{"id":"60337a006cee070007cf1808","slug":"lifespan-en","title":"Lifespan ","audio_url":"https://hls.blinkist.io/bibs/60337a006cee070007cf1808/60337a006cee070007cf180a-T1619706481.m4a?Expires=1643242821&Signature=aO3FpliA0TFLvSzVcBKVAq19Cq0SV9GEASq54hiZnHdd7T0lpLtoha0AkD3cOd5X~QL6AttkhZoH-TWwjhAnCtLP5Vex--sEys8Sxcz9VjOvFwBK9q1p19TGglbORwpjbIlODnktfM3mOw9hpHJFDCo8gZmVoNO6eho8AN1qtFBEIRCo8eCOHfDzbz7HcQ-ApMUHy7npc9xhOBAJJb0RCNrvOLNTVeN0mJVGPkLqSFjyI-GkXYkWZDSokwdzWdokkpvOsDSScZBNyYbQZ8yuX1fPs9BJGcU47kZjA891N~V72mSUfruA1uKSiupqFlhmSosRAKLhn7ZRV4-aqUvHbw__&Key-Pair-Id=APKAJXJM6BB7FFZXUB4A","chapters":[{"id":"60337a006cee070007cf180a","title":"We view aging as inevitable, but it’s actually a treatable disease.","text":"

At the turn of the twentieth century in the United States, influenza, pneumonia, tuberculosis and gastrointestinal conditions accounted for approximately 50 percent of all deaths. It was all but inevitable that one person in two would die from one of these afflictions.

Today, only 10 percent of the people in the United States who contract influenza or pneumonia are in any danger of dying, and the country’s mortality rate for both tuberculosis and gastrointestinal conditions is so low that it’s statistically irrelevant.

Thanks to medical advances, diseases that once spelled death are now rarely life-threatening.

What if we thought of aging as a disease, just like pneumonia or tuberculosis? Like any disease, aging presents a host of symptoms, like dementia, organ failure, loss of bone density, just to name a few. Wounds also take longer to heal when we age, our bodies become more susceptible to infections and viruses, our organs slowly yet inexorably fail and our brain function is impaired.

Recent breakthroughs in genetics show that aging actually is a disease. Not only that, it’s a disease that’s potentially curable, and eliminating it would add years to our lifespans. Without the symptoms of aging to deal with, the quality of our newly extended lives would be improved immensely.

Of course, like any disease, aging is best treated not by tackling its symptoms one by one but by targeting its root cause. Cancer provides a useful comparison here. Up until the 1960s, researchers didn’t understand what caused cancer, so treatment focused on symptoms, not root causes. Doctors removed cancerous cells where they found them, often destroying healthy cells in the process.

In the 1970s, molecular biologists discovered the oncogene. This is the specific gene that causes cancer when it mutates. Instead of attacking symptoms at random, subsequent cancer treatments could specifically target the oncogene, leaving healthy cells unscathed and improving patient survival rates.

So why haven’t we done something similar in our approach to aging? Because until now, very little was known about its root cause. However, a spate of recent breakthroughs are bringing scientists ever closer to pinpointing it.

"},{"id":"60337a006cee070007cf180b","title":"Our genes are hardwired for longevity.","text":"

The freshwater polyp Hydra vulgaris – a small water-dwelling organism – has long fascinated geneticists. Why? It’s evolved to resist biological senescence. This is the slow deterioration of function that occurs when cells that have stopped dividing accumulate in an organism. It’s also, essentially, the cause of aging.

In the wild, Hydra vulgaris are vulnerable to predators and other environmental factors; when kept in lab conditions, however, they seem to be effectively immortal as they show no signs of aging. Other “immortal” creatures, like the bristlecone tree, the Greenland shark and the bowhead whale, have also seemingly evolved to defy or significantly defer biological senescence.

Could humans possibly evolve in a similar way? Our genetic hardwiring seems to indicate we could.

While most living organisms haven’t evolved to resist senescence, they have all survived by evolving the same gene circuit, a kind of closed system in which the action of one gene triggers the reaction of another, and so on.

To understand this gene circuit, we need to go back to the very beginning of biological life and the primordial soup, filled with rapidly dividing and multiplying cells. Scientists speculate that these early cells all had two genes inside of them. Let’s call them gene A and gene B.

Gene A is a caretaker gene that shuts down cell reproduction in response to environmental stressors. After all, there’s no point in reproducing in an inhospitable environment. Gene B is a silencing gene; when environmental conditions improve, it wraps gene A in protein, shutting it down and thereby restarting the process of reproduction. Basically, gene A is the red light for cell reproduction, and gene B is the green.

But in order to survive, some cells evolved a gene circuit in which gene B didn’t just shut off gene A, it also actively repaired any damaged DNA within the cell before reproduction started up again. This meant that damaged DNA wasn’t replicated, which was important because replicating damaged DNA is one way in which cells can lose the ability to replicate altogether. And cells that can’t replicate become senescent.

Humans now exhibit a more evolved version of this survival circuit, but its basic function is the same: to repair DNA and prevent the loss of genetic information that causes cells to stop replicating, become senescent and contribute to the aging process. In this sense, we’re hardwired to avoid senescence. So, why aren’t we immortal? The answer to this question lies in that very same survival circuit.

"},{"id":"60337a006cee070007cf180c","title":"The Information Theory of Aging proposes that aging is the loss of cellular information.","text":"

The author’s Information Theory of Aging posits that aging occurs because of a loss of cellular information. This loss of information is caused by the repair process that should prevent aging. As we’ve seen, DNA can be damaged when it’s repaired incorrectly. That means a cell losing the vital information it needs to replicate perfectly, eventually leading to the cell ceasing to function altogether.

Now, if the vital information that makes us who we are were just contained within our DNA, this wouldn’t be a problem – DNA can replicate perfectly on its own. But our epigenome is equally vital.

What’s that? Well, let’s say that the fertilized human egg, where our parents’ DNA is combined and resequenced into our own personal DNA, is the source of our personal genetic information. Then the epigenome – the collective term for all the processes and structures that regulate our genes and their expression – is the transmitter of that information to its receiver, our bodies.

One of these epigenetic processes is called gene marking, and it’s important as it’s also a contributing cause of information loss. Basically, gene marking occurs when genes place chemical tags on cells that tell them what they should be – telling a kidney cell that it’s a kidney cell and not a brain cell, for example.

Some of the genes involved in this process, like sirtuin genes, also play an important role in DNA repairing, extending our lifespan and promoting vitality. These genes encode a family of proteins called sirtuins which can be deployed to move around inside their home cell, switching other genes within the cell on and off in response to emergencies like illness or inflammation, as they go. Sirtuins are like roaming caretakers, making the repairs and adjustments each cell needs to stay healthy and functional.

Obviously, “longevity genes” like sirtuin genes are tremendously important in the fight against aging. The flip side is that when they don’t function correctly, they can also cause aging. That’s because when sirtuins are mobilized to respond to emergencies, they don’t always find their way back to their rightful place inside their cell. They can turn into unregulated agents, switching off genes that should be switched on, and vice versa. When sirtuins go rogue, they contribute to the loss of cellular information that causes aging.

"},{"id":"60337a016cee070007cf180d","title":"You can help your longevity genes fight aging.","text":"

Geneticists may be on the cusp of finding a cure for aging, but in some parts of the world, people have been defying the effects of aging for centuries. These pockets of longevity were first identified in the mid-2000s by author Dan Buettner, longevity expert Dr Michel Poulain, and medical doctor Gianni Pes. The trio dubbed these pockets Blue Zones. Blue Zones boast unusually high rates of nonagenarian – people in their 90s – and centenarian residents. What’s more, these long-lived residents remain active and vital despite their age. So what’s their secret?

For one, residents in Blue Zones all eat predominantly plant-based diets low in animal protein. Eating protein delivers essential amino acids to the body, which function as the “building blocks” for all our internal proteins. These amino acids are only obtainable through diet, and animal proteins deliver them in huge quantities. That’s a good thing, right? Well, maybe not. When we’re sated with amino acids, the body leaves survival mode. As a result the genetic instinct to repair DNA and promote healthy cell replication, which kicks in during times of stress, is shut down.

Plant-based proteins, on the other hand, deliver just enough amino acids to maintain healthy bodily functions while still keeping the body in a state of desirable stress: cells are under enough stress that the survival instinct to repair and preserve DNA stays active without reaching a state of emergency where overall health and function is compromised.

There’s something else Blue Zone residents do to cultivate a healthy level of bodily stress. They restrict their food intake. A 1978 study showed that residents of Blue Zone Okinawa Island consumed 20 percent fewer calories than their mainland Japanese counterparts. And in Ikaria, Greece, residents follow the Greek Orthodox calendar, which mandates periods of fasting.

It’s believed that fasting is another simple way to create the desirable stress that mobilizes the longevity genes without sending them into overdrive. In 1935, researchers at Cornell University even proved that rats whose diets were restricted lived significantly longer.

Long-term calorie restriction might not be for everyone though. Luckily, a 2011 study from Yeshiva University found that intermittent fasting, where participants fasted for five days over the course of a month, can achieve the same effects as long-term fasting. After three months of intermittent fasting, study participants reported lower levels of the hormone IGF-1 or Insulin Growth Factor 1. High levels of IGF-1 are believed to play a role in aging and disease; meanwhile, geneticist Nir Barzilai, has found that families where females routinely live past 100 have lower levels of IGF-1 in common.

"},{"id":"60337a016cee070007cf180e","title":"A cure for aging may be closer than we think.","text":"

A world in which aging has been completely eradicated may sound like the stuff of science fiction, but geneticists are working to make it a reality.

And while anti-aging medicines may be on the cutting edge, they’re more often than not derived from the natural world. From soil bacteria to wildflowers, the keys to curing aging might lie in nature.

One potential cure has its origins in Rapa Nui, the island off the coast of Chile, more commonly known in the West as Easter Island. In the 1960s, a team of scientists discovered a new type of bacteria in the soil under one of the island’s famous head statues. It was found to contain an antifungal compound which was subsequently named rapamycin. Initially used as an immune suppressor that prevented the bodies of organ-transplant recipients from rejecting their new organs, rapamycin has since been discovered to have life-extending potential.

Studies have shown that fruit flies dosed with rapamycin live up to 5 percent longer. And when mice at the end of their natural lifespans are fed rapamycin, they’ve been found to live 9 to 14 percent longer than expected. Why did the flies and mice dosed with rapamycin live longer? The reason is that rapamycin inhibits the longevity gene mTOR. How does inhibiting a survival gene promote longevity? Well, when mTOR is behaving as it should it promotes cell growth. But, just like sirtuins, as we age, our mTor genes can go rogue, and actually direct cells to stop dividing. Rapamycin thus regulates our mTOR genes so they don’t work against us.

While further research is needed into rapamycin’s effect on humans, there’s another anti-aging wonder drug that’s already being prescribed, albeit as a treatment for diabetes rather than an antidote for aging. It’s called metformin, and it’s derived from goat’s rue, a type of wildflower.

Studies have found that metformin activates AMPK, an enzyme which in turn restores mitochondrial activity. The mitochondria are tiny organelles in the cell that transform nutrients into energy. Stimulating them thus means giving a big boost to the energy that’s available for cellular repair and function. Metformin has additionally been found to inhibit the metabolism of cancerous cells. A 2017 study found that in elderly humans, regular doses of metformin reduced dementia by 4 percent, heart disease by 19 percent, and frailty, an age-related syndrome whose symptoms include weakness, unintentional weight loss, and exhaustion, by 24 percent.

Within our lifetimes, it’s possible that metformin, rapamycin or one of the many other aging antidotes in development will be widely prescribed to prevent aging and extend vitality in old age. In the meantime, researchers are also waging war against aging on a different front – by targeting senescent cells, or as they’re also known; zombie cells.

"},{"id":"60337a016cee070007cf180f","title":"To fight aging, first get rid of your zombie cells.","text":"

Over time, our cells can become senescent: their DNA is damaged, and they lose the information they need to replicate. Even worse, the build-up of senescent cells kicks the aging process into overdrive. What’s more, although senescent cells are no longer functional, they’re also not exactly dead. Rather than quietly fading away, they can send out panic signals, signalling a false “state of emergency.” This causes the cells around them to senesce as well, speeding the aging process further. As they signal, these zombie cells also release cytokine, a form of protein that causes inflammation – and inflammation is at the root of many age-related ailments, such as heart disease and dementia.

There are lots of ways that DNA can become damaged. One way, according to anatomist Leonard Hayflick, is through the shortening of its telomeres, which are protective caps wrapped around the end of each cell’s DNA sequence. Observing the division of human cells, Hayflick found that as they divided their telomeres grew shorter, eventually exposing the DNA strand.

Once the DNA strand is exposed, two things can happen. The cell can read this as a break in the DNA chain and work to repair it by fusing the broken chain together again. The problem is that when DNA is incorrectly re-fused it causes the cell to turn cancerous. Alternatively, the epigenome, the complex system of chemical compounds and proteins that regulates our genes can kick into action. It can signal for our sirtuins to shut the cell down altogether. This prevents the formation of cancerous cells but also directly causes a build up of senescent zombie cells.

What’s the solution to this plague of zombie cells? It’s complicated. We need to terminate the senescent cells without damaging the remainder of our delicate cellular ecosystems. Senolytics, an emergent class of pharmaceuticals, might be up to the task.

Senolytics are drugs intended to target senescent cells specifically for termination. Researchers at the Mayo Clinic have already trialled two forms of senolytic molecules on mice – quercetin, a molecule found in kale, capers and red onions, and dasatinib, commonly used in chemotherapy. Mice treated with senolytics enjoy, on average, a 36 percent increase in their lifespan. While these results are far from conclusive they are incredibly promising, and the potential for senolytics to combat aging in humans is immense.

"},{"id":"60337a016cee070007cf1810","title":"There is an aging reset button!","text":"

In 1996, when Dolly the sheep was cloned from a single adult sheep cell, the world looked on in amazement. For some scientists, however, the most amazing thing about Dolly was the cell from which she had been cloned.

Dolly had been created from an older sheep’s cells. That meant that old cells had the potential to produce young cells – that even old DNA retains a blueprint for youth. If youth is encoded in our DNA, can we turn back the clock and hit the reset button on aging? Potentially, yes.

As we’ve seen, aging occurs through the loss of information at a cellular level. That loss of information can be dramatic. In fact, scientists estimate that over our lifetimes, we’ll lose 80 percent of our original cellular information!

Thanks to experiments in cloning, we now also know that not only is this original information locked somewhere inside our DNA, it can also potentially be unlocked. Japanese scientist Shinya Yamanaka may have already discovered the key.

Yamanaka has isolated four genes that can be induced to transform into pluripotent stem cells, or young cells that haven’t yet been assigned a function by the epigenome. These four genes, now known as Yamanaka factors, can be reset to perform any function in the body – and researchers at Harvard say they’ve already seen promising results from reprogramming Yamanaka genes in mice.

What will life look like if we successfully manage to reprogram these genes in humans? Well, potentially, we’d be injected with a “virus” containing the Yamanaka factors some time in our thirties. The virus would lie dormant until our forties, when we’d get another injection, this one containing a molecule like doxycycline, which would activate the Yamanaka factors to start reprogramming our cells.

We’d repeat the process cyclically, in our sixties, in our eighties, and potentially to well past the age of 100. Which poses another question: How will the world be impacted when the average lifespan stretches to well over a century?

"},{"id":"60337a016cee070007cf1811","title":"An aging population might be a good thing.","text":"

According to the book The 100 Year Life, by L. Gratton and A. Scott, half of the children born in Japan in 2019 will live to the age of 107. Similarly, half of children born in the United States in 2019 will live to 104. And, as scientists come ever closer to curing the disease of aging, our longevity prognosis is steadily improving. With every month we survive, we add a week onto our lifespans.

But what will the world look like when human beings routinely live for over a century?

We already have an aging population. And people past retirement age are costly. They no longer contribute to GDP through work, and their health care and social benefits costs are increasingly expensive.

Surely, a greater proportion of humans living for a longer period of time would put further strain on an already overburdened world? Actually, it all comes down to how our lifespans are extended. If we can not only prolong life but also cure the disease of aging, our future prospects look far sunnier.

Economists at the University of Southern California have suggested that, because deferred aging would mean people being able to continue working and contributing to the GDP for longer than ever before, the United States alone could stand to profit by up to $7 trillion by 2069! This makes sense, as a 2009 EU report has already shown that countries with lower retirement ages have lower GDPs.

When people are able to work longer, their spending power becomes greater too. After retirement, people tend to spend less and make fewer large investments. With prolonged lifespans and enhanced vitality, potentially trillions of dollars in untouched retirement savings will be unlocked and injected into the economy.

Curing aging will certainly boost the global economy. But the benefits don’t stop there. As a society, we’ll all be in a position to lead more vital, productive, healthy and happy lives. Once we’ve fully grasped the positive effects that eradicating the disease of aging will bring, perhaps we’ll join leading geneticists in wholeheartedly pursuing its cure.

"},{"id":"60337a016cee070007cf1812","title":"Final summary","text":"

The key message in these blinks:

If we want to live longer, healthier and better lives, it’s vital that we reframe our approach to aging. Aging isn’t a fact of life, it’s a disease that has the potential both to be understood and to be cured. Genetics researchers are coming ever closer to turning back the clock on the aging process; we might be on the cusp of a world in which aging is eradicated and people live longer than ever before.

Actionable advice:

Hit the gym!

Through fasting, long-lived residents of Blue Zones reach a cellular state of “desirable stress” when their longevity genes are activated without going into overdrive. But fasting isn’t the only way to activate these genes. Regular exercise produces a similar effect. So, get active! An hour at the gym now could add weeks to your life later.

Got feedback?

We’d sure love to hear what you think about our content! Just drop an email to remember@blinkist.com with the title of this book as the subject line and share your thoughts!

What to read next: The Telomere Effect, by Elizabeth Blackburn and Elissa Epel.

In these blinks you’ve learned why aging happens and how we might counteract it, so why not zoom in further on the biological processes that underpin aging? The Telomere Effect, by Nobel-prize winning physician Dr. Elizabeth Blackburn and acclaimed health psychologist Dr Elissa Epel, puts telomeres under the microscope. The blinks to this book unpack in detail what telomeres are, how they can indicate our biological age, and how, though lengthening our telomeres, we might be able to extend our lifespans, too!

"}]}

Log in to Blinkist

Sign up for Blinkist

Learn more, live more