All across the wrinkly expanse of the brain’s outer layer, a constellation of different regions handle the meaning of language, scientists report online April 27 in Nature.
One region that responds to “family,” “home” and “mother,” for example, rests in a tiny chunk of tissue on the right side of the brain, above and behind the ear. That region and others were revealed by an intricate new map that charts the location of hundreds of areas that respond to words with related meanings. Such a detailed map hints that humans comprehend language in a way that’s much more complicated — and involves many more brain areas — than scientists previously thought, says Stanford University neuroscientist Russell Poldrack, who was not involved in the work.
In fact, he says, “these data suggest we need to rethink how the brain organizes meaning.”
Scientists knew that different concepts roused action in different parts of the brain, says study coauthor Jack Gallant, a computational neuroscientist at the University of California, Berkeley. But people generally thought that big hunks of the brain each dealt with different concepts separately: one region for concepts related to vision, for example, another for concepts related to emotion. And conventional wisdom said the left hemisphere was most important.
Previous studies, though, tested just single words or sentences, and made only rough estimates of where meaning showed up in the brain, Gallant says. That’s like looking at the world’s countries in Google maps, instead of zooming in to the street view.
So he and colleagues mapped the activity of some 60,000 to 80,000 pea-sized regions across the brain’s outer layer, or cerebral cortex, as people lay in a functional MRI machine and listened to stories from The Moth Radio Hour. (The program features people telling personal, narrative tales to a live audience.) “People actually love this experiment,” Gallant says.
It stands out from others because the authors use “real life, complicated stories,” says Princeton University neuroscientist Uri Hasson. “That’s really meaningful to see how the brain operates.”
Gallant’s team used a computer program to decipher the meaning of every 1- to 2-second snippet of the stories and then cataloged where 985 concepts showed up in the brain. Meanings conveyed by different words didn’t just engage the left hemisphere, the team found, but instead switched on groups of nerve cells spread broadly across the brain’s surface. After mapping where meaning, or semantic content, was represented in the brain, the researchers figured out where individual words might show up. Often, the same word appeared in different locations. For instance, the word “top” turned up in a spot with clothing words, as well as in an area related to numbers and measurements.
The brain maps of the seven participants in the study looked remarkably similar, Gallant says. That could be due to common life experiences: All seven were raised and educated in Western societies. With so few people, the researchers can’t pick out any gender differences, he says, but ideally he’d like to repeat the experiment with 50 or 100 people.
For now, Gallant hopes the map can serve as a resource for other researchers. One day, the work could potentially help those with ALS or locked-in syndrome communicate — by decoding the words in a person’s thoughts. But that’s just one piece of the puzzle, Gallant says. Researchers would also need to devise a method for measuring brain activity that’s portable, unlike MRI machines.
Between around 6,000 and 4,000 years ago, skilled surgeons in southwestern Russia cut holes the size of silver dollars, or larger, out of the backs of people’s skulls. But the risky procedure wasn’t performed for medical reasons: These skull surgeries fulfilled purely ritual needs, a new study suggests. And those on the cutting end of the procedure usually lived.
Skulls of 13 people previously excavated at seven ancient sites in this region contain surgical holes in the same spot, in the middle of the back of the head, say archaeologist Julia Gresky of the German Archaeological Institute in Berlin and her colleagues. That’s a particularly dangerous location for this kind of skull surgery, also known as trepanation, the scientists report online April 21 in the American Journal of Physical Anthropology. It’s not an area of the skull typically targeted in ancient trepanations, which go back roughly 11,000 years in West Asia. “There may have been an original medical purpose for these trepanations, which over time changed to a symbolic treatment,” Gresky says.
Archaeologist Maria Mednikova of the Russian Academy of Sciences in Moscow agrees that skulls in Gresky’s new study probably represent cases of ritual trepanation. She previously examined some of the same skulls. Trepanation may have been used in some ancient cultures as part of a rite of passage for people taking on new social roles, Mednikova speculates.
Carving a center hole in the back of peoples’ heads was a potentially fatal procedure. Surgeons would have needed to know precisely how deep to scrape or grind bone to avoid penetrating a blood-drainage cavity for the brain. They also had to know how to stop potentially fatal bleeding of veins nicked during surgery. The procedure must have been performed as fast as possible to minimize bleeding, the researchers suspect.
Yet 11 of 13 skull openings show signs of healing and bone regrowth, indicating that these individuals survived the operation and often lived for years after. The researchers identify six males and six females in the skull sample. One specimen’s sex couldn’t be determined from skull features.
Most individuals died between ages 20 and 40. One female with a layer of bone that had regrown from the inside border of a trepanation hole died between ages 14 and 16, suggesting her skull surgery had occurred as young as age 10, the researchers estimate.
CT scans, X-rays and analyses of bone surfaces produced no evidence of injuries or brain tumors that could have motivated surgery. Ancient skull surgery intended as a medical treatment often involved holes on the side of the head, near fractures from some type of blow to the head (SN Online: 4/25/08). It’s impossible to determine from bones whether trepanations were aimed at treating chronic headaches, epilepsy, psychological problems or difficulties attributed to evil spirits.
Other evidence, in addition to the risky and unusual location of trepanation holes, points to ritual skull surgeries in southern Russia, Gresky says. Many of these individuals were interred according to special customs, suggesting they ranked high in their societies. For instance, the skulls of seven people buried in a pit at one site had been grouped together near bundled fragments of limb bones in a special display. Incisions on the limb bones indicate that bodies had been dismembered after death before being ritually buried. Of the seven skulls, five display surgical openings at the back of the head. Another contains scrapes from a partial trepanation. Partial trepanations were probably intentional rather than unfinished, with their own cultural significance, Mednikova says.
Trepanation holes on the sides of another six skulls found at the same southern Russian sites were probably made to treat medical conditions, Gresky says. Surgical openings on several of these skulls are located near bone fractures.
Rituals and meanings attached to ancient trepanations in southern Russia will remain mysterious, Mednikova predicts. “We don’t know the myths and religions of tribes that lived there 6,000 years ago.”
Physicists of all stripes seem to have one thing in common: They love smashing things together. This time-honored tradition has now been expanded from familiar particles like electrons, protons, and atomic nuclei to quasiparticles, which act like particles, but aren’t.
Quasiparticles are formed from groups of particles in a solid material that collectively behave like a unified particle (SN: 10/18/14, p. 22). The first quasiparticle collider, described May 11 in Nature, allows scientists to probe the faux-particles’ behavior. It’s a tool that could potentially lead researchers to improved materials for solar cells and electronics applications. “Colliding particles is really something that has taught us so much,” says physicist Peter Hommelhoff of the University of Erlangen-Nuremberg in Germany, who was not involved with the research. Colliding quasiparticles “is really interesting and it’s really new and pretty fantastic.”
It’s a challenge to control these fleeting faux-particles. “They are very short-lived and you cannot take them out of their natural habitat,” says physicist Rupert Huber of University of Regensburg in Germany, a coauthor of the study. But quasiparticles are a useful way for physicists to understand how large numbers of particles interact in a solid.
One quasiparticle, known as a hole, results from a missing electron that produces a void in a sea of electrons. The hole moves around the material, behaving like a positively charged particle. Its apparent movement is the result of many jostling electrons.
The new quasiparticle collider works by slamming holes into electrons. Using a short pulse of light, the researchers created pairs of electrons and holes in a material called tungsten diselenide. Then, using an infrared pulse of light to produce an oscillating electric field, the researchers ripped the electrons and holes apart and slammed them back together again at speeds of thousands of kilometers per second — all within about 10 millionths of a billionth of a second.
The smashup left its imprint in light emitted in the aftermath, which researchers analyzed to study the properties of the collision. For example, when holes get together with electrons, they can bind into an atomlike state known as an exciton. The researchers used their collider to estimate the excitons’ binding energy — a measure of the effort required to separate the pair. The collider could be useful for understanding how quasiparticles behave in materials — how they move, interact and collide. Such quasiparticle properties are particularly pertinent for materials used in solar cells, Huber says. When sunlight is absorbed in solar cells, it produces pairs of electrons and holes that must be separated and harvested to produce electricity.
The researchers also hope to study quasiparticles in other materials, like graphene, a sheet of carbon one atom thick (SN: 08/13/11, p. 26). Scientists hope to use graphene to create superthin, flexible electronics, among other applications. Graphene has a wealth of unusual properties, not least of which is that its electrons can be thought of as quasiparticles; unlike typical electrons, they behave like they are massless.
Obliterating bacteria in the gut may hurt the brain, too.
In mice, a long course of antibiotics that wiped out gut bacteria slowed the birth of new brain cells and impaired memory, scientists write May 19 in Cell Reports. The results reinforce evidence for a powerful connection between bacteria in the gut and the brain (SN: 4/2/16, p. 23).
After seven weeks of drinking water spiked with a cocktail of antibiotics, mice had fewer newborn nerve cells in a part of the hippocampus, a brain structure important for memory. The mice’s ability to remember previously seen objects also suffered. Further experiments revealed one way bacteria can influence brain cell growth and memory. Injections of immune cells called Ly6Chi monocytes boosted the number of new nerve cells. Themonocytes appear to carry messages from gut to brain, Susanne Wolf of the Max Delbrück Center for Molecular Medicine in Berlin and colleagues found.
Exercise and probiotic treatment with eight types of live bacteria also increased the number of newborn nerve cells and improved memory in mice treated with antibiotics. The results help clarify the toll of prolonged antibiotic treatment, and hint at ways to fight back, the authors write.
When molecular biologist Kate Rubins blasts off from Kazakhstan on June 24, strapped into the Soyuz spacecraft bound for the International Space Station, the trip will cap off seven years of preparing — and 30 years of hoping.
As a child, Rubins plastered her Napa, Calif., bedroom with pictures of the space shuttle, proudly announcing her intention to be an astronaut. A week at Space Camp in Huntsville, Ala., in seventh grade cemented her vision. But by high school, she concluded that astronaut wasn’t “a realistic job,” she says. Flash forward to 2009: Rubins is running a lab at the Whitehead Institute for Biomedical Research in Cambridge, Mass., focusing on virus-host interactions and viral genomics. A friend points out a NASA ad seeking astronaut candidates, and Rubins’ long-dormant obsession awakens. Since then, she has learned how to fly a T-38 jet, speak Russian to communicate with her cosmo-naut crewmates, conduct a spacewalk, operate the robotic arm on the ISS and even fix the habitable satellite’s toilet.
Joining NASA meant leaving her 14-person lab behind. But Rubins gained the rare opportunity to collaborate with dozens of scientists in fields as diverse as cell biology and astrophysics. On the space station, she’ll be “their hands, eyes and ears,” conducting about 100 experiments over five months.
She will, for instance, probe how heart cells behave when gravity doesn’t get in the way. And she’ll test a hand-held DNA sequencer, which reads out the genetic information stored in DNA and will be important to future missions looking for signatures of life on Mars.
At times, Rubins will be both experimenter and subject. In one study, she will observe bone cells in a lab dish, comparing their behavior with what happens in a simulated gravity-free environment on the ground. Because astronauts in space are vulnerable to rapid bone loss, CT scanning before and after the mission will also document changes in Rubins’ own hip bone.
Rubins is particularly eager to examine how liquid behaves in microgravity on a molecular scale. In 2013, Canadian astronaut Chris Hadfield created an Internet sensation when he demonstrated that wringing out a wet washcloth in space caused water to form a bubble that enveloped the cloth and his hands. “It’s incredibly bizarre,” Rubins says. Understanding how fluids move in test tubes in space will help NASA plan for Mars exploration, among other applications. Before any of the research can begin, Rubins has to get off the ground. As treacherous as accelerating to 17,500 miles per hour may sound, she’s not worried.
“An important part of the training experience is making all the information and skills routine,” she says. She predicts that sitting down in the Soyuz spacecraft, pulling out her procedures and getting ready to launch will feel a lot like going into the lab and picking up a pipette — “a normal day at the office.”
Until the engines turn on, anyway. “I think it’s going to feel different when there’s a rocket underneath.”
Hair, scales and feathers arose from one ancestral structure, a new study finds.
Studies in fetal Nile crocodiles, bearded dragon lizards and corn snakes appear to have settled a long-standing debate on the rise of skin coverings. Special skin bumps long known to direct the development of hair in mammals and feathers in birds also turn out to signal scale growth in reptiles, implying all three structures evolved from a shared ancestor, scientists report online June 24 in Science Advances. In embryonic birds and mammals, some areas of the skin thicken into raised bumps. Since birds evolved from ancient reptiles, scientists expected that modern snakes, lizards and crocodiles would have the same structures. A study at Yale University last year found that one protein already known to be important in hair and feather development is also active in the skin of developing alligators. But the team did not find the telltale skin thickening. Without that evidence from modern reptiles, scientists weren’t sure if the bumps had been lost in reptiles, or if birds and mammals had evolved them independently, using the same set of genes. The new results are “a relief,” says Michel Milinkovitch, whose lab led the new study at the University of Geneva. Scientists had come up with a variety of complicated ideas to explain how birds and mammals could share a structure that reptiles lack. But, he says, “the reality is much simpler.”
Clues from a mutant lizard inspired Milinkovitch’s team to probe the mystery. Nicolas Di-Poï, a coauthor of the new study who is now at the University of Helsinki, found that a hair-development gene called EDA was present, but disrupted, in scaleless, or “silky,” bearded dragons. Di-Poï and Milinkovitch searched for similar molecular signals in normal reptile embryos and found genes and proteins associated with hair and feather growth studding the skin. Cell staining revealed characteristic skin thickening at those signal centers.
Reptilian skin bumps eluded previous researchers because they are tiny, appear briefly and don’t all come in at once as they do in mammals, Milinkovitch speculates. “You have to look in the right place at the right time to see them,” he says. “Then boom, you see them, and you’re like, ‘Whoa, they are exactly the same.’”
This study “addresses a fundamental question about identity for skin structures,” says paleontologist Marcelo Sánchez of the University of Zurich, who was not involved in the new research. It’s especially important that the team used crocodiles, lizards and snakes, which are far from typical lab animals, he says. Using nonmodel organisms “gives new insight into evolution we wouldn’t get otherwise.”
The next step is to understand how hairs, feathers and scales diversified from the same ancestral structure. That primordial body covering wasn’t necessarily a scale, says evolutionary biologist Günter Wagner, an author of the 2015 Yale study. “Even though intuitively you would think reptilian-like skin is ancestral, compared to mammals,” he says “it’s entirely unclear what kind of structure the scales and feathers on the one side and hair on the other has evolved from.”
A gaping wound in Earth’s atmosphere is definitively healing. Since 2000, the average size of the Antarctic ozone hole in September has shrunk by about 4.5 million square kilometers, an area larger than India, researchers report online June 30 in Science. While the hole won’t close completely until at least midcentury, the researchers say the results are a testament to the success of the Montreal Protocol. That international treaty, implemented in 1989, banned ozone-depleting chemicals called chlorofluorocarbons worldwide.
Ozone helps shield life on Earth from hazardous ultraviolet radiation. Tracking the ozone layer’s recovery process is tricky because natural phenomena such as volcanic eruptions and weather variations can alter the size of the ozone hole. While some earlier studies suggested that the ozone had already begun healing (SN: 6/4/11, p. 15), many scientists questioned whether the work had been detailed enough to separate out the effects of natural variability.
MIT atmospheric scientist Susan Solomon and colleagues used a sophisticated 3-D atmospheric simulation to distinguish between the forces acting on atmospheric ozone. The work suggests that about half of the ozone hole’s recent shrinkage resulted from a drop in chlorofluorocarbons in the atmosphere; the remainder stemmed from weather changes.
Volcanic eruptions obscure healing signs. Last October, the ozone hole reached a record-setting average size of 25.3 million square kilometers — an area larger than Russia — thanks to the April 2015 eruption of Chile’s Calbuco volcano. That large size doesn’t disprove that the ozone hole is healing in the long run, though. Without the temporary 4.2-million-square-kilometer boost from the volcano, the hole’s average size would have peaked at a more modest 21.1 million square kilometers, the researchers estimate.
For a “three-parent baby,” getting disease-free mitochondrial DNA from a surrogate may do more than just avert disease: For better or for worse, a donor’s mitochondria could also affect the course of aging, new research shows.
Two strains of mice – genetically identical except for the source of their mitochondria, the energy centers of cells – aged very differently, researchers report online July 6 in Nature. Even though both mouse strains had healthy mitochondrial DNA, the mice with mitochondria that did not come from the same source as the rest of their DNA fared better later in life: After two years, these mice showed fewer signs of aging and had a lower incidence of tumors. The results don’t necessarily mean that a mitochondria transplant leads to a healthier life. This is just one case, researchers caution. Other DNA mixes and matches could turn out differently. But the study’s finding does point to a larger relationship between mitochondrial DNA and aging and raises new questions about the long-term effects of creating three-parent babies.
What the new results mean for people is still unclear, says Michio Hirano, a neurologist at Columbia University who was not involved in the study. But if the findings do apply to humans, he says, “you can blame your mother for how you age.”
Mitochondrial DNA is passed down from mother to child. Three-parent babies are created through an in-vitro fertilization technique that substitutes a mother’s diseased mitochondria for the healthy mitochondria of a surrogate (SN: 11/17/12, p. 5). In the procedure, which is legal in the United Kingdom and deemed ethical by a U.S. panel of experts this year (SN Online: 2/3/16), a baby inherits its nuclear DNA — the majority of its genetic fingerprint — from mom and dad. But a small amount of DNA — just 37 genes — comes from the mitochondria of a second, healthy woman.
Mitochondria do more than just power cells; they also play big roles in cell-to-cell communication and metabolism. Over the last two decades, mitochondria have also been implicated in aging but without conclusive evidence. The new research, Hirano says, “adds fuel to this debate.”
In the study, José Enríquez of the Spanish National Center for Cardiovascular Research in Madrid and colleagues bred two strains of mice. The original strain was called C57/Black 6. A second strain of C57/Black 6 carried mitochondria from another kind of mouse called NZB. This mismatch mimicked the effects of a mitochondrial transplant. Early in life, normal C57 mice bulked up faster than those carrying NZB mitochondria and had 11 percent longer telomeres (protective caps at the ends of chromosomes that get shorter over time, so are used as a proxy for aging). But later in life, the mice with NZB mitochondria had longer telomeres, less fat in their muscles and lower risk of having liver tumors at the end of their lives. Young C57 mice “tend to be stronger,” Enríquez says, probably because their mitochondrial and nuclear DNA are a good match and make efficient mitochondria. The weaker batteries in the mice with mismatched mitochondria may cause more cellular stress early on, he says, which may toughen up these mice to age more gracefully.
Since the study was done in mice, researchers don’t know how mitochondrial substitution would affect aging in humans. To avoid unforeseen and unwanted consequences, Enríquez urges caution. “Before we understand it better,” a mitochondrial transplant should mimic natural conditions, he says: “Why don’t we match the mitochondrial DNA of the donor and receptor?”
On the inevitability scale, death and taxes are at the top. Aging is close behind.
It’s unlikely that scientists will ever find a way to avoid death. And taxes are completely out of their hands. But aging, recent research suggests, is a problem that science just might be able to fix.
As biological scientists see it, aging isn’t just accumulating more candles on your birthday cake. It’s the gradual deterioration of proteins and cells over time until they no longer function and can’t replenish themselves. In humans, aging manifests itself outwardly as gray hair, wrinkles and frail, stooped bodies. Inside, the breakdown can lead to diabetes, heart disease, cancer, Alzheimer’s disease and a host of other problems. Scientists have long passionately debated why cells don’t stay vigorous forever. Research in mice, fruit flies, worms and other lab organisms has turned up many potential causes of aging. Some experts blame aging on the corrosive capability of chemically reactive oxygen molecules or “oxidants” churned out by mitochondria inside cells. DNA damage, including the shortening of chromosome endcaps (called telomeres) is also a prime suspect. Chronic, low-grade inflammation, which tends to get worse the older people get, wreaks so much havoc on tissues that some researchers believe it is aging’s prime cause, referring to aging as “inflammaging.” All these things and more have been proposed to be at the root of aging. Some researchers, like UCLA’s Steve Horvath, view aging as a biological program written on our DNA. He has seen evidence of a biological clock that marks milestones along life’s path. Some people reach those milestones more quickly than others, making them older biologically than the calendar suggests. Others take a more leisurely stroll, becoming biological youngsters compared with their chronological ages.
Many others, including Richard Miller, a geroscientist at the University of Michigan, deny that aging is programmed. Granted, a biological clock may measure the days of our lives, but it’s not a ticking time bomb set to go off on a particular date. After all, humans aren’t like salmon, which spawn, age and die on a schedule.
Instead, aging is a “by-product of running the engine of life,” says biodemographer Jay Olshansky of the University of Illinois at Chicago. Eventually bodies just wear out. That breakdown may be predictable, but it’s not premeditated. Despite all the disputes about what aging is or isn’t, scientists have reached one radical consensus: You can do something about it. Aging can be slowed (maybe even stopped or reversed). But exactly how to accomplish such a counterattack is itself hotly debated. Biotechnology and drug companies are developing several different potential remedies. Academic scientists are investigating many antiaging strategies in animal experiments. (Most of the research is still being done on mice and other organisms because human tests will take decades to complete.) Even researchers who think they have finally come up with real antiaging elixirs say they don’t have the recipe for immortality, though. Life span and health span, new research suggests, are two entirely separate things. Most researchers who work on aging aren’t bothered by that revelation. Their goal is not necessarily extending life span, but prolonging health span — the length of time people live without frailty and major diseases.
Aging as disease Many health problems are so commonly associated with aging that some researchers take the highly controversial stance that aging itself is a disease, says Saul Villeda of the University of California, San Francisco.
If aging is a disease, in Villeda’s lab it’s almost a contagious one: He can artificially spread aging from old lab mice to young ones. One mode of aging transmission is to give genetically identical mice transfusions of young or old blood. In another approach, researchers sew together pairs of mice so that their blood vessels will join up and link their circulatory systems.
This artificial joining of two separate animals, known as parabiosis, was a staple of physiology experiments for over a century before Irina Conboy got the idea to pair an old mouse with a young one. Conboy, a stem cell researcher at the University of California, Berkeley, made headlines with her experiments. Those headlines focused on the good news: Young blood rejuvenated old mice. In further studies by other researchers, infusions of young blood made broken bones in old mice heal better (SN Online: 5/19/15), gave their muscles extra spring and improved their memories (SN: 5/31/14, p. 8). Apparently some substances in the blood triggered the rejuvenation. Some candidates for those rejuvenation factors have been identified, although none are universally agreed on.
But news accounts mostly ignored the flip side of the experiment: Being tethered to an old mouse made young mice age faster. One substance in the blood of old mice, a protein called Beta‑2‑microglobulin, or B2M, seemed to prematurely age the young ones, Villeda and colleagues reported last year in Nature Medicine (SN: 8/8/15, p. 10). Parabiosis experiments don’t last very long, so no one knows whether youth or decrepitude will win in the end — or if the two mice would have settled into middle age together.
UCLA’s Horvath has evidence that the mice may never totally sync. He monitors aging by examining molecular tags called methyl groups, which attach to various locations on DNA in a process called methylation. Methylation is an epigenetic modification of DNA. Such modifications work something like flagging passages in a book with sticky notes. Attaching a tag doesn’t change the information in the book — it just draws attention to some passages and signals that others should be ignored.
Horvath measures DNA methylation changes at 353 different spots in the human genetic instruction book, or genome. As people age, 193 locations accumulate tags, like playbills plastered on urban buildings. At 160 others, methylation is gradually stripped away with age. Knowing how much methylation is normally found at each spot at a given chronological age allows Horvath to calculate biological age. Some people age at different rates than others, he discovered. For instance, semi-supercentenarians — people who live to be 105 to 109 — are about 8.6 years younger epigenetically than their chronological age. Their children are slow to age, too, though not as slow as their parents. Epigenetic clocks indicate that the offspring are about five years younger biologically than other people of the same chronological age.
People often joke about certain abilities, such as eyesight, memory or hearing being “the first to go.” Some of Horvath’s work suggests that the notion isn’t entirely far-fetched. He calculated the epigenetic age of specific organs and discovered that body parts can age at different rates. The cerebellum, the part of the brain that sits at the top of the brain stem and helps coordinate movement, speech and other activities, ages the slowest of the brain regions that Horvath analyzed. While there are natural differences in organ aging, some conditions, such as HIV infection and obesity, can prematurely age certain organs, Horvath and colleagues have found.
These experiments demonstrate that aging and its effects are malleable. “Aging is really plastic — it’s not set in stone,” says Conboy. Consequently, she and other researchers agree, something can be done to slow aging, or perhaps turn it around entirely. But exactly what can be done is vigorously disputed.
Interpret with caution Most scientists working on aging urge caution in extrapolating promising results in animal studies to humans. For instance, one of the most promising early candidates for a rejuvenation factor from young blood was a protein called GDF11. Reports in 2013 and 2014 concluded that GDF11 levels in blood decline with age; restoring the protein in old animals could reverse some heart problems, improve muscle strength and spur nerve cell growth in the brain. Since those reports, other researchers have disputed the protein’s revitalizing powers. In a recent study, researchers measured GDF11 levels in 140 people aged 21 to 93. Levels of the protein didn’t decline with age, Mayo Clinic researchers reported in the June 14 Cell Metabolism. Previous researchers may have gotten GDF11 mixed up with a similar protein called myostatin, which does dip as people get older. Not only does GDF11 not decline with age, having too much of it could be bad, the Mayo team found. People with higher blood levels of the protein were more likely to be frail, have diabetes and heart problems, and have a more difficult time recovering from surgery than people with lower levels of the protein.
Beyond the blood experiments, scientists have examined various ideas about what goes wrong in aging and have devised strategies to counteract it. For instance, some evidence suggests that stem cells run out of steam as they get older. Restoring old stem cells to youthful vigor may enable them to repair or replace damaged tissues and turn back the biological clock. Keeping stem cells youthful may involve sheltering them from inflammation or things that could damage their DNA.
One way to keep stem cells and other cells working is to avoid the loss of telomeres capping the ends of chromosomes. As cells divide, their telomeres grow shorter until they are so short that chromosomes can no longer safely replicate. That may be a signal for the cell to shut down or die. So some researchers think that lengthening telomeres could give cells the protection needed to survive longer.
One biotechnology company executive flew from the United States to Colombia to try out her company’s gene therapy for lengthening telomeres. That decision bypassed U.S. government and other safety measures designed to protect human study participants. And no one knows whether it will work or doom her to cancer, which often relies on long telomeres to keep growing.
Other researchers are exploring more measured approaches to antiaging therapies. One study in dogs is testing rapamycin, the first drug shown to lengthen mouse life spans. Rapamycin is an immune suppressant that also has anticancer effects. The rationale for using it came from research on caloric restriction, the world-champion method for making animals live longer. Animals on calorie-restricted diets typically eat at least 25 percent fewer calories than normal. Such low-cal treatment has increased life spans in mice, dogs, fruit flies, yeast, worms and other lab organisms. Results from primate studies have been mixed (SN: 8/1/09, p. 9; SN: 10/6/12, p. 8). Some people have put themselves on caloric-restriction regimes (SN: 10/25/08, p. 17). A handful of studies suggest that those people have better health, but it’s too soon to know whether they will outlive their peers.
Exactly why drastically reducing food intake can extend life isn’t known. But researchers have good evidence that a series of biochemical reactions known as the mTOR pathway is involved. The protein mTOR helps monitor nutrient levels in cells and regulates cell movement, protein production, and cell growth and survival. When starvation sets in, cells turn off mTOR’s activity, which allows a self-cannibalizing process called autophagy to scavenge nutrients by digesting some of the cell’s internal organs. This internal garbage disposal and recycling method also removes old, worn-out mitochondria and proteins that may otherwise keep cells from functioning efficiently. That process and other cellular activities governed by mTOR may be responsible for making cells, and organisms, live longer. Rapamycin gave mTOR its name — mechanistic target of rapamycin. Giving the drug might do what caloric restriction does without requiring superstrict diets (SN: 6/4/11, p. 22). Matt Kaeberlein, a geroscientist at the University of Washington, and colleagues conducted a safety study of the drug last year in 24 dogs. The study was only 10 weeks long, so the researchers can’t yet draw any conclusions about long-term effects on aging. But the dogs had no major side effects from taking low doses of the drug, a worry because rapamycin impairs immune system function and could make animals (including people) who take it more vulnerable to infection or cancer.
Rapamycin’s drawbacks make it unattractive for human studies. The diabetes drug metformin may instead be the antiaging drug of choice for people, says gerontologist Nir Barzilai. In addition to mTOR, metformin targets an insulin-like growth protein known as IGF-1. That protein has been implicated in a variety of biological processes that promote aging.
Barzilai, of Albert Einstein College of Medicine in New York City, and researchers at more than a dozen centers around the country plan to test metformin for its ability to fight aging in people 65 to 79. Barzilai and colleagues laid out the case for using metformin in the June 14 Cell Metabolism. Metformin is generally safe, with few major side effects. It has been shown to improve a variety of health measures and to impair cancer development in people with type 2 diabetes (SN: 11/30/13, p. 18). Barzilai says the drug may help people who don’t have diabetes also live healthier when they are elderly. If it does, commercials touting metformin might have to add another disclaimer, he jokes. “The commercials will go on: ‘This will make you healthy, but we have to apologize because you might live longer.’ ”
But studies of mice suggest that disclaimer may not be necessary. Research by Miller and others suggests that metformin may not prolong life. They have been dosing mice with various chemicals, including metformin and rapamycin, looking for drugs that will make mice healthier and live longer. In a new study, published online June 16 in Aging Cell, Miller and colleagues fed mice metformin starting when the rodents were 9 months old — middle age for a mouse. Combining metformin and rapamycin didn’t make the mice live much longer than rapamycin alone did in previous trials.
Cellular zombies Other researchers are hoping to stave off death by getting rid of the undead. Cellular zombies called senescent cells are stressed cells that have entered a type of stasis — they’re not dead, but they’re not functioning either. Stress for cells usually means severe DNA damage that could produce cancer, critically short telomeres or other molecular catastrophes that trigger shutdown mode. That lockdown is for the greater good, says aging researcher Judith Campisi, who studies senescence at the Buck Institute for Research on Aging in Novato, Calif. “It’s protective,” she says. “You don’t want defective cells to propagate.” (When damaged cells continue to grow they may become cancerous.)
Unfortunately, says Campisi, the senescent cells don’t die. Instead they send out messages to neighboring cells: “Hey, there’s a problem. Be prepared. What happened to me could happen to you.” Such messages are probably intended as public service announcements, but they could trigger mass panic and inflammation. Like zombies putting the bite on the living, senescent cells damage surrounding cells and accelerate aging.
Researchers have worked out methods for hitting the zombie cells with genetic shots to the head, effectively destroying the cells and removing them from the body. Mice from which senescent cells have been removed had increased median life span and improved health, researchers reported in Nature in February (SN: 3/5/16, p. 8).
Campisi and other researchers are working on ways to clear senescent cells from humans, too. But no antiaging treatment makes mice or any other animal live forever. Researchers have yet to increase a mouse’s life span (which rarely goes above two years) to five years, although one mouse fell just short of that mark.
Much research suggests that things that extend life span, such as rapamycin, might not stretch health spans. Mutations that make millimeter-long transparent worms known as Caenorhabditis elegans live longer also extend the proportion of their lives the worms spend being frail, Heidi Tissenbaum of the University of Massachusetts Medical School in Worcester and colleagues reported last year in the Proceedings of the National Academy of Sciences.
But living healthy doesn’t guarantee longevity either, a new study of sea urchins suggests. Red sea urchins (Mesocentrotus franciscanus) live well past 100 years old in the wild, while purple sea urchins (Strongylocentrotus purpuratus) make it to 50. But variegated (also called “green”) sea urchins (Lytechinus variegatus) normally die after four years. The difference in the species’ life spans might be due to different rates of aging, thought aging researcher Andrea Bodnar at the Bermuda Institute of Ocean Sciences in St. George’s and developmental biologist James Coffman of the MDI Biological Laboratory in Salisbury Cove, Maine. Instead, they found, none of the species seem to age at all . Young and old members of each species are similar in their abilities to reproduce and to regenerate spines and tube feet, the researchers reported online April 20 in Aging Cell . Even though the short-lived variegated urchins have no signs of slowing down, they still die. Why is a mystery, Coffman says. Ways to be wellderly A similar paradox is also seen in “wellderly” people that geneticist Ali Torkamani has been studying at the Scripps Research Institute in La Jolla, Calif. About eight years ago, Torkamani started bringing in people over 80 who had made it to an advanced age without any sign of chronic disease. The idea was to study their DNA and learn the secrets of healthy aging.
Despite living healthy, the wellderly didn’t carry genetic variants connected with extremely long lives, Torkamani and colleagues discovered. The wellderly also had no genetic advantage when it comes to cancer, stroke or diabetes. What they did have was a lower risk of getting Alzheimer’s and heart disease. Each of the wellderly seemed to have their own genetic recipe for success, suggesting there are lots of ways to stay healthy into old age. The researchers didn’t rule out that diet and lifestyle also help. “There’s hope for everybody,” Torkamani declares.
But his cloud of optimism may have a tarnished lining. His findings, along with the sea urchin and worm results, suggest that aging and longevity aren’t the same things. If that’s the case, it would mean that stopping aging would not extend human life span by much. The oldest (verified) person to have ever lived was Jeanne Louise Calment, a French woman who died at age 122 in 1997. People might top out at 130 if aging is controlled (and most people still would not make it that long because they just don’t have the necessary makeup). As a species, humans probably can’t go further without changing whatever controls longevity too, some researchers think.
Exactly how long people can live won’t be answered until proven antiaging therapies are developed. If aging and longevity are linked, then treating aging could very well make people live longer, healthier lives. If they are separate phenomena, then people could forgo the cancer, heart disease and other ailments of aging, but they would still have limited life spans. In that case Star Trek’s Mr. Spock might need to revise his usual parting words. When talking to humans, he should wish that they will live long or prosper. We may not get both.
Happy 40th anniversary, Viking 1! Four decades ago — July 20, 1976 — the robotic probe became the first U.S. mission to land on Mars. Its sister spacecraft, Viking 2, touched down 45 days later.
Launched August 20, 1975, Viking 1 spent over 6 years snapping pictures and studying the soil at its landing site, an ancient crater named Chryse Planitia. An experiment to look for Martian microbes turned up nothing definitive, though some researchers continue to argue otherwise.
Viking 1 wasn’t the first to successfully touch down on the Red Planet. That honor goes to the Soviet probe Mars 3, whichgently landed on Mars in 1971, though its only transmission — a partial, garbled image — lasted just 20 seconds.
Today, seven probes actively call Mars home. A European-led orbiter and lander, ExoMars, is on its way, and NASA has two missions lined up: the Insight lander, whose launch was recently delayed to 2018, and the Mars 2020 rover, which will pick up where the Vikings left off and search for Martian life.
