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Pirates of the Caribbean, the once youthful franchise, isn't as vibrant as it once was. While The Curse of the Black Pearl was a verifiable pop culture moment, the sequels have seen diminishing returns both in the zeitgeist and at the box office.
It is perhaps appropriate that just as the series was showing signs of its age, the fourth film, On Stranger Tides, which turns 10 this week, dealt with the pursuit of everlasting life. Jack (that's Captain Jack Sparrow to you) is tasked with leading an expedition to find Juan Ponce de León's famed Fountain of Youth.
While Jack's expedition is successful in locating the fountain, real-life pursuits for the mythic spring have only met with failure. Science, however, just might succeed where legend has failed.
THE BIOLOGICAL CLOCK
We all know that our genome is what defines how our bodies are built and how they behave. Sure, there are environmental factors that impact things like personality, but the physical reality of who we are is entirely dependent on our DNA, right? Not exactly.
You can think of your genome as a set of written instructions. Those instructions remain more or less the same throughout your life, regardless of experience or environmental factors. But that doesn't mean they're always expressed in the same way. If you imagine your genome as a book, that book can hit bookshelves in myriad ways. It can be printed in hardcover or paperback and there are font sizes, typefaces, margins, and the color and texture of the paper to consider. None of these change the content of the text — the story remains the same — but they do change the way it's experienced.
The same sort of thing is happening inside your body, and those variations are known as epigenetics. What you eat, how much you exercise, exposure to the Sun, and more, all of these things impact the way your genes express themselves and those changes have an impact on how your body ages.
Each of us makes decisions every day that change the way our genes express, and it's nearly impossible to know what epigenetic impact those decisions have, while they're happening. There is, of course, no scientific control against which we can compare those choices. Luckily, there is research to which we can refer.
In 2015, NASA selected twins Mark and Scott Kelly to participate in a year-long experiment to measure the influence of long-term space travel. Scott was sent to the International Space Station, where he lived from March 27, 2015, until March 1, 2016. Meanwhile, his twin brother, Mark, remained on Earth. The Kellys, being genetically identical, served as both experimental and control test subjects, and researchers were able to study the way differing environments impacted the bodies of genetically identical people. And they found a number of factors that impact aging.
There were changes in Scott's telomeres, the protective caps at the end of DNA strands. Surprisingly, these actually extended while Scott was in space, indicating a relative reduction in the aging process. Importantly, the telomeres returned to normal upon Scott's return to Earth, but it does indicate an environmental epigenetic influence.
Likewise, researchers observed a number of variations in genetic expression as a result of Scott's time in space, but the vast majority of them also reverted back to "normal" expression once the mission was over.
These findings tell us a couple of important things. First, environmental and behavioral variations do impact the way our genes are expressed. Second, those variations can be reversed when our environment or behaviors are altered.
All told, we're not entirely certain what causes aging, but we've learned that aging is a process amenable to influence. Your biological clock marches ever onward, but the spaces between ticks are dependent, at least in part, by environmental and behavioral variables.
TURNING BACK THE CLOCK
The mythic Fountain of Youth offered waters which, if ingested or bathed in, would turn entropy on its head, restoring you to a more youthful version of yourself. Almost without exception, single cells and more complex organisms experience senescence, the process by which function is lost over time. It's the reason our bodies weaken and become more susceptible to disease. Our cells don't die, but they stop dividing and growing.
There are some species who don't experience senescence, at least not in the same way we do. A lot has been made about the so-called immortal jellyfish. While they can still fall victim to disease or predation, they have the potentially unique ability to revert to an early stage in their lifecycle. These jellies begin life as a polyp before maturing into what we would normally consider a jellyfish. Under certain circumstances, however, they are capable of turning back the proverbial clock and returning to the polyp stage before maturing again.
It's the brainless invertebrate equivalent of deciding that being an adult is too tough and winding back to before puberty to give it another go.
Lobsters have a similar, albeit different, relationship with biological aging. A popular bit of internet trivia made the rounds several years ago, claiming that lobsters could, if left uninterrupted, live forever. It's the sort of story which hits a little harder because, unlike jellyfish, lobsters often find themselves on the dinner menu. Eating any animal comes with a certain level of guilt, but it gets turned up to eleven if the life you ended could have gone on forever.
Fortunately for you, and unfortunately for the lobster, it isn't true. At least not wholly. Lobsters don't experience senescence in the ordinary sense. They have indeterminate growth, meaning they continue growing as long as they live. They also keep reproducing. Unlike humans and most other animals, there seems to be no moment in a lobster's life when its body dusts off its hands and calls it a day.
Still, lobsters do have a natural end. Even if they avoid predation or disease, their bodies won't go on forever. In order to accommodate the continual growth, lobsters have to molt. This process not only leaves lobsters vulnerable, but it also takes up a lot of energy. At a certain point in their lives (we're not quite sure precisely when that is) the energy needed to molt exceeds what the lobster is capable of. Their soft internal bodies keep growing, but the hard exoskeleton remains the same. The lobster is stuck and dies as a result. A pretty gruesome way to go.
Jellyfish and lobsters are pretty distant from us on the evolutionary tree, but they do provide some evidence that senescence isn't an absolutely necessary process, despite its almost near-ubiquity.
Researchers are working to identify the processes that cause aging in humans and reverse them. Building on the epigenetic hypothesis of aging, scientists at the Salk Institute for Biological Studies activated four genes known as Yamanaka factors.
Yamanaka factors are most commonly used in converting adult cells, like skin cells, to pluripotent stem cells. However, in this study, Juan Carlos Izpisua Belmonte and his colleagues activated the factors temporarily to measure the impact on aging in mice. In doing so, they were able to heal injuries and extend lifespan by 30 percent.
The ultimate goal here is to extend the years for which a person is healthy — a period known as the healthspan, which is an important distinction. Most of us would like to live longer, but we want those years to be fruitful. Some scientists believe this research could not only be applied to humans but might also be capable of reversing aging, not just delaying it. But there are risks. In the same study, if the Yamanaka factors were left activated too long or too often, tumors developed. The mice died within a week, proving the old adage about too much of a good thing.
Science and technology have already extended the average human lifespan considerably, and there is reason to believe those incremental improvements in longevity will continue. But we should all be wary of hitching our wagons to another Fountain of Youth, even one based on scientific research.