Lifespan. Dr David A. Sinclair

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Lifespan - Dr David A. Sinclair


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a company will succeed in making a vaccine that prevents LINE-1 infections. New generations who are vaccinated at birth will live fifty years longer than their parents did—it will turn out that that’s our natural lifespan and we had no idea. The new generation of healthy humans will pity previous generations, who blindly accepted that physical decline at 50 was natural and an 80-year life was a life well lived.

      Of course, this is a science fiction story I just invented. But it might be truer than you think.

      A few recent studies have suggested that the so-called selfish genes we all carry in our genome, actually called LINE-1 elements, replicate and cause cellular havoc as we get older, accelerating our physical demise. We’ll discuss them in more detail later, but for now, it’s the idea I want to focus on because it raises important questions: Does it matter whether LINE-1 comes from your parents directly or via a virus? Would you want to eradicate LINE-1 from humanity or let it grow in your kids and inflict horrible diseases on them? Would you say that LINE-1 causes a disease or not?

      If not, is it simply because more than half of all people carry it?

      Whether it’s a virus, a selfish DNA element, or simply the makeup of our cells that causes these health problems, what’s the difference? The end result is the same.

      The belief that aging is a natural process is deep-rooted. So even if I’ve somewhat convinced you that aging should be considered a disease, let’s do another thought experiment.

      Imagine that everyone on our planet typically lives to 150 years in good health. Your family, though, doesn’t. You become wrinkled, gray-haired, diabetic, and frail at 80. Upon seeing these poor, unfortunate souls in this poor, unfortunate state of existence, what doctor would not diagnose your family with a disease, name it after him- or herself, and publish horrid photos of you with your eyes blacked out in medical journals? Communities would raise money to understand and find a cure for your family’s wretched inheritance.

      That was exactly what happened when the German physician Otto Werner first described a condition that causes people to look and feel as though they are 80 when they are in their 40s. That’s Werner syndrome, the disease I was studying when I first arrived at MIT in the 1990s. Nobody said I was studying something that is inevitable or irreversible. Nobody said it was crazy to call Werner syndrome a disease or to work to find a breakthrough therapy. Nobody told me or the Werner patients that “that’s just the way it goes.”

      In front of us is the deadliest and costliest disease on the planet, a disease that almost no one is working on. It is as if the planet is in a stupor. If your first thought is “But I don’t want to live past 90,” let me assure you: I don’t want you to live a year longer than you wish.

      But before you make your decision, let’s do one final thought experiment.

      Imagine that a clerk at City Hall has found a mistake on your birth certificate. It turns out that you are actually 92 years old.

      “You’ll get a new one in the mail,” the clerk says. “Have a nice day.”

      Do you feel any different now that you are 92? Nothing else has changed in your life—just a few numbers on your identification. Do you suddenly want to kill yourself?

      Of course not. When we stay healthy and vibrant, as long as we feel young physically and mentally, our age doesn’t matter. That’s true whether you are 32, 52, or 92. Most middle-aged and older adults in the United States report feeling ten to twenty years younger than their age, because they still feel healthy. And feeling younger than your age predicts lower mortality and better cognitive abilities later in life.22 It’s a virtuous cycle, as long as you keep pedaling.

      But no matter how you feel at this moment in your life, even with a positive outlook and a healthy lifestyle, you have a disease. And it’s going to catch up to you, sooner rather than later, unless something is done.

      I acknowledge that calling aging a disease is a radical departure from the mainstream view of health and well-being, which has established an array of medical interventions addressing the various causes of death. That framework evolved, however, largely because we didn’t understand why aging occurs. Up until very recently, the best thing we had was a list of aging hallmarks. The Information Theory of Aging could change that.

      There is nothing wrong with using the hallmarks to guide interventions. We can probably have a positive impact on people’s lives by addressing each of them. It’s possible that interventions aimed at slowing telomere deterioration will improve people’s long-term well-being. Maintaining proteostasis, preventing deregulation of nutrient sensing, thwarting mitochondrial dysfunction, stopping senescence, rejuvenating stem cells, and decreasing inflammation might all be ways to delay the inevitable. Indeed, I work with students, postdocs, and companies around the globe that are developing solutions to each one of these hallmarks and hope to continue.23 Anything we can do to alleviate suffering we should do.

      But we’re still building nine dams on nine tributaries.

      In coming together to tackle the “new science of aging,” as the attendees of the Royal Society meeting termed this fight in their 2010 meeting, increasing numbers of scientists are starting to acknowledge the possibility and potential inherent in heading upstream.

      Together we can build a single dam—at the source. Not just intervene when things go wrong. Not just slow things down. We can eliminate the symptoms of aging altogether.

      This disease is treatable.

       PART II

       WHAT WE’RE LEARNING

       (THE PRESENT)

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