
Figure 9. Therapies according to replacement, removal, reinforcement and repair processes.
An example of what this therapy process would look like is if we could offer someone with a high risk of developing cancer, say, 80% better resistance for the following 10 years.
In ten years’ time, the same person will be able to go to a clinic and leave with, say, a 10% healthier metabolism and 95% more resistant to Alzheimer’s and heart disease for the following five years. In five years’ time, they will go again, but this time may leave with a 25% better metabolism, and the same benefits as before but now with 95% resistance to ten types of cancer and completely immune to three.
As this process repeats, we may be able to take the momentum out of aging. A human who is mostly immune to the first four factors in Figure 7 will be impervious to diseases that have historically wiped out millions or even billions of humans. This immunity will buy them time to gain further factor-immunity, until they are less vulnerable to Death 2.0 than when they were born.
The impact of this research is huge, as humans may be best able to robustly improve the metabolism of those who have not yet been born. Genetic engineering of embryos offers the most freedom; directly changing stem cells at this early stage may make beneficial genotype and phenotype expression significantly more present in the lifestyle of that child when they are born.
Early designer babies Lulu and Nina were conceived from embryos which had been genetically modified using CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) to protect them from contracting HIV from one of their parents. While designer babies are ethically controversial, given the feasibility of creating a generation impervious not just to HIV, but cancer and cardiovascular disease, there are grounds that their development could extend the human life indefinitely. [8]
4.3. The Cyborging Approach
The “Cyborging” approach is an umbrella term for digital or inorganic internal-state-displacement. Put simply, the previous approaches are working to develop an enhanced organic state, but with modern advancements in machine technology, there may be another route all together.
Figure 10. The Fourth Horseman of Longevity is the divergence away from our organic metabolism.
On July 2016, retired school finance director Brian Stanley, received a double-lung transplant, considered the most vulnerable organs to transplantation. Four years later, Brian received a second double-organ transplant of his liver and kidney. Despite being around 7% transplanted, Brian Stanley feels no different to before. [9]
To live, humans simply require an internal state that is familiar to themselves –hat is it. The nature of substrate independence makes it possible to live as a human without being in a humanoid body (see my previous essay). A digitally uploaded mind will continue to exist as long as a copy is stored somewhere.
With computational power tending towards that of the human brain by 2033, futurist Ray Kurzweil believes we will be able to upload our minds by the end of that decade. Some believe that “mind uploads” are the logical next step for humanity as a species. But how we go from organic to digital isn’t clear in 2022. [10]
One route would be to use increasingly invasive implants to take over the operation of the mind. Cochlea implants have been shown to provide sensory signals to the mind of those who are profoundly deaf or hard-of-hearing, suggesting that inorganic matter can tap directly into the dynamic system of electrical impulses we recognise as our consciousness. [11]
By replacing the ears with inorganic implants, then the eyes, then certain organs, then expanding into the brain function, we may be able to relocate the source of our experience onto matter that does not break down like other organic cells. From this state, we could then remove the remaining organic parts of our body with surgery and live on indefinitely in an inorganic and ever-changing body.
Another route is the “digital upload” which posits that the mind can be transferred as electronic signals. If we find evidence to believe that the transferred mind is the exact same mind as before, all humans could continue their experience in digital form. In fact, the technology we use would probably be analogue.
My belief is that a collective of pharmaceutical, bio-tech, and cloud computing technologies will be what drive the longest liveable human lifetime upwards.
Appendix
An alternative version to this table is talked about by Aubrey de Grey here.
Notes
[1] - Hydra stem cells are incredible… here’s a good study.
[2] - Find the story of the oldest Earth-dwelling organisms here and the paper here.
[3] - An amazing breakdown of age structures is available here. Everyone should have access to this resource.
[4] - Animals born to mate-themselves-to-death are particularly unlucky and deserve an awareness day. Almost as important as an International Party Day. While that happens, here’s more on projectile erections.
[5] - For a timeline on human flight that casually omits rocket tech, look here.
[6] - Extending human life with drugs are here.
Fontana, L., Partridge, L. & Longo, V. D. Extending healthy life span–from yeast to humans. Science 328, 321–326 (2010).
[7] - Interestingly, Cancer (the proliferation of cells due to molecular mutation), is inherent in almost every organism, and we have evidence of cancer in hominins from at least 1.7 million years ago according to this.
[8] - Lulu and Nina are doing fine now. Click for CRISPR babies.
[9] - The story of Brian Stanley and his insane transplantations is here.
[10] - I write about the prediction for machine-human brain capacity in this essay.
[11] - State of the art cochlea implants are insane, check them out here.