Lifespan by David Sinclair

1. Earth had oceans of salty water but other wise a very harsh climate, a toxic blanket of nitrogen, methane, and carbon dioxide (Sinclair does not get into how this environment came to be in the first place, that is, he assumes you know about the Big Bang and the events leading up to the formation of Earth about four billion years ago).
2. Earth has been delivered a variety of various organic molecules courtesy the meteorites that smashed its surface.
3. Earth has many basaltic islands pockmarked with thermal vents. Water pools around these vents and due to the warmth, moisture and the process of cyclical wetting and drying, a “special chemistry” takes place in some of the organic molecules.
4. These are special molecules whose inherent properties make them form polymers (chains of molecules linked together). This polymer is called RNA.
5. Eventually, some of the RNA gets ensconced/trapped in fatty acids (delivered, again, courtesy of the meteorites). Why? Because fatty acids, due to their inherent properties, tend to join with other similar fatty acids and form spheres (“micelles“) – and due to random chance sometimes they’ll form a sphere around one or more RNA polymers, trapping it inside.

6. So, now you have a some pretty useless RNA “cells” . These cells that cannot do the main things that cells are supposed to do – grow and divide. All they are right now are just information (RNA) contained in a bag (fatty acid sphere).
7. But RNA is a special polymer because it not only stores genetic information (nucleotides) but can also act as a catalyst. So, as the cell engages with its outside environment, the catalytic part of the RNA (ribozymes) in the cell uses the available energy from the environment (such as heat from thermal vents or sunlight) to drive chemical reactions. These reactions act on reactant molecules, i.e. the nucleotides (that could be the on the same RNA or other RNA molecules trapped inside the cell), to create new RNA strands or other molecules that can help create new RNA strands subsequently.
8. As the RNA strands inside the cell increase in count, its membrane, made of fatty acids, expands to accommodate the increasing volume. Eventually, the cell membrane may become unstable due to its increased area. This instability can cause the cell to pinch inward and divide into two smaller cells (like how soap bubbles divide when they get too large).

9. When the cell divides, the replicated RNA molecules can be distributed between the two new cells. Each new cell will contain one or more RNA molecules, allowing them to carry on with metabolic activities and further replication.
10. Okay, so now our RNA cells are dividing. But there is one more thing to be done: When the RNA in the cell gets damaged (which is quite a lot because of the cosmic radiation bombardment), it cannot just go about replicating and end up with broken/incomplete instructions in the daughter cell that may spell the end of the generation. No, whenever damaged, it needs to stop replication and focus on repair.
11. Because mutations are happening even in these early cells (because of replication errors, radiation from the sun, high temperatures etc.) some of the cells evolve a “… genetic survival mechanism … a gene circuit …”.
12. This gene circuit basically makes the cell stop replicating and focus on repair during times of damage, and focus on growth during times of non-damage (how exactly this happens will come up later).
13. Those lucky RNA cells that that are able to do this make the template for life and due to natural selection quickly propagate.

“The human body, though far from perfect and still evolving, carries an advanced version of the survival circuit that allows it to last for decades past the age of reproduction.“.

Though how life came about to be on Earth is not the point of the book, the point is that this genetic circuit, the same one that kick started life on Earth, “… is also the reason we age“. Yes, not A reason but THE reason we age.

I would like to point out that while the emergence of life on Earth was a chance event, but once it had emerged, the proclivity to propagate (the “will to live”) was not chance.

A drive to propagate is inherent in life, because only those molecules propagated in whose nature it was to propagate. In fact, that which propagates is what we call life. Tautological? Sure.

Not sure though why I feel this is important to point out, but something in me tells me that I should.

Ah yes, now I remember why I needed to make the previous point. Because we need to think about what is actually being propagated.

Because individual pieces of matter can be destroyed or be converted into other things, so really, what is being propagated?

The answer is information. When we talk about life, as something that propagates, essentially is information.

The information being propagated is the genetic information encoded in nucleic acids (DNA and RNA).

This genetic information specifies the instructions for building and maintaining the organism who will preserve and propagate that information to the next generation of organisms who will do the same.

It may be counterintuitive to think how something conceptual and non-material as information can be life, but if you think about it, the same individual organs, bones, tissues and cells do not propagate, only the information contained in them does.

We commonly call this information “code”, “instructions” if you will.

I think of it as “arrangement”, “configuration”, yes.

It does not exist per se, it just appears.

What I mean is, when matter (starting from the very bottom, say, subatomic particles) eventually takes on a configuration that makes it mould other matter in its environment to the same configuration, starting a cycle of replication, life appears.

The matter is still very much dead, endlessly coming and going, never staying the same – but the configuration, the code, the information riding on the matter is alive, hopping from matter to matter through aeons.

Oh BTW, think about this: If life is information, then what are you? If you do not consider yourself as information then are you alive? Moving on.

I think this is the great poetic irony of existence: If life is that which can propagate, then that which truly propagates is information, something that we would not usually call “alive”.

Beautiful.

How is this connected with the book? Because in the book, Sinclair presents the “Information Theory of Aging” – According to which, aging occurs because of the gradual loss of both genetic and epigenetic information.

Over time, cells accumulate damage and errors in their DNA and epigenetic markers, leading to a decline in their ability to function properly, compromising the stability of the system and leading to its eventual decline.

If life is information (that can successfully propagate), then ageing is the loss of that information. Entropy.

Nothing to do with disease, injuries, hallmarks of ageing and such – these are just symptoms, the underlying cause is loss of the right information.

Let’s dive deeper.

1. Gene A: A caretaker gene that stops cells from reproducing when activated.
2. Gene B: Encodes a “silencing” protein that shuts off Gene A when conditions are good, allowing the cell to reproduce. It also has a second function: DNA repair.

3. When DNA is broken, the silencing protein encoded by Gene B shifts from Gene A to the site of DNA damage and tells the cell to repair the DNA.
4. This action turns on Gene A, temporarily halting sex and reproduction.

5. Hence, the cell has prioritised DNA repair over reproduction. By pausing reproduction during DNA damage, the cell has prevented genetic material loss or duplication. This ensures the integrity of its genetic information and prevents uncontrolled cell multiplication.
6. When the DNA repair is complete, the silencing protein returns to Gene A, deactivating it and thus the cell resumes reproduction.

Humans are more complicated than a single cell and have multiple circuits that depend on “… more than two dozen …” genes in our genome (as of this writing), and ensure that we remain healthy and recover from environmental stressors. These genes are hence called “longevity genes” the circuits they power form a sort of “… surveillance network within our bodies …”.

A few popular longevity genes, like I also covered during my read of Outlive by Peter Attia, are FOXO3 (DAF-16), MTOR, RPTOR, MLST8, and SIRT1 to SIRT7.

And a few popular pathways (sections of the genetic circuit) are the mTOR Pathway, AMPK pathway, sirtuins, and Insulin/IGF-1 Signalling (IIS) Pathway.

“Hidden within the sometimes byzantine way scientists talk about science are several repeating themes: low energy sensors (SNF1/AMPK), transcription factors (MSN2/DAF-16/FOXO), NAD and sirtuins, stress resistance, and longevity. This is no coincidence—these are all key parts of the ancient survival circuit.“

1. DNA – Digital information – Makes the genome – A discrete sequence of nucleotides (A, T, C, G) that are instructions for building and maintaining an organism. This information is discrete and, much like digital data, remains stable over time.
2. Chromatin – Analogue information – Makes the epigenome – The DNA wrapped around proteins (histones) that make up the chromosomes. This information is not discrete but emergent (best term I can think of right now), that is, it emerges from the configuration of epigenetic modifications on chromatin, such as DNA methylation and histone modification. This information degrades over time.

If DNA is letters on a page, then chromatin is the parts you’ve highlighted. The letters can only be one of twenty six, but the highlights can be anywhere on the page – literally thousands, hundreds of thousands of different places.

The thing is, it is the highlights that matter – “If the genome were a computer, the epigenome would be the software.“. Your body is not governed by the genome on a day to day basis. The genome sets the boundaries of what the body can achieve, acting as a blueprint.

However, it is the epigenome that plays a crucial role in daily life – the highlighter.

The epigenome regulates gene expression, determining which genes are turned on or off, and modulates cellular function and responses to environmental changes.

“Every one of our cells has the same DNA, of course, so what differentiates a nerve cell from a skin cell is the epigenome, the collective term for the control systems and cellular structures that tell the cell which genes should be turned on and which should remain off. And this, far more than our genes, is what actually controls much of our lives.“

Ageing, therefore, is the loss of epigenetic information more than the loss of genetic information (though both are important). Also, “loss” does not only mean deletion – in the context of a being that desires to live optimally given its surroundings – it also means change.

When highlights (epigenetic information) are either deleted or changed, though the instructions (genome) are still the same, the body will not know which ones to read and act on, or will read and act on something else what it should have.

DNA breaks: Cause sirtuins to move away from their usual positions, shifting their focus to DNA repair, and the cell’s usual epigenetic profile is changed. Note: Because this is energy intensive to maintain, cells don’t produce enough sirtuins to handle both gene silencing and DNA repair simultaneously, causing sirtuins to shuttle between tasks.

Repeated Emergencies: Frequent DNA damage over time (caused by chemicals, radiation, or DNA copying) leads to a series of emergencies. Sirtuins constantly moving to address damage can’t/don’t always return to their original positions.

Epigenetic Noise: This disruption causes genes that should be off to turn on and vice versa, altering the epigenome and leading to cellular malfunction. Cells get confused as to what instructions to follow and function improperly.

Sinclair summarises: “… aging is caused by overworked epigenetic signalers responding to cellular insult and damage … sirtuins are rushing all over the place … leaving their typical responsibilities … sometimes returning to other places … silencing genes that aren’t supposed to be …”.

So, wouldn’t it be great if that did not happen. If epigenetic information was not lost and could be restored even if it was. In other words, wouldn’t it be great if we could prevent ageing.

Sinclair spends a full chapter (chapter 3) telling us that humanity has taken a fatalist approach to ageing and assumed “that’s just how it goes”.

It has spent a lot of time and effort in curing the symptoms of ageing like cancer, ASCVD, dementia, diabetes but frustratingly has never tackled the root cause – ageing – loss of epigenetic information.

He makes a case that while we may cure one symptom of ageing like cancer, there are a whole host of other symptoms that can take us to the grave. We need to fight the real issue.

“In front of us is the deadliest and costliest disease on the planet, a disease that almost no one is working on … This disease is treatable.“.

These are the basics, and expectedly are what I have read before in places like Outlive and Genius Foods.

Eat food, mostly plants, not too much – Yes, I have borrowed Pollan’s famous quote but only because it is true.

I suppose I do not need to tell patrons of Sunchaser the benefits of eating wholesome, nutritious, minimally processed and ideally home-made food.

Mostly composed of what your ancestors have been eating, with a considered approach to more exotic/foreign foods based on their demonstrated health benefits.

“There isn’t much debate on the downsides of consumption of animal protein. Study after study has demonstrated that heavily animal-based diets are associated with high cardiovascular mortality and cancer risk. Processed red meats are especially bad.“.

Most of your calories should some from plant based sources, with a careful approach towards animal proteins meaning that while it should be a part of your diet, it should not be the main part.

Not only should you practice moderation in eating, some form of fasting where you are limiting the calories going in, either by eating less each time (calorie restriction) or eating for a lesser window of time each day (time restriction a.k.a. intermittent fasting) or going on longer multi-day fasts set times a month/quarter – “… almost any periodic fasting diet that does not result in malnutrition is likely to put your longevity genes to work in ways that will result in a longer, healthier life.“.

Many have pointed out that strength training (particularly in our older years) delivers outsize benefits, like in this video I saw today.

There is also benefit from high intensity interval training exercises (HIIT) that increase your VO2 max threshold.

Much more can be said about exercise than I have time for right now, but the point is both cardio and strength training should be part of your routine, along with focus on stability and flexibility.

Exposing your body to cold, a.k.a. cryotherapy, through a cold plunge, ice bath has many benefits like reducing muscle soreness and fatigue after intense exercise, faster recovery (by reducing inflammation), promoting blood flow once the cold exposure ends, (helps deliver oxygen and nutrients to tissues, promoting healing and recovery).

It also increases metabolism (activates brown fat, body works to maintain core temperature) and can also lead to improved mood and reduced symptoms of depression and anxiety (via release of endorphins and other mood-enhancing chemicals).

Even simple exposure to the cold like going for brisk walk in the winter with just a shirt on, sleeping with windows open in the winter and not using too heavy blankets. Exercising in the cold is particularly beneficial.

“… exposing your body to less-than-comfortable temperatures is another very effective way to turn on your longevity genes.“.

This is practically everything, and Sinclair concedes “… it’s impossible to completely avoid DNA breaks and the epigenetic consequences of those breaks …”.

So the next best thing is to use common sense and avoid at least the main things like cigarette smoke, air pollution, PCBs and other chemicals in plastics, exposure to azo dyes, UV light and organohalides.

Metformin is a widely used medication for type 2 diabetes. It improves insulin sensitivity and lowers blood glucose levels.

The best part is that metformin is easily accessible in many places and is not costly.

Metformin also activates AMPK (AMP-activated protein kinase), an energy sensor that promotes energy-producing processes and inhibits energy-consuming processes.

AMPK activation can indirectly inhibit mTOR, leading to similar benefits as rapamycin, such as enhanced autophagy and improved metabolic health.

“It’s among the medications on the World Health Organization’s Model List of Essential Medicines, a catalog of the most effective, safe, and cost-effective therapies for the world’s most prevalent medical conditions. As a generic medication, it costs patients less than $5 a month in most of the world.“.

As I’ve previously covered, the geneticist Nir Barzilai, through the TAME study, is seeking to make metformin the world’s first ever anti-ageing drug.

The study officially began in November 2019 and was to run for six years. Indeed it would be quite something for the world to have a pill it can swallow and start to feel better from age related issues.

Sirtuin Activating Compounds (STACs) are a class of compounds that can activate sirtuins, particularly SIRT1.

Resveratrol: One of the most well-known STACs. It binds to SIRT1, enhancing its activity.

This activation leads to the deacetylation of various proteins involved in cell survival, DNA repair, metabolism, and other functions.

By activating SIRT1, resveratrol and other STACs can mimic the effects of caloric restriction, which has been shown to extend lifespan and improve healthspan in various organisms.

This includes benefits such as improved metabolic health, reduced inflammation, and enhanced cellular maintenance.

Resveratrol’s benefits are seen as evidence of “xenohormesis“, a hypothesis that suggests certain molecules produced by stressed plants can confer health benefits to organisms that consume them.

NAD+ (Nicotinamide Adenine Dinucleotide) is a crucial coenzyme that plays several vital roles in the body.

NAD+ is involved in DNA repair processes.

It acts as a substrate for enzymes called PARPs (poly ADP-ribose polymerases), which detect and repair damaged DNA.

By facilitating DNA repair, NAD+ helps maintain genomic stability and cellular health.

NAD+ is a critical cofactor for sirtuins, a family of proteins that regulate various cellular processes, including gene expression, metabolism, and aging.

Sirtuins rely on NAD+ to remove acetyl groups from proteins, thereby influencing cellular functions and promoting longevity.

Both NR and NMN are precursors to NAD+, meaning they are used by the body to produce NAD+.

NR is smaller and can enter cells more easily, where it is then converted into NMN and subsequently into NAD+.

NMN can also increase NAD+ levels but may need to be converted into NR first to enter cells efficiently.

When cells reach the end of their life they are supposed to undergo apoptosis (programmed cell death). The ones that do not die are called senescent cells (zombie cells if you will).

Zombie cells, apart from refusing to die, send out lots of panic signals (Senescence-Associated Secretory Phenotype or SASP) that cause a lot of inflammation in the body (a.k.a. inflammaging) and cause other cells to become zombies too. Chronic inflammation is bad.

Senolytics are a class of pharmaceuticals that clear senescent cells from the body. A few examples are: quercetin, dasatnib, FOXO4-DRI.

Cancer cells are easy to kill, the problem is that since they’re usually in the vicinity of healthy cells there is a lot of unnecessary collateral damage.

So we need a precise to tool that kills only the cancer cells and leaves the healthy ones. the most specific tool we have is to use the patient’s own immune system – this is immunotherapy.

“Therapies such as PD-1 and PD-L1 inhibitors, which expose cancer cells so they can be killed, and chimeric antigen receptors T-cell (CAR-T) therapies, which modify the patient’s own immune T-cells and reinject them to go kill cancer cells …”

Checkpoint Inhibitors (checkpoint blockade therapy): These drugs block proteins that prevent immune cells from attacking cancer cells, essentially “releasing the brakes” on the immune system.

CAR-T Cell Therapy: This involves modifying a patient’s T cells (a type of immune cell) to recognise and attack cancer cells. “CAR-T therapy and checkpoint inhibition are less than a decade old … results thus far are promising …”.

Monoclonal Antibodies: These lab-created molecules can bind to specific targets on cancer cells, flagging them for destruction by the immune system.

Transdifferentiation: Another form of cellular reprogramming, where one type of differentiated cell is directly converted into another type without going through a pluripotent state. For example, converting skin cells directly into neurons.

Gene therapy: Introducing, removing, or altering genetic material within a person’s cells to treat or prevent disease. This can be done using various techniques, such as viral vectors to deliver therapeutic genes.

Cellular reprogramming: The holy grail, telling a cell to become young again. A process where differentiated (specialised) cells like skin cells, muscle cells, neurons are converted back into a pluripotent state, meaning they can develop into any type of cell in the body. This process essentially “resets” the cell’s identity, allowing it to become a different cell type or the same cell type anew. “I have little doubt that cellular reprogramming is the next frontier in aging research.“.

Induced Pluripotent Stem Cells (iPSCs): One common method of cellular reprogramming involves creating iPSCs. This is done by introducing specific genes or factors (Oct4, Sox2, Klf4, and c-Myc a.k.a. the Yamanaka factors) into differentiated cells. These factors “reprogram” the cells, reverting them to a pluripotent state similar to embryonic stem cells.

Tailoring medical treatment to the individual characteristics of each patient.

“Thanks to the plummeting prices of DNA sequencing, wearable devices, massive computing power, and artificial intelligence, we’re moving into a world in which treatment decisions no longer have to be based on what is best for most people most of the time.”.

Data Integration: Precision medicine integrates various types of data, including genetic, environmental, and lifestyle factors, to create a comprehensive understanding of a patient’s health.

This holistic approach helps in identifying the best possible interventions for each individual.

Preventive Measures: By analyzing genetic predispositions, precision medicine can also help in taking preventive measures.

For instance, individuals with a higher genetic risk for certain diseases can be monitored more closely and provided with personalised preventive strategies.

“Our flawed, symptom-first approach to medicine is about to change. We’re going to get ahead of symptoms.”.

Personal health tech. and AI: End of the latest decade saw a boom in personal health trackers and this decade does not seem to be any different.

Devices like pedometers and heart rate tracker are commonplace and cheaply available now, while more advanced devices like the smart watches (and rings lately) available from technology giants can additionally measure one’s blood oxygen, sleep quality, skin temperature, blood pressure, ECG readout and more.

Then there are “prosumer” devices like continuous glucose monitors (CGMs), handheld breath analysers, and smart toilets (they analyse your poop, it really has a wealth of information). All these devices generate a wealth of data that previously was impossible (or even practical) for an average person to record.

This data can then be analysed using AI (esp. the correlation between different data sets) to generate real, relevant, personalised and useful insights into your health.

“Real-time monitoring of our bodies, the likes of which we could hardly have imagined a generation ago, will be as inherent to the experience of living as dashboards are to the experience of driving.”.

That said, regular blood work should always be something you do while you wait for this technology to arrive.

This particular intervention addresses the traumatic injury part of your life.

This technology involves using 3D printers to create complex tissue structures layer by layer.

If ever you get caught in an accident where one or more of your organs gets damaged beyond recovery, all of the interventions that I have mentioned above will not be very useful – what will, in fact, be useful is quick access to donor organs that are perfectly compatible with your body.

Instead of using traditional printing materials like plastic or metal, bioprinters use “bioinks” made from living cells, including your own stem cells, and other biological materials.

Death has been humanity’s great equaliser since forever. It has been and continues to be the one thing that connect us all irrespective of whatever other divisions we may choose to see.

It is a pusher of progress as it consumes old people and old ideas, allowing new ones to take their place.

It is the muse of the poet and the philosopher, and the ultimate prize that kings and rulers have forever longed for yet never won. Truly deserving the title: Invictus.

If Sinclair is to be believed, it is the first time we stand at the precipice of significantly pushing back against the great equaliser – “… as we move faster and faster … for every month you manage to stay alive … Things could get really interesting around the end of the century if, for every month you are alive, you live another four weeks.“.

This is known as the longevity escape velocity – the point at which medical advancements in lifespan extension progress rapidly enough that for every year you’re alive, you gain more than a year of additional life expectancy. Essentially, it’s the idea that scientific and medical breakthroughs could potentially outpace the aging process, allowing people to live significantly longer, healthier lives.

If humanity achieves longevity escape velocity, it would mark a profound shift in how we perceive aging and mortality. Instead of the inevitability of age-related decline, individuals could look forward to prolonged periods of good health and vitality. This could have far-reaching implications for society, including changes in healthcare, retirement, and the economy.

Humanity has a lot of problems, starting with a mindset problem in my opinion: somewhere down the road we started viewing “progress” as the ultimate goal, and then started equating the ability to consume with progress, and then forgot that for everything we consume someone has to pay the price whether it be the planet, its flora and fauna or its less fortunate people.

“The problem is not just population, it’s consumption … we use and use and use, and return little of value to our natural world.“.

I do not need to remind you of the growing list of what we should be worried about, about how the people of the world feel increasingly concerned about the future.

And now adding to the problems is a population base that is expected to live beyond a hundred years old on average.

“There is simply no model in which more years of life does not equate to more people and in which that does not lead to more crowding, more environmental degradation, more consumption, and more waste.“.

The economic model of the world today assumes that most people will live to 75-80, not contributing economically for the last 10-15 years of that time. And hence appropriately calculated tariffs are imposed on the people younger than the retirement age to support this older population in the form of social security programs.

But as the world has generally been getting older, the ratio of workers to beneficiaries has been falling, for instance, from 41 workers to one beneficiary in the 1940s United States, to a mere 3 workers to one beneficiary today. “… there is simply no economic model for a world in which people live forty years or more past the time of traditional retirement.“.

Also, the benefits of increased longevity will likely come to the rich first (as have most kinds of benefits through history), and this will just exacerbate the divide between the haves and the have nots, “Imagine a world of haves and have-nots unlike anything we have experienced since the dark ages …”.

It’s not easy to reverse ageing (though Sinclair might disagree), because entropy acts on all parts of the genome and the epigenome at once and at all times.

Whereas what humanity is trying to do is aiming to restore order to only a few parts with the calculated understanding that they are connected to the whole in a way that the entire system is impacted.

Yes, absolutely that is possible, but it will take time.

And until that time, to no one’s great surprise, we’ll often see statements like the following: “We’d tried many different approaches: the Notch gene, Wnt, the four Yamanaka factors. Some had worked a little, but most were turning into tumor cells.“.

Some might take these attempts or news reports like He Jiankui creating the world’s first designer babies as an act against divine will.

They might say that God does not want us messing about with what is “natural”.

Well, Sinclair asks us in the book, “Look around. What about your current situation is ‘natural’?“.

It is possible to imagine our ancestors calling agriculture “unnatural” and that picking fruit off trees and hunting wild game was the “natural” way to sustain oneself – But today no one will call agriculture “unnatural”.

It is possible to imagine our ancestors calling writing “unnatural” preferring instead to remember everything by memory (indeed Socrates himself warned us against the potential harm of writing) – But today no one will call writing “unnatural”.

It is possible to imagine our ancestors calling automobiles “unnatural” – But today, people will think you’re the weirdo if you decide ditch your car and instead walk to the neighbouring town.

With such a history of tinkering, indeed, shouldn’t one think that the only thing “unnatural” is to “accept limitations on what we can and cannot do to improve our lives.“.

And it’s this very same tinkering, the very same ingenuity that Sinclair believes will be used to find a solution to the problem of an increasing population base as longevity science continues to make strides.

What will change is that people will start to live healthier for longer and what will need to change is the mindset towards the aged and ageing.

Treating the elderly as a burden

A lot more old people are going to be around in the future, but unlike our expectation of “old people” they’ll be energetic, sharp and (many of them) willing to tontine in the workforce and contribute to society as a wellspring of experience and wisdom.

Treating ageing as inevitable

Simply “… define aging as a disease. Nothing else needs to change.“. Sinclair says that the nation progressive and courageous enough to make the first move and support the research will “… change the course of the future.“, its citizenry enjoying many more productive years that will grow its national product.

Denying the right to die

As it gets increasingly possible to lengthen people’s healthspans, we may be tempted to think that everyone wants to live. That will not be true, in fact the opposite, more people will start demanding the right to a peaceful death when they feel the time is right for them. We need to be cognisant and respectful of this.

Denying the right to be treated

Because we have culturally accepted ageing as an inevitable, the medical establishment may have a tendency today to just “give up” on its older patients, this attitude “often limits what doctors are even willing to discuss in terms of treatment options, because they assume that people are supposed to slow down, begin dealing with a bit of pain, and gradually experience the degradation of various body parts and functions.“.

This needs to change and we need to start treating both young and old with the best treatment basis the state of their health and nothing else.

Sinclair does not expect cost of treatment to be the limiting factor simply because treating ageing directly (i.e. loss of analog epigenetic information) is a much cheaper affair than treating the individual symptoms of ageing (cancer, ASCVD etc.).

“Right now, the overwhelming majority of the money we spend on medical care is spent fighting diseases. But when we are able to treat aging, we will be tackling the biggest driver of all disease. Effective longevity drugs will cost pennies on the dollar compared to the cost of treating the diseases they will prevent.“.

Close mindedness to science and technology

From eradicating polio to achieving flight human ingenuity has solved many problems that many suspected were unsolvable.

The problems that an increasing and increasingly older population will bring will also be eventually solved by human ingenuity, we should help that process along and not hinder it.

“We need more smart legislation to speed, not impede, the adoption of Earth-saving technologies.“.

Considering life “stages” as a one-way street

The era of the four or five distinct “stages of life” is quickly vanishing before our eyes – especially the stages after childhood where one is expected to learn for some time, then spend time in a job, and finally retire to die.

The future will be one where it will be normal to go back to school for upskilling every half a decade, to take a break from work and come back a year later, indeed to redefine the definitions of “work” and “gainful employment”.

It will be a world where health and wellness aren’t the things you focus on when you’re old, a world where 80 will not even be considered “old”, a world where we’ll not even think about our chronological age choosing instead to focus on our biological age.