Category: News

The elixir of longevity: scientists find a method to prolong life.

American researchers from the Baylor University of Medicine and the Health Center of the University of Houston (Texas, USA) said they had found a method to lengthen the life of human beings. The study carried out by the specialists has been published in the journal Cell.

Through a system based on the use of intestinal flora, scientists have already determined which are the strains of microorganisms that prevent the accumulation of beta-amyloids, molecules formed by the union of several amino acids and linked to the development of Alzheimer’s. . Likewise, they have managed to slow the growth of malignant tumors also with the use of bacteria.

“We are increasingly aware that the interaction of our organism with millions of microbes influences many processes, such as metabolic activity and aging,” said Meng Wang, one of those responsible for the study.

During the investigations, the specialists carried out experiments in nematodes (Caenorhabditis elegans), commonly known as roundworms.
“We introduced the bacteria into primitive organisms and then we analyzed the life span of the worms.” Of about 4,000 bacterial genes that were subjected to experiments, the elimination of 29 turned out to have a positive effect on the longevity of the nematodes. The bacteria also protected the worms from tumor growth and the accumulation of beta-amyloid, closely linked to Alzheimer’s disease in humans, “the scientist added.

Based on the results of the study, the researchers determine that it is possible to create medicines that contain intestinal flora that slows aging.

A artiche of:

The Man Who Would Stop Time

Bill Andrews has spent two decades unlocking the molecular mechanisms of aging. His mission: to extend the human life span to 150 years–or die trying

By Joseph Hooper

A article of;

Bill Andrews’s feet are so large, he tells me, that back when he was 20 he was able to break the Southern California barefoot-waterskiing distance record the first time he put skin to water. Then he got ambitious and went for the world speed record. When the towrope broke at 80 mph, he says, “they pulled me out of the water on a stretcher.”

The soles of the size-15 New Balances that today shelter those impressive feet strike a steady clap-clap on the macadam as Andrews and I lope down a path along the Truckee River that takes us away from the clutter of cut-rate casino hotels, strip malls and highway exit ramps that is downtown Reno, Nevada. Andrews, 59, is a lean 6-foot-3 and wears a close-cropped salt-and-pepper Vandyke and, for today’s outing, a silver running jacket, nicely completing a package that suggests a Right Stuff–era astronaut. He is in fact one of the better ultramarathoners in America. I am an out-of-shape former occasional runner, so it gives me pause to listen as Andrews describes his racing exploits. “I can run 100 miles, finish, turn around, and meet friends of mine on the course who are still coming in,” he says. “I’ve been in many races where I’m stepping over bodies of people who have collapsed, and I’m feeling great.”

“I want to cure my aging, my friends’ and family’s aging, my investors’ aging, and I want to make a ton of money,” Andrews says.His return to running after a middle-aged break was, he says, inspired by a revelation he had at a time when he and a small team of scientists at his biotech start-up, Sierra Sciences, had been working 14 to 18 hours a day in the lab for five years, rather obsessively pursuing a particular breakthrough. Finally, his doctor told him he was headed for an early grave. “I thought, god, I don’t want to cure aging and then drop dead,” Andrews says.

That would indeed be ironic. Because Andrews does intend to cure aging. This stated ambition induces in some listeners the suspicion that Andrews might suffer from delusions of grandeur, but he has a scientific pedigree that insists he be taken seriously. Unlike his friend Aubrey de Grey, the University of Cambridge longevity theorist who relentlessly generates media attention with speculations that straddle the border between science and science fiction, Andrews is an actual research scientist, a top-drawer molecular biologist.

In the 1990s, as the director of molecular biology at the Bay Area biotech firm Geron, Andrews helped lead a team of researchers that, in alliance with a lab at the University of Colorado, just barely beat out the Massachusetts Institute of Technology in a furious, near-decade-long race to identify the human telomerase gene. That this basic science took on the trappings of a frenzied Great Race is a testament to the biological preciousness of telomerase, an enzyme that maintains the ends of our cells’ chromosomes, called telomeres. Telomeres get shorter each time a cell divides, and when they get too short the cell can no longer make fresh copies of itself. If we live long enough, the tissues and organ systems that depend on continued cell replication begin to falter: The skin sags, the internal organs grow slack, the immune-system response weakens such that the next chest cold could be our last. But what if we could induce our bodies to express more telomerase? We’ll see, because that is what Andrews intends to do.

Andrews had scheduled this afternoon’s run as an 18-miler, but he graciously downscaled those ambitions on my behalf long before we set out from the parking lot of the Grand Sierra Resort Hotel. Four miles in, he’s hardly winded—and I’m out of gas. As we make our way back to his car, he consults his training watch and informs me that our pace was an almost respectable 8:40, excepting the latter stretches when I walked, pushing our average up to 10 minutes a mile.

The embrace of fitness has for Andrews a telomeric logic. Make poor lifestyle choices, and you’re likely to die of heart disease or cancer or something well before your telomeres would otherwise become life-threateningly short. But for the aerobicized Andrews, for anyone who takes reasonable care of himself, a drug that activates telomerase might slow down the baseline rate at which the body falls apart. Andrews likens the underlying causes of aging, free radicals and the rest, to sticks of dynamite, with truncated telomeres being the stick with the shortest fuse. “I believe there’s a really good chance that if we defuse that stick,” he says, “and the person doesn’t smoke and doesn’t get obese, it wouldn’t be surprising if they lived to be 150 years old. That means they’re going to have 50 more years to be around when somebody solves the other aging problems.”

Check out our brief history of immortality, from antiquity up to the 21st century.

But in his race to cure aging, Andrews may himself be running out of time. The stock-market crash of 2008 nearly wiped out two investors who had until then been his primary funders. Without the money to continue refining the nearly 40 telomerase-activating chemicals he and his team had already discovered, Andrews made the decision last September to cut a deal with John W. Anderson, the founder of Isagenix, an Arizona-based “network marketing” supplement company. This month, Isagenix will launch an anti-aging product containing several natural compounds that Sierra Sciences has verified to have “telomere-supporting” properties. It’s not the powerful drug Andrews originally envisioned, but he says he believes it will promote “health and well-being” and just possibly generate enough cash to underwrite the expensive “medicinal chemistry” required to come up with a more fully developed anti-aging compound—one attractive enough to bring in a billionaire or a Big Pharma partner with pockets deep enough to take a drug candidate through the FDA’s time-consuming and fabulously expensive approval process.

“I want to cure my aging,” Andrews tells me, “my friends’ and family’s aging, my investors’ aging, their friends’ and families’ aging, and make a ton of money. And I want to cure everybody else’s aging too—I put that probably equal to making a ton of money.”

Doctors tend to look at bodily decline through the prism of so-called diseases of aging, our increasing susceptibility over time to killers like cancer and heart disease. But in the 1950s, research biologists began to view aging itself as the disease. When free radicals scavenge electrons from their neighbors, they set in motion some ugly chain reactions. Cholesterol molecules become oxidized and begin to interact with the artery walls to form atherosclerosis-causing plaque, for instance, or the DNA in the cell nucleus suffers mutations, laying the groundwork for cancer. Later refinements of this theory emphasize the role of the mitochondria, the cellular power plants that help convert glucose into energy. As the mitochondria age, they spew out increasing amounts of the free radicals that hamper energy production and damage the entire cell, accelerating our all-systems decline.

Among cell biologists, these mechanisms remain to this day the most accepted ways of explaining what’s happening to that face reflecting back at us in our bathroom mirror. But telomere science has opened up the possibility of drilling even deeper into the molecular bedrock of aging. The fledgling field was energized in 1984, when biochemist Elizabeth Blackburn of the University of California at Berkeley and her then-grad student Carol Greider discovered the telomerase enzyme in a pond-scum protozoan, an achievement that won them a Nobel Prize. Since then, our picture of human telomeres and telomerase has sharpened considerably.

“A magic pill?” says Nobel Prize winner Elizabeth Blackburn. “I think we’ve been there about a million times before.”Telomeres are made of repeating sequences of six DNA bases—two thymine, one adenine, three guanine (TTAGGG)—that serve to “cap” chromosomes, preventing potentially cancerous breaks; the analogy usually trotted out is the plastic aglet that prevents a shoelace from fraying at the ends. Telomeres also assist cell division. Every time a cell splits, the ends of its chromosomes fail to get fully copied in the two new daughter cells, and a bit of telomeric DNA gets lost. No harm is done to the rest of the chromosome, but in cells that divide frequently, the telomeres shorten with each replication. Telomerase’s job is to synthesize new DNA to add to the shrinking telomeres, slowing down the decline.

Human life, it turns out, is a losing effort to hang on to our telomeres. At conception, telomeres have roughly 15,000 DNA base pairs. Because telomerase can’t keep up with rapid cell division in utero, they shrink to about 10,000 base pairs at birth. At that point, the telomerase gene is mostly turned off. Without the enzyme, we continue to lose telomeric DNA—once we’re out of our teens, usually at a rate of 50 base pairs a year. By the time some of our telomeres drop below about 5,000 base pairs, typically well into our “golden” years, our cells may have lost the ability to divide. They become senescent, bad at doing the work they were designed to do but good at doing things like releasing inflammatory chemicals that harm their neighbors. Or they may be targeted for cell death.

Andrews sounds almost giddy when he describes the “aha” moment 20 years ago when he first heard his soon-to-be boss at Geron, pioneering telomere biologist Calvin Harley, lecture about telomeres as a “mitotic clock,” in which the steady shortening of the telomeres serves as the tick-tock of the aging cell. “I was floored,” Andrews says. He found the lockstep precision suggested by the metaphor irresistible.

Cultured in the lab, cells can divide just 50 to 70 times before packing it in (this is known as the Hayflick Limit, after longevity-research eminence Leonard Hayflick, who discovered the phenomenon). The human body is significantly more complex than a petri dish, but some similar limit must be enforced there, Andrews says, to account for the fact that the maximum human life span is so tightly regulated, with the longest-lived humans making it to 100 and, to the best of our knowledge, nobody surviving past 125. If free-radical damage were really the primary driver of aging, he says, people’s rate of bodily decline would vary widely based on the amount of environmental damage they had absorbed, a major contributor to the free-radical load, and therefore so would their maximum life span. “But you can look at a person and have a 95 percent chance of guessing their age within five years,” he says. “There has to be some kind of internal clock ticking inside of us.”

Biologists continue to debate the extent to which aging at the cell level determines the aging of the whole organism. Most have argued that short or damaged telomeres aren’t as big a deal as Andrews, or even the more measured Harley, make them out to be. Tissues and organ systems that depend on cell division have a fair amount of reserve capacity, and the cells that seem to play the biggest role in our decline, neurons and heart-muscle cells, hardly replicate at all.

But over the past few years, the case for telomeres as a major player in aging, possibly even the prime mover, has grown stronger. Heart health, telomere biologists point out, depends heavily on the endothelial cells that line the blood vessels, and brain health on the glial and schwann cells that make the myelin that protects neurons, all of which are cell types that hear the ticking of the mitotic clock. And last year, Harvard University researcher Ron DePinho published two studies in the journal Nature that have reframed the debate about telomerase activation. DePinho created an ingenious model whereby he could turn telomerase off in a mouse and then restore it, simply by administering, or withholding, a synthetic estrogen drug. In the first study, the mice with turned-off telomerase exhibited signs and symptoms of decrepitude akin to what we might endure at the age of 80 or 90: wrinkled skin, sluggish intestines, shrunken brain. When telomerase production was turned back on, the tissues rejuvenated within a month.

“We treated these animals that were the equivalent of your grandmother,” DePinho says, “and they became like young adults.” He says he had expected to be able to stop or slow down the rate of aging. What he found was the proof-of-concept that living tissue could actually go back in time. (When Andrews talks about the possibility of running a seven-minute mile at the age of 130, he’s got the Harvard mice for backup.)

The second Nature paper was DePinho’s attempt at developing a unified theory of late-life aging, “the death spiral,” as he calls it, that can transform a spry, alert 80-year-old into a shell of herself at 90 or 100 even in the absence of diagnosable disease. His mice data suggest that the major aging processes—free-radical damage, mitochondrial dysfunction, and short or damaged telomeres—interrelate and that the telomeres can instigate decline, acting as the first domino that sets in motion the rest. If the telomeres can be preserved, the entire system may be granted at least a temporary reprieve.

DePinho says he envisions more animal-model research leading to human clinical trials leading—years or, more likely, decades down the road—to FDA-approved drugs. The high-speed, low-rent workaround of a telomerase-activating supplement beyond the reach of the FDA doesn’t please him. “Even if you did get telomerase activity,” he says, “you sure as hell would want to know where and when to turn it on. Telomerase can be deleterious as well.” Elizabeth Blackburn, now at the University of California at San Francisco, has reservations about a good-for-what-ails-you supplement. “A magic pill?” she says. “I think we’ve been there about a million times before in human history.”

Sierra Sciences operates out of a small, dun-colored office park near downtown Reno. From the outside, it could be mistaken for a Sun Belt Staples, but inside are touches that speak to Andrews’s specific history and sense of mission. He walks me into a conference room decorated with plaques commemorating U.S. patents issued, and a whiteboard with an “Aging Sucks” bumper sticker plastered on it. “Dad sent that,” Andrews says, identifying the handiwork of Ralph Andrews, a retired Los Angeles game-show producer (his biggest hit was You Don’t Say!, which ruled the daytime airwaves in the 1960s). For reasons Andrews can’t adequately explain, his father, still hale at 84, has always been dead set against aging, and once suggested to his preteen son that he might want to take a shot at solving the problem. “My dad probably told me to do a lot of things, but this just struck a chord,” he says. “I never thought aging was inevitable. I just thought nobody had figured it out yet.”

In the late ’90s, Andrews came to feel that Geron had lost the true telomerase-activating religion, having redirected most of its resources into stem-cell therapies. He left Geron, crossed the Sierras, and in 1999 gathered around him in the Nevada desert a small circle of researchers who believed almost as ardently as he that it might be possible to engineer a “small molecule” drug that would flip the telomerase gene’s “on” switch inside a living human body. Since then, the company has gone through two distinct phases, pre-crash and post-crash. In the first era, two especially beneficent investors unquestioningly underwrote his efforts to crack the telomerase code. (Start-ups working on an actual product in development attract venture capitalists. More-speculative ventures like Sierra Sciences typically draw individual “angels”—in the anti-aging field, often older, wealthy men willing to risk losing money in the hopes that somebody will come up with a way to extend their fruitful lives.)

During this first phase, Andrews and his team deployed an elegant recombinant DNA approach, arguably better suited to an academic lab than a start-up that needed marketable results. They would painstakingly alter one or two DNA bases out of the thousands that make up the telomerase gene, cycling through thousands of slight variations in an effort to find one that the regulatory molecule that normally keeps the gene turned off, the “repressor,” would no longer recognize. This would reveal the molecular identity of the repressor, and the team could then create a drug to neutralize it—repressing the repressor and switching the telomerase gene back on.

By 2006, after seven years of effort and one excruciatingly close miss (they found “a” repressor but apparently not “the” repressor), Andrews finally shifted strategies. If developing a telomerase-activating drug with recombinant-DNA methods was a bit like trying to find a needle in the haystack by analyzing the haystack molecule by molecule, the new approach was brute force: Grab a pitchfork and start digging. The company bought libraries of several hundred thousand chemical compounds and tested each one to see if it would activate telomerase in cultured human cells.

The cells Andrews chose were fibroblasts, which are found in skin and connective tissue and which are relatively cheap and easy to culture. They also have little ability to express telomerase in a lab setting. When Andrews first started the company, he ran into skepticism from some of his high-profile scientific advisers, who doubted his overall strategy of trying to turn on telomerase. “They were even laughing at it,” he says. Now at this later stage of the game, a few of his paid consultants questioned his decision to use fibroblasts. “Bill is the most persistent guy I’ve ever met,” says Bryant Villepointeau, a Geron alum and a former Sierra Sciences consultant. “Sometimes if he’s committed to something, he will go beyond the point where it’s wise.”

(Click the above image for more details.)

But Andrews had his reasons—the fibroblasts behave themselves in the lab and don’t change into other cell types, unlike stem cells, which can be moving targets. And after a year and a half of testing for telomerase activation, running compound after compound through a screening assay, he finally caught a break. On the 57,684th run, the team got a chemical hit. C0057684 was too toxic to be easily transformed into a drug prospect, but it gave the company a positive control. In other words, they could use it to tune their detection tests to recognize fainter and fainter levels of telomerase activation, which is essential when you’re working with stodgy, underperforming fibroblasts.

By then, however, the market crash of 2008 had clipped the wings of the company’s two angels, radically altering Andrews’s job description. Rather than spending his days and nights in the lab, he became a telomerase-activation evangelist, crisscrossing the country in search of funding. “Where’s Bill?” became a regular link on the company’s website. His doleful SOS bounced around the life-extension blogosphere: “The bottom line is that Sierra Sciences needs $200,000 per month as soon as possible.”

The worst part for Andrews was leaving the day-to-day responsibilities of the lab and retreating to his office, where he works the phones and e-mail trying to pilot the company out of financial peril. The long hours and personal austerity required by the new mission are by now second nature and, this afternoon, become grist for an enthusiastic show-and-tell. The office fridge: “For breakfast, I have a protein shake, and every two weeks I go to Trader Joe’s or Whole Foods and buy a whole bunch of frozen foods that I heat up for dinners.” The low-slung chest of drawers with the cushion on top where he spends many of his nights, cutting down on the commute in from his ranch 25 miles outside of town: “My legs overhang the edge, but that’s OK. If I bend my knees, my legs are on the cushion.” (The last bed I saw with such awkward dimensions belonged to Father Junipero Serra, the 18th-century founder of the California Franciscan missions—his attempt to mortify the flesh presented a resonant contrast to Andrews’s efforts to make it something closer to immortal.)

“Unequivocally, he’s paid a price with his scientific peers,” Federico Gaeta says. “How big, I don’t know. But Bill’s not going to break.”For all the monastic devotion he brings to the cause, Andrews is a pure gene jock. It’s a sign of our nutraceutical-besotted times that such a scientist has made a marriage of convenience with a supplement industry often equated with hippie herb lovers and cynical marketers looking to exploit the next pseudoscience fad. Gone are the bulk shipments of synthetic chemicals to be assayed, replaced by a small weekly delivery of ingredients derived mostly from traditional Chinese and Indian medicinal herbs that John W. Anderson prepares in his five-man Arizona lab. To Andrews’s surprise (and considerable relief), at least three of these compounds have tested positive for telomerase activation in the lab, even though many of the source materials are readily available in health-food stores. Have longtime devotees of traditional Chinese and Indian medicinal herbs been activating their telomerase without knowing it? Anderson, a self-described nutraceutical research scientist and medicine hunter, demurs, saying only that his nonchemical extraction and refining process concentrates and enhances any healing properties they may have previously exhibited. As Jon Cornell, Andrews’s administrative lieutenant at Sierra Sciences, says, if herbs and roots naturally had the level of telomerase-inducing activity that Andrews and his team are really looking for, “we’d probably already have immortal people.”

Andrews leads me through a succession of compact lab rooms, each of which contains more equipment than people to run it. (Since 2008, he has cut the number of staff scientists from 34 to eight.) The center of the complex is a single cramped room where a couple of cell biologists and lab techs tend to plastic flasks holding millions of human fibroblast cells. The cells will be transferred to tiny plastic vials, frozen in liquid nitrogen, and then, when their number is called, thawed and bathed for 24 hours in one of Anderson’s natural ingredients. Then they’re whisked across the hall, where another small group of scientists and techs run a production line that sends plates of the treated cells through a LightCycler analyzer, which amplifies what’s going on at the molecular level using PCR (polymerase chain reaction, better known as the perp-catching technology on CSI). Telomerase is made up of two components—the RNA, which serves as a template to be used by the second part, a catalytic protein that synthesizes the DNA added back to telomeres. The LightCycler scans for RNA activity suggestive of telomerase expression. Promising compounds are then run through a slower, by-hand assay to look for hard evidence of the protein at work. “It’s cherry picking,” Andrews says. “The machine selects the reddest cherries.”

The analogy sounds so delightful that it’s jarring to remember that the measuring rod, the “standard control” the lab uses to evaluate telomerase activity in test compounds, is cancer—specifically the HeLa cancer cells that were the first cell line to achieve immortality. Back when Andrews was working with the more potent synthetic chemicals that he says were, in theory, capable of putting the brakes on aging, his team was able to get one compound up to a 16. That would be 16 percent of the telomerase required to make the HeLa cells live forever. “What we really want to do is to get it to 100 percent and above,” he says.

Telomerase, as Blackburn once noted, is a Dr. Jekyll and Mr. Hyde proposition. Though it will not cause a cell to turn cancerous by itself, telomerase in its uncivilized Mr. Hyde mode does fuel the unregulated growth of most cancers. By activating the enzyme, Calvin Harley says, “there is a risk, a small probability, that it could cause a premalignant cell to divide enough times to become malignant.” But both Harley and Andrews say they believe that any increased cancer risk is outweighed by the potential rewards. Telomerase can also be a benign Dr. Jekyll that protects against the chromosomal breakage and re-fusion that can lead to cancer, and it can help drive the proliferation of immune-system cells whose job it is to fight cancer.

A study in the July 7, 2010, Journal of the American Medical Association highlighted the correlation between cancer and short telomeres: People with shorter-than-average telomeres had three times the risk of developing cancer and 11 times the risk of dying from it. Andrews is not shy about talking with cancer patients—seemingly the group most vulnerable to the Mr. Hyde risks of runaway telomerase—about the potential health advantages of telomerase activation. “I’m always careful to qualify that I’m not an M.D., I’m not able to provide medical advice,” he says. “I do say that if I had cancer, I’d be taking as much telomerase activator as I could get my hands on.”

As it happens, he already is. In 2002, a New York City entrepreneur and former appliance manufacturer, Noel Thomas Patton, licensed the rights to Geron’s research on a telomerase-activating compound found in the Chinese medicinal herb astragalus, for supplement use only. (Geron is finalizing a plan to send an astragalus-based telomerase-activating drug candidate through clinical trials.) Three years ago, Patton’s TA Sciences test-launched its TA-65 supplement with 100 clients, each willing to pay $25,000 a year to be anti-aging guinea pigs. Paying patient number one: Bill Andrews.

TA Sciences has this year ramped up production and dropped the stratospheric price tag, although so far the most impressive effects remain anecdotal—more energy, greater mental clarity, a sexual boost, even improved vision. Andrews says his ultramarathon times dropped when he started taking TA-65. An observational study co-authored by Harley, who helped discover the original molecule at Geron, found improvements in the immune system of those first 100 clients. Andrews was hoping for a more pronounced effect. As he describes what it was like to take that first dose of the supplement in 2008, I can hear the voice of a kid who hasn’t entirely grown up, anti-aging as a never-ending Hardy Boys adventure: “I remember Noel and I sitting having dinner, and we were wondering, What are we going to look like two weeks from now? We talked on the phone practically every day, and we were both disappointed that we didn’t look any younger right away.”


Bill Andrews has run more than 100 races of 50 miles or more. His longest ever was 135 miles through Death Valley, California

John B. Carnett

Andrews’s tendency to let his enthusiasms take him out on a limb, especially when he’s trying to attract investors, makes him a polarizing figure in the research community. To some academics, his standard pitch-cum-sound-bite, “We age because our telomeres shorten,” is a crude oversimplification. Even Andrews seems to suspect that Sierra Sciences’s company motto, “Cure Aging or Die Trying,” isn’t winning him many friends among people who possess advanced biology degrees. “Some people like it and other people say it’s embarrassing,” he says. “So I don’t know what to do.”

“I can’t be happy unless I’m working on this,” Andrews says. “The mission won’t die unless I die.”I later ask Federico Gaeta, Geron’s former head of chemistry and a current Sierra Sciences consultant, whether Andrews’s reputation has suffered for his damn-the-nuance pursuit of longevity. “Unequivocally, he’s paid a price with his scientific peers,” he says. “How big a price, I don’t know, but there is an excellent chance that he will ultimately be vindicated.” Now, Gaeta says, “he’s in a position where he has to show that he’s done something.” The years of angels with blank checks are over, and the pressure to produce—and to raise the money to buy the time to produce—is tremendous. “He’s not going to break,” Gaeta says. “I know that about him. Bill’s not going to break.”

By 5 P.M., midwinter darkness is beginning to fall, and the skeleton crew at Sierra Sciences is mostly gone, though Andrews is looking at another long night that will probably end on his makeshift bed. The last employee to leave is Randy Lee, the IT guy, an old Southern California prep-school buddy of Andrews’s. He’s been hanging around because he has some bad news to deliver. Lee has the unenviable job of reconfiguring the lab’s now inadequate computer system. Today he lost a cache of valuable data when the system crashed. When he delivers the news, Andrews visibly compresses, as if another 10 pounds has been added to the weight already on his shoulders. Then he collects himself. “I told people we’re either going to never move forward with our system or we’re going to take the chance of losing things,” he says. “Well, try to get a good night’s sleep. I’m sorry for your sake that it happened.”

After Lee heads for home, I ask Andrews to consider a hypothetical. If I wrote him a check for $10 million, would that be enough to send him back to the lab to find that home-run telomerase-activating chemical? “No,” he says, “but that would increase our chances of getting a really good natural product that nobody could compete with. To do the pharmaceutical, we’d need $30 million.” I toss out a flip rejoinder—”Sorry, Bill, I can only do the $10 million”—and Andrews freezes for a half-second, then slumps back in his chair. “I’ve got business plans that have all that budgeted,” he says. “What the money would be used for.”

I ask Andrews what the worst-case scenario would be for Sierra Sciences. “The worst-case scenario,” he says, “is that we put out a telomerase activator and everybody who takes it dies right away.”

“No,” I clarify, “the worst-case financial scenario?”

Andrews, his voice phlegmy with fatigue, tries again. “The company folds. I find another job, but I still work on trying to find more investors to resurrect it. I can’t be happy unless I’m working on this. The mission won’t die unless I die.”

Do the Caps of Your Chromosomes Hold the Secret to More Years?

After 40 years, leading scientists in the field of telomere research are getting closer to finding therapeutics that could treat diseases of aging, if not aging itself.

By Kristen French

Illustration by Victor Mosquera

July, Outside magazine ran a profile of a woman named Elizabeth Parrish. “Liz Parrish Wants to Live Forever,” the headline shouted. A few years earlier, in 2015, Parrish had become the first human guinea pig in an experiment intended to reverse aging through gene therapy. She, and the scientists who designed the therapy, were optimistic. They thought they might have found a formula that would, essentially, stop time.

Conducted in a private clinic in Bogota, Colombia, Parrish’s treatment was aimed at lengthening her cells’ telomeres, the caps of DNA at the ends of our chromosomes. Telomeres function like our bodies’ internal clocks, determining the rate at which we age. They shorten over time, as our cells divide, and when they become short enough, the chromosomes can no longer replicate and the cells that house them typically stop dividing and undergo senescence, or else die. This shortening is associated with a number of age-related conditions, such as diabetes, hypertension, Alzheimer’s disease, and cancer, as well as idiopathic pulmonary fibrosis, bone marrow failure, and cryptogenic liver cirrhosis.

In 2016, Parrish’s company BioViva announced some good news: a lab in Houston had determined that the gene therapy she received in Colombia had extended the telomeres in her white blood cells — as measured by counting DNA base pairs — by 9 percent. According to the press release, this was equivalent to 20 years of aging. (Newborns have telomeres that are about 8,000–13,000 DNA letters long, and they are thought to decline by about 20–40 base pairs each year.) But BioViva did not publish a formal research paper to go with the findings, rendering them useless to most scientists.

Today, Parrish looks pretty much the same as she did in 2015, and no further findings about her health or rate of aging have emerged. But plenty of other promising telomere research has. Some scientists have even characterized the current state of telomere research as nothing short of a “revolution.”

What Are Telomeres?
Telomeres are like nubs protecting the ends of our chromosomes from damage, much in the way a thimble protects the thumb of a seamstress. The term telomere comes from the Greek: telos, which translates as “end,” and meros, which means “part.” Composed of DNA and specialized proteins, telomeres form protective loops that prevent the chromosome ends from being recognized as sites of DNA damage, which could attract unnecessary and even harmful “repairs.”

The longer one’s telomeres are, the better they protect the ends of one’s chromosomes. But not all people start life with equally long telomeres, and the length of your telomeres is at least partly genetic, says Jerry Shay, a professor of Cell Biology at the University of Texas, Southwestern Medical Center in Dallas, who has been studying telomeres for decades. Likewise, not all telomeres shorten at the same rate because not all cells renew at the same rate, says Shay.

Cells in the intestinal tract, for instance, turn over every seven days. Cells in the lung turn over every six months. But in a span of minutes, tens of millions of new blood cells will be created in the average human. Anything that causes damage can shorten a cell’s telomeres. Smoking, for example, can severely shorten telomeres in lung cells — as well as increase the risk of lung cancer.

“But not all people start life with equally long telomeres, and the length of your telomeres is at least partly genetic.”
Today, some companies, such as TeloYears, purport to measure your telomeres and spit out a longevity score. But this is difficult to do accurately. What matters for both disease and aging is not the average length of your telomeres, but rather the length of your shortest telomeres, according to Shay. It is the critically short telomeres that lead to either cell death or to activation of telomerase, an enzyme that adds nucleotides to telomeres, lengthening them, and that is highly active in cancer cells. (More on telomerase and cancer below.) Measuring the shortest telomeres is much harder to do than taking an average.

Telomere Caps (U.S. Department of Energy Human Genome Program)
Where Did Telomere Research Begin?
The role that telomeres and telomerase play in protecting chromosomes was first discovered in the late 1970s and early 1980s by Jack Szostak, Elizabeth Blackburn, and her then-graduate student Carol Greider. Together they showed that certain nucleotide repeats found protecting the ends of chromosomes in single-celled protozoan also were found performing the same function in yeast cells, which suggested something basic to all living organisms was at work. Blackburn and Greider then were able to identify telomerase, the enzyme that makes telomere DNA.

“When we started we just said well this is a long shot experiment that’s worth a try. Now it’s become a whole field in itself because it’s so relevant to aging and cancer.”
Telomerase — which is composed of an RNA subunit, and a catalytic protein subunit called TERT, or telomere reverse transcriptase — is naturally found in fetal tissues, adult germ cells, and is otherwise primarily active during development. Its purpose is to allow stem cells to replicate themselves and develop into more specialized cells in embryos and fetuses. But it is also found in tumor cells, where it is 10–20 times more active than in resting adult stems cells. “When we started we just said well this is a long shot experiment that’s worth a try,” Szostak said about their earliest investigations into telomeres.

That turned out to be quite an understatement. “Now it’s become a whole field in itself because it’s so relevant to aging and cancer,” he said. In 2009, the trio won a Nobel Prize for their work. Almost forty years after their discovery, scientists are still puzzling out the precise function, structure, and role of telomeres and telomerase in both aging and cancer.

The real hurdle now is how to deliver telomere targeting treatments to human cells, says Szostak, who is no longer doing telomere research, but still watches the field closely. “Really targeted delivery is the general problem that tons of people are working on,” he said. He is skeptical that this problem of delivery will be resolved any time soon.

What Is the Link Between Short Telomeres and Cancer?
The biggest obstacle to successfully arresting aging via telomere tinkering is the cancer risk. “When telomeres get really short, they send off a DNA damage signal and it makes the cell stop dividing,” said Shay. With short telomeres, you get oncogenic changes, tumor suppressor losses, and all of a sudden you have such short telomeres that the cells start fusing their ends together. “There’s all kinds of DNA damage, and the way a cancer cell survives is by up-regulating telomerase,” he said.

Because most of the cells in our bodies do not regularly use telomerase, they age, but when telomerase is activated in a cell, the cell can become immortal, dividing forever, and with other changes, become cancerous. Telomerase gets shut off during development, and it stays shut off unless you get cancer.

As it turns out, telomerase goes silent because it’s right by a telomere and the TERT gene, said Shay. When telomeres get long enough they loop over and turn off the telomerase gene. When the telomeres get short this telomerase gene is no longer protected and can be turned back on. That’s why it’s turned on in 85 or 90 percent of all cancers.

“There’s all kinds of DNA damage, and the way a cancer cell survives is by up-regulating telomerase.”
But so far, telomerase inhibitors have not been shown in clinical trials to successfully treat cancer, according to Ronald DePinho, another giant in the field of telomere research. “Those trials have not progressed as quickly as I would have liked to see them progress,” said DePinho.

Recent Advances in Telomere Research
Several major breakthrough findings have advanced the field of telomerase research over the past decade. DePinho, who initially studied telomeres at Harvard University’s Dana-Farber Cancer Institute, was able to link telomeres to the three major theories of aging — DNA damage, mitochondrial dysfunction and free-radical accumulation — in one elegant formulation.

His work in mouse models showed that telomere dysfunction activates a gene called p53, which suppresses a protein called PGC, which normally promotes expression of genes that make mitochondria work well and protects us from free-radicals. Then in a 2010 study, his lab showed that turning on the telomerase gene in lab-engineered artificially-aged mice caused a dramatic return of youthfulness — new growth of the brain and testes, heightened fertility, and restored cognitive function.

Two years later, Spanish telomere researcher Maria Blasco showed that lengthening the telomeres of normal mice using a viral vector called AAV9 to deliver a gene therapy called TERT increased their healthspans, without causing cancer. More recently, Blasco was able to show that the same therapy did not cause cancer even in cancer-prone mice. “We still do not know whether in humans, with a much longer survival, telomerase may favor or not tumorigenesis,” wrote Blasco in an email, “but our results certainly indicate that telomerase overexpression per se is not acting as an oncogene.”

Blasco has further shown that AAV9-TERT can improve the symptoms of pulmonary fibrosis, a fatal lung disease associated with shortened telomeres, as well as aplastic anemia, a rare blood disorder caused by failure of the bone marrow to make enough new blood cells. She is working on developing mouse models that demonstrate that short telomeres can lead to cognitive impairment, in order to better understand whether TERT therapies could be used to treat diseases such as Alzheimer’s.

Are We Close To Telomere Therapies?
In the meantime, a race seems to be on to get human clinical trials going for telomerase therapies that target specific diseases of aging and premature aging. Leading telomere researcher Helen Blau of Stanford University, together with former colleague John Ramunas, founded Rejuvenation Technologies, which has already received funding for preclinical studies to prepare human trials for a modified messenger RNA therapy that would be used to treat diseases associated with premature aging. Blau predicts these human clinical trials could be run under an accelerated FDA track because of the severity of the diseases and a lack of treatments that address the underlying telomere defect.

Blau and Ramunas, who previously worked in Blau’s lab, published research in 2015 that showed their modified mRNA therapy can temporarily extend telomeres in human cells. The modified mRNA sticks around for just 48 hours, which means that the treated cells don’t go on to divide indefinitely, reducing cancer risk. And yet those 48 hours were enough to extend the telomeres in human muscle and skin cells by about an entire kilobase, the equivalent of ten years of lifespan.

The findings have huge implications for diseases that have been found to be associated with short telomeres, such as dyskeratosis congenita, duchenne muscular dystrophy, liver cirrhosis and even heart disease and heart failure. “We’re focusing on specific diseases involving short telomeres initially,” says Ramunas. “We’re at a very early stage still.”

The biggest challenge is delivery because each individual cell type requires a slightly different mechanism — viral vectors work for certain kinds of cells, but not others. Blau was tight-lipped about the kinds of alternative delivery mechanisms her lab is testing but said they are making progress toward a clinically applicable solution.

“We’re focusing on specific diseases involving short telomeres initially. We’re at a very early stage still.”
Jerry Shay, meanwhile, is currently focused on lengthening the healthspan of centenarians. He recently studied a group of centenarians, some of whom were in robust health and others who were suffering from age-related disease, and found important genetic differences as well as differences in the lengths of telomeres in their T-cells, immune cells found in the blood. Shay would like to design a therapy that would allow him to extend the T-cell telomeres of those individuals who are genetically predisposed to the greatest decline in old age.

A key difference from other treatments targeted at live humans is that he would work ex-vivo. That means that Shay and his team would remove the T-cells from patients, transfect these cells with purified telomerase, then study these modified T-cells to be sure they hadn’t introduced cancer or mutations or defects, and infuse the T-cells back into the patients’ blood. Helen Blau, the director of the Baxter Laboratory for Stem Cell Biology at Stanford University, has pointed out that extending the telomeres of T-cells is risky because they divide so frequently and are predisposed to cancer, but Shay says that’s why his group would examine the cells closely before they injected them back into the body. Regardless, FDA approval could take time, said Shay.

It’s Too Soon for Miracle Drugs
Elizabeth Parrish’s former partner Bill Andrews thinks he has the answer to the difficult riddle of targeted delivery of telomere therapy. A leading expert on telomeres, Andrews initially supported Parrish’s experiment in Colombia, but later disavowed the results, saying he wasn’t sure Parrish had used a legitimate protocol and that the study didn’t produce enough data. Andrews is now conducting his own clinical trial in Colombia using a similar telomere targeting gene therapy, though details are sparse.

Some of Andrews colleagues in the field caution that it’s too soon for such testing in humans — that the cancer risk is too high. For this reason, and because the FDA doesn’t treat aging as a disease, it would be difficult to get approval to do these clinical trials in the U.S.

But others are cautiously optimistic about his work. “All power to Bill Andrews for sticking to it and searching far and wide for a better drug,” said John Ramunas, a telomere researcher from the Stanford lab of Helen Blau, which has made a number of critical findings. “In principle, it would reverse the aging process to extend telomeres in all of our cell types,” said Ramunas. “I think that’s worth aiming for.”

Finding the right gene therapy mechanism that would safely activate telomerase in every single human cell type is likely many years off, however — different cell types require different approaches.

“In principle, it would reverse the aging process to extend telomeres in all of our cell types. I think that’s worth aiming for.”
Aubrey de Grey, a leading and sometimes provocative figure in the field of longevity research, was more brash. “At the end of the day, what I suspect, is that we’re only going to get real answers to this question as it relates to humans, by studying humans. By actually observing what happens to the crazy people who are actually supplementing the telomerase into cells via medical tourism.”

It’s obviously not ideal that these experiments are open-label and are neither randomized, double-blinded nor controlled, said De Grey — if you’re paying proper money to get a risky life-extending gene therapy you don’t want to be a control.

But if the follow up on patients is thorough enough, then we should be able to at least get some “tentative answers,” he said.

An article of

Death and aging will be an option in the not too distant future, experts say

Death will be optional in the year 2045 and aging a curable disease, according to the engineer José Luis Cordeiro and the co-founder of the Symbian operating system, David Wood, during the presentation in Barcelona of his new book, “Death of death “(Ediciones Deusto).

The two engineers defend the scientific possibility of immortality and rejuvenation and ensure that in the coming decades humans “will die because of accidents, but never in a natural way”, reason why they consider it very important that “aging be declared as a disease “and thus be able to investigate from the public road.

The Cambridge mathematician David Wood explained during the presentation, held at the Equestrian Circle of Barcelona, ​​that this will be possible thanks to various technological techniques, in which nanotechnology is of great importance.

Thus, according to Wood, genetic editing will be possible to turn bad genes into healthy ones, regenerative medicine, the elimination of dead cells from the body, treatments with stem cells, the repair of damaged cells and the printing of organs in 3d

The main objective is “to cure aging: to reverse it and rejuvenate”, explained the engineer from the Massachusetts Institute of Technology, José Luis Cordeiro, who has already made it clear that he does not intend to die, and that, in addition, in 30 years “it will be more young today. ”

Wood and Cordeiro, this last Venezuelan of Spanish parents, have argued that in ten years diseases such as cancer will be cured, and have argued that companies like Google “are entering the field of medicine because they have realized that cure the aging is possible. ” In addition, the authors have explained that Microsoft announced a cryopreservation center, in which one of the scientists is investigating the cure of cancer in ten years.

They have also justified that, “although people do not know”, in 1951 it was discovered that cancer cells are immortal, that is, that “cancer causes the cells to stop aging”, when a patient, Henrietta Lacks, becomes ill of cervical cancer, he died and the doctors removed the tumor, which “is still alive today.”

On the other hand, although it might seem that immortality leads to overpopulation, the authors say that there are still many people on Earth, that currently people do not have as many children as before and that “space can also be inhabited.”

“Japan and Korea – if they continue with the current trends of not procreating – are on the way to extinction, so there will be no Japanese or Koreans in two centuries”, but said that “thanks to these techniques, yes there will be because they will to live indefinitely young. ”

In addition, regarding what it would cost to undergo a treatment of rejuvenation, the technologist Wood has affirmed, comparing it with smartphones, that “at the beginning it will be expensive, but with a competitive market the price will go down because it will benefit everyone”. “The technologies, when they start, are bad and expensive, but then they become democratized and they become cheap,” added Cordeiro.

The Venezuelan explained that two years ago it began, experimentally and illegally in Colombia, a country where there are fewer regulations, a treatment of rejuvenation for the first human patient, Elisabeth Parrish, a woman who has pointed out the Venezuelan “He started to see symptoms of aging and asked what he could do to avoid it.” Although he has affirmed that this treatment is being done with many risks, “including illegality”, according to Wood, the treatment is going well, there are no side effects and the level of telomeres in blood is twenty years younger than before.

“I want to position Spain in the world with these technologies and show that we are not crazy, what happens is that people still do not know,” he concluded.

The book is scheduled to be published in four languages ​​- Spanish, English, Portuguese and Korean – and the authors have donated copyright benefits to research in this discipline.

A news of:

A clam lived 507 years and you can also

A book tells how scientists work so that we live much more and better.
The oldest animal in the world lived 507 years. It was an Icelandic clam that had been born in 1499, before Miguel de Cervantes. He died in 2006 after being collected by scientists. A year later, in 2007, a boreal whale appeared in Alaska with a harpoon nailed since the 19th century, suggesting that this mammal can live two centuries. And monarch butterflies, which normally only live for a few weeks, produce a Methuselah generation once a year that reaches six months to migrate from Canada to the temperate forests of Mexico.

Aging in living beings is surprising. A rat lives three years, while a squirrel reaches 25. There are seemingly capricious mechanisms that regulate the process. And what happens in humans? “In the future we will die young. At 140 “, he proclaims a new book about how scientists work to make us live more and better. It is entitled, precisely, Die young, at 140 (editorial Paidós). The volume defends that aging is not obligatory and that scientists will soon be able to prolong youth. And it is not a butade. Its authors are Monica G. Salomone, journalist specializing in science, and molecular biologist Maria Blasco, director of the National Center for Oncological Research (CNIO) in Madrid and, without exaggeration, one of the leading experts in aging in the world.

Blasco’s hypothesis is that aging is the common cause of diseases associated with aging: cancer, Alzheimer’s, diabetes, cardiovascular disease, and so on. If aging were attacked as if it were a pathology, the youth would be prolonged and the rest of the ailments would disappear. You could die young, at 140 years old. “It’s not about living 120 years as a person of 120 years lives today; it’s about being 70 years old with the appearance, health and vitality of the 40 “, explains Blasco.

The molecular biologist believes that this brake to old age exists and is called telomerase, one of the tens of thousands of proteins that make up the human body. Salomone, tanned in national and international media, masterfully explains the role of this macromolecule in aging and the history of its discovery, interviewing almost all the scientists who have painted something on this journey.

The journalist travels to the nucleus of the cell, on scales of millionths of a millimeter, until it reaches DNA, our instruction book, packaged in chromosomes. Our cells are constantly dividing. The face of a person, for example, is completely renewed every month. And every time a cell divides it duplicates its DNA packets, but in such a way that the ends of the chromosomes are not copied until the end. After each division, the chromosomes are a tad shorter.

What is shortened, says Salomone, is “a structure of DNA and proteins called a telomere, a protective cap that forms the end of each chromosome.” The older the cell is, the more divisions it has suffered and the shorter its telomeres. And that’s where the telomerase protein comes in, which naturally stops this biological clock in stem cells. It makes the telomeres grow back. It makes the cells immortal. The trouble is that, in most of the cells of an adult being, the gene that produces telomerase is deactivated.

Our cells are going to die, with their tiny telomeres, and we with them. Or not. Maria Blasco returned to Spain in 1997, after spending four years in the USA in the laboratory of biochemistry Carol Greider, Nobel Prize in Medicine for discovering telomerase. The objective of the Spanish scientist was to verify if increasing telomerase could delay the aging of a mouse. The problem is that the protein makes immortal both healthy cells and those that have mutations that cause tumors. So telomerase favors cancer.

Blasco came up with an ingenious solution. His colleague Manuel Serrano had created a transgenic mouse with three genes that protected against cancer by eliminating cells with dangerous mutations. Blasco crossed his rodents with telomerase with mice resistant to Serrano cancer. The result was Triple, a lineage of superratons born in 2008 who lived 40% more than normal, without diseases. “In worms it has been possible to multiply by 10 the normal life expectancy in the species, but in mammals, which do develop diseases associated with aging like those of humans, Triple still holds today the record of longevity”, highlights Salomone in Morir young, at 140.

The future is promising. The investigation of aging is boiling. At the end of 2014, María Blasco’s laboratory at the CNIO managed to use telomerase to treat myocardial infarction in mice, which is lethal in people in rich countries. The team, led by the young German researcher Christian Bär, treated the mice with telomerase and then caused a heart attack. The protein rejuvenated the heart tissue of rodents and increased their survival after attack by 17%.

Researchers from the Blasco team have four other experiments under way with the same strategy: activate the telomerase gene in specific parts of the body and temporarily, to avoid the risk of cancer. They get it through modified viruses. The technique is underway against Alzheimer’s, Parkinson’s, idiopathic pulmonary fibrosis and aplastic anemia, a disease caused by the malfunctioning of blood stem cells.

At the moment, everything is promising in mice, but Maria Blasco is optimistic. “The origin of Parkinson’s and cancer is the same, the deterioration of our cells, and this occurs associated with the passage of time, which goes hand in hand with alterations in the cell division process, tissue regeneration, exposure to environmental stress, etc. It’s what I think. If I have to put all the eggs in a basket, I would put them in this one. That is why we are with an idea to fixed gear: if we aim at the aging processes will be not one, but many, the diseases that we will understand and delay. In our case, the way to aim at aging to end it is through the activation of telomerase and the rejuvenation of telomeres. ” To die young, at 140 years old.

An article written by:

What are telomeres, one of the keys studied by scientists to understand aging.

What are telomeres, one of the keys studied by scientists to understand aging

WritingBBC Mundo
    March 27, 2018

Telomeres are like the protective shields of our cells’ DNA.
Its name, of Greek origin, literally means “final part”, and that is that the telomeres are that: the ends of the chromosomes, something similar to the plastic tips of the shoelaces.
But they are very repetitive and non-coding parts of DNA: their main function is to protect the genetic material that carries the rest of the chromosome.
As our cells divide to multiply and to regenerate the tissues and organs of our body, the length of the telomeres is reduced, and therefore they become shorter over time.
When finally the telomeres are so small that they can no longer protect the DNA, the cells stop reproducing: they reach a state of old age or old age.

Therefore, the length of telomeres is considered a key “biomarker of aging” at the molecular level, although it is not the only one, and in recent years it has attracted the attention of numerous researches.
How much do our telomeres measure and how fast do they deteriorate?
The length of the telomeres is measured in “base pairs”, which are the opposite and complementary nucleotide pairs that are connected by hydrogen bonds in the DNA chain.
The length of telomeres varies widely among different species.
In the case of humans, the length of the telomeres deteriorates from an average of 11 kilobases at birth to about 4 kilobases in old age.
Can you “intervene” on telomeres?
In 2009, three American researchers won the Nobel Prize in medicine for their work on cell aging and its relationship to cancer.
Elizabeth Blackburn, Carol Greider and Jack Szostak investigated the telomeres and discovered that the telomerase enzyme can protect the chromosomes from aging: it can cause the telomeres to regenerate, it can prolong them.
This enzyme helps prevent telomeres from shrinking with cell division, which helps maintain the biological youth of cells.
Much of the research on telomeres has nothing to do with an aesthetic aspiration of longevity, but with the potential cure of diseases.
The Spanish María Blasco, who worked in the United States with Greider, is now the director of the Telomeres and Telomerase Group of the National Center for Oncological Research of Spain.
Blasco led the development of a new technique that blocks the ability of glioblastoma, one of the most aggressive brain cancers, to regenerate and reproduce, precisely by attacking the telomeres of cancer cells.
In tests with mice, his team managed to reduce the growth of the tumors and increase the survival of the animals, something that could open the doors to potential treatment alternatives in humans.
But Blasco and his team are still investigating with strategies in reverse, according to Gabriela Torres, of BBC Mundo.
They aspire to activate telomerase in such a way that they can cure people who are dying of rare diseases due to genetic mutations associated with very short telomeres.
Do they keep the secret to make us younger?
But stopping the aging of cells does not necessarily have an anti-aging effect on the whole body.
According to Dr. Carmen Martin-Ruiz, researcher on aging at the Institute of Neuroscience at the University of Newcastle, in England, the longer a person’s telomeres can be said, the “stronger is biologically”.

When a person has the longest telomeres, it is because they have metabolic mechanisms that protect them, “the specialist told BBC Mundo.
“It’s like your body had better defense systems,” he explained.
But one of the current problems of scientific research in this field, according to this expert, is that there is no standardized and universal method to measure telomeres.
A recent study from the United States concluded that maternity shortened women’s telomeres more than tobacco or obesity, while another fact among Mayan women, smaller but with a “more robust” methodology, according to Martin-Ruiz, reached the opposite conclusion: that motherhood made women biologically younger, since their cells had longer telomeres.
Martin-Ruiz says that each laboratory uses different techniques and methodologies, which makes it difficult to compare studies and results because the calculations can be interpreted in many different ways.
So “the technical solidity of measuring telomeres is not as much as when you go to the hospital and they measure your glucose”, concludes the expert.

In any case, there is a large community of scientists who are investigating different aspects of human aging, including telomeres, mitochondria, the shape of proteins and many other aspects of that process.
According to the BBC, Gordon Lithgow, a scientist at the Buck Institute, aging is all these things, it affects all the systems of our body.

    An article of the BBC:

Elizabeth Parrish, the woman who rejuvenates every day.

He has skipped all the rules to try an anti-aging treatment. Today she is the only patient of a pioneering method. She is 45 years old and is determined to overcome aging and convince science that it is possible.

Science claims that astronauts, when on a mission, age more slowly. Just microseconds, but they return to Earth more “young”. Maybe Elizabeth Parrish tries to imitate them with so much travel. In the last two weeks he has traveled tens of thousands of kilometers flying between the United States and Germany (twice), a flight to South America, another to Russia, an air excursion to London and several transfers between Washington, where he has his headquarters, and other American cities. That’s why finding it has been so complex, but by combining phone and email in different continents we have managed to land and explain to Quo how he plans to cure aging. Because for Liz, as she prefers to be called, getting old is a disease, not a process. She is the zero patient of a therapy that she has designed so that time is more benevolent with her body. And, judging from the first results, he’s getting it. Although it is facing governments, regulatory agencies and scientific colleagues, with the aim of testing in humans a therapy whose side effects are unknown.

An update to be younger
“I was not prepared to discover that biological aging is really a disease,” Parrish explains to Quo. I took the time to talk to many experts and discovered that some of the agents that cause diseases in children are accelerated aging processes. It was necessary to understand that the cells of the body are like a computer and much of the damage they cause over time is because they are programmed for it. Some people suffer from this deterioration at a young age, that is, some have programming problems, genetic. But we are all accumulating these damages that will eventually lead us to the symptoms of old age and cause us death. ” What Elizabeth Parris tries, continuing with the simile, is to update us.

“Exact!” Exclaims Liz. “For that, one of the most important things we need is to obtain information in humans. We have cured the cancer hundreds of times in mice, reverse the formation of arteriosclerosis plaques and biological aging with telomerase inducers. But we are not using those techniques in humans. So I decided to try them on myself. I’m going to show that it’s a safe therapy. ”

The first results indicate that Parrish has made his cells 20 years younger. But the scientific community demands more data
That therapy to which Parrish refers has two parts. On the one hand are the telomeres. In 2009, Elizabeth Blackburn won the Nobel Prize for her discovery of the “scissors” that divide cells: telomeres. These are repetitive sequences of DNA that protect them from degradation after each division. In a sense, they are like ink in a photocopier: they try to make the copy of the copy as close as possible to the original. The problem is that no matter how much ink you have, the copy of a copy of a copy (and so on) is not as good as the original: in cellular terms this amounts to saying that when a cell is divided, the two resulting have less telomeres than his “mother.”

And this is the reason for aging: the more our cells divide, the less similar they appear to the original, until they are so different that the differences could produce a risk and that branch of the family immolates itself for the sake of the rest. Thus, if we had a constant contribution of telomerase, the “nutritional supplement” of the telomeres, in charge of adding pieces of DNA so that there are no bad readings, aging would be much slower.

This has already been demonstrated by one of the pioneers in this field, María Blasco, director of the National Center for Oncological Research (CNIO) who has carried out a telomerase therapy in mice and managed to extend her life by 30%. But how has Parrish done it? Is there any way to explain it in a simple way?

“Surely, the patient responds zero to this treatment-. It is a gene therapy, but we did not put the genes directly, we use vectors through which we transmit the information we want. And these vectors are viruses. We know that viruses are essentially good at making us sick, but we use viruses that do not make us sick and we use them because they have the ability to connect with our cells and transmit their genetic material. In gene therapy, we remove viruses from the ability to get sick and put the information we want in our cells. In a certain sense it is very simple science. We are not creating molecules that you have to eat and go to a place in your body to create an effect. What we are doing is delivering a gene to the cell,

The risks of being the patient zero
There is only one small drawback. This therapy has not yet been tested in humans. When we consulted María Blasco about it, her answer was clear. “We do not know if in humans the extension (achieved in mice) would be the same or not. From the outset, humans are much more protected from aging than mice. While in humans up to 40 years it is very rare to suffer diseases associated with aging, such as heart attack, Alzheimer’s disease or cancer, in mice everything happens much faster and they begin to develop diseases at one year of age. At 2 years, most of the mice have already died. Therefore, something that extends life in mice by 30% could extend life in humans by 3% or 300%, we do not know … Anyway, The objective of understanding how to modulate longevity in mice or other model organisms is to understand which are the important molecular processes, determine the speed of aging to be able to intervene with the intention of preventing diseases linked to the passage of time or even treat them more efficiently. Right now there are many pathologies associated with old age that we neither know how to prevent nor how to cure, “says María Blasco.

And this is exactly what Parrish intends. What happens is that in the United States the trials with humans are regulated by the Food and Drug Administration (FDA) and until this agency does not approve, they can not be started … Unless it is in another country.

“If you manage to treat aging with this therapy, it will only be long-term,” predicts María Blasco
That’s why Parrish went to Colombia to start the first phase of the trial. Before starting, the Bioviva team, the company that Parrish runs, measured the length of the leukocyte telomeres and did it again after the therapy. The results show that their telomeres lengthened from 6.71 kb or kilobases (kb: a thousand DNA base pairs) to 7.33 kb. In a nutshell, your cells are 20 years younger.

Muscles for your stem cells
The other part of the treatment Parrish underwent involves the use of inhibitors of myostatin, a protein that obstructs muscle growth. In fact, sarcopenia (the loss of muscle mass from 30 years of age) kills 6% of the population. “So we block myostatin and our muscles keep growing,” says Parrish. But not only that. The benefits also include increased insulin sensitivity, decreased fat and an aid for the signals from the stem cells. Many people die looking very old, even if their stem cells are very healthy. That’s because they never received the signal to help the body regenerate. ”

A therapy to challenge them all
Is this enough information for FDA to approve human trials? Is there any context that justifies skipping the regulatory agencies and becoming “guinea pig”? For Maria Blasco is more than clear and her answer is Spartan: “None.” George Martin, pathologist, expert in genomic sciences and until a few weeks ago a member of the scientific board of BioViva, something similar happens. “Liz is an extremely hardworking and conscientious woman,” he explained to Quo in a telephone conversation, “but in my opinion the goal of the medical sciences is to cure and for that we must follow certain rules. That is the reason why I asked to leave the council. ”

Another member of the same council, which remains in him, is the well-known geneticist George Church. Church’s work is one more proof that BioViva investigates with diffuse ethical limits. He was the one who proposed to resuscitate a Neanderthal and came to look for a human who wanted to breed him. Church is aware that such work would be declared illegal in many countries, but this is something that does not stop him.

There is no controversy for Parrish either. “I think it’s a right to be able to do what you want with your own body and that we should be able to pay a doctor to do it as safely as possible. Initially, we kept the site where the trials were conducted and the people involved in it secret, because as the director of the company I wanted to protect my staff. Now that the results have proven to be positive, we have released the data. ”

The step has undoubtedly been risky. Not only because of the adverse effects that treatment could have on humans, but because when requesting approval from the FDA, the agency may not view this “insubordination” against the established order with good eyes, an act that could set precedents . The question then is, how do you plan to convince the FDA to approve this treatment and be able to begin the trials?

And Parrish already has it in mind. “Every day we lose close to 100,000 people because of aging,” he says in his conversation with Quo. And we are not facing this reality as the catastrophe that it is. We think that it is a normal process, but we must bear in mind that it is a very expensive one. In 2020 there will be more people over 65 who are under 5 years old. We have to think about how to make people work longer and be more active and healthy. There is no point in preventing the development of a technology that would allow us to save the billions of dollars spent on finding the cure for diseases related to aging, when we can directly treat what produces them. ”

If successful, Parrish’s commitment could not only extend our life expectancy, it would also have a huge impact on the economy, especially on pensions. At what age should we retire? How much would education extend? How would the pensions be paid if we live 20 more years? Have you thought about it? “The truth is that I do not ask myself those kinds of questions,” says Parrish. My job is to mitigate the diseases that we can cure. If we think we have a possible solution, it would be immoral not to share it. How long will we live? I do not know, but I would like it to be as long as possible and in the best conditions. ”

The therapy being carried out Elizabeth Parrish could have potential to treat diseases related to aging such as cancer, duchenne, Alzheimer’s, Parkinson’s, kidney problems, leukemia, esophagitis of Barret … The list is long. “The first people who should benefit from it,” Parrish explains, “are terminal patients. Then, if the data obtained are positive, we could start with patients with milder diagnoses and finally reach the area of ​​preventive care “. For this to happen, only one requirement will be necessary: ​​”That the regulatory agencies recognize old age as a disease”, concludes María Blasco.

Why do you add Miostatin?

From 50 years of age, muscle mass decreases between 1 and 2% and strength 1.5% annually and up to 3% from 60 years. Myostatin, also known as growth differentiation factor 8, not only solves this muscle loss. “He also works with telomerase,” says Parrish. This increases the supply of stem cells and myostatin would allow more stem cells to activate
and regenerate tissues. ”


Maria Blasco, director of the CNIO: Aging is not natural.

“It’s a laboratory like any other,” confesses modestly its director, Maria Blasco, as we walk between microscopes, test tubes, stills and retorts. It is nothing less than the laboratory of the Telomerase and Telomerase Group of the CNIO (National Center for Oncological Research), whose management also has Blasco. It will be like any other, but in other laboratories it has not been discovered how to significantly extend the life of small mammals, nor have deadly tumors been eliminated, nor has a gene therapy been developed that could extend our life, according to the most conservatives, up to 140 years. That is the figure that Maria Blasco ventures in the book she signs next to Mónica G. Salomone, Morir joven, at 140 (Paidós, 2016), of recent appearance. Disciple of the pioneers in their discipline, Molecular Biology, it is possible that Maria Blasco has found the exact distillation of the elixir of eternal youth. And yet modesty, once again, seems to be a distinctive feature of his character at the sight of his office, attached to the laboratory. Narrow, elongated and dominated by a large window from which you can see the treetops of this residential area in the vicinity of the Plaza de Castilla, there is barely room for the desk and the work chair. From this office Maria Blasco glimpses the future of human longevity and the fight against cancer, myocardial infarction and Alzheimer’s. On the wall, next to the computer, family photos. And in front, a horizon without mapping on which to blur the look.

Javier Redondo Jordán
this news has been extracted from: