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article imageIs aging a disease that can be cured? Special

By Les Horvitz     Oct 18, 2017 in Science
New York - The oldest person that we know of lived to be 122 years old. Is that the limit? Is aging a disease that can be conquered and reversed? Scientists think it may be possible – and sooner than we think.
At a gathering at The New Yorker’s TechFest in early October, Bill Maris , a venture capitalist involved in aging research, and Thomas Rando, a professor of neurology at Stanford University acknowledged that the study of aging is a tricky business – and it’s relatively new.
“This wasn’t considered a serious science,” Marris said, “I tried to raise money. It was of interest to individuals who liked to think outside of the box. Most traditional investors weren’t interested. They’d ask what’s the product? How do we make money out of it?” Ultimately, it was Google Ventures which came to the rescue, leading to the creation of the Calico project (short for California Life Company), a multibillion-dollar life-extension company dedicated to the study of aging and age-related diseases. Most longevity scientists consider themselves healthspanners, not immortalists. In other words, they’re seeking ways to give us a longer, healthier life and a quick, painless death (“compressed morbidity” is the term they use for it) rather than trying to make us all into Methuselahs.
Calico has its share of detractors. One of them is geneticist Nir Barzilai who specializes in aging. “’The truth is, we don’t know what they’re doing, but whatever it is doesn’t really seem to be attacking the problem,’” he told Tad Friend in a New Yorker articleabout Silicon Valley’s efforts to make aging obsolete. Another scientist quoted in the same article was even more derisive: “’This is as self-serving as the Medici building a Renaissance chapel in Italy, but with a little extra Silicon Valley narcissism thrown in. It’s based on the frustration of many successful rich people that life is too short: ‘We have all this money, but we only get to live a normal life span.’”
If you’re trying to cure cancer or diabetes you know more or less what you’re up against. That’s not true when it comes to aging. Is aging a disease? “It goes back to fundamental science,” Marris said, “We don’t have a computer model. We don’t have models for aging. If we don’t have a model how can we study the problem?” Rando believes that eventually that model will come into focus.
“The fundamental question is what aging is. What is the convergence point for telomeres, caloric restriction, etc. – pharmacological, dietary – where people age with fewer diseases? We still don’t have a unified theory. These interventions converge somewhere but we still don’t know where it is.” (Telomeres are the nucleotide sequences at each end of a chromosome; as we age, telomeres grow shorter, leading many researchers to think that that shortening may be a key to aging and disease formation.) “You can’t give a number to aging,” Marris said, “There’s no quantitative measure. How can we treat something we don’t know?”
For argument’s sake, let’s say that aging is a disease. Even then, it would be a mistake to think that scientists could target it like other diseases. “Some cancers you can flip a few genes and cure them,” says Rando, “You can’t do that with aging.” There are so many factors involved – not only genetic, but also epigenetic (the environmental effects on genes which vary from individual to individual) – that scientists are unlikely to make a big breakthrough. Progress is probably going to be incremental.
While there’s no consensus among experts about whether aging is a disease at all, there’s no question that aging can make people more susceptible to diseases. “So if we can target aging we may be able to target these diseases,” Rando said.
After 45, cancer is the leading cause of disease; after 65, it’s heart disease. But the dilemma for the so-called healthspanners is that even if we cured cancer, say, we’d only extend human life span an average of 3.3 years. Curing heart disease would give us an extra four, which, while definitely a worthwhile goal, isn’t going to turn us into vigorous centenarians. Most gains in lifespan that we have achieved have come from lowering child mortality rates thanks to antibiotics and improved sanitary conditions. It’s the other end of the spectrum that’s difficult to change. Is 122 years where life draws the line? “To live longer, we’d have to slow aging itself,” declared one writer.
It would be helpful, of course, to have a drug that acted on the aging process and then wait and see how effective it is in three months or a year, says Rando, but we don’t have such a drug, and even if we did, it would be unethical to try it out on humans without having any idea what its long-term effects might be. That’s why, for the time being, Rando is limiting experiments to mice. In his lab Rando and his team are exploring how muscle stem cells age and how these cells restore and repair themselves.
“Can you reprogram an old cell into a younger cell?” His team has carried out some promising experiments. “In (experimental) mice, cells seem to be getting younger. They don’t just look younger. So we may be able to get a handle on that.” Of course, what may work with mice may not be applicable to humans even though we have many genes in common.
Not long ago, it was believed that once a stem cell turned into a liver cell or a skin cell – once it was differentiated – it was fixed.
“Cells go from undifferentiated to differentiated, from young to old,” Marris says, “Can we move the clock far back? But how far back?” And can scientists reverse one without the other – retard the aging in cells rather than try to transform them back into stem cells? No one knows.
Says Rando: “Development happens in a sequence. Aging is much more stochastic (random). I would argue that it’s a system failure. Until the point of reproduction, evolution doesn’t care what happens to the body. We’re discovering what the body does after a hundred years. It falls apart.” So are scientists engaged in a quixotic venture, fighting against millions of years of mammalian evolution?
On the other hand, maybe evolution holds the secret to rejuvenation. We all owe our existence to the fortuitous union of a sperm cell and an egg. “They arose from humans that have decades between them,” Rando points out, “but you put them together and you have a cell that is age zero. If this didn’t happen we’d age ourselves into extinction.” In Rando’s words, “There’s all this regenerative potential in the body.” The problem is how to identify the mechanism and exploit it.
Scientists talk of ‘escape velocity’ -- can we get younger faster than we get older?
How long do scientists believe that it will take to reach escape velocity? “I don’t think it’s a hundred years in the future,” Rando says, citing the transformative innovations of the last century like computers, the Internet and antibiotics, “I think it’ll happen in our children’s lifetime.”
Both Rando and Maris are dismissive of other alternative anti-aging approaches like the idea of Singularity championed by futurist Ray Kurzweil who envisions a merger of human and artificial intelligence to transcend biological limitations.
“What if we could upload ourselves?” Rando asks, referring to the concept of transferring all our thoughts, memories and feelings from our brain into some kind of avatar, for instance. “What does that even mean? What we’re really trying to do is help people and try to keep them from getting sick. I don’t recommend that they try an avatar. The focus I find more appealing is regenerative biology, not the transplantation of consciousness.”
Nor do the two men give much credence to cryogenics where corpses (or at least their heads) are frozen until some time in the distant future when the diseases they succumbed to can be cured and they can be resurrected, presumably as good as new. Maris and Rando can, however, understand the appeal that cryogenics has for some individuals.
“If you’re on a plane and it’s going to crash and there’s a parachute and there’s a small chance that it’ll work, most people would take the shot,” Rando says. But he offers a caveat: when you’re in a plane you at least have an idea what’s below you. “With a frozen brain you don’t know where you’ll land.”
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