Is Human Life Extension Possible? – Longevity Advice

Update 3/8/2021: This post has been updated since we originally published it in August 2020. Several new studies showing the possibility of life extension in animals and humans have been added, and the post has been cleaned up and links made current.

You might live to be 150 years old.

In fact, if some scientists are to be believed, you might live to be a good deal older even than that.

Sounds crazy right? Like some wild fantasy birthed in the fevered brain of a modern-day Ponce de Len?

Perhaps.

But we thinkfrom our own initial research into the many medical, technological, and scientific advances targeting agingthat it could also be true.

Which is a very exciting possibility.

And whats more exciting is that as human life extension research becomes more mainstream, the advances it makes possible are becoming more accessible, if you know where to look.

Today tons of money and talent and time are being poured into developing life-extension treatments and technology, yet most people remain totally ignorant of the rapid progress made in the quest to reverse aging.

We live in a unique moment where life-extension science has advanced to a point that credible life-extension methods and supplements already existindeed many therapies are currently in clinical trialsbut before most of this knowledge has filtered out to the broader public and non-scientists.

We believe that theres a need for a resource for the transition. That resource is Longevity Advice.

We started researching the possibility of radical human life extension out of personal curiosity (and probably also from having read too much science fiction). But the more we dug into the subject, the more interesting discoveries we made, and so the more we felt compelled to share what we learned with a wider audience.

Buried in the reams of obtuse medical studies and scientific papers are actionable insights that we think most people can take advantage of today, not in five years, not in ten years, but right now, to extend their healthy lifespan.

Buried in the reams of obtuse medical studies and scientific papers are actionable insights that we think most people can take advantage of today, not in five years, not in ten years, but right now, to extend their healthy lifespan.

And thats exactly what we hope to do here on Longevity Advice: translate the cutting-edge of longevity science into accessible lessons so that you and your loved ones can learn what to do to live longer, starting today.

Dont believe human life extension is possible? Think were navely buying into junk science from snake oil salesmen?

Let us share with you some of the evidence thats convinced us (and many, many, practicing scientists and doctors) that treatments to delay and even reverse human aging could already be here.

Though, for that evidence to make sense to you, we first have to answer the question: What is aging?

Youd think thatd be an easy answer.

Youd be wrong.

As humans get older, they face creeping physical and psychological decline.

Wrinkles, for example, are a sign of aging. According to Scientific American, the amount of collagen the body naturally produces diminishes every year after turning about 20-years-old. Our bodies age out of producing enough elastinAn important protein that keeps skin and other tissues elastic. and glycosaminoglycansA type of polysaccharide (sugar molecules) that includes keratan and keeps tissues like skin hydrated and able to repair themselves. to keep the skin stretchy and hydrated. The result? Older skin is drier, less stretchy, and less able to protect itself from damage.

In other words, as we get older, some natural bodily functions predictably dont work as well as wed like them to.

But look at these faces. All of these people were born in the same year. Notice how some have significantly more wrinkles than others. Were their collagen, elastin, and glycosaminoglycans dissipating at roughly the same rate?

The differences in the formation of wrinkles may be genetic. For example, one study found that genetics determine whether women face a greater chance of wrinkles earlier in life depending on how efficiently their bodies process lung toxins. African-Americans have more compacted skin and a higher intercellular lipid content, which may contribute to more resistance to skin aging than Caucasians. Even epidermal thickness, which is determined entirely by your genes, impacts how quickly your skin starts to show fine lines.

With all that said, however, research has consistently shown that genetics and aging processes account for only a small fraction of what causes variability in wrinkling skin. Lifestyle factors play a massive role; one oft-cited study found that up to 90% of visible skin aging can be attributed to UV light exposure. Smoking, alcohol, and sugar consumption can all affect when and how you get wrinkles over the course of your life.

Lets think back on those 60-year-olds pictured above. They were all born in 1960they have all lived the exact same number of years. Sixty is their chronological age, but their biological age varies widely; the difference explains why one person can be 60 but look 30. Its also why some people get cancer at 65, and others dont get it until 85: their biological ages are different.

While wrinkles might be a visible indicator of biological age, scientists still disagree on the cause (or causes) of aging itself. That said, there are nine hallmarks of aging that, while were not 100% sure cause aging, are associated closely enough with aging to be able to describe it pretty comprehensively.

If these hallmarks remind you of Star Trek technobabble, youre not alone. The science of biological aging is ridiculously complicated, often requiring a Ph.D. to wade through. The point is this: chronological aging and biological aging are two separate concepts, and we are only concerned with biological aging.

Why?

The possibility of human life extensionchronological life extension, as in living to 150may be a consequence of mitigating the causes of biological aging.

(Curious about what your biological age is? We reviewed the top biological age tests available for 2021.)

In 1950, life expectancy in the United States was 63 years old. In 2020, it was 77 years old (its worth noting that COVID played a role in the decline from 78 the year prior). Thats about a 25% increase in life expectancy over 70 years but thats not the whole picture.

Calculating life expectancy is a force of averages; Americans are far more likely to survive childhood than they were 70 years ago, average life expectancy increased. Americans who survive childhood arent necessarily living longer than their parents.

Throughout history, there have been people who have lived to 100. There have even been a few who have lived to 110 (currently, there are about 60 to 70 supercentenarians total in the United States and 300 to 450 internationally). Only one person has been verified to have lived past 120. Maximum human lifespan has not increased over the course of human history. Researchers from the Albert Einstein School of Medicine concluded in 2016 that, the probability in a given year of seeing one person live to 125 anywhere in the world is less than 1 in 10,000. In other words, its incredibly unlikely to happen naturally.

Now picture being 110 years old. You might imagine yourself in a wheelchair. A lack of focus and personal independence. A life of loneliness and incontinence pads. Living for a very long time is hardly appealing because of the physical, mental, and social limitations old age tends to bring with it.

Human life extension addresses both chronological and biological aging; it asks not just how can we live longer, but how long can we live well. Healthspan, or the years of our lives when were unencumbered by disease or disability, addresses just that. What if you could have the body you had at 25 well into your 80s or 100s or 120s? What more could you do with those extra rich years of life? Who could you become?

Extending our healthspans also forces us to ask what we can do individually and as a society to change the odds of living to 110 and beyond. Right now, only 0.002% of women and .00002% of men live to become a supercentenarian. What if we could change those odds to the current odds of reaching 60 years of age after surviving childhood (91% for women and 85% for men)?

Human life extension is both science and art. It seeks to extend the maximum human lifespan while also lengthening the amount of time people spend in the prime of their physical lives.

As beautiful as the possibility sounds, theres a lot of skepticism about whether or not its possible to accomplish.

There is one major scientific discovery that indicates human life extension beyond 125 may be impossible, or at least highly improbable. Its worth acknowledging this discovery before going into all the reasons why we do think human life extension is possible.

That discovery is called the Hayflick limit.

Like cells in every other living organism, human cells divide to create daughter cells. Cell divisionand the accuracy of their replication of the mother cellis important to sustaining a healthy body; without it, you would likely die almost immediately, as its cell division that underpins the systems keeping your skin attached to your body, your brain secured in your head, and your heart beating reliably.

After several divisions, cells can either continue dividing, die, or become senescent. In broad terms, senescent cells are cells that are no longer capable of dividing. These cells are not dead but, like undead zombies, they remain active in the body.

While senescent cells are useful for repairing tissue damage, they are largely harmful to the body. Research has correlated senescent cells with cancerous tumor progression, Alzheimers, and age-related loss of muscle mass. In other words, the more senescent cells you have, the more likely you are to be biologically olderand the more prone you are to age-related diseases (youll remember cellular senescence is one of the nine hallmarks of aging we listed above).

While researching cellular division in 1961, Leonard Hayflick discovered that human fetal cells can divide up to 60 times before dying (entering apoptosisA programmed 'cell death' to get rid of damaged or malfunctioning cells. Cancer cells are cells that have malfunctioned but avoided apoptosis and continue dividing.) or becoming senescent. This theory was bolstered when Elizabeth Blackburn and her colleagues discovered telomeres. Telomeres are like a bleed for a printing jobthey protect the DNA inside chromosomes from getting cut off when a cell divides (or prints). Every time a cell divides, its telomeres get shorter. Cells with shorter telomeres are more likely to become senescent.

The Hayflick limit would support what some other scientists have found from census data and mathematical models: it is impossible for humans to live past 125 because of the inevitable accumulation of senescent cells and absence of healthy cells.

The Hayflick limit is the best argument against investing more time and energy into human life extension research (unless you believe that its unethical to try to extend human life). And though the Hayflick limit is compelling, we argue that its not a good enough reason to cease all investigations into living longer, healthier lives. For example:

So now that weve gone over the main arguments against the possibility of human life extension (that our cells have an in-built limit that, even if we cured every other disease, would still cause us to age and die), now we want to share the scientific evidence that has made us so excited about this field.

The first thing you should be aware of is that scientists know, and have known for decades (or almost a century in some cases) how to extend the healthy lifespan of a host of different organisms. In fact, in many of these organisms, specifically in animal studies, life extension interventions are so trivially easy and commonplace they are almost unremarked on anymore.

For instance, in 1988 scientists discovered that a gene mutation in the worm C. elegans that promoted greater autophagyThe process cells use to clean out damaged parts of themselves and regenerate new healthy cells. Ancient Greek for 'self' (auto) 'eating' (phagein). (literally meaning self eating of the junk and damaged cells that build up in the body over time) resulted in extending the maximum lifespan of the mutant worms by 110%, an extension that, in humans, would have extended average lifespan to 168 years.

This led to lots of research around methods to induce autophagy without having to breed a genetically altered organism. One of the most successful methods of doing so was caloric restriction. Basically, if you starve an organism, its body activates autophagy pathways in order to convert its accumulated molecular junk (like dangerous senescent cells and mutated pre-cancerous parts of cells) into energy.

The longevity-promoting effects of moderate starvation have been known as far back as 1914, when a study showed that caloric restriction in mice inhibited tumor growth, while in 1935 a different study showed that caloric restriction increased average rat lifespan from 483 days to 894 days. In humans, that would be the equivalent of getting an extra seven decades of life.

Caloric restriction has now been found to extend lifespan in organisms as varied as yeast, fish, dogs, worms, and hamsters. It also has longevity-promoting effects even if started later in life. The fact that it extends healthy lifespan in such a wide variety of different animals and life forms means it likely impacts humans in similar ways, too.

And, luckily for those of us who dont want to be perpetually hungry, recent research has shown intermittent fasting (limiting the time you eat to a specific daily window, but not limiting the amount you eat) and even drugs that act as calorie restriction mimetics can have similar effects.

In addition to caloric restriction, scientists have also found a host of different genetic pathways they can tweak to increase lifespan in fruit flies, worms, mice, and all kinds of other animals.

One method found you could breed longevity into fruit flies by pairing off the longest-lived members of a group of flies until, after a few generations, you had fruit fly descendants that live twice as long as their ancestors.

Other methods have shown genes that downregulate insulin signalling can increase lifespan by 18% in mice, and as much as 500% in roundworms, genes that activate sirtuinsLongevity enyzmes that repair damaged parts of DNA. Named after the first sirtuin gene discovered in yeast, SIR2. (a type of body-repair protein) also increase mice lifespan, and a gene therapy that increases telomeres (the caps at the ends of DNA chromosome strands) in mice increases lifespan up to 24%.

A 2020 paper showed that treatment with specific stem cell genetic factors could reverse the age of damaged mouse optic nerve cells and even allow them to regrow and restore vision.

And beyond the genetic angle, a multitude of other therapies and interventions have shown life extension and even aging reversal in lots of different animals.

One such intervention you may already be familiar with given its popularization by the media and comedy TV shows like HBOs Silicon Valley: blood transfusions.

A 1972 study stitched together old and young mice in a process known as parabiosisLiterally meaning 'living beside' and referring to the anatomical joining of two individuals. A little creepy., allowing the two to share each-others blood, and found that older mice lived four to five months longer than controls.

Since then, additional studies of mice and rats have shown that older mice given transfusions of blood from younger, healthy mice exhibit lots of signs of increased vitality and healthy tissue rejuvenation as well as signs of actually reversed aging up to 54% (as measured by an epigenetic clockA blood test that looks at epigenetic changes to the body, like methyl groups attached to DNA, to predict biological age.).

And, in fact, even just replacing a portion of old blood with a saline-albumin solution seems to rejuvenate mice, possibly by removing toxic, pro-aging signaling molecules from circulation.

But certain drugs have also been shown to increase lifespan in animals, possibly by mimicking the effects of things like caloric restriction or by activating other body repair and longevity pathways.

For instance, metformin, a common (and inexpensive) diabetes drug, has been shown to extend maximum lifespan in mice more than 10%.

Resveratrol, a compound found in small amounts in things like red wine and blueberries, increases lifespan in a host of different organisms from yeast to worms, and also increases survival rates for mice fed an unhealthy, high-calorie diet.

And rapamycin, an immunosuppressive drug first discovered in bacteria on Easter Island, has been shown to extend life in fruit flies, worms, and rather famously in aged mice (this specific study won the Methuselah Foundations M-Prize for its results) .

FOXO4-DRI, a senolyticA drug being developed to selectively destroy senescent cells. From 'senescent' and '-lytic,' meaning 'destroying.' peptide that induces apoptosis (programmed cell death) in senescent cells, has been shown in mice to restore fitness, hair density, and renal function in fast-[aging] and naturally aged mice.

Two other senolytics, Dasatinib and Quercetin, have been shown to alleviate age-related cognitive impairment and brain inflammation in mice.

As you can see, there are reams upon reams of studies showing we can slow, treat, and even reverse aging across a whole host of different animals and model organisms.

And all the stuff discussed and linked above? All that is only scratching the surface of all the anti-aging animal research thats out there.

Really, its a lot.

So if youre still of the opinion that aging cant be treated or prevented, the sheer volume of studies showing it can be done in animals should maybe give you pause.

But of course, all the animal studies in the world dont mean a thing if none of that can be translated into humans.

Luckily, theres already quite a bit of evidence that these results can be replicated in our own species.

While its very difficult for a human trial to show actual life extension from any particular treatment (because youd have to wait 80+ years for everyone in the trial to die) other measures of healthspan can be used in humans to show apparent longevity and anti-aging effects.

For example, things like immune function, tissue elasticity/regrowth, and decreased cancer risk can all be used as longevity biomarkers to measure possible anti-aging treatments on humans.

And many of the same methods that increase lifespan in animals have been shown to have positive impacts on health indicators in humans as well.

For example, a recent two-year study of 238 healthy men and women aged 21-50 called CALERIE found that caloric restriction lowers blood pressure, lowers cholesterol, and decreases inflammatory factors in the blood while increasing insulin sensitivityThis is a good thing. You want to be more sensitive to insulin because it allows your cells to use blood glucose more efficiently and reduce blood sugar..

A 1957 Spanish study of older people in a nursing home also found that intermittent fasting using an alternate-day fasting method (fewer calories every other day but the same total calories as controls) led to fewer deaths in the subjects (6 vs. 13 for people not doing the intermittent fasting) and fewer days spent in the hospital as well (123 days vs. 219 for controls).

Intermittent fasting has also been shown in men to lower blood pressure, decrease oxidative stress, and increase insulin sensitivity even without weight loss.

Drugs that have been shown to extend lifespan in animals, like rapamycin, have also been shown in humans to have positive effects like improved immune function, better response to vaccines, and lower incidences of respiratory disease and other infections.

Metformin, the diabetes drug that was shown to possibly extend lifespan in mice by 10%, seems to be acting as a longevity drug in humans as well. In addition to being associated with lower cancer risk, according to a recent metformin meta-analysis, Diabetics taking metformin had significantly lower all-cause mortality than non-diabetics.

Additionally, dozens of drugs and therapies that target different aspects of the aging process have moved past animals and are already in human clinical trials.

In fact, a study much like the one that showed certain genetic factors could reverse aging in mouse retinas and restore vision has shown human cells can be similarly reprogrammed to look and act younger.

Two additional trials, both recent and both getting larger follow-up trials to attempt replication, have shown the first-ever recorded epigenetic age reversal in actual human beings (as opposed to just human cells in a culture dish).

The first, called the TRIIM trial (for ThymusThe small organ in your chest that creates immune T-cells. They're literally called 'T' cells for 'thymus.' Regeneration, Immunorestoration, and Insulin Mitigation), treated nine men for one year using rhGH (human growth hormone), DHEAA natural hormone used by the body to create male and female sex hormones like androgen and estrogen. Like other hormones it declines in the body with age., metformin, zinc, and vitamin d3. The goal was to regenerate the thymus and help restore immune function in older men but, almost as an afterthought, each subject had their epigenetic age tested before and after the trial using Horvaths clock, one of the most accurate measures of biological age we have.

At the end of the trialand after a year of treatmentthe subjects were, on average, 2.5 years younger than they should have been (i.e. 1.5 years younger than their epigenetic ages at the beginning of the trial).

In addition, a whole host of relevant biomarkers improved, including regeneration of healthy thymus and bone marrow tissue, improved kidney function, positive changes to the ratio of immune cells in the blood, and even a reversal of gray hair reported in three subjects (and documented in two).

Already a larger TRIIM-X trial is being planned with the hopes of replicating these results with a bigger pool of subjects across a more varied range of age, sex, and ethnicity.

A second recent, but promising, intervention to show biological aging reversal in humans comes from a pilot consumer study by the company Ponce de Leon Health. The company makes a supplement called Rejuvant LifeTabs, whose active ingredient, calcium-alpha-ketoglutarateA form of mineral calcium used to restore normal calcium levels in the blood. Often used by bodybuilders who have low calcium due to high intake of protein supplements. or CaAKG, has been shown in a recent study to extend the median lifespan in mice by almost 20%.

According to Ponce de Leon Health, 17 customers had their biological age tested using an epigenetic clock before taking Rejuvant, and then again after taking it for four to six months. The results were encouraging, showing an average 8.5-year reduction in biological age across all 17 subjects.

Similar to the planned follow-up to the TRIIM trial, the company is hoping to replicate this early success with a larger, more rigorous clinical trial: Ponce De Leon is currently enrolling participants for a larger, randomized, double-blind, placebo-controlled clinical trial, to be conducted at Indiana University Medical Center later this year.

And, finally, a third study has also shown a reversal of human biological age by 1.96 years after eight weeks of treatment using diet and lifestyle interventions, including a Mediterranean-style diet high in cruciferous vegetables with some high-quality proteins like eggs and liver every week, plus 30 minutes of physical activity a day, and other interventions like breathing exercises.

While all the above is not conclusive evidence that eternal life is right around the corner, there are still compelling data showing that human life extension treatment is likely. Whats more, it may even be already available to a limited degree.

For the length of this article so far, weve been saying we a lot, and you may be wondering just who the authors of Longevity Advice are and why you should listen to these internet randos.

Well, first, to get the most important stuff out of the way right up front, there are a couple of things we are not:

What we are is a couple of interested amateurs who wanted to research this space for our own personal edification (and possible application) and who didnt really see a resource for people like us: people who want an introductory, but smart, guide to human life extension and to what sorts of things they can be doing now (not perpetually five years from now) to extend their lives and the lives of their loved ones based on good research.

On to the introductions:

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Is Human Life Extension Possible? - Longevity Advice