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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 elastin and glycosaminoglycans 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 there are some natural bodily functions that predictably don’t work as well as we’d like them to.
But look at these faces. All of these people are 60-years-old. Notice how some people have significantly more wrinkles than others in spite of 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.
Let’s think back on those 60-year-olds pictured above. They were all born in 1960—they 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. It’s also why some people get cancer at 65, and others don’t 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 we’re not 100% sure cause aging, are associated closely enough with aging to be able to describe it pretty comprehensively.
- Altered Intercellular Communication: Cells struggle to “talk” to one another reliably and effectively, particularly in relation to hormone and inflammation production.
- Cellular Senescence: Old cells stop dividing but stick around as dangerous “zombie” cells—we get into more detail on these later in the article.
- Deregulated Nutrient Sensing: The body stops focusing on maintaining and repairing existing cells.
- Epigenetic Alterations: Changes and damage to the machinery that reads and expresses DNA without changing the DNA coding sequence itself (this can affect the chances of developing hereditary conditions).
- Genomic Instability: DNA gets so damaged that it can’t keep up with repairing itself, resulting in cancer cells.
- Loss of Proteostasis: Protein regulates almost all of the chemical reactions in your body. Proteins that are not correctly produced are damaging to the entire body’s functions.
- Mitochondrial Dysfunction: Mitochondria (the “power plants” of the cells) synthesize too many or too few high-energy molecules, disrupting cell function.
- Stem Cell Exhaustion: A loss in our body’s ability to recover from tissue and organ damage.
- Telomere Attrition: The caps on the end of DNA in cells get so damaged that cells can no longer safely create new copies of themselves.
If all of these “hallmarks” remind you of the kind of technobabble Julian Bashir or Leonard McCoy used to explain their unconventional treatment plans to their intergalactic patients on Star Trek, you’re not alone. The science of biological aging is ridiculously complicated, often requiring a PhD 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 extension—chronological life extension, as in living to 150—may be a consequence of mitigating the causes of biological aging.
What is human life extension?
In 1950, life expectancy in the United States was 63 years old. In 2020, it’s now 79 years old. That 25% increase in life expectancy is comforting, but it’s not the whole picture. Calculating life expectancy is a force of averages; because Americans are far more likely to survive childhood than they were 70 years ago, average life expectancy increased. Americans who survive childhood aren’t 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 75 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, it’s 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 we’re 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, there’s a lot of skepticism about whether or not it’s possible to accomplish.
Is human life extension possible? The Hayflick limit and why some scientists say “no.”
There is one major scientific discovery that indicates human life extension beyond 125 may be impossible, or at least highly improbable. It’s 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 division—and the accuracy of their replication of the mother cell—is important to sustaining a healthy body; without it, you would likely die almost immediately, as it’s 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, Alzheimer’s, and age-related loss of muscle mass. In other words, the more senescent cells you have, the more likely you are to be biologically older—and the more prone you are to age-related diseases (you’ll 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 apoptosis) or becoming senescent. This theory was bolstered when Elizabeth Blackburn and her colleagues discovered telomeres. Telomeres are like a bleed for a printing job—they 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 it’s unethical to try to extend human life—we’ll address those concerns in another article). And though the Hayflick limit is compelling, we argue that it’s not a good enough reason to cease all investigations into living longer, healthier lives. For example:
- The Hayflick limit speaks to the chronological age of cells, but does not address interventions into changing their biological age. It’s a classic correlation versus causation conclusion.
- Mouse studies have proven that the Hayflick limit does not necessarily limit lifespan.
- Senescent cells may be treatable.
- Telomere interventions using telomerase may extend the number of times a cell can safely divide.
The science supporting human life extension
So now that we’ve 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.
Successful life extension in animal trials
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 autophagy (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 don’t 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 descendents that live twice as long as their ancestors.
Other methods have shown genes that downregulate insulin signalling can increase lifespan by 18% in mice, genes that activate sirtuins, a type of gene therapy that increases telomeres (the caps at the ends of DNA chromosome strands) in mice increases lifespan up to 24%.
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 HBO’s Silicon Valley: blood transfusions.
A 1972 study stitched together old and young mice in a process known as parabiosis, allowing the two to share each-other’s 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 clock).
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 signalling 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 Foundation’s M-Prize for its results).
FOXO4-DRI, a “senolytic“ 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.”
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 that’s out there.
Really, it’s a lot.
So if you’re still of the opinion that aging can’t be treated or prevented, the sheer volume of studies showing it can be done in animals should maybe give you pause.