Archive for the ‘aging’ Category

by Lindsay Peterson

We think of aging as something we do alone, the changes unfolding according to each person’s own traits and experiences. But researchers are learning that as we age in relationships, we change biologically to become more like our partners than we were in the beginning.

“Aging is something that couples do together,” says Shannon Mejia, a postdoctoral research fellow involved in relationship research at the University of Michigan in Ann Arbor. “You’re in an environment together, and you’re appraising that environment together, and making decisions together.” And through that process, you become linked physically, not just emotionally.

It’s like finishing each other’s sentences, but it’s your muscles and cells that are operating in sync.

Doctors tend to treat people as individuals, guided by the need to ensure patient confidentiality. But knowing about one partner’s health can provide key clues about the other’s. For instance, signs of muscle weakening or kidney trouble in one may indicate similar problems for the other.

Looking at married couples who were together less than 20 years and couples together for more than 50, Mejia and her colleagues have found striking similarities between partners who have spent decades together, especially in kidney function, total cholesterol levels and the strength of their grips, which is a key predictor of mortality. They presented their findings at the annual meeting of the Gerontological Society of America.

The data came from 1,568 older married couples across the United States. The couples were part of a larger dataset that included information on their income and wealth, employment, family connections and health, including information based on blood tests.

One obvious reason for partner similarity is that people often choose partners who are like them — people from the same stock, with similar backgrounds. But that didn’t explain why there were more similarities between the long-time partners, compared to the others.

To learn more about this element of partner choice versus spending decades together, the researchers analyzed couples by age, education and race. When they accounted for the effect of partner choice, they found that the biological similarities persisted, based on markers in blood tests.

The way Mejia puts it, this likeness includes “something the couples co-created” over time, not just what they started with because they were similar at the beginning.

She’s now studying what may be causing these “co-created” biological similarities. “We’re working on a few things,” she said, such as the effect of partners’ shared experiences and of sharing an environment where they have similar advantages and disadvantages, like the ability to walk in their neighborhoods or find other ways to stay active.

Mejia’s work follows that of Christiane Hoppmann, an associate professor at the University of British Columbia, in Vancouver. She and her colleagues found that longtime couples experienced similar levels of difficulty with daily tasks, such as shopping for food, making a hot meal and taking medications. They found the same for depression, and with both depression and daily task difficulties, they found that the couples changed, for better or for worse, in sync.

They also found that the effects crossed over from the mental to the physical. In other words, increases in feelings of depression in one spouse led to more daily task limitations in the other.

Hoppmann and Denis Gerstorf, of Humboldt University in Berlin, suggest that a key factor here could be physical activity. For instance, if a depressed partner refuses to leave the house, the other may feel compelled to remain at home, too. The longer the two remain sedentary, the more vulnerable they become to a range of problems, from worsening depression to diabetes, that can limit their ability to function from day to day.

But the news in these partner studies is not all bad.

William Chopik, an assistant professor of psychology at Michigan State University, has found evidence of the power of optimism. He and his research colleagues studied optimism, in addition to health and activity limitations, in 2,758 older couples in a national dataset. Optimism scores came from a test that measured their level of agreement or disagreement with statements such as “in uncertain times, I usually expect the best.”

The researchers found that over a four-year period, when one partner’s optimism increased, the other partner experienced fewer illnesses such as diabetes and arthritis compared to people whose partners did not become more optimistic. So, “the fact that (your spouse) increased in optimism is good for you,” even if your optimism didn’t rise, Chopik said.

He isn’t sure why this is happening in their study, also presented at the Gerontological Society meeting. He and his colleagues had accounted for age, gender and education differences. He speculates that optimists are more likely to live healthy lives and use their influence over their partners to get them to live healthier, too.

Chopik is currently studying how two partners’ levels of cortisol, a hormone related to stress, change and become coordinated over time. He plans to compare couples whose relationships span at least 40 years to those who have been together for less than two.

These investigations of how couples affect each other’s health are relatively new, particularly the research into the biological changes, and the researchers are still searching for explanations.

Nevertheless, they say, the implications for health care are clear. People in relationships don’t experience chronic health problems on their own. When a spouse comes in with a problem, the other spouse could be part of the cause — or the solution.

Five places in the world are now considered so-called “Blue Zones” – geographic areas where people are living much longer and more active lives. The first Blue Zone identified was Sardinia’s Nuoro province, which researchers Gianni Pes and Michel Poulain found to have the greatest number of male centenarians. Four other Blue Zones have since been identified by National Geographic explorer Dan Buettner and his team of longevity researchers. In these Blue Zones people are reaching the age of 100 at a much greater rate than anywhere else in the world. So what exactly sets these places apart from the rest? In his book The Blue Zones: Lessons for Living Longer From the People Who’ve Lived the Longest, Dan Buettner discusses the lessons he learned from the people inhabiting the Blue Zones and what specific lifestyle characteristics allow these people to live longer and better lives.

Ikaria, Greece

The tiny Mediterranean island boasts nearly non-existent rates of dementia and chronic disease and an isolated culture with a focus on socialization. Residents often drink goat’s milk and herbal teas and eat a Mediterranean diet full of fruits and vegetables, whole grains, beans, potatoes, and olive oil. Because this population is comprised traditionally of Greek Orthodox Christians, many fast for nearly half the year (caloric restriction has been linked to a slowing of the aging process in mammals). They also exercise by gardening, walking, or completing yard work but also nap regularly.

Loma Linda, CA

It may be surprising that one of the Blue Zones is located in the U.S., but Loma Linda is home to about 9,000 Seventh-day Adventists who form an extremely close community. Many Seventh-day Adventists adhere to a vegetarian diet rich in fruits and vegetables and consume water and nuts in lieu of soda and unhealthy snacks. They also spend time with family and friends, particularly during the weekly 24-hour Sabbath, and give back by volunteering.

Nicoya, Costa Rica

Besides their diet, the secret to a longer life for Nicoyans may be in their sense of purpose and strong social connections. They eat a traditional diet of fortified maize and beans, drink water with the country’s highest calcium levels, and eat a light dinner early in the early evening. Nicoyan residents often live with family members for support and strongly wish to contribute to a greater good. Their physical work keeps them fit and is embraced in everyday life.

Okinawa, Japan

Although this area is experiencing a decline in life expectancies from the influence of factors like fast food, older residents have consumed a plant-based, soy-rich diet most of their lives and eat pork only for infrequent ceremonial occasions in small amounts. Okinawans spend time outside every day and nearly all grow or have grown gardens (a source of vitamin D and fresh vegetables). It is also traditional to form a moai, or social network, for emotional and financial support.

Shuri Castle in Okinawa, Japan

Shuri Castle in Okinawa, Japan

Sardinia, Italy

Sardinia has nearly 10 times more centenarians per capita than the U.S., which could be attributed to a combination of genetics and a traditional lifestyle. The rare genetic M26 marker is common in this population and has been associated with longevity; due to the geographic isolation of the island, this gene is not prevalent in other areas worldwide. Sardinians eat a plant-based diet with pecorino cheese made from grass-fed sheep that is high in omega-3 fatty acids and drink wine in moderation. Laughter may be good medicine on this island – men in particular here are known for their afternoon laughing sessions in the street.

View of Cala Domestica beach, Sardinia, Italy

View of Cala Domestica beach, Sardinia, Italy

Why are some people sharp as a tack at 95 years old, while others begin struggling with mental clarity in their 50s?

A lot of it has to do with genetics, but certain lifestyle factors also play an important role in how our brain ages. So while you can’t control your genes, you can take advantage of the latest science and avoid these seven big brain mistakes:

Mistake No. 1: Eating a standard American diet

Foods high in sugar, unhealthy fats and processed foods — i.e., the typical American diet — can wreak havoc on your brain over time. Studies have shown that excess sugar consumption can impair learning and memory, and increase your vulnerability to neurodegenerative diseases like Alzheimer’s. Some scientists have even referred to Alzheimer’s as “Type 3 Diabetes,” suggesting that diet may have some role in an individual’s risk for developing the disease.

A Mediterranean-based diet, on the other hand, can help protect the brain from signs of aging and ward off cognitive decline. A recent study showed that following this type of diet — which is a good source of brain-healthy nutrients and includes a lot of fish, healthy fats, whole grains and vegetables — could slash Alzheimer’s risk by up to 50 percent.

Mistake No. 2: Living next to a highway

Living in a smoggy city might be bad news for your brain. According to research published this month in the journal Stroke, exposure to air pollution is linked with premature aging of the brain.

The researchers found that people who lived closer to a major highway had greater markers of pollution in their lungs and blood, which increased their risk for a form of brain damage known as “silent strokes,” or symptomless strokes. Increased pollution volume was also linked to decreased brain volume — a major sign of aging.

Mistake No. 3: Drinking a few evening cocktails

Don Draper’s daily cigarettes and two-martini lunches might seem glamorous on “Mad Men,” but research suggests that they’re a fast track to neurodegeneration.

It should come as no surprise that excessive drinking and cigarette smoking at any stage of life can have a negative effect on the brain, damaging brain tissue and leading to cognitive impairment. Alcoholism can cause or accelerate aging of the brain.

But just a couple of glasses of wine a night could pose a risk to brain health, even though there are some cardiovascular benefits. A 2012 Rutgers University study found that moderate to binge drinking — drinking relatively lightly during the week and then more on the weekends — can decrease adult brain cell production by 40 percent.

“In the short term there may not be any noticeable motor skills or overall functioning problems, but in the long term this type of behavior could have an adverse effect on learning and memory,” one of the study’s authors, Rutgers neuroscience graduate student Megan Anderson, said in a statement.

Mistake No. 4: Giving in to stress

Living a stressful lifestyle may be the worst thing you can do for your health as you age. Chronic stress is known to shorten the length of telomeres, the sequences at the end of DNA strands that help determine how fast (or slow) the cells in our body age. By shortening telomeres, stress can accelerate the onset of age-related health problems.

What about the brain? Well, some research has suggested that high levels of stress hormones can increase an individual’s risk for age-related brain damage.

“Over the course of a lifetime, the effects of chronic stress can accumulate and become a risk factor for cognitive decline and Alzheimer’s disease,” Howard Fillit, a clinical professor of geriatric medicine at The Mount Sinai School of Medicine, wrote in Psychology Today. “Several studies have shown that stress, and particularly one’s individual way of reacting to stress (the propensity to become ‘dis-stressed’ often found in neurotic people for example), increases the risk for Alzheimer’s disease.”

If you’re feeling stressed out, try picking up a meditation practice. Research has shown that meditation is effective in lowering levels of the stress hormone cortisol and protecting the brain from aging.

Mistake No. 5: Getting by on less sleep than you need

There are a number of scary health effects associated with sleep deprivation, from a higher risk of stroke and diabetes to impaired cognitive functioning. Over the years, losing shut-eye can also accelerate brain aging. In a study conducted last year, researchers from Singapore found that the less that older adults slept, the faster their brains aged.

The study’s lead author explained in a statement that among older adults, “sleeping less will increase the rate their brain ages and speed up the decline in their cognitive functions.”

Mistake No. 6: Sitting all day

It’s a well-established fact that sitting for long periods is terrible for your health. A growing body of research has linked a sedentary lifestyle with health risks including heart disease, diabetes, cancer and early death, even among people who get the recommended daily amount of exercise.

And it turns out that sitting is also pretty bad for your brain. Research has linked physical inactivity with cognitive decline. Moreover, weight gain in older adults — which may result from too much sitting — has been linked with shrinkage in brain areas associated with memory.

So when in doubt, move around. Physical activity has been linked with a number of brain health benefits, including improved learning and memory.

Mistake No. 7: Zoning out

Use it or lose it! If you want to keep your brain sharp, keep it engaged. It doesn’t have to be a challenging intellectual task or a brain-training game, either — simply engaging in everyday activities like reading, cooking or having a conversation (as opposed to vegging out in front of the TV or computer) can make a difference.

But mental exercises like crossword puzzles and sudoku can help, too. A 2013 study published in the Canadian Medical Association Journal found that brain exercises are more effective than drugs in preventing cognitive decline.

The bottom line? Doing new and novel things promotes neurogenesis, the creation of new neurons in the brain. So get outside, learn, discover and try something new to keep your brain sharp through the decades.

Why do some people remain healthy into their 80s and beyond, while others age faster and suffer serious diseases decades earlier? New research led by UCLA life scientists may produce a new way to answer that question—and an approach that could help delay declines in health.

Specifically, the study suggests that analyzing intestinal bacteria could be a promising way to predict health outcomes as we age.

The researchers discovered changes within intestinal microbes that precede and predict the death of fruit flies. The findings were published in the open-source journal Cell Reports.

“Age-onset decline is very tightly linked to changes within the community of gut microbes,” said David Walker, a UCLA professor of integrative biology and physiology, and senior author of the research. “With age, the number of bacterial cells increase substantially and the composition of bacterial groups changes.”

The study used fruit flies in part because although their typical life span is just eight weeks, some live to the age equivalent of humans’ 80s and 90s, while others age and die much younger. In addition, scientists have identified all of the fruit fly’s genes and know how to switch individual ones on and off.

In a previous study, the UCLA researchers discovered that five or six days before flies died, their intestinal tracts became more permeable and started leaking.

In the latest research, which analyzed more than 10,000 female flies, the scientists found that they were able to detect bacterial changes in the intestine before the leaking began. As part of the study, some fruit flies were given antibiotics that significantly reduce bacterial levels in the intestine; the study found that the antibiotics prevented the age-related increase in bacteria levels and improved intestinal function during aging.

The biologists also showed that reducing bacterial levels in old flies can significantly prolong their life span.

“When we prevented the changes in the intestinal microbiota that were linked to the flies’ imminent death by feeding them antibiotics, we dramatically extended their lives and improved their health,” Walker said. (Microbiota are the bacteria and other microorganisms that are abundant in humans, other mammals, fruit flies and many other animals.)

Flies with leaky intestines that were given antibiotics lived an average of 20 days after the leaking began—a substantial part of the animal’s life span. On average, flies with leaky intestines that did not receive antibiotics died within a week.

The intestine acts as a barrier to protect our organs and tissue from environmental damage.

“The health of the intestine—in particular the maintenance of the barrier protecting the rest of the body from the contents of the gut—is very important and might break down with aging,” said Rebecca Clark, the study’s lead author. Clark was a UCLA postdoctoral scholar when the research was conducted and is now a lecturer at England’s Durham University.

The biologists collaborated with William Ja, an assistant professor at Florida’s Scripps Research Institute, and Ryuichi Yamada, a postdoctoral research associate in Ja’s laboratory, to produce an additional group of flies that were completely germ-free, with no intestinal microbes. Those flies showed a very dramatic delay in intestinal damage, and they lived for about 80 days, approximately one-and-a-half times as long as the animal’s typical life span.

Scientists have recently begun to connect a wide variety of diseases, including diabetes and Parkinson’s, among many others, to changes in the microbiota, but they do not yet know exactly what healthy microbiota look like.

“One of the big questions in the biology of aging relates to the large variation in how we age and how long we live,” said Walker, who added that scientific interest in intestinal microbes has exploded in the last five years.

When a fruit fly’s intestine begins to leak, its immune response increases substantially and chronically throughout its body. Chronic immune activation is linked with age-related diseases in people as well, Walker said.

Walker said that the study could lead to realistic ways for scientists to intervene in the aging process and delay the onset of Parkinson’s disease, Alzheimer’s disease, cancer, stroke, cardiovascular disease, diabetes and other diseases of aging—although such progress could take many years, he said.

By Starre Vartan

Some of the most innovative ideas for the future are rooted in the past. Take the Mount Intergenerational Learning Center in Seattle. Within its walls, elderly people are teaching and spending time with preschool students.

But if it also seems odd, that’s because it’s not something you typically see in Western societies. These two groups of people tend to be almost completely isolated from each other, except maybe during holidays. Of course, that wasn’t always the case. When people lived in family groups — and in those places in the world where people still do — this was and is completely normal. And it makes sense, as both the very old and the very young seem to live at a slower, less focused, more in-the-moment state of being.

Here’s what the Mount Center says about its program: “Five days a week, the children and residents come together in a variety of planned activities such as music, dancing, art, lunch, storytelling or just visiting. These activities result in mutual benefits for both generations.”

In one of those moments of kismet, I happen to be reading Marge Piercy’s “Woman on the Edge of Time,” which is an influential feminist-utopian novel written in 1976. One of the characters from the year 2137 explains to a from-the-’70s visitor why the young children in their advanced society are being cared for by the very old: “We believe old people and children are kin. There’s more space at both ends of life. That closeness to birth and death makes makes a common concern with big questions and basic patterns. We think old people, because of their distance from the problems of their own growing up, hold more patience and can be quieter to hear what children want.”

Behind the project is Seattle University adjunct professor Evan Briggs. She told ABC News, that when the children and the residents come together there’s a “complete transformation in the presence of the children. Moments before the kids came in, sometimes the people seemed half alive, sometimes asleep. It was a depressing scene. As soon as the kids walked in for art or music or making sandwiches for the homeless or whatever the project that day was, the residents came alive.”

Like the quote from the book above, Briggs writes on her Kickstarter page that when she first saw what was happening at the Mount, she noticed: “…with neither past nor future in common, the relationships between the children and the residents exist entirely in the present. Despite the difference in their years, their entire sense of time seems more closely aligned.”

Hence the name, “Present Perfect,” for her documentary. It seems like this is an idea that might spread, an idea whose time has come — again.

Read more:

There’s always the Magic 8 Ball, but when it comes to determining life expectancy, some people want a little more scientific help. Thankfully, there are some useful tests and calculators to help us figure out how many more years we have left — at least until the Fountain of Youth is available in pill form. With that in mind, here are six ways to help predict whether you should keep on working and paying the mortgage or just blow it all on a big beach vacation.

Treadmill test
Want to know if you’ll survive the decade? Hop on a treadmill. Johns Hopkins researchers analyzed more than 58,000 stress tests and concluded that the results of a treadmill test can predict survival over the next 10 years. They came up with a formula, called the FIT Treadmill Score, which helps use fitness to predict mortality.

“The notion that being in good physical shape portends lower death risk is by no means new, but we wanted to quantify that risk precisely by age, gender and fitness level, and do so with an elegantly simple equation that requires no additional fancy testing beyond the standard stress test,” says lead investigator Haitham Ahmed, M.D. M.P.H., a cardiology fellow at the Johns Hopkins University School of Medicine.

In addition to age and gender, the formula factors in your ability to tolerate physical exertion — measured in “metabolic equivalents” or METs. Slow walking equals two METs, while running equals eight.

Researchers used the most common treadmill test, called the Bruce Protocol. The test utilizes three-minute segments, starting at 1.7 mph and a 10 percent grade, which slowly increase in speed and grade.

Researchers analyzed information on the thousands of people ages 18 to 96 who took the treadmill test. They tracked down how many of them died for whatever reason over the next decade. They found that fitness level, as measured by METs and peak heart rate reached during exercise, were the best predictors of death and survival, even after accounting for important variables such as diabetes and family history of premature death.

Sitting test
You don’t need special equipment for this adult version of crisscross applesauce that uses flexibility, balance and strength to measure life expectancy. Brazilian physician Claudio Gil Araujo created the test when he noticed many of his older patients had trouble picking things up off the floor or getting out of a chair.

To try, start by standing upright in the middle of a room. Without using your arms or hands for balance, carefully squat into a cross-legged sitting position. Once you’re settled, stand up from the sitting position — again, without using your arms for help.

You can earn up to 10 points for this maneuver. You get five points for sitting, five for standing, and you subtract a point each time you use an arm or knee for leverage or 1/2 point any time you lose your balance or the movement gets clumsy.

The test seems fairly simple, but Araujo found that it was an accurate predictor of life expectancy. He tested it on more than 2,000 of his patients age 51 to 80, and found that those who scored fewer than eight points were twice as likely to die within the next six years. Those who scored three points or even lower were five times more likely to die within the same time frame.

Araujo didn’t have anyone under 50 try the test, so the results won’t mean the same if you’re younger. As MNN’s Bryan Nelson writes, “If you’re younger than 50 and have trouble with the test, it ought to be a wake-up call. The good news is that the younger you are, the more time you have to get into better shape.”

Test your telomeres

A simple test may help determine your “biological age” by measuring the length of your telomeres. Telomeres are protective sections of DNA located at the end of your chromosomes. They’re sometimes compared to the plastic tips of shoelaces that keep the laces from fraying.

Each time a cell replicates, the telomeres become shorter. Some researchers believe that lifespan can be roughly predicted based upon how long your telomeres are. Shorter telomeres hint at a shorter lifespan for cells. Longer telomeres may mean you have more cell replications left.

Originally offered a few years ago only as an expensive — and relatively controversial — blood test in Britain, telomere testing in now available all over the world, and some companies even test using saliva. The results tell you where your telomere lengths fall in relation to other participants your age.

The link between genetics and longevity has been so embraced that testing companies have since been founded by respected scientists and researchers including Nobel laureate Elizabeth Blackburn of UC San Francisco and George Church, director of Harvard University’s Molecular Technology Group.

The increase in the number of at-home tests is getting the attention of concerned federal regulators and other researchers who question whether the science should stay in the lab.

“It is worth doing. It does tell us something. It is the best measure we have” of cellular aging, aging-researcher and Genescient CEO Bryant Villeponteau told the San Jose Mercury News. But testing still belongs in a research setting, he said, not used as a personal diagnostic tool.

As more people take them, he said, “I think the tests will get better, with more potential to learn something.”

Grip strength

Do you have an iron handshake or a limp fish grasp? Your grip strength can be an indicator of your longevity.

Recent research has shown a link between grip strength and your biological age. Hand-grip strength typically decreases as you age, although many studies have shown links between stronger grip strength and increased mortality.

You can keep your grip strong by doing regular hand exercises such as slowly squeezing and holding a tennis or foam ball, then repeating several more times.

Take a sniff

Does every little smell bug you? People who wear too much perfume? Grilled fish in the kitchen? A sensitive sense of smell is good news for your lifespan.

In a study last fall, University of Chicago researchers asked more than 3,000 people to identify five different scents. The found that 39 percent of the study subjects who failed the smelling test died within five years, compared to 19 percent of those with moderate smell loss and just 10 percent of those with a healthy sense of smell.

“We think loss of the sense of smell is like the canary in the coal mine,” said the study’s lead author Jayant M. Pinto, M.D., an associate professor of surgery at the University of Chicago who specializes in the genetics and treatment of olfactory and sinus disease. “It doesn’t directly cause death, but it’s a harbinger, an early warning that something has gone badly wrong, that damage has been done. Our findings could provide a useful clinical test, a quick and inexpensive way to identify patients most at risk.”

Life expectancy calculator

There are many online calculators that can serve up you estimated last birthday — thanks to some fancy algorithms. Some only take into account a few simple factors such as your age, height and weight. The better ones consider a range of variables including family health history, diet and exercise practices, marital and education status, smoking, drinking and sex habits, and even where you live.

Enter as much data as you can into an online form, like this one from researchers at the University of Pennsylvania, and click to get your results:

Read more:

Erika Check Hayden
Nature Medicine 20,1362–1364(2014)doi:10.1038/nm1214-1362Published online 04 December 2014

In 1889, the pioneering endocrinologist Charles Edouard Brown-Séquard told Parisian doctors that he had reinvigorated himself by injecting an extract made from dog and guinea pig testicles. Thousands of physicians began administering the extract—sold as “Elixir of Life”—to their patients. Though other researchers looked derisively on his salesmanship, his was among the early investigations that led to the eventual discovery of hormones.

The quest to end aging, rife with bizarre and doomed therapies, is perhaps as old as humanity itself. And even though researchers today have more sophisticated tools for studying aging, the hunt for drugs to prevent human decay has still seen many false leads.

Now, the field hopes to improve its track record with the entrance of two new players, Calico, which launched in September 2013, and Human Longevity, which entered the stage six months later. South San Francisco–based Calico, founded by Google with an initial commitment of at least $250 million, boasts an all-star slate of biotechnology industry leaders such as Genentech alums Art Levinson and Hal Barron and aging researchers David Botstein and Cynthia Kenyon. Human Longevity was founded by genome pioneer Craig Venter and hopes to use a big data approach to combat age-related disease.

The involvement of high-profile names from outside the aging field—and the deep pockets of a funder like Google—have inspired optimism among longevity researchers. “For Google to say, ‘This is something I’m putting a lot of money into,’ is a boost for the field,” says Stephanie Lederman, executive director of the New York–based American Federation for Aging Research, which funds aging research. “There’s a tremendous amount of excitement.”

The lift was badly needed; in August 2013, a major funder of antiaging research, the Maryland-based Ellison Medical Foundation, founded by billionaire Larry Ellison, had said it would no longer sponsor aging research. But so far, neither Calico nor Human Longevity has progressed enough to know whether they will be able to turn around the field’s losing track record, and the obstacles they face are formidable, say veterans of antiaging research.

“We’ve made inroads over the past 20 years or so,” says molecular biologist Leonard Guarente of the Massachusetts Institute of Technology in Cambridge, who has founded and advised high-profile companies in the space. “But I think there’s a long way to go.”

Pathway to success?

Calico appears to be taking the approach that worked for Barron and Levinson at Genentech, the pioneering biotechnology company that has become among the more successful drug companies in the world by making targeted medicines—largely engineered proteins—that disrupt disease pathways in diseases such as cancer. The hallmark of Genentech’s approach has been to dissect the pathways involved in disease and then target them with biotechnology drugs. This past September, Calico announced an alliance with AbbVie, the drug development firm spun out of Abbott Laboratories in 2013. In that deal, Calico and AbbVie said they would jointly spend up to $1.5 billion to develop drugs for age-related diseases including neurodegenerative disorders and cancer.

Such an approach is representative of one way to cure aging: targeting the diseases that become more prevalent as people grow older. This follows the argument that treating such diseases is itself treating aging. The opposing view is to see aging as an inherently pathological program that, if switched off or reprogrammed, could be halted. But because regulators don’t consider the progression of life itself a disease, the semantic debate is moot to drug companies: they can only get drugs approved by targeting diseases that become more common with age, such as cancer, diabetes and neurodegenerative disorders.

Calico has a close view on disease targets. In another September announcement, the company revealed one of its first development areas: drugs related to a class of compounds called P7C3s, which appear to protect nerve cells in the brain from dying by activating an enzyme called nicotinamide phosphoribosyltransferase that inhibits cell death. The P7C3 compounds, discovered in 2010 by researchers at University of Texas Southwestern in Dallas, have been tested in numerous models of neurodegenerative diseases associated with aging, including Alzheimer’s disease and Parkinson’s disease.

The AbbVie and P7C3 deals signal that Calico may focus on a traditional drug development strategy aimed at developing drugs that affect molecular players in the aging process in animal models. That approach makes sense to many who have been in the field for a long time, who say there is still much to learn about the molecular biology of aging: “The way Calico has said they are approaching this is the right way, which is to understand some fundamental aspects of the aging process and see how intervening in them affects that process,” says George Vlasuk, the chief executive of Cambridge, Massachusetts–based Navitor Pharmaceuticals and former head of the now defunct antiaging company Sirtris Pharmaceuticals.

But so far that approach has been difficult to translate successfully into interventions that delay aging or prevent age-related disease. For the most part, the biology of aging has been worked out in animal models; Kenyon’s foundational discoveries, for instance, were made in Caenorhabditis elegans roundworms. But the legion of companies that have failed to commercialize these discoveries is large, and some in the field now think that further progress can be made only by studying human aging. Screening for drugs that affect lifespan in model organisms such as yeast and nematodes is a gamble, says physician Nir Barzilai of the Albert Einstein College of Medicine in New York, who leads a large study of human centenarians. “I’m not sure those are going to be so important.”

Human focus

Craig Venter is squarely in the camp of those who believe the focus must shift towards humans. His Human Longevity is taking a big data dive into human aging, planning to sequence the genes of up to 100,000 people per year and analyze a slew of phenotypic data about them, including their protein profiles, the microbial content of their bodies and digitized imagery of their bodies. “We’re trying to get as much information as we can about humans so that we can find the components in the human genome that are predictive of those features,” Venter told Nature Medicine. “The model organism approach has largely failed. There’s only one model for humans, and that’s humans.”

Venter has a point, according to Judith Campisi, a cell and molecular biologist at the Buck Institute for Age Research in Novato, California. “We now have lots of targets, so I think there’s room for optimism,” she says. “But we’re still swimming in a sea of ignorance about how all these pathways and targets are integrated and how we can intervene in them safely.”

Michael West, CEO of the California-based regenerative medicine company BioTime, knows this well. In 1990, West founded a company, Geron, with $40 million from Silicon Valley venture capitalists such as Menlo Park, California–based Kleiner Perkins, dedicated to activating an enzyme called telomerase to forestall human aging. Telomerase activity, discovered in 1984, extends telomeres—the ends of chromosomes, thought to function as timekeepers of the age of a cell. But researchers soon found that human cancer cells have overactive telomerase, and it’s now thought that telomerase serves a highly useful function as a defense against unchecked cell growth that could lead to cancer1. Geron has shifted its telomerase strategy to blocking telomerase to fight cancer; it no longer works on longevity. “The focus on aging was abandoned,” West says.

Other companies, however, carried forward with the search for drugs against aging, inspired by a 1982 finding that mutating some genes in roundworms could enable them to live longer2. For example, one mutant lived for an average of 40% to 60% longer than normal, and at warm temperatures more than doubled its maximum life expectancy from 22 to 46.2 days. It was the first demonstration that aging was not an inevitable process. The work triggered a flurry of activity to find genes linked to aging and use them in interventions to stave off age-related disease.

Companies rooted in this strategy include Elixir Pharmaceuticals, cofounded in 1999 by Guarente and Kenyon, and Sirtris, established in 2004 by one of Guarente’s former students, David Sinclair. Kenyon had discovered genes in nematodes that extended life; with Guarente, she hoped to make drugs that could do this in humans. Guarente and Sinclair founded different companies, but both were interested in a pathway discovered at MIT that, they believed, acted similarly to a drastic treatment, called calorie restriction, long known to extend the lives of rats. If the rats were fed 40% fewer calories than normal, they could live up to 20–40% longer than the average rat. Guarente’s lab discovered that boosting the dose of genes called sirtuins could prolong the lives of roundworms3, and Sinclair published similar evidence in yeast. They thought that sirtuins worked through the same pathway as calorie restriction and that this same pathway was targeted by a naturally occurring compound called resveratrol found in red grapes and red wine. Both companies began looking for chemicals similar to resveratrol that, they predicted, might ultimately cure aging.

Sirtuin stepbacks

UK-based GlaxoSmithKline bought Sirtris for $720 million in 2008, a move seen as an important endorsement of that “calorie restriction mimetic” strategy. But other researchers were not able to reproduce some of Sinclair’s key studies4—for instance, those showing that resveratrol exerted its antiaging effects through sirtuins. It was also later found that the kind of diet fed to lab mice could affect whether or not sirtuins extended their lifespans; those eating a very high-fat diet seemed to benefit5, but it wasn’t clear that this was the most relevant model for human beings. Similar arguments about diet composition have yielded conflicting results for calorie restriction studies in monkeys and have raised the question of whether animal models of caloric restriction that appear to find a benefit are really just proving that bringing fat animals down to normal weight helps keep them disease free, thus extending lifespan.

Last year, GSK closed Sirtris, absorbed its drug development work and laid off some of Sirtris’s 60 employees. Elixir shut down some time after 2010, having burned through $82 million in venture capital.

The Sirtris experience underscored the unpredictability of aging research. Since the field does not agree on biological readouts of aging, such as altered signaling of certain pathways or expression of particular molecules that serve as proximate measurements of the aging process, the only way to do these studies was to follow animals until they died in order to record their lifespan.

The US National Institute on Aging stepped in, organizing a 1999 meeting that led to the Interventions Testing Program, aimed at bringing some order to the field. The program would systematically run experiments of candidate life extension treatments in mice at three separate sites. The hope was that the studies, which began in 2004, would help identify candidate life extension interventions that most deserved to be taken forward.

Already, most researchers agree, the program has succeeded in building more consensus around some drugs. One of the winners from the program so far, for instance, has been rapamycin, a relatively old drug given to kidney transplant recipients and some patients with cancer. In 2009, the drug was shown to extend the lives of genetically diverse mice7. (Resveratrol failed to prolong mouse lifespan in these same studies.) It was also shown to work in much older mice—the equivalent of about 60-year-old people—than had been studied in previous experiments, a situation that researchers say is much more relevant to the way antiaging drugs would be used in human patients. “You’re not going to give these drugs to teenagers,” says Matthew Kaeberlein of the University of Washington in Seattle. “You’ll probably want to give them to people who are certainly post-reproductive, and perhaps in their 60s and 70s.”

Strong signals

Rapamycin suffers from some of the same issues as previous failed antiaging treatments. It’s an old, unpatentable drug, like resveratrol, and has side effects such as a diabetes-like syndrome when given to transplant patients, who continue to take the drug for life after their surgeries. The side effects are worrying for a potential medicine that might be given over years to delay aging. But the signal from the rapamycin studies in mice is so strong that it’s now seen as one of the most promising leads in aging research, even despite these problems. Navitor, for instance, is looking for compounds that influence the mTOR, short for the ‘mammalian target of rapamycin’, pathway, through which rapamycin seems to extend lifespan. The pathway has the potential to influence a wide range of diseases, including neurodegenerative, autoimmune, metabolic and rare diseases and cancer. That’s been enough to entice investors to fund a $23.5 million financing in the company in June. By targeting a specific branch of the mTOR pathway, Navitor hopes they can elicit the benefits of rapamycin without its side effects.

Vlasuk says that companies like his now focus on treating age-related diseases rather than trumpeting the potential to cure aging itself and all associated maladies. “I’m acutely aware that I don’t want to be caught up in the same hype cycle that Sirtris was at one time,” Vlasuk says.

The field is also maturing in other ways. For instance, there’s a growing realization that the people who wish to take life extension drugs will be more old than young, but that it might be difficult to reverse age-related pathology once it has already set in.

Meanwhile, young researchers are taking the field in new directions. In May, three groups published results of experiments in which they transferred blood or blood products from young to old mice. They showed that the technique can rejuvenate muscle, neurons and age-related cognitive decline. A batch of companies is now forming to translate the finding into people; one, privately funded Alkahest, has begun enrolling patients into a study that will test whether blood donated from young adults and infused into patients with mild to moderate Alzheimer’s disease can improve their symptoms. Importantly, says regenerative biologist Amy Wagers of the Harvard Stem Cell Institute in Cambridge, Massachusetts, one of the pioneers of this approach, it seems to reverse some signs of age-related disease: “This notion that you can do some good even after pathology begins means its much more likely that we can come to a place where we can support people with more healthy aging,” she says.

The challenge of clinical trials for aging-related illnesses is familiar to the brains behind the newest antiaging companies. One solution could be to prove that an intervention prevents the sick from becoming sicker. It’s long been suspected, for instance, that the diabetes drug metformin has antiaging properties, but it can have potential side effects because it inhibits glucose production by the liver, so it can’t be given to healthy people. This year, however, UK-based researchers reported in a large retrospective trial that patients with diabetes taking metformin lived a small but significantly longer time than both diabetics taking another class of drugs and healthy people who were not taking metformin.

Barzilai has been impressed enough by these and other findings to try to round up funding for an international clinical trial to test whether metformin or some other drug improves health of the elderly by delaying the onset of a second disease in those who begin taking it when they are newly diagnosed with diabetes. He argues that second diseases, which can include cancer, become much more likely once a patient has been diagnosed with a first. Preventing the onset of a second disease is a way of extending longevity, he argues, by reducing the disease burden in any one patient. “Let’s show that we can delay aging and delay the onset of a second disease,” he says. “If we can do that, we can make FDA [the US Food and Drug Administration] change its review process and look at better potential drugs that delay aging.”

The challenges of testing treatments in patients with age-related diseases, such as Alzheimer’s, are formidable. Hal Barron knows this well; he presided over a failed Genentech trial of an antibody called crenezumab, which was designed to alleviate symptoms of mild to moderate Alzheimer’s disease. Still, that hasn’t deterred him or Levinson from going all in on neurodegenerative diseases with Calico.

“Art Levinson is one of the smartest guys around in terms of his perception of what drug discovery can do,” Vlasuk says. “His involvement in Calico and the group that he’s assembling there and the backing that Google has provided for this has really opened a lot of people’s eyes.” The question now is what Levinson, Venter and others are seeing—and whether it will be enough to lead aging research to finally fulfill its potential.