Can Exercise Keep You Young?

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exercise reduced or eliminated almost every detrimental effect of aging in mice that had been genetically programmed to grow old at an accelerated pace

The New York Times, March 3, 2011, by Gretchen Reynolds  —  We all know that physical activity is beneficial in countless ways, but even so, Dr. Mark Tarnopolsky, a professor of pediatrics at McMaster University in Hamilton, Ontario, was startled to discover that exercise kept a strain of mice from becoming gray prematurely.

But shiny fur was the least of its benefits. Indeed, in heartening new research published last week in The Proceedings of the National Academy of Sciences, exercise reduced or eliminated almost every detrimental effect of aging in mice that had been genetically programmed to grow old at an accelerated pace.

In the experiment, Dr. Tarnopolsky and his colleagues used lab rodents that carry a genetic mutation affecting how well their bodies repair malfunctioning mitochondria, which are tiny organelles within cells. Mitochondria combine oxygen and nutrients to create fuel for the cells — they are microscopic power generators.

Mitochrondria have their own DNA, distinct from the cell’s own genetic material, and they multiply on their own. But in the process, mitochondria can accumulate small genetic mutations, which under normal circumstances are corrected by specialized repair systems within the cell. Over time, as we age, the number of mutations begins to outstrip the system’s ability to make repairs, and mitochondria start malfunctioning and dying.

Many scientists consider the loss of healthy mitochondria to be an important underlying cause of aging in mammals. As resident mitochondria falter, the cells they fuel wither or die. Muscles shrink, brain volume drops, hair falls out or loses its pigmentation, and soon enough we are, in appearance and beneath the surface, old.

The mice that Dr. Tarnopolsky and his colleagues used lacked the primary mitochondrial repair mechanism, so they developed malfunctioning mitochondria early in their lives, as early as 3 months of age, the human equivalent of age 20. By the time they reached 8 months, or their early 60s in human terms, the animals were extremely frail and decrepit, with spindly muscles, shrunken brains, enlarged hearts, shriveled gonads and patchy, graying fur. Listless, they barely moved around their cages. All were dead before reaching a year of age.

Except the mice that exercised.

Half of the mice were allowed to run on a wheel for 45 minutes three times a week, beginning at 3 months. These rodent runners were required to maintain a fairly brisk pace, Dr. Tarnopolsky said: “It was about like a person running a 50- or 55-minute 10K.” (A 10K race is 6.2 miles.) The mice continued this regimen for five months.

At 8 months, when their sedentary lab mates were bald, frail and dying, the running rats remained youthful. They had full pelts of dark fur, no salt-and-pepper shadings. They also had maintained almost all of their muscle mass and brain volume. Their gonads were normal, as were their hearts. They could balance on narrow rods, the showoffs.

But perhaps most remarkable, although they still harbored the mutation that should have affected mitochondrial repair, they had more mitochondria over all and far fewer with mutations than the sedentary mice had. At 1 year, none of the exercising mice had died of natural causes. (Some were sacrificed to compare their cellular health to that of the unexercised mice, all of whom were, by that age, dead.)

The researchers were surprised by the magnitude of the impact that exercise had on the animals’ aging process, Dr. Tarnopolsky said. He and his colleagues had expected to find that exercise would affect mitochondrial health in muscles, including the heart, since past research had shown a connection. They had not expected that it would affect every tissue and bodily system studied.

Other studies, including a number from Dr. Tarnopolsky’s own lab,  have also found that exercise affects the course of aging, but none has shown such a comprehensive effect. And precisely how exercise alters the aging process remains unknown. In this experiment, running resulted in an upsurge in the rodents’ production of a protein known as PGC-1alpha, which regulates genes involved in metabolism and energy creation, including mitochondrial function. Exercise also sparked the repair of malfunctioning mitochondria through a mechanism outside the known repair pathway; in these mutant mice, that pathway didn’t exist, but their mitochondria were nonetheless being repaired.

Dr. Tarnopolsky is currently overseeing a number of experiments that he expects will help to elucidate the specific physiological mechanisms. But for now, he said, the lesson of his experiment and dozens like it is unambiguous. “Exercise alters the course of aging,” he said.

Although in this experiment, the activity was aerobic and strenuous, Dr. Tarnopolsky is not convinced that either is absolutely necessary for benefits. Studies of older humans have shown that weightlifting can improve mitochondrial health, he said, as can moderate endurance exercise. Although there is probably a threshold amount of exercise that is necessary to affect physiological aging, Dr. Tarnopolsky said, “anything is better than nothing.” If you haven’t been active in the past, he continued, start walking five minutes a day, then begin to increase your activity level.

The potential benefits have attractions even for the young. While Dr. Tarnopolsky, a lifelong athlete, noted with satisfaction that active, aged mice kept their hair, his younger graduate students were far more interested in the animals’ robust gonads. Their testicles and ovaries hadn’t shrunk, unlike those of sedentary elderly mice.

Dr. Tarnopolsky’s students were impressed. “I think they all exercise now,” he said.

Reprogrammed Stem Cells Are Rife with Mutations

Screening cells: New research reveals that induced pluripotent stem cells (shown here) carry a number of genetic mutations, which could have implications for their therapeutic use. Credit: James Thomson, University of Wisconsin-Madison

The findings cast doubt on a promising alternative to the use of embryonic stem cells in medicine

MIT Technology Review, March 3, 2011, by Emily Singer  —  Adult cells that have been reprogrammed into stem cells harbor a number of genetic mutations, some of which appear in genes that have been linked to cancer. While scientists don’t yet know how this might affect the use of the cells in medicine, they say the findings show that the cells need to be studied much more extensively.

“As we think about using [these] cells for therapy, we will want to consider what kinds of screening tests we want to do,” says Lawrence Goldstein, a professor of molecular biology at the University of California, San Diego. One of the major concerns about stem-cell-based therapies has been whether they carry a risk of cancer; both stem cells and cancer cells are distinguished by their ability to continually divide.

In two studies published today in Nature, researchers analyzed the genome of induced pluripotent stem (iPS) cells, adult cells that have been genetically or chemically reverted to the stem cell state. These cells have attracted intense interest from both scientists and the public as a potential alternative to embryonic stem cells. Like their embryo-derived cousins, iPS cells can develop into any type of tissue, making them a good candidate for cell-replacement therapies. They are also genetically matched to the patient, meaning they don’t carry the risk of immune rejection associated with existing cell transplants.

In one study, Goldstein, Kun Zhang, and collaborators at the University of California, San Diego, sequenced the gene-coding portion of the genome in 22 iPS cell lines that had been reprogrammed using several different methods. “Every cell line we looked at, we found single [genetic-letter] mutations in the protein-coding region, an average of six mutations per cell line,” says Zhang.

Different cell lines had mutations in different genes, but a disproportionate number of the mutations appeared in genes involved in cell growth or in genes that have been previously linked to cancer.

Some of the mutations probably arise from the evolutionary pressure of growing in a dish. If a random mutation that occurs during cell division helps daughter cells grow faster than others, that mutation will take root in the population. However, Zhang’s team found that the mutation rate in iPS cells is 10 times the typical rate for cultured cells.

It’s not yet clear why iPS cells have such a high mutation rate. Researchers found that roughly half the mutations occurred before reprogramming and could be found in a few cells in the initial population from which the iPS cells were derived. The others might have occurred during the process of reprogramming or as the newly created iPS cells grew. The team is now planning similar tests of embryonic stem cells.

In the second study in Nature, researchers from Canada and Finland used microarrays—chips dotted with pieces of target DNA—to analyze another type of genetic mutation in iPS cells: small deletions or duplications of DNA known as structural variations. They found that iPS cells had more of these variations than either skin cells or embryonic stem cells did early in the reprogramming process but that cells bearing abnormalities quickly died off as the population continued to grow.

Researchers say that more research is needed to understand what the findings mean for future use of these cells in therapies. “The big question is which of these changes really matter,” says Jeanne Loring, director of the Center for Regenerative Medicine at Scripps Research Institute. “We need to figure out which are relevant and which are just noise.” Loring has published results similar to the second study this year.

“For some type of genetic changes—mutations in cancer-linked genes, for example—we clearly would not want to use cells in patients,” says Martin Pera, director of the Broad Center for Regenerative Medicine at the University of Southern California, who wrote a commentary accompanying the publication in Nature.  “But for the vast range of changes, we don’t really understand functional significance.” As is the case in many genomics studies, “the ability to collect in-depth genetic information has outstripped our ability to interpret it,” he says. “That’s the real challenge going forward.”

Part of the problem is that scientists know little about the mechanisms underlying reprogramming. “We can’t yet identify what particular aspect of the reprogramming process or cell culture is responsible for engendering these changes,” says Pera. “If we want to fix this, we need to understand what aspect of the process is critical.”,, March 3, 2011, by Mike Stobbe, ATLANTA — More than a third of U.S. adults sleep less than seven hours a night, and many of them report troubles concentrating, remembering and even driving.

The Centers for Disease Control and Prevention reported the statistics Thursday in two separate studies.

In one study, about 35 percent of people surveyed in 12 states said they slept less than seven hours a night, on average.

The second study based on a national survey found about 23 percent said they had trouble concentrating because they were tired. Another 18 percent struggled to remember things, and 11 percent had difficulty driving or commuting.

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The New York Times, March 3, 2011, by Catherine Saint-Louis  —  In this anti-aging age, perhaps it’s unsurprising that vampires — ancient, but with forever-young skin — are a cultural obsession. Now a cosmetic treatment to fill in wrinkles or to plump up hollow cheeks is being marketed as a “vampire filler” or a “vampire face-lift.”

In fact, it’s not surgery, but an in-office procedure that entails having blood drawn from your arm, then spun in a centrifuge to separate out the platelets. They are then injected into your face, with the hope of stimulating new collagen production. Selphyl, as the system is called, arrived on the booming facial-rejuvenation market in 2009, and is now used by roughly 300 doctors nationwide in the name of beauty, said Sanjay Batra, the chief executive of Aesthetic Factors, which manufactures the Selphyl system.

This year, the “vampire face-lift” has been promoted on “The Rachael Ray Show” and “The Doctors.” It’s also gotten air time on more than a dozen local news programs, some of which presented unproved claims that results will last two years.

Dr. Drew Ordon, one of the hosts of “The Doctors” and a board-certified plastic surgeon, gushed on air, “Vampires have moved into plastic surgery, too, and I’m one of them.” The patient in his segment had also recently had her own fat injected into her face to plump it, so it wasn’t clear that platelets had anything to do with her fresher appearance. (Not that that stopped audience applause.)

Ghoulish as the procedure sounds, some patients prefer the idea of using their own blood rather than a neurotoxin or synthetic filler to rejuvenate their faces. “We all want to look better,” said Joan Sarlo, 56, who underwent a Selphyl “vamp-lift” performed by Dr. Lisa A. Zdinak, a Manhattan-based doctor whose specialty is ophthalmic plastic surgery. But the “less unnatural the better,” Ms. Sarlo said. “What could be better than your own blood?”

Some doctors say that fillers taken from one’s body are less likely to cause irregularities and bumps in thin-skinned areas than synthetic ones like Sculptra Aesthetic. But at this point, it’s hard to tell whether “platelet-rich fibrin matrix,” or P.R.F.M. (the medical term for the golden-hued platelets that Selphyl extracts), is an effective filler for hollowed-out cheeks and wrinkles.

Dr. Anthony P. Sclafani, the director of facial plastic surgery at the New York Eye and Ear Infirmary, said he’s seen the revivifying effects of P.R.F.M. on cosmetic patients last for more than a year — sometimes 18 to 24 months. (Dr. Sclafani is a paid consultant for Aesthetic Factors, and most of his research on Selphyl has been financed by the company.)

But no national clinical trial has been done to prove such claims. “There simply isn’t any objective data out there supporting the claim of two years,” Dr. Jeffrey M. Kenkel, a board-certified plastic surgeon and a spokesman for Physicians Coalition for Injectable Safety, wrote in an e-mail.

Dr. Phil Haeck, the president of the American Society of Plastic Surgeons, is troubled by the lack of research proving the efficacy of Selphyl, which costs $900 to $1,500 for a procedure that takes less than a half-hour. “There are no scientific studies, only personal attestations,” he said, adding that he thinks the “creepy” concept is as antiquated as bloodletting to cure disease. “This is another gimmick that people are using to make themselves stand out on the Internet in a real dog-eat-dog part of medicine.”

What’s more, doctors and consumers aren’t clear on where Selphyl stands with the F.D.A. In a YouTube video featuring Dr. John Argerson, a board-certified family medicine doctor who works out of Refine MediSpa in Johnson City, Tenn., tells consumers that Selphyl is a “newly F.D.A.-approved filler” for nose-to-lip folds. And in a December 2009 article in Dermatology Times, a trade publication, Dr. Ranella Hirsch, a board-certified dermatologist, said Selphyl is “a new F.D.A. approved dermal filler.” This week, Dr. Hirsch, who doesn’t use Selphyl in her practice, said that she couldn’t explain why she misspoke, adding in an e-mail that “the lack of clarity between F.D.A. approval versus F.D.A. clearance to market is a key point.”

Indeed. The F.D.A. has not approved or cleared P.R.F.M. derived in a Selphyl centrifuge to be marketed for facial rejuvenation. In 2002, the agency cleared a blood-collection system called Fibrinet, whose platelet-rich byproducts orthopedic doctors then used to speed tissue repair. In 2009, this same machine was born again as Selphyl, and since then, the company promoted it as a way to “reverse the natural aging process.” This week, Shelly Burgess, an F.D.A. spokeswoman, said that Selphyl’s maker would have to file an amendment to get clearance to market its blood collection system in a new way, and no such amendment could be found at this writing.

Asked whether Aesthetic Factors’ marketing of Selphyl for cosmetic rejuvenation violated any F.D.A. policy, Ms. Burgess simply wrote, “As a regulatory agency we would not discuss whether a firm’s claims violate our regulations.”

Dr. Anthony Youn, a board-certified plastic surgeon who introduced the vampire face-lift to viewers of “Rachael Ray” this year, admitted in an interview, “There’s very little data behind Selphyl” and that he’s injected just a half dozen patients with P.R.F.M. “Patients tolerate it beautifully, but I haven’t seen any dramatic results yet,” said Dr. Youn, based in Troy, Mich.

Dr. Sclafani, who has injected roughly 150 patients, wrote in an e-mail that Selphyl can correct early signs of aging like crow’s feet, loss of facial volume and under-eye hollows “in a progressive, natural way and rejuvenate a person’s appearance in a subtle but distinct way.”

Dr. Joseph M. Gryskiewicz, the chairman of the emerging trends committee for the American Society of Plastic Surgeons, said he was impressed by Dr. Sclafani’s before and after photos, some taken with appropriate lag time to test longevity. “They look as good as any filler out there,” he wrote in an e-mail. Dr. Gryskiewicz, a board-certified plastic surgeon in Edina, Minn., who doesn’t offer the “vampire filler,” doesn’t feel P.R.F.M. derived from Selphyl can be compared with Botox, because, he wrote, “one fills a space, the other inhibits muscle action.” But he sees the point of using Selphyl’s P.R.F.M. as a volumizer, considering the alternatives. “Lots of patients are freaked out about the lumps with Sculptra, and lots of patients don’t want to do surgery that is fat transfer, but they want their hollow cheeks fixed.”

Last week, a retrospective no-placebo study of 50 of Dr. Sclafani’s patients injected with their own platelet-rich fibrin matrix one to five times and then assessed on average 9.9 months later was published online in the Archives of Facial Plastic Surgery. It didn’t prove that P.R.F.M. is an effective filler, but Dr. Kenneth R. Beer, a dermatologist in West Palm Beach, Fla., said it did suggest that it was generally safe to use to treat nasiolabial folds or sunken cheeks. That said, Dr. Beer, who is a paid consultant and investigator for Medicis and Allergan, the makers of Restylane and Juvéderm respectively, wrote of Selphyl in an e-mail: “The major risk, in my estimation, will be from people that don’t understand the anatomy or the procedure injecting this into veins or arteries.”

Since last March, Dr. Ali Vafa, a board-certified internist who now injects fillers at New York Medical Aesthetics in SoHo, has offered Selphyl to patients afraid to use Botox or synthetic injectables — thus far about 35, some in conjunction with other fillers. But there isn’t a lot of “good clinical research behind” the procedure, he said. “You sort of go by what other doctors have seen who have been doing it for a period of time.”

Ann, a 39-year-old preschool teacher from Brooklyn who wanted to use only her first name for privacy’s sake, had her hollow cheeks treated by Dr. Vafa last August. “As part of the aging process, all our faces will thin out,” Ann said. She saw a gradual improvement after Selphyl, and liked that she didn’t have any palpable bumps as she had after using Perlane, a hyaluronic acid filler approved by the F.D.A.

“When they come to me, I don’t promise it will improve everything,” said Dr. Vafa, who charges $1,000 to $1,200 to inject P.R.F.M. “I say it’s for prevention, it will improve skin quality and volume.” He calls the procedure a “vampire face-lift” on one of his Web sites, though with some squeamishness about its sensationalism..

But Dr. Charles Runels, a cosmetic doctor in Fairhope, Ala., liked the term so much he trademarked it. Dr. Runels, who used to be a board-certified internist, said this was to standardize the offering so patients know what to expect. His vampire face-lift entails first volumizing the face with Juvéderm, a hyaluronic acid filler that lasts up to a year, then “using Selphyl to polish off under the eyes, and thinner-skin areas,” he said.

Now any doctors who want to promote the vampire face-lift must pay Dr. Runels $47 a month to follow his protocol, posted online. (So far, 10 have signed up.) Asked what he intends to do about all the doctors already using vampire face-lifts, he said, “I don’t know how I’m going to rein it back in but I will.” Maybe Dracula could help.

House cats like these appear to be vulnerable to catching flu from humans.  –  Derek Speirs for The New York Times

The New York Times, by Tara Parker-Pope  —  A few days after two members of an Ames, Iowa, family came down with the flu, they noticed their 13-year-old cat wasn’t feeling too well either. The cat has since become the first documented case of a feline with the new H1N1 virus, commonly called swine flu.

The unusual case has riveted pet owners and health officials. Companion animals have been known to contract flu from other species — canine influenza (H3N8) originated in horses, and cats contract avian influenza (H5N1) from eating birds. But this appears to be the first time a cat has contracted influenza from a human. Two pet ferrets, one in Oregon and one in Nebraska, have also tested positive for H1N1, and the virus has also been transmitted between humans and pigs.

The cat was treated at the College of Veterinary Medicine at Iowa State University by veterinarians Dr. Brett A. Sponseller and Dr. Albert Jergens. Although the family has asked not to be identified, Drs. Sponseller and Jergens have disclosed additional details about the case.

The cat, a 16-pound orange tabby, began acting lethargic and lost his appetite on Oct. 27. He is the only pet in the house and never goes outside. The cat, described as “large framed but not chubby,” stopped eating and drinking and stopped cleaning himself. He also rested by hunching on all four feet, rather than sprawling out on his side as usual, a sign of respiratory discomfort. A few days earlier, two out of three family members in the home had developed flu-like symptoms, with fever and body aches.

The worried pet owner called Dr. Sponseller, a specialist in large animal internal medicine and molecular virology, who happened to be a family friend. At the time, neither Dr. Sponseller nor the pet owner suspected the flu — because the cat had vomited, they wondered whether he might have a gastrointestinal problem.

The next day, the cat arrived at the veterinary school, where he was seen by Dr. Jergens, a small animal specialist and immunologist. Upon examination, it appeared the cat had a respiratory condition, so Dr. Jergens performed a bronchial lavage, injecting fluid in and out of the lungs to collect cells to determine what was making the animal sick.

“It didn’t reveal anything that was consistent with what we typically see with pneumonia in a cat,” Dr. Sponseller said.

Although cats can contract flu from birds, this cat never left the house and was never exposed to any other pet. At that point, it occurred to the veterinarians that since the family members had been recently ill, they might be seeing a case of flu transmitted from human to cat. The school is the site of a major diagnostic lab, so the veterinarians were able to test the cat and quickly confirm he had H1N1, a finding that was later confirmed by additional testing by the U.S. Department of Agriculture.

Additional testing is being conducted to confirm that the family members had H1N1 and to try to verify that the flu was transmitted from human to cat. However, the circumstantial evidence is strong that the cat was infected by its owners and not the other way around. “This cat does not go outside,” Dr. Sponseller said. “Whatever came in, came to the cat.”

Dr. Sponseller says the cat is about 85 percent recovered. He was given fluids for dehydration and put on antibiotics to prevent a secondary bacterial infection. “He’s eating well, moving around well, and he’s back in his window watching the squirrels outside,” he said.

While the Iowa tabby is the first documented case of H1N1 in a cat, it’s possible that other cats who haven’t been tested also have contracted the virus from pet owners. “Since this news story broke, I’ve had owners from around the country sending me e-mails about their experiences,” Dr. Sponseller said. “It’s suggestive that it has happened before, but there’s no confirmation.”

Dr. Sponseller said there is no evidence that a cat could give a person the flu, and transmission is unlikely because cats with flu typically don’t cough or sneeze.

It’s not clear how the cat contracted the virus, but given how easily flu is transmitted between family members, it’s not particularly surprising that a friendly cat would come into contact with the virus as well.

“He’s a very social cat,” Dr. Sponseller said. “He would visit with them in their laps when they were watching television or reading. He was known to climb up on the bed. He’s a very charming cat with a lot of personality.”