The Life Extension Revolution — Part 1

The Life Extension Revolution — Part 1

Note 1: It is possible (and very likely) that I missed some very important points or got some things plain wrong. If you find errors, then please let me know (especially about theories of aging and approaches to life extension). I’ll update the blog.

Note 2: This blog is Part 1 of a 3 part series. Part 1 is about aging, Part 2 will be about death, and Part 3 will be a deep dive into approaches to eliminate aging and death.

Note 3: This blog is structured as follows: what happens to you as you age, do all species age, why do you age, how do you age, how can aging be attacked, and why it’s important to attack aging.

Before we begin, how would you answer these three questions:

  1. Do you think the field of longevity (or life extension) is a legitimate field?
  2. Do you think aging can be eradicated and/or reversed? Should it be eradicated and/or reversed?
  3. Would you want to live for 100s or 1000s of years or more — ideally?

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 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.

https://medium.com/media/00b7774a585160e8aba24dca278dd9ed/href

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 that because you are imagining a long life which is an extension of current your aches and pains — either you’re imagining your current state for a 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.

So 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 aging — 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 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.

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 chronologically older, 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:

  • Blanding’s turtle (Emydoidea blandingii) — 77 years
  • Olm (Proteus anguinus) — 102 years
  • Eastern box turtle (Terrapene carolina) — 138 years
  • Red sea urchin (Strongylocentrotus franciscanus) — 200 years
  • Rougheye rockfish (Sebastes aleutianus) — 205 years
  • Ocean quahog clam (Arctica islandica) — 507 years
  • Great Basin bristlecone pine (Pinus longaeva) — 5,062 years

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:

  1. 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.
  2. 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.
  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 HeLa cell 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 we said, 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 the 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):

Source: Our World in Data (check out the website — it’s interactive. Side note: notice the the high mortality of the 1918 flu epidemic in UK and of 1945 in Japan) — life expectancy drops sharply)

This chart shows life expectancy at birth — from 1543 until 2013. For most of the period, only data from UK is available. In any case, 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.

Source: Our World in 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). This shows how long a 10 year old is expected to live in 1850.
  • 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.

Source: Our World in Data (Note that, less than 50% of the people born in 1851 in England and Wales made it past their 50th birthday. 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 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.

Many people have debated whether survival among the elderly could be extended, and that’s exactly what has been done until now. 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:

Many of these people (and others) outlived most of their ancestors. They lived until “old age” when old age wasn’t the norm — they probably survived dysentery, smallpox, pneumonia, typhoid, malaria, flu, and many other infections.

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!

Source

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?” It’s about why do we even age?

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.

Source
  • 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.
Source (Interactive)
Source I know it’s hard to read, go to the source — it’s worth it.

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

World Map of Life Expectancy in 2015 (Source: Max Roser, Our World in Data)
  • 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)
WHO Life Expectancy

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

World Maps of Life Expectancy in 1800, 1950, and 2011 (Source: Max Roser, Our World in Data)
  • 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

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.

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 ants, which have a single reproductive female — their existence provides evidence against trade-offs between longevity and reproduction.
  4. Evolutionary theories seem to imply all organisms age so they don’t explain organisms that appear not to age (earlier list).
  5. There are animals (Painted turtles) where older females (compared to younger females) had increased reproductive output and offspring quality while maintaining survivorship.
  6. Apoptosis, which is programmed cell death is responsible for killing cancerous cells, infected cells, and other cells that are problematic during development. Now, this is beneficial (but a problem is it seems to increase later in life) so it hints that senescence may have arisen because of an evolutionary advantage, and not because of some side effects.

In conclusion, evolutionary theories provided a theoretical framework that explained many observations, but 1) they don’t offer a complete picture and 2) they don’t offer a mechanistic picture of aging — how do we age?

The good news is that we don’t (yet) need to know the complete evolutionary “why” to try to push back aging and age-related diseases. And that’s because we know a lot about the “how”, the mechanisms of aging and they how to intervene — that’s the next section.

How is all this happening — what’s making you age?

In this section, I’ll quickly talk about the biological basis of aging — the mechanisms, factors, and processes that are making you age. [I strongly suggest you read The Life Extension Revolution: Theories of Aging for details.]

All aging starts with genetics. Aging is correlated with changes in a variety of biochemical and physiological processes in the body. Determining cause and effect is hard in aging — is A causing or contributing to aging or is A an effect of aging? Scientists examine these processes in a variety of animal models and propose theories to explain the mechanisms that contribute to aging. These, we hope, in turn may help us push back aging and hence extend life.

The theories that attempt to explain the mechanisms of aging are generally categorized as follows: programmed theories and damage-related theories.

Programmed theories (read here)

Programmed theories say that we are designed to age and die — both aging and death are genetically predetermined and programmed — and the body follows a biological timeline. “Programmed” does not mean evolutionarily programmed; it only means that aging is predetermined by set of instructions. This “programming” may be controlled via different clocks: molecular, genetic, neurological or hormonal or through the hypothalamus.

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

Damage-related theories we’ll discuss (read here)

Damage-related theories say that aging results from an ongoing process of damage accumulation, where damage is both by-products of metabolism as well as environmental assault on the body. This process of damage accumulation is ongoing throughout your entire life and eventually causes aging.

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

It turns out that aging has both of these — both genetic factors as well as various forms of damage contribute to aging. The difference really is about which factor — programmed or damage — is the predominant one. Many theories are a combination of programmed and damage theories.

It is now generally believed that the “accumulation of cellular damage” is the general cause of aging.

Hallmarks of Aging

A breakthrough paper in 2013 outlined Hallmarks of Aging — it defined aging as 9 distinct categories (hallmarks) and explained how these processes interact with each other. The paper discussed aging through the lens of damage theory.

The 9 hallmarks can be grouped into 3 categories.

The first four (Genomic instability, Telomere attrition, Epigenetic alterations, Loss of proteostasis) — these are considered to be the primary causes of cellular damage.

The next three (Deregulated nutrient-sensing, Mitochondrial Dysfunction, Cellular senescence) — these are considered to be part of antagonistic responses to the damage. These may initially be beneficial and mitigate damage, but eventually they become a problem themselves.

The last two (Stem cell exhaustion, Altered intercellular communication) — these are the end result of the previous two categories of hallmarks and they are responsible for the functional decline associated with aging.

I talk about these hallmarks in a separate blog here — there will be more in Part 3, when I talk about approaches.

For us laypeople, here’s a crude visual summary of the hallmarks of aging.

Source

These 9 hallmarks are determined mainly by genetics, but are affected by environmental factors. And all of them contribute to damage and over time our bodies can’t repair this damage, which eventually leads to aging, age-related diseases, and death — The Self-Destruction Countdown and then The Ultimate Cliff.

Aubrey de Grey and SENS

A massive figure in the field of rejuvenation is Aubrey de Grey — he’s a world famous gerontologist. But more importantly, he’s been fighting this fight for a few decades — before most people cared about it and before people wanted to put money in this field.

When Aubrey’s mother died, she left him with $16 million. He could’ve done anything with the money, but he dedicated $13 million to attack and eradicate aging. He thinks this is one of the biggest problems facing humanity and he’s been working relentlessly to fight it.

He describes aging as follows: Metabolism causes damage and damage eventually causes pathology. He says, “Metabolism (the hugely messy network of homeostatic processes that keep us alive) causes pathology (the hugely messy network of anti-homeostatic processes that kill us).”

Source: “Metabolism causes pathology”

Therefore, his approach to solving aging is via maintenance and repair. He uses the analogy of a 50- year-old car that still runs well due to exceptional maintenance to make his point. This maintenance approach, he says, should extend the human life span if we keep damage at manageable levels throughout the human body.

Again, “accumulation of cellular damage” is the general cause of aging.

Over decades, many attempts have been made to understand aging and researchers have made tremendous progress. In fact, recent research suggests that there may be a limited number of these mechanisms, giving scientists hope that it may be possible to develop approaches and strategies that could help humans live longer and healthier lives.

Can’t anyone stop this?

Good news: scientists think they can*.

(*Not all scientists agree, but still. For the first time in human history, there are (many) scientists who believe we may be able to change how future humans think of and experience life — a new paradigm could result — one that will challenge and change the generally accepted human life limitations.)

More good news: scientists have already extended life span in other species. Scientists have increased the lifespan of nematode worms (through genetic engineering) and yeast (through genetic engineering and caloric restriction) by 10-fold. They have also extended life span in mice by over 30%.

But preventing (or eliminating) aging in humans is hard and complicated. It’s not going be easy and it’s not going to be quick, especially if there is no societal, political or financial support — which is why we need to find ways to get support.

Even more good news: Even though solving aging is hard, scientists are already pursuing some exciting and promising approaches.

High level approaches — as of now

Below are some of the (high level) approaches scientists are taking in order to extend the maximum human lifespan . They hope to reduce damage and slow down aging by doing the following (in part 3, I’ll talk in detail about what different approaches mean, how they work, and who is doing what in this field):

  • Collecting and analyzing data: The idea is to build a massive database of human genome sequences, including data from supercentenarians. This would help us 1) understand what makes a life long and healthy, 2) catch illnesses early, and 3) identify risk factors for diseases later in life. Those working on life extension can then use this database.
  • Anti-aging drugs: Currently, a number of drugs that are intended to slow aging are being studied in animal models. (See Geroprotectors database). For example, calorie restriction (CR) has been shown to extend lifespan so there are attempts to develop drugs that will mimic this process. Several drugs that are already approved for other uses have been studied for possible longevity effects because they might be mimicking CR effect — these drugs are rapamycin, metformin, MitoQ, resveratrol and pterostilbene. Other drugs have taken different paths, for example enhancement of telomerase activity (see below).
  • Tissue engineering: Tissue engineering combines ideas from engineering and life sciences — the idea is to periodically replace damaged tissues or to build biological structures that restore, repair or even replace tissue parts (or even whole tissues), such as bone, cartilage, bladder, muscles, etc. Tissues and whole organs involve specific mechanical and structural properties to function properly. The goal is to engineer tissues with these properties to restore or improve tissue function or entire organ function. This term is sometimes used synonymously with regenerative medicine, but regenerative medicine focuses more on the use of stem cells to produce tissues.
  • Stem cells: Stem cells are cells that can be made to grow into other types of cells. In regenerative medicine, new cells can be grown to treat a variety of problems: use a patient’s own stem cells to grow organs (such as kidneys) in a lab and replace the patient’s existing failing organs, grow new nerve cells to treat diseases like Alzheimer’s, etc. So, how can stem cells treat so many conditions? A high level answer is because “the root cause of most of these conditions is either lack of stem cells or the ones you have left aren’t working properly.”
Source: Diseases and conditions where stem cell treatment is being investigated.
  • Rejuvenation therapies: As noted earlier, aging is the accumulation (over time) of damage to cells, tissues and organs. If any of that damage can be repaired, the result is rejuvenation. (Gerontologist Aubrey de Grey’s Strategies for Engineered Negligible Senescence (SENS) studies how to reverse the damage caused by aging)
  • Enhancement of telomerase activity: There is something called the Hayflick limit: a normal human fetal cell will divide between 50–70 times before experiencing senescence — it will not divide past this point.) Telomeres are specialized DNA sequences at the end of chromosomes and they serve as a protective cap. They shorten at each cell division and when telomeres become too short, the cells senesce and die, i.e. cells stop dividing. Telomeres place a limit on how many times a cell can divide and during each cell division, telomere shorten. And as long as cells have enough of the enzyme telomerase, they keep the telomeres long(er). The problem is that with time, telomerase levels decrease. The idea is to slow aging by reversing the shortening of telomeres — by activating telomerase. It may be possible to remove the Hayflick limit and hence make individual cells “immortal”.
  • Gene therapy: The idea is to introduce beneficial genes or modify genes in the cells — these genes that are delivered in a patient’s cells act as a drug to treat disease and hopefully repair the damage that occurs with aging. FDA has already approved several such therapies. For example, take a field mouse, whose lifespan in the wild is 6–8 months — it’ll get eaten by then. Now, if you put a mouse in a lab, where there are no predators, then the mouse has double the lifespan — it lives 12–18 months. But if you put a mouse on calorie restriction, then the lifespan is doubled to 26–30 months! Now, here’s the magic — enter gene therapy — if you change one gene in the mouse (FGF21 — which humans also have), then the mouse lives 60 months — that’s without changing diet or exercise or anything else except just one gene. Imagine the possibilities!
Source

Repairing the 9 hallmarks of aging

Remember the 9 hallmarks listed above? Here’s the roadmap of some of the approaches to fix the 9 hallmarks — it’s maintained by Lifespan.io (Part 3 will have details):

Source: Therapies and technologies

See The Life Extension Revolution: Theories of Aging for a summary of approaches.

Aubrey de Grey and SENS

Aubrey de Grey believes rejuvenation via maintenance is the idle approach — not the other two traditional approaches.

Paradigms for intervention

For each damage type, his organization — SENS — has suggested an approach to attack it (more on this in Part 3).

These were some high level approaches being tried right now. Next are some high level approaches we hope to see in the future.

High level approaches — down the road

  • Nanomedicine / Nanobiotechnology (a nanometer is one-billionth of a meter): This is at the intersection of nanotechnology, biology, and medicine. The idea is to manufacture and program nano molecular machines or robots that can enter cells and repair damage, giving us far more control than other approaches. This approach holds one of the greatest promise for curing disease and extending health span. K. Eric Drexler, one of the founders of nanotechnology, hypothesized such cell repair machines and Ray Kurzweil said that that advanced medical nanorobotics could completely remedy the effects of aging by 2030. According to Kurzweil, the accelerating pace of technology is already has already had massive impact. For example, “it took us 15 years to sequence HIV; we sequenced SARS in 31 days,” he said during a 2005 interview, referring to efforts to sequence the genomes of HIV in the 1980s and ’90s and of SARS (Severe Acute Respiratory Syndrome) in 2003.
  • Cloning and body part replacement: Some people suggest that cloning and stem cell research could provide a way to generate cells, body parts, or even entire bodies. The US Department of Defense runs a program to research the possibility of growing human body parts on mice.
  • Cryonics: The idea is to preserve a human corpse, with the hope that reviving it might be possible in the future. More on this in Part 2 (Death) and Part 3 (Approaches)
  • Cyborgs: The idea is to replace biological organs with mechanical ones could extend life. More on this in Part 2 (Death) and Part 3 (Approaches)
  • Mind uploading: The idea is scan the mental state(s) of an individual and copying it to a computer. More on this in Part 2 (Death) and Part 3 (Approaches)

Here’s a summary of high level approaches to eradicating aging:

The takeaways

There is no magic bullet that will cure aging. Eliminating aging and extending lifespan will require a wide variety of different therapies. For example, geroscientists can kill off senescent cells, but we need fresh new stem cells to replace the lost ones. In the meantime, medications can help correct our declining metabolism and improve our declining DNA repair processes.

Most approaches, as of now, are either in early research or have only been tested on mice — not on humans. In other words, there are no guarantees on how they will work on humans, but to find out, researchers need to perform human clinical trials. According to American Federation for Aging Research, “For a drug that targets a single, specific disease, it currently takes about 17 years from discovery in the lab to completion of clinical trials. It takes eight more years for physicians to adopt the drug, making it available to people who need it. That’s 25 years in all. The cost: $500 million to $1 billion, on average. Over the past three years, the Geroscience Network has brought together leading aging researchers from 18 aging centers and academic groups in the United States to design the strategic infrastructure needed to dramatically cut the time and cost required to gain regulatory approval for a new class of drugs that tackle fundamental aging processes.”

This is why more awareness and funding is needed — existing infrastructure takes too long to bring drugs to the market.

All of us need to help

“No problem can stand the assault of sustained thinking.” — Voltaire

Extending life is not crazy. Buying more time is not crazy.

A short story: It is December 31, 2017. My friends and I are having a New Years Eve get together. At midnight, I go around the room and ask everyone what they want in life (that they can work towards in 2018) — the answers vary — wealth, health, success, love, happiness, peace, travel / adventure, and even nothing. After each answer, there’s a note of encouragement — some sort of a cheer — some sign of good wishes. My turn is last, and I say “time” or “more time”. This time the reaction is different, it ranges from chuckle to laughter to dismissal. “Come on, give another answer”, “That’s not a real thing”, “There must be something else you want more”, etc. etc. etc.

They knew what I meant by “time” — I meant time, as in more time than my very short finite life provided — I wanted the option to live longer (and live well, of course). I wanted more years, more days, more hours, more minutes added to my life (and to the lives of people I love). I don’t want to age, say goodbye and leave the world in my 70s, 80s, 90s, or 100s. Equally importantly, I don’t want my loved ones to go — I can’t imagine the loss. But most importantly, I want humankind to have an option, an option to get more time, should they want more time. An option to keep staying healthy and living longer. An option to say no to aging and suffering. (And an option to not die — but that’s part 2).

That night, I realized that most people have accepted aging as an inevitable process and death as an inevitable result of that process. They’ve accepted The Self-Destructing Time Bomb and The Ultimate Cliff (or they are avoiding thinking about it). And this acceptance is what’s keeping people from seriously and carefully thinking about aging and life extension.

It is important to eradicate aging

Most of us are searching for meaning in our lives. I think what we do with our lives — contributing to the world, having relationships with people, loving other people, being creative, thinking originally, understanding what’s around us and how things work, understanding ourselves, striving to improve ourselves — is what gives meaning to our lives. And the time we get to do all this and more, is not nearly enough.

And no healthy and happy, satisfied person wants to die today. Research shows that people want more time; they want to live longer than their average life expectancy.

When people were asked what they thought was the ideal length of life, 86% said 79 or older: 69% said between 79–100 years of age — the most interesting part is that life expectancy was 78.7 years at that time — this means most people wanted to live longer than their life expectancy. In fact when they were asked about their ideal life span, they said around 90 years (= median ideal life span), this was 11 years longer than the average U.S. life expectancy then (2013).

Source — The median ideal life span is 90 years — about 11 years longer than the current average U.S. life expectancy, which is 78.7 years

Looks like people want to live longer than what is given to us.

The problem is that we age and we deteriorate. And this robs us of a good quality of life. That is why it is important to attack and eradicate aging — doing so would both improve people’s healthspan and extend lifespan. In doing so, humankind will have an option to live healthier and longer lives.

Life extension is just the natural progression of existing medical practices — we would go from curing diseases (and the side effects of aging) to preventing them.

This is the goal:

The goal is to not live a really really long time as an old person, it’s to stop and reverse aging.

There’s dedicated effort to overcome disease and aging — a) to eradicate cancer and diseases so people won’t have to worry about them in their 60s and 70s, b) to overcome frailty so people won’t have to worry about it in their 80s, 90s, and beyond, and c) to eliminate aging so people won’t ever have suffer from age-related diseases.

And once we succeed, future generations will look back and wonder why didn’t do this sooner.

Why now

The current technological (and biotechnological) revolution could make us the first generation of humans with a life expectancy of over 1000 years. We are standing on the brink of a revolution — one that will slow down aging, then eradicate it. There’s a massively profound transformation coming our way in the next 10 or 20 years.

You might be wondering that some subset of humans have always wanted this, so what’s so different now?

  1. Major investments and efforts are now starting to be made in this field — more in part 3. [I’m working on compiling approaches in a spreadsheet and visually representing a “map” of approaches. It’s taking much longer than I had anticipated. When it’s done, I’ll add a link with details.]
  2. Technologies and tools we have now are improving exponentially: genomic sequencing, gene editing, big data management, artificial intelligence, simulation and actual models (of animals and non-animals) are all getting better day by day. Health and medicine have now merged with technology — this wasn’t always the case. For example, after the genome project, we can now reprogram biology and life — something we couldn’t do before.
  3. So much is now known about the pathways, genes, proteins, processes that contribute to aging. A lot of people are now trying a variety of approaches (aided by the technologies and tools listed above) to interfere with these contributing factors, and translating the research to clinical trials of drugs and therapies to extend lifespan is imminent. Genetic therapies have increased mice lifespan, allowing them to live about 30% longer. Imagine living 30% longer — we’d be living up to 105 — on average! Recent stem cell therapy application has doubled life expectancy in a particular type of mouse. Imagine doubling our life expectancy — we’d be living up to 160!

The purpose of these drugs and therapies is to put an end to aging and its terrible consequences — deterioration, dysfunction, disease, and subsequent death. The idea is to get a few extra decades, during which we’d have new ways to attack this problem, and hence get few (or more) extra decades and so on.

One last thing

Let’s revisit the three questions from the beginning of the blog.

  1. Do you think the field of longevity (or life extension) is a legitimate field?
  2. Do you think aging can be eradicated and/or reversed? Should it be eradicated and/or reversed?
  3. Would you want to live for 100s or 1000s of years or more — ideally?

Did any of your answers change? I’d love to hear from you about why or why not.

Before we stop, let’s go one step further. Does eradicating aging allow everyone to live healthy lives for as long as they want? No, not yet. First: even if in the next 20 years we have therapies that allow us to live for a few decades more, then would they really help people in their 70s, 80s, 90s and beyond? Unless we can reverse aging by then, these therapies may not buy them more time. Second: even if we eradicate aging, we can still die from other events. The option to live long isn’t really an option in these two scenarios. People can and probably will die in these scenarios.

Eradicating aging isn’t sufficient to truly give humankind an option to live longer or an option to not die. But eradicating aging is still a necessary problem to solve.

I think we would all agree that death of someone close to us, independent of the cause, is heartbreaking at a personal level. Furthermore, the cost to humanity of individual deaths is equally heartbreaking, even though it is something we rarely think about. Each individual has tremendous knowledge, insight, life experience, and loving relationships. All of those are gone when an individual is gone. So, eradicating aging is step 1. Step 2 is seriously thinking about death and finding a way to control it.

That’s Part 2 — Coming soon-ish.


The Life Extension Revolution — Part 1 was originally published in Hacker Noon on Medium, where people are continuing the conversation by highlighting and responding to this story.