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The Life Extension Revolution: Part 1

[Also on Medium]


One truly serious problem of our time is death.


It is because when time is up, time really is up. You are no more. All your learnings, attempts, trials, errors, emotions, ideas, experiences, wishes, yearnings, dreams are no more. No matter how large your desire to live, you will not live.


There are no second chances. And you will never add to the Great Ledger.

“Now discontent nibbled at him — not painfully, but constantly. Where does discontent start? You are warm enough, but you shiver. You are fed, yet hunger gnaws you. You have been loved, but your yearning wanders in new fields. And to prod all these there’s time, the bastard Time. The end of life is now not so terribly far away — you can see it the way you see the finish line when you come into the stretch — and your mind says, “Have I worked enough? Have I eaten enough? Have I loved enough?” All of these, of course, are the foundation of man’s greatest curse, and perhaps his greatest glory. “What has my life meant so far, and what can it mean in the time left to me?” And now we’re coming to the wicked, poisoned dart: “What have I contributed in the Great Ledger? What am I worth?” And this isn’t vanity or ambition. Men seem to be born with a debt they can never pay no matter how hard they try. It piles up ahead of them. Man owes something to man. If he ignores the debt it poisons him, and if he tries to make payments the debt only increases, and the quality of his gift is the measure of the man.” — John Steinbeck

What does it feel like to know you’ll end?


That you end like this:


That everyone you love ends like this:


That everyone — every human being ever — either ended like this or will end like this.

That almost* every species’ ends like this:

*I said “almost” because there are some species that have been around for a long time and there are some species, for example, hydra, who don’t seem to die from aging at all.



There have been very few exceptions — and there have been no human exceptions. Every human is vulnerable. Every human has fallen off The Ultimate Cliff.


Every human who inspired you, every human who frustrated you, every human who fought for ideals you hold dear, every human who destroyed those very ideals, every human who helped you understand our place in the universe, every human who served as your moral compass, every human you love(d) so much that you would gladly lose yourself for them, every human who would do the same for you, and every human who ultimately added to the Great Ledger — every human ever — has either fallen off The Ultimate Cliff or will fall. Everyone died or will die — that is the norm. Unless we do something.


And life after death seems like nothing more than just another one of our deepest yearnings.

It probably feels sad and scary to be getting closer to The Ultimate Cliff — but then why aren’t you feeling scared?


Because you most likely don’t really see that cliff or think of it as The Ultimate Cliff. You know there is a cliff…somewhere…down the road…but far away from where and when you are right at this moment. And you can’t imagine non-existence so it’s probably meaningless to you.


Here’s how you actually see it:

But you are wrong. You will eventually face The Ultimate Cliff and you will end.


Furthermore, what if I told you that you are carrying a time bomb inside you which will self-destruct in 1 week, or 1 month , or 1 year — and you will not have a choice. Now imagining your end isn’t that hard because I just ruined all your plans.


And that’s why you should think about the problem seriously — you are indeed carrying a ticking time bomb.


“And you run, and you run to catch up with the sun, but it’s sinking / Racing around to come up behind you again / The sun is the same in a relative way, but you’re older / Shorter of breath and one day closer to death / Every year is getting shorter; never seem to find the time / Plans that either come to naught or half a page of scribbled lines…”


To live or to die, to age or not to age


Another truly serious problem — that inevitably leads to death — is aging.


I believe humanity should have a choice — to live or to die, to age or not to age. And we should have this choice as early as possible.


Some of you will think, “I am fine with death. I don’t want to live forever. Anyway, there is no such thing. (And even if there was, I don’t want it.)”


Ok, your choice. But the rest of us should at least have an option to not die, or at least to not die within 120 years of being born. Or an option to choose to live longer.


Our world is so precious and our human species even more so. There is so much to know: are we alone? will we create sentient beings? when do we finally colonize another planet? when do we achieve interstellar travel? do we transcend our human condition? do we ever become digital (or some other form)? do we ever truly understand one another? does it become possible to time travel? can we jump universes? and so much more. We got this extraordinary opportunity called life — non-existence and death are norms, not life, so life is that precious. There is so much we can add to the Great Ledger. But we need time.


We need time — may be extra 10 years, 30 years, 200 years, 500 years or 1000 years or 100,000 years or longer? Who knows. All we can say is that as of now, we can’t (yet) opt-out of death.


Some of you will think “I don’t want such a long life! I want a good life, one without pain and suffering.” You are saying this because you are imagining a (long) life which is a simple extension of your current aches and pains — either you’re imagining your current state for a very long time or you’re imagining deterioration that comes with age. That’s why you say you want a good quality of life, even if it’s short. You don’t want to suffer for hundreds or thousands of years! And you would be right — but only because you’re picking one over the other. We should have both.


Think of it this way: That self-destructing time bomb I mentioned earlier? Well it is inside of you. And if you’re reading this, then it’s already ticking and it will self-destruct one day. I bet most of you will not want it to self-destruct tomorrow or next week, especially if you are healthy, happy, and satisfied.


Now, would you want it to self-destruct one year from now? Ten years from now? Probably not if you are still healthy, happy, and satisfied. Twenty years from now? Probably not if you are healthy, happy, and satisfied. I think you get the pattern.


You may not know how much time you want, but you still don’t want that bomb to self-destruct anytime soon.


The worst part is — the probability of the time bomb self-destructing grows exponentially after a certain age. The longer you live, the higher the chance of the bomb going off. And the harder to stop the bomb.

Most of us will disagree about how long we want to live, but we will all agree that we all want to live a healthy life.


Now, what if I told you this: science can give you a healthier life and in doing that, science can simultaneously give you a longer life. There is no way to extend the lifespan of a sick person. Really sick people usually die, sooner rather than later. Living longer will occur as a side effect of living healthier.


In some sense, this has been the case so far — we have already extended life — we live almost twice as much time as people did in the early 1900s. That’s incredible! We’ve gone from an average life expectancy of around 47 in the 1900s to around 77 today.

We got an average of 30 years more and none of us want to give this time back!

But we’ve paid a different price for it — aging. And aging sucks. And we also can’t opt-out of aging (yet).


Aging brings a variety of chronic conditions and diseases that we don’t have to deal with when we’re young. We start with minor aches and pains. Soon the cushioning of our joints is thinner, our eyesight is blurry, our kidneys are less effective, our hearts are weaker, our immune systems are weaker, leaving us prone to infections that probably couldn’t have touched us earlier. Inevitably these minor aches and pains deteriorate into chronic conditions and diseases. Diabetes. Cataract. Osteoarthritis. Heart disease. Cancer. Alzheimers. Stroke. And more. We got more years to live, but we also got a whole bunch of chronic diseases that go with these extra years — and these illnesses rob us of a good quality of life. A lot of people currently spend their last 10–15 years of their lives in pain and misery due to illnesses.

Many of these age-related diseases (for example, Alzheimer’s) don’t have effective treatment options. Others, such as high blood pressure, stroke, or heart disease, require continuous monitoring and medication, costing us tremendous amount of money and grief.


Aging is natural — why not just cure all those diseases?

“Every man desires to live long, but no man wishes to be old.” — Jonathan Swift

Here’s the most important point: We know that the elderly have a higher rate of chronic degenerative diseases than the young. But that’s not the biggest problem. The real problem is the relationship between aging (as a whole) and diseases — an individual’s risk of diseases rises exponentially with age — and these diseases eventually kill — and this is the root problem.


Aging is the self-destructing time bomb.

For example, we know heart disease is the number one killer in the Western world. So, we’re trying to develop ways to solve this problem. Let’s say we can prevent heart disease — then yes, it will save all those people who have heart disease. But if those individuals are older in age, then it won’t save them for that long — it doesn’t do much for them in terms of giving them many more healthy years — it won’t necessarily extend those individuals’ healthspans (# of healthy years) by much. This is because an elderly individual who no longer has heart disease would only get a few healthy years before another disease kicks in — cancer, Alzheimers, etc. — because each year, this individual’s risk of diseases increases (most times exponentially) with his age.

In short, attacking diseases separately for the elderly means taking whack-a-mole approach — you’re just swapping heart disease for some other disease a few years later. Attacking individual diseases basically means attacking symptoms without attacking the root of the problem.


It is far better to attack aging as a whole. Solving aging must be prioritized — because that gives us more time and better health. Because a side effect of undoing aging is that these diseases are either cured or under control. And that is why we would live longer. Now, do the earlier questions seem so unreasonable?


If we all want to live healthy, which means we all want science to cure diseases like cancer, heart disease, diabetes, Alzheimer’s, and thousands other diseases, then it makes most sense to try to solve aging (and perhaps even death)? So even if you only care about health and not longevity, it still makes more sense to try to solve aging — unless you think giving older people more (healthier) years is not a worthy endeavor.


And all this isn’t science fiction. With new approaches and technologies, we may finally be in a position to improve our health drastically and as a result extend our lives drastically.


Aging seems to be a treatable (and hence solvable) problem. (Death, I hope, is as well.)


What we need is for many more of us to think, advocate, and work on the problems of aging and death seriously — we need to architect, augment, and accelerate approaches that attempt to solve the problem of aging (and hopefully death).


Aging: inching closer to The Ultimate Cliff

The immortal Gods alone have neither age nor death! All other things Almighty Time disquiets” — Oedipus by Sophocles

Everyone is aging.


The process of aging has two major components: 1) how long an organism lives and 2) the physiological deterioration (known as senescence) that characterizes old age.

And all aging eventually leads to death. Sooner or later the bomb self-destructs. The Ultimate Cliff always shows up. Always.

It’s strange how we talk about aging, but most of us don’t really understand what aging is. We realize (sometimes) we’re getting older, but we don’t really know the processes that drive aging.


So let’s first see what happens to us as we age.


What happens to you as you age?


Trillions of cells in your body (more than 37 trillion cells!) are changing — some are dying, some are getting destroyed, and some are forming. But cells in your body are constantly changing.


In humans, aging represents the accumulation of changes over time, these changes are at the molecular and cellular level and have physical, psychological, and social impact. Majority (or at least a significant proportion) of humans experience the following symptoms of aging during their lifetimes (and many more):


Young — teens

Young children have the ability to hear high-frequency sounds above 20 kHz. Teenagers lose this ability.


20s

In your mid-20s, cognitive decline begins.If you are a female, your fertility peaks in the mid-20s, and then decline begins.In your 20s and 30s , you start developing wrinkles.

30s

From 30–70, your body mass starts to slowly decline.Your ability to focus clearly on close objects worsens after 35.


40s and 50s

You will need reading glasses by age 45–50, if not earlier.Around age 50, if not earlier, your hair starts to turn grey. By 50, 30%-50% of males and about 25% of females notice hair loss.If you are a female, menopause will typically occur between 49 and 52.


60s and early 70s

In your 60–64 years of age, the incidence of osteoarthritis rises to 53%. About 20% will report disabling osteoarthritis at this age.Atherosclerosis, which leads to cardiovascular disease (for example stroke and heart attack) and globally is the most common cause of death, is classified as an aging disease — this is because symptoms, if they occur, do not usually begin until middle age.Dementia becomes more common with age. About 3% of people between the ages of 65 and 74 have dementia. Furthermore, many types of memory decline with aging. Most patients with demential have no family history and as high as 95% of cases could arise from spontaneous mutations — result of cellular aging.


Mid 70s and mid 80s

Almost half of people older than 75 have hearing loss, inhibiting spoken communication. (Many vertebrates such as fish, birds and amphibians do not suffer from this in old age as they are able to regenerate their cochlear sensory cells, whereas mammals including humans have genetically lost this ability — thanks evolution.)Dementia becomes more common with age. About 19% between 75 and 84 have dementia. Nearly half of those over 85 years of age have dementia.By age 80, more than half of all Americans either have a cataract or have had cataract surgery. Frailty, defined as loss of muscle mass and mobility, affects 25% of those over 85. Macular degeneration causes vision loss and increases with age, affecting nearly 12% of those above the age of 80. This degeneration is caused by systemic changes in the circulation of waste products and by growth of abnormal vessels around the retina.


Oh wait, I didn’t add these:


There are changes to the brain: as we age, there is a loss of white matter.Age can result in visual impairment — so non-verbal communication is generally reduced, leading to isolation and possible depression.The maximum human lifespan is suggested to be 115–120 years “for the foreseeable future”. The oldest reliably recorded human was Jeanne Calment, who lived until 122 years (and 164 days) and died in 1997.Chronic conditions account for about 80% of total health care expenditures in the US and approximately 80% of older adults have one chronic disease, and 68% have two or more.


Thanks biology. Thanks evolution. Thanks nature. Thanks society.


Some positive things: Becoming old also brings a lot of advantages — people have more time, more experience, more knowledge, more perspective, and important relationships. Many positive social and financial things happen over time, but the biological deterioration and chronic diseases make it hard to enjoy these for too long.


The worst part: The truth is that aging is among the greatest known risk factors for most human diseases: of the roughly 150,000 people who die each day across the globe, about 100,000 die from age-related causes.


As Aubrey de Grey says, “it’s about thirty World Trade Centers, sixty Katrinas, every single day”.


That’s scary. Insanely scary. So scary that it should be unacceptable.


In industrialized countries, this number is even higher — something around 90% of people die from age-related causes. Yes, this bucket is broad, but that’s because aging comes with a broad range of deterioration.


In short — remember — mortality risk rises with aging!

At this point, you might be wondering “Ok, all this scary stuff happens in my body, and as a result my body and mind get weaker and then I die…[panic a bit or panic a lot]…um…it doesn’t sound so great, so why do we even age then — why didn’t evolution just weed it out? Does everyone [you mean every species] experience this or is it just me? And does everyone die as a result? How do we age again? Can’t someone stop this?


Good questions. Let’s get some answers.


Gerontologists (folks who study aging and age-related diseases) think about these questions (well, not specifically about stopping aging for you (or me), but for all of humankind). And the approaches to understanding aging can be divided into two very broad categories: those that try to answer the question “Why do we age?” and those that try to answer the question “How do we age?”


Wait…but you don’t really know how to think about aging so let’s work on that first.


Understanding Aging: Some high-level stuff


A multicellular organism is able to exist for only so long. Then the organism begins to age — and it begins to deteriorate. In this sense, aging of any organism is related to time — the deterioration is over time — its physiological functions necessary for survival begin to deteriorate over time.


[In another sense, aging doesn’t need to be stuck to time. If you think about it, time can continue, but deterioration doesn’t have to occur. What I mean is, suppose you’re a 60 year old, but you’re very healthy and your body is as good as a 45 year old’s body instead of an average 60 year old’s body. This means chronologically you are 60, but biologically you are closer to 45, i.e. your mortality rate is not higher at 60 than it was at 45. [I’ll talk about this in the context of mortality rate later.]]


Over time, humans came up with many theories about aging — ranging from depletion of something called “life force” to accumulation of simple wear and tear and damage. But throughout our history, there haven’t been that many concrete theories about aging. In fact, even at the beginning of the 20th century, the biology of aging was still mostly unknown.


It was the discovery of DNA in the 1950s that opened up new formulations around the genetic basis of aging. In the 1950s, the free-radical theory of aging — the first molecular theory of how aging occurs — was first put forward; this talked about aging as being a result of accumulation of molecular damage. In the mid-1950s, it was suggested instead of attacking each disease associated with aging individually, we would have most success if we attacked aging as a whole — that was 60 years ago! In the 1960s, many publications started talking about the role of telomere length in diseases. In the 1970s, National Science Foundation (NSF) funded a 3-year project on the future of aging, which resulted in book titled Human Life Span: Social Policy and Social Ethics — this was one of the first times delaying aging was discussed formally. Over time, people began to develop theories on the causes and processes of aging.


By the end of the 20th century, gerontology, the study of aging, and geroscience, the interdisciplinary field that tries to understand the relationship between aging and age-related diseases, had come into their own. These fields are relatively new, but have made incredible progress over the last several decades.


This summer (2018), the World Health Organization (WHO) took an important step toward better understanding aging by adding an extension code for “ageing-related” disease to its 11th revision of the International Classification of Diseases for Mortality and Morbidity Statistics, or ICD-11.


In WHO’s ICD-11, the extension code for “ageing-related” is defined as “caused by pathological processes which persistently lead to the loss of organism’s adaptation and progress in older ages.”


This was a result of a joint proposal submitted to the WHO’s ICD-11 Task Force by researchers from the Biogerontology Research Foundation, the International Longevity Alliance, and the Council for Public Health and the Problems of Demography.

The ‘ageing-related’ extension code gives the opportunity to link various outcomes to aging-related causes,said John Beard, MBBS, Ph.D., director of WHO’s Department of Ageing and Life Course. “It will be interesting to see how widely it is applied.” [can’t wait to see the data over the next few years.]


As mentioned earlier, the process of aging has two major components: 1) how long an organism lives, 2) physiological deterioration (known as senescence) that characterizes old age.


At a very high level:

  1. Aging is a series of processes over time — these include damage, accumulation of waste, errors and as well as the responses to them. These processes result in the signs of aging we’re already familiar with (grey hair, wrinkles, join pain, etc.) and gradual deterioration, which ultimately leads to age-related diseases that kill us all — aging always leads to death. This characteristic of aging — the gradual deterioration leading to death — is known as senescence.

  2. Aging can refer to both single cells that have ceased to divide (cellular senescence) and to the population of a species (population aging).

  3. Aging can be thought of as chronological aging vs. biological aging: actual number of years you are now (say, 60 years old — you’ve existed for 60 years) vs. internally how old your body is (say, 50 years old — the health indicators of your internal body show that you’re younger).

Keep these points in mind as you read the next few sections.


Now back to your earlier questions: Does every species age? Does every species die as a result? Why do we even age? How do we age? Can’t anyone stop this?


Does every species experience aging or is it just us?


First: who ages and who doesn’t? (and who dies and who doesn’t?)

Almost all species age, and almost all species die. But some don’t.


Some species can be considered immortal: bacteria fission to produce daughter cells, strawberry plants grow runners to produce clones of themselves, Hydras have a regenerative ability and do not undergo senescence, and planarian flatworms appear to regenerate (i.e. heal) indefinitely.


How can you think about this? Remember the distinction between chronological age vs. biological age? Well, in these biologically immortal species, these two are decoupled: senescence and thus age-related diseases have been delayed in these organisms. Sure they’re getting chronologicallyolder, but the usual deterioration characterized by aging, which ultimately results in death, has been delayed (and may be delayed indefinitely some organisms).


Earlier we said mortality rate increases with aging (in senescent organisms), but if the mortality rate of the species does not increase after maturity, we say that the species does not age and is biologically immortal — thus decoupling mortality rate from chronological age.


Why use this definition and not the comic book / movies definition of immortality (that of being completely indestructible)? Because even a biologically immortal organism can still die (from means other than senescence) — it can still die from falling off a cliff, getting run over by a vehicle, or earth getting destroyed by asteroids or a billion other ways.


So strictly speaking, if we use our superhero definition, no species is indestructible or lives forever — no one is immortal. But if we think of it biologically, then some species are immortal — they don’t deteriorate over time (like we, and most other species, do). Their risk of death stays low and constant throughout their existence — this is the next best thing.


Next best thing: some species are negligibly senescent. They do not experience deterioration that characterizes aging.


According to the Animal Aging and Longevity Database, the following organisms have negligible senescence, i.e. they appear not to age:


It seems that aging is not inevitable.


These species age chronologically, i.e. they can become 50 years, 100, years, 500 years, or whatever (that’s how long they’ve existed so far), but they don’t necessarily age (or age as fast) biologically, i.e. they don’t deteriorate from aging. Note that the lifespans of these organisms vary, but none of these species experience deterioration.

But…here’s the problem:


Each organism listed above (including a biologically immortal organism) can still die from means other than senescence — it can still die from falling off a cliff, getting run over by a vehicle, or earth getting hit by enough asteroids to be totally destroyed or a billion other ways.None of the organisms listed above are humans. Senescence is the inevitable fate (as of now) of all humans. We’re not biologically immortal. And if that is not bad enough, some rare human mutations can cause accelerated aging diseases. Thanks nature.


But…before you get too depressed, here’s some hope:

  1. The above list of long-lived species shows that living organisms can live very long (or what we would currently call very long), without facing deterioration of old age. That an individual tree has lived for more than 5000 years says that there may not be some fundamental limitation on how long an individual living organism can live (or that limit is at least 5000 years).

  2. May be potentially immortal species such as Hydra can tell us about delaying senescence (and hence about death from age-related diseases).

  3. Senescence, in some species, can be actively delayed! Scientists have shown this. In 1934, it was discovered that calorie restriction can extend lifespan by 50% — but wait — in rats! Not humans. But still. (This was controversial because some studies showed a significant effect, while others did. Some studies in monkeys show that calorie restriction has positive impact on monkeys’ health and some claim even on longevity. In any case, scientists now do think that calorie restriction has a positive effect on health.)

  4. Something incredible happened in the 90s — scientists found that a single mutation in a microscopic worm could double its lifespan. Again, not humans, but still… Also, in the last 15 to 20 years, scientists have identified a whole series of pathways that are really key in regulating how we age. (More on this later).

  5. Even in humans, there are some cells with the potential for immortality, such as 1) cancer cells which have lost the ability to die, such as the HeLacell line (it is the oldest and most commonly used human cell line — it was derived from cervical cancer cells taken on February 8, 1951 from Henrietta Lacks), 2) certain type of stem cells, such as germ cells(producing ova and spermatozoa). These remain immortal for as long as we are alive and even after we die, they can continue replicating in labs!

In summary, 1) there are species that do not age, 2) in some species that do age, senescence can be delayed — and hence healthspan and lifespan can be extended, and 3) some species (hydra) are already immortal — they have the capacity for indefinite self-renewal.


While it is true that researchers have a long way to go before they can reduce or eliminate human senescence, these cases give us reasons to be optimistic.


As noted earlier, for most species, the mortality rate of the species increases with aging. And we said if the mortality rate of the species does not increase after maturity, we say that the species does not age and is said to be biologically immortal. Now, if this mortality rate remains constant, this rate determines the mean lifespan. The lifespan can be long or short, though the species technically “does not age”. Check out Wikipedia’s List of longest-living organisms)).


Let’s dig into longevity and lifespans a bit more to better understand this.


Second: what about longevity? who’s living for how long?


Longevity can be thought of as life expectancy — the amount of time a member of a species can be expected to live. Lifespan is longest time the species is capable of living — upper limit at the species level.


Mortality rate and life expectancy are tied.


How you can think about this: life expectancy, at any given age, is the average number of years a member of a group would continue to live if their mortality rate for remainder of their lives stayed the same as their current mortality rate.


Let’s look at this chart (read the wonderful presentation by Max Roser in Our World in Data):

This chart shows life expectancy at birth — from 1543 until 2013. For most of the period, only data from UK is available. Look at that incredible increase in life expectancy over the last century. In 1550s, a newborn was expected to live only until 25–40 years. And today, he would be expected to live between 65–85 years!

Let’s look at England — for which there is longest time-series data.


Before the 20th century there was no trend for life expectancy: life expectancy fluctuated between 25 and 45 years. In fact, this was the case for a long time before the 20th century.

Note that this is nuanced (apart from a) how good the data is, 2) how small the sample sizes were, 3) how this expectancy was modeled):

  • In 1850 a newborn was expected to live around 40 years (red line).

  • Now, if he made it to 5 years of age, he was expected to live about 45 more years (yellow line) — making his life expectancy around 50–55 years! This shows that child mortality rates were very hight back then (child mortality is defined as the number of children dying before their 5th birthday). If a child makes it to his 5th birthday, his prospects of surviving improve quite a bit.

  • Next, if he made it to 10 years of age, he was expected to live 45–50 more years — making his life expectancy about 55–60 years. (light green line).

  • Again, if he made it to 20 years of age, he was expected to live 40 more years — making his life expectancy 60 years.

  • And so on…

  • Here’s the take away: In 1850 a newborn was expected to live around 40 years (red line)…but if infant or child mortality is subtracted, individuals who lived to adulthood (that is at least 20 years of age), then could end up living between 60–80 years!

Notice the drastic increase in life expectancy at age 0 between 1850s and 2011. What’s happening?

  1. In the 1850s, the average life expectancy at birth was about 40 years (red line).

  2. In 2010, the average life expectancy at birth was about 75–85 years — an increase of 35–35 years!

  3. In 1850 a 5-year old was expected to live about 55 years. In 2013, a 5-year was expected to live a little over 80 years — that’s an increase of 25 years.

  4. Back then, life expectancy changed dramatically after childhood — there was a dramatic increase in life expectancy once adulthood was reached. This was largely because back then, young children died from all sort of diseases that we now know how to cure — medicine and scientific knowledge have lowered the risk of death of young people.

  5. In our current time, life expectancy at birth is not very different than life expectancy after childhood — this is largely because we have drugs, therapies, and cures for most diseases that young people face.

Next, notice the somewhat impressive, but not-nearly-as-drastic increase in life expectancy at age 70 or 80. What’s happening?

  1. In the 1850s, if an individual made it 60 years of age, he was expected to live to about 73 years (dark blue line), and if he made it to 70, he was expected to live to until a little less than 78 (purple line).

  2. In 2013, if an individual made it to 60 years of age, he was expected to live to be around 83years and if he made it to 70 years, he was expected to live to 88 years — an increase of about 10 years!

  3. This increase is quite a bit, but not as drastic as the increase in life expectancy at birth — this is because aging still kills. As you get older, you’re essentially swapping out one age-related disease for another. The risk of disease rises exponentially with age. In this sense, fighting individual age-related diseases is a losing battle — curing any individual (aging) disease only adds two to three years of life before another aging disease hits.

But it is true that there have been improvements in survival after age 65 and this has led to the rise in the length of people’s lives. So even though getting a handle on aging and age-related diseases has been hard and slow, we’ve made quite a bit of progress. We’ve increased the percent of people who live longer and longer. More people live longer now than earlier.


Let’s look at another chart.

This chart shows the percent of people who are expected to survive up to and beyond various successive ages in England and Wales.


Note that, less than 50% of the people born in 1851 in England and Wales made it past their 50th birthday (see where the 1851 line crosses 50 years of age). But by 1911, a little over 70% of people made it past their 50th birthday. And more than 95% of the people born in England and Wales today live longer than 50 years. This says we have been delaying mortality! (Yes this data is only for England, but trends in many other places look similar.)

Longevity is something scientists and the medical field have influenced greatly. Life expectancy has steadily increased — it has been an extraordinary human achievement — one of our greatest achievements.


This incredible achievement by scientists and the medical field brings up a question: is human life expectancy approaching its limit? Is there an upper limit on the human lifespan? This question has been asked again and again throughout history.


Over time, many people have said that life expectancy is close to this maximal limit and these experts have repeatedly been proven wrong. For example, a crude calculation made in 1928 indicated that the average human life span would not exceed 64.75 years. At that time, life expectancy in the United States was only 59.4 years. What was not considered was the fact that Australia, by then, had already achieved a life expectancy of 62.83 years. In 1990, it was again projected that the life expectancy 50 year olds could not go beyond 85 years, but Japanese females surpassed that limit in 1996.


Mortality has been postponed and life has been extended! In this sense, we’ve continuously been working on life extension.

And this has been a result of improving overall health — we have not even attacked aging as a whole yet. Even then, in some sense, human senescence has been delayed. But the argument is that by attacking aging as a whole (and hopefully eradicating it), we can buy even more time and even better health.


Third: what about maximum lifespan? is there a limit, and if yes, then can’t we live longer than that limit?


Life expectancy differs from maximum life span. Life expectancy is an average for all people in the population — including those who die as infants and children, those who die in early adulthood, those who die in middle age, and those who live until old age. Maximum lifespan, on the other hand, is an upper bound of life. The maximum number of years any human has lived is 122. There have been many examples of people living significantly longer than the life expectancy of their time period:

It turns out that species age at different rates. And maximum lifespan is determined by the rate of aging. Maximum lifespan is the maximum amount of time one or more members of a species have been observed to survive. The apparent maximum human lifespan limit is 125 years of age (the longest a person has lived is 122 years).


Most living species have at least one upper limit on the number of times the cells can divide. (This is called the Hayflick limit, although the number of cell divisions does not necessarily control lifespan). In any case, aging and lifespan vary greatly between species, even very similar species.


For example, a mouse does not live more than 5 years yet humans can live over 100. A mouse, therefore, is considered elderly at 3 years while a human is elderly at 80 years.

Mammal lifespans also vary significantly — bowhead whales (oldest mammals) have been estimated to have lived at least to 211 years of age, while the shortest-lived mammal was a mouse that lived for ~0.8 years.


And there may be no limit to the Hydra’s lifespan!



See AnAge (Animal Aging and Longevity Database) if you’re interested in the maximum life span of species.


These differences in life span between species are thought to be a result of genetics, but they are still a puzzle.


Here’s where it gets really interesting and where the previous part is used:


According to US social security data, the probability of a 20-year-old male dying before his 30th birthday is 1.1% and for a female it is 0.4%. However, the risk of a 60-year-old male dying before his 70th birthday is 15.3% and for a female it is 10.8%. And the risk of an 80-year-old male dying before his 90th birthday is 70% and for a female it is 58%.


What does this mean? This means (what we said earlier), as you get older, the risk of dying increases. Mortality risk does not stay constant — it increases with age. And it increases with age because of age-related diseases.


But here’s the hope — here is what the community is trying to do: they’re trying to keep this risk low and (mostly) constant. This risk increases with your age — and as of now, your age = your chronological age = your biological age (mostly). But now if we can let your chronological age increase, while keeping your biological age low (and near constant), then this risk of death would not increase (or would not increase enough to affect you very much). If we could somehow keep this risk low and constant throughout life, then the average person would live for a long time, may be 1000 years (or more).


For example, earlier we saw that the probability of a 20-year-old male dying before his 30th birthday is 1.1%, while the risk of a 60-year-old male dying before his 70th birthday is 15.3% and the risk of an 80-year-old male dying before his 90th birthday is 70%. But now suppose we could attack processes that cause aging (and hence age-related diseases) so that we can keep this risk of death at any age around 1.1% (or even if is not constant, it would increase very slow), then the risk of a 60-year-old male dying before his 70th birthday would also be around 1.1% and similarly for an 80-year-old and a 90-year-old, etc. That’s the goal.

The argument is this:

  1. The apparent maximum lifespan limit of 125 years is tied to our current risk,

  2. Our current risk is tied to age-related diseases,

  3. Our age-related diseases are a direct result of aging,

  4. So let’s try to eradicate aging (as a whole) to lower this risk and push human lifespan past this apparent limit.

In part 3 of this series, I’ll talk about several approaches to do this.


A few points to note (and why this isn’t that simple, but worth all the effort, in my opinion):

  1. Researchers have long debated whether humans have an upper age limit — no one knows.

  2. The consensus in the field is that the risk of death starts increasing in adulthood, up to about age 80 or so.

  3. BUT after this everything is unclear — there’s massive disagreement about what happens as people enter their 90s and 100s. Death rates seem to level off in late life. Death rates are still pretty high though.

  4. AND because death rates seem to level off in late life, some people say that there is no fixed upper limit to human longevity, or fixed maximum human lifespan.

A quick side note: death rate is just one metric that scientists used to get a handle of maximum human lifespan. Another suggested metric is a person’s VO2max value (a measure of the volume of oxygen flow to the cardiac muscle), which decreases as a function of age. Therefore, the idea is, that your maximum lifespan could be determined by calculating when your VO2max value would drop below the metabolic rate necessary to sustain life (which is approximately 3 ml per kg per minute). I need to read more about this (and other potential proxies for maximum human lifespan), so once I do that, I’ll come back and update this part.


Below is a brief detour for the curious reader, feel free to skip* it to go the next section titled “Why is this (aging) even happening to you?”

*But, honestly, if you’re already reading a 50+ minute article, then you might as well take out another 3–5 minutes. I promise it’s cool.


For the curious reader:

First: A story about the world’s oldest person.


In 1965, a 47-year old lawyer, Andre-Francois Raffray, thought he had made a great deal. In exchange for the ownership of her apartment, he agreed to pay a 90-year-old woman 2,500 francs (about $500) per month until she died — at which point he would get the apartment.

She was born on February 21, 1875, about 10 years after Abraham Lincoln was assassinated. When she was around 12 years old, she met Vincent van Gogh, who visited her father’s shop. She married in 1896 — when she was 21. She outlived her only child, a daughter who died in 1934. In 1942, her husband ate cherries that were treated with copper sulfate; he developed jaundice and died of poisoning after one and a half months. She had eaten fewer of the cherries and survived. She also outlived her only grandson, who died in 1963.


And yes, she outlived the lawyer Andre-Francois Raffray. He died Christmas of 1995 — at age 77 — soon after her 120th birthday! By that time he had paid three times the worth of the apartment!


She died on August 4, 1997, when she was 122 years 5 months and 14 days old and she is believed to have been world’s oldest person.


Second: How you are (most likely) going to die, based on your age group. Causes of death are ordered by rank.

  • Early teens: unintentional injury (accidents), suicide, cancer

  • Late teens — early 30s: All external causes — accidents, suicide, and homicide. This means if you survive young age, you’re at low risk of dying from diseases, at least for a while.

  • Late 30s — early 40s: accidents, cancer, and heart diseases. According to Harvard Medical School as much as 4% to 10% of all heart attacks occur before age 45, and most of these in men. And about 4% of cancers are diagnosed before age 39. Oh gosh — this is where the scary stuff starts.

  • Late 40s — early 50s: cancer, heart disease, accidents. Notice that the ordering has changed. Notice that until early 40s, accidents are the leading cause of death. In your late 40s, you’re more likely to die from diseases than accidents.

  • Late 50s — early 60s: cancer, heart disease, accidents. There’s a difference between what kills men and women in their 60s. Men are most likely to die of cancer, while women are about as equally likely to die of cancer as they are of circulatory diseases.

  • 65+: heart disease, cancer, chronic lower respiratory disease.

  • 70s: Your risk of getting rarer cancers, such as throat, esophagus, kidney, and pancreatic cancers, is higher in your 70s ; the risk of cancer peaks in your 70s. Men are at risk of prostate, colon, and lung cancer and women are at risk of breast, colon, and lung cancer.

  • 80s: People 80 years and older have around 40% chance of dying from a heart disease. We would think it’s due to cancer, but surprisingly it’s heart disease.

Third: Life Expectancy: What does life expectancy look like across the world? It varies, quite a bit.

  • Average life expectancy at birth of the global population in 2016: 72.0 years

  • Developed countries: 77–90 years (e.g. Switzerland: 83.3 years, 2016)

  • Developing countries: 32–80 years (e.g. Sierra Leone: 53.1 years, 2016)

Population longevities are increasing as life expectancies around the world grow:

  • South Sudan: 39.21 years in 1981, 56.32 years in 2015

  • Ethiopia: 43.67 years in 1981, 65.04 years in 2015

  • Nigeria: 45.63 years in 1981, 52.99 years in 2015

  • India: 54.29 years in 1981, 68.3 years in 2015

  • Turkey: 59.3 years in 1981, 75.5 years in 2015

  • Brazil: 62.26 years in 1981, 75.28 years in 2015

  • Mexico: 67.04 years in 1981, 76.93 years in 2015

  • UK: 73.82 years in 1981, 81.41 years in 2015

  • USA: 74.12 years in 1981, 79.24 years in 2015

  • Australia: 74.68 years in 1981, 82.73 years in 2015

  • Canada: 75.4 years in 1981, 82.21 years in 2015

  • Spain: 75.64 years in 1981, 82.98 years in 2015

  • Japan: 76.58 years in 1981, 83.62 years in 2015

See, told you it would be short. Ok, next section.


Why is this (aging) even happening to you?


This question is asking about some general or fundamental nature of aging — what is aging and why does it happen? Why has aging — a characteristic that seems so detrimental to an organism — been maintained in natural selection? Aging has posed an evolutionary paradox: if natural selection leads to organisms that are optimal for survival and reproductive success, then why or how could evolution favor a process that increases mortality and decreases reproductive capacity? How could genes that cause aging evolve? Does aging have an evolutionary advantage? Evolutionary disadvantage?


Theories that attempt to answer why aging occurs from an evolutionary perspective are known as evolutionary theories.


Focusing on the group, not the individual

Efforts to understand why we age go back for centuries. Early attempts suggested that both aging and death are beneficial for humans because they gave new organisms a chance to play and test which variants are more suited for survival and reproduction, i.e. they make room for the next generation. In other words, sacrifice the individual for the greater good.

In 1889, the German biologist August Weismann suggested that natural selection would favor species survival and hence aging and death were programmed — in order to make space and free resources for younger and fitter individuals. This theory doesn’t identify a mechanism for aging — it gives the purpose of aging, but doesn’t explain how individuals age.


Many early explanations revolved around group selection and survival of the species. This view was held by biologists until some time in the 20th century.


It was later argued, in the 40s and 50s, that long-lived individuals could leave more offspring than short-lived individuals so the cost of death of an individual exceeds the benefit to the group. This meant aging most likely did not evolve for the “good of the species”.

Weismann later abandoned his theory.


New theories said that since it didn’t make sense for natural selection to favor aging and death, aging must have evolved because natural selection becomes “inefficient at maintaining function (and fitness) at old age”.


See The Life Extension Revolution: Theories of Aging for details.

MA does not suppose any fundamental cause of aging. In this theory, aging is the result of detrimental mutations. Therefore, if these mutations could be removed or fixed, longevity may be extended.


The idea that mutations end up causing adverse effects has been verified and accepted by scientists trying to understand human genetic diseases: “many human diseases have been traced to errors that have occurred in genetic code.” However, the current view is that MA is too simplistic.


According to AP theory, aging is the detrimental side effect of selection for survival and reproduction during youth. The current view is that AP is the prevailing theory today for why (in evolution) aging occurs, but it’s not fully well-supported. On one hand, biologists have found many genes that do enhance fertility in the young (or carry some other benefits early in life) and are associated with aging later in life. But on the other hand, they have found many other aging genes that have no benefit associated with them in early life (or at least none that have been identified).


In any case, the idea that genetic trade-offs may be the cause of aging is prevalent today.


So, what’s missing?

Some of the things that evolutionary theories of aging don’t necessarily explain:

  1. There are some organisms that die suddenly following reproduction (e.g. salmon, octopus, etc.). And sudden death seems to be an example of programmed death (and not a result of gradual aging that is characterized by the side-effect or trade-off explanations.

  2. Scientists have found that manipulating some genes seem to delay aging while not affecting reproduction — this also contradicts the evolutionary theory of aging.

  3. These theories don’t explain animals like (some) ants, which have a single reproductive female — their existence provides evidence against trade-offs between longevity and reproduction.