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Aging, Genetics, Research, Science, Stanford News

“Are we there yet?” Exploring the promise, and the hype, of longevity research

"Are we there yet?" Exploring the promise, and the hype, of longevity research

Brunet photoThe days are getting longer, and it’s no longer dark outside when I drop my teenager at school for her early-bird class. I appreciate the light, of course, and there’s something soothing about the rhythmic change of seasons.

If only we could extend our lifespan in a similar gentle, reliable manner.

The idea of living longer, and healthier, is the theme of my story for the new issue of Stanford Medicine magazine. It’s my favorite kind of article – a dash of juicy science history, a panoply of dedicated scientists and a brand-new animal model (and my newest crush) that may open all kinds of research doors. Best of all, there’s a sense of real progress in the field. From my article:

“Ways of prolonging human life span are now within the realm of possibility,” says professor of genetics and newbie fish keeper Anne Brunet, PhD. Brunet, who is an associate director of Stanford’s Paul F. Glenn Center for the Biology of Aging, focuses her research on genes that control the aging process in animals such as the minnowlike African killifish I’d watched fiercely guarding his territory.

The killifish is especially important to researchers like Brunet because it has an extremely variable, albeit short, life span. One strain from eastern Zimbabwe completes its entire life cycle — birth, maturity, reproduction and death — within about three to four months. Another strain can live up to nine months.

It’s also a vertebrate, meaning it belongs to the same branch of the evolutionary tree as humans. This gives it a backbone up over more squishy models of aging like fruit flies or roundworms — translucent, 1-millimeter-long earth dwellers you could probably find in your compost pile if you felt like digging.

I hope you’ll read the rest of my piece to learn more.

Previously: My funny Valentine – or, how a tiny fish will change the world of aging research, Stanford Medicine magazine reports on time’s intersection with health and Living loooooooonger: A conversation on longevity
Photo of Anne Brunet by Gregg Segal

Aging, Applied Biotechnology, Biomed Bites, Research, Science, Videos

Are your cells stressed out? One Stanford researcher is helping them relax

Are your cells stressed out? One Stanford researcher is helping them relax

Welcome to Biomed Bites, a weekly feature that introduces readers to some of Stanford’s most innovative researchers. 

In her family, Daria Mochly-Rosen, PhD, is the odd woman out: One parent and four of her siblings are architects.

But as the George D. Smith Professor in Translational Medicine at Stanford, Mochly-Rosen brings her family’s focus on space and design to her work as a biomedical researcher. “I’m looking at the cell as a physical space as a room or a building where things need to touch each other in certain ways,” Mochly-Rosen says in the video above.

She applies this lens of the world to address several basic research questions, including learning about how cells deal with stress. For a cell, stress isn’t a bad day at work or a rough commute home. Instead, its prolonged exposure to chemicals or physical forces that build up and impair cellular function.

In healthy cells, there are “lots of little machines” that reduce the stress, Mochly-Rosen said. In her lab, researchers work to enhance the efficacy of these built-in destressors and to capitalize on the cell’s existing machinery. She says:

We are really interested in finding ways to boost them up and to increase their activity so we can deal better with stresses that are associated with disease or even with simple aging.

And what we do there is we try to find small molecules — in other words, drugs — that will boost the system.

For example, Mochly-Rosen and her team have discovered a molecule that helps with the negative effects of alcohol and alcohol-related cancers.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: Why drug development is time consuming and expensive (hint: it’s hard), New painkiller could tackle pain, without risk of addiction and Stanford researchers show how hijacking an enzyme could help reduce cancer risk

Aging, Chronic Disease, In the News, Media, Neuroscience, Women's Health

Science Friday explores women’s heightened risk for Alzheimer’s

Science Friday explores women's heightened risk for Alzheimer's

More than two-thirds of the Americans living with Alzheimer’s are women — some like the character Alice in the movie “Still Alice,” who suffers from an early onset form of the disease.

Science Friday tackled that topic Friday, with guests Michael Greicius, MD, MPH, associate professor of neurology and director of the Stanford Center for Memory Disorders, and Roberta Diaz Brinton, PhD, professor of pharmacology at the University of Southern California. The two quickly disputed the belief that more women get Alzheimer’s disease because they live longer.

“The way women age puts them at risk,” Brinton said. As they transition through menopause, some women develop cognitive symptoms such as insomnia, depression and short-term memory loss, leaving them at greater risk for Alzheimer’s, she explained.

Women who have a form of a gene called APOE-e4 are particularly at risk, although it doesn’t seem to affect men, Greicius said. The gene interacts with estrogen.

Scientists are continuing to decipher the link between estrogen and Alzheimer’s and the possibility of hormone therapies, as well as the connection — if any — between pregnancy and Alzheimer’s risk, the scientists told listeners.

The 18-minute segment is available here.

Previously: Blocking a receptor on brain’s immune cells counters Alzheimer’s in mice, The state of Alzheimer’s research: A conversation with Stanford neurologist Michael Greicius, Having a copy of ApoE4 gene variant doubles Alzheimer’s risk for women but not for men and The toll of Alzheimer’s on caretakers

Aging, Cancer, Emergency Medicine, Medical Education, Pregnancy, Stanford News

Stanford Medicine magazine reports on time’s intersection with health

Stanford Medicine magazine reports on time's intersection with health

Why is it that giant tortoises typically live for 100 years but humans in the United States are lucky to make it past 80? And why does the life of an African killifish zip past in a matter of months?

I’ve often mused about the variability of life spans and I figure pretty much everyone else has too. But while editing the new issue of Stanford Medicine magazine’s special report on time and health, “Life time: The long and short of it,” I learned that serious scientists believe the limits are not set in stone.

“Ways of prolonging human life span are now within the realm of possibility,” says professor of genetics Anne Brunet, PhD, in “The Time of Your Life,” an article on the science of life spans. My first thought was, wow! Then I wondered if some day humans could live like the “immortal jellyfish,” which reverts back to its polyp state, matures and reverts again, ad infinitum. Now that would be interesting.

Also covered in the issue:

  • “Hacking the Biological Clock”: An article on attempts to co-opt the body’s timekeepers to treat cancer, ease jetlag and reverse learning disabilities.
  • “Time Lines”: A Q&A with bestselling author and physician Abraham Verghese, MD, on the timeless rituals of medicine. (The digital edition includes audio of an interview with Verghese.)
  • “Tick Tock”: A blow-by-blow account of the air-ambulance rescue of an injured toddler.
  • “Before I Go”: An essay about the nature of time from a young neurosurgeon who is now living with an advanced form of lung cancer. (The neurosurgeon, Paul Kalanithi, MD, is featured in the video above, and our digital edition also includes audio of an interview with him.)

The issue also includes a story about the danger-fraught birth of an unusual set of triplets and an excerpt from the new biography of Nobel Prize-winning Stanford biochemist Paul Berg, PhD, describing the sticky situation he found himself in graduate school.

Previously Stanford Medicine magazine traverses the immune system, Stanford Medicine magazine opens up the world of surgery and Mysteries of the heart: Stanford Medicine magazine answers cardiovascular questions.

Aging, Genetics, In the News, Mental Health, Neuroscience, Research, Women's Health

Are women at greater risk for Alzheimer’s? Stanford expert to discuss on today’s Science Friday

Are women at greater risk for Alzheimer’s? Stanford expert to discuss on today's Science Friday

2187905205_158290644d_zConfession: I named my parents’ cat (who died recently) Watson after listening to Ira Flatow interview James Watson, PhD, while driving cross country with my dad in 2000. Both before and after the all-critical cat-name-inspiring program, Science Friday has been a part of my Friday as often as I can squeeze it in.

So I was happy to hear that today’s program (which airs locally from 11 a.m. to 1 p.m. on KQED) will feature Stanford’s Michael Greicius, MD, MPH. He’ll be talking about Alzheimer’s disease and why the disease affects men and women differently.

Greicius, medical director of the Stanford Center for Memory Disorders, has worked with the gene variant known as ApoE4 – the largest single genetic risk factor for Alzheimer’s, particularly for women. Last spring, he published a study showing that healthy ApoE4-positive women were twice as likely to contract the disease as their ApoE4-negative counterparts.

Greicius is expected to be on in the second hour, from 12 to 1 p.m. Pacific time.

Previously: Blocking a receptor on brain’s immune cells counters Alzheimer’s in mice, Examining the potential of creating new synapses in old or damaged brains, The state of Alzheimer’s research: A conversation with Stanford neurologist Michael Greicius and Having a copy of ApoE4 gene variant doubles Alzheimer’s risk for women but not for men
Photo by *Ann Gordon

Aging, Genetics, Research, Science, Stanford News

My funny Valentine – or, how a tiny fish will change the world of aging research

My funny Valentine - or, how a tiny fish will change the world of aging research

YoungFishI admit it. I have crush on a fish. The object of my affection is the African turquoise killifish – a tiny, colorful fish that lives in seasonal ponds and puddles under the hot sun of Mozambique and Zimbabwe. Because the pools dry out regularly, the fish have evolved to have a normal lifespan of only a few months. In fact, it’s one of the shortest-lived vertebrates known. It’s also zippy, territorial and (maybe it’s just me?) seemingly possessing a degree of chutzpah noticeably absent in your average goldfish.

The killifish’s compressed lifespan, plus the ease and speed with which it can be housed and bred, make it an ideal model for genetic studies of aging and longevity. But in the absence of a fully sequenced genome and little information about gene expression patterns or a way to introduce selective mutations, it’s been difficult for researchers to get a scientific handle on the slippery creature.

Today, geneticists Anne Brunet, PhD, and Itamar Harel, PhD, published a comprehensive genetic toolbox for use by researchers around the world wanting to draw parallels between humans and my tiny, finned crush. The article appears online in Cell; a charming video abstract describing their work is also available.

As I describe in our release:

Although the similarities between fish and humans may not be immediately evident, people have much more in common with the tiny, minnowlike creature than with other short-lived laboratory animals.

“This fish gives us the best of both worlds,” said postdoctoral scholar Itamar Harel, PhD. “As a vertebrate, it shares many critical attributes with humans, including an adaptive immune system, real blood and similar stem cell biology.

At the same time, its very short life span mimics those of the laboratory worms, yeast and fruit flies that until now have served as the traditional models of aging research.”

A short life span allows researchers to quickly assess the effect of genetic variations among different strains of fish. It also allows them to breed and raise hundreds of progeny for study within the span of months, rather than the many years required to conduct similar experiments in other vertebrates.

“The life span of a mouse can be as long as three to four years,” said Anne Brunet, PhD, professor of genetics. “This is close to the average length of a postdoctoral or graduate student position. This means that it would be very difficult for a researcher to conduct a meaningful analysis of aging in the mouse within a reasonable time period.”

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Aging, Health Policy, Patient Care, Stanford News

A call to “improve quality and honor individual preferences at the end of life”

A call to "improve quality and honor individual preferences at the end of life"

ICU IllustrationThis week’s New England Journal of Medicine featured a perspective piece co-authored by Philip Pizzo, MD, former dean of Stanford’s School of Medicine, and David M. Walker discussing recommendations for how U.S. physicians can approach the issue of end-of-life care. Pizzo and Walker co-chaired an Institute of Medicine (IOM) committee on the issue that culminated in a report that we wrote about last September.

In a recent survey, most physician respondents said they “would forgo high-intensity end-of-life treatment” for themselves. Yet many patients in their care are subjected to aggressive treatments that prolong the dying process unnecessarily. The editorial outlines the challenges that we face as a nation regarding end-of-life care and notes that the aging population of the country will soon make end-of-life care a critical issue. The authors recommend, among other things, adding end-of-life care to physician training, incorporating end-of-life conversations into patient care, even before they become terminally ill, and incorporating end-of-life decisions into health care delivery and payment programs.

In an email, Pizzo discussed why fixing our end-of-life care predicament is so important, telling me:

Unfortunately, all too frequently, individual preferences are not honored at the end of life – with many individuals experiencing more invasive interventions than they wished at the end of their life. It is important that we value the quality of life throughout the life journey, including at the end of life. As a nation, our current health-care system fails in end of life care – which has an enormous impact on individuals, their families and loved ones, and our community and nation.

The situation is complicated by politics. In 2009, end-of-life care became a hot-button issue when critics of the Affordable Care Act claimed that a provision to reimburse physicians for advising patients on living wills or advance directives would lead to “death panels.” Pizzo said of the debate:

Having conversations with our families and physicians about the end of life that allow us to express our personal preferences should not be seen as controversial… Sadly, what has made this issue controversial is egregious political rhetoric. The suggestion that health-care reform would result in “death panels” was wrong and highly destructive, frightening many Americans unnecessarily. When such hyperbole and soundbites become the story they have highly negative consequences. That is why the IOM committee underscored the importance of a more accurate and fact based public discussion about end of life care that made it clear that our intentions, as a society, must be to improve quality and honor individual preferences at the end of life.

Previously: No one wants to talk about dying, but we all need to, Study: Doctors would choose less aggressive end-of-life care for themselves, Former School of Medicine dean named to expert panel to reform end-of-life care in America, Communicating with terminally ill patients: A physician’s perspective and On a mission to transform end-of-life care
Image, “A portrait of death in modern America,” by Neils Olson

Aging, In the News, Neuroscience, Research

The distinctly different brains of “SuperAgers”

The distinctly different brains of “SuperAgers”

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Scientists are gaining insights into the cognitive abilities of “SuperAgers” and why their memories are more resilient against the ravages of time than are other older people’s. ABC News reports today on new research:

The SuperAgers were picked to be studied because all were over age 80 and had the memory capability of a person 20 to 30 years their junior according to the study recently published in the Journal of Neurology.

To understand how SuperAgers managed to keep their mental ability intact, researchers performed a battery of tests on them, including MRI scans on 12 SuperAgers and post-mortem studies on five other SuperAgers to understand the make-up of their brains.

“The brains of the SuperAgers are either wired differently or have structural differences when compared to normal individuals of the same age,” Changiz Geula, a study senior author and a research professor at the Cognitive Neurology and Alzheimer’s Disease Center, said in a prepared statement. “It may be one factor, such as expression of a specific gene, or a combination of factors that offers protection.”

The article goes on to explain that participants’ unusual brain signature had three common components in comparison to normal people of similar ages: notably fewer tangles (a primary marker of Alzheimer’s disease), a thicker region of the cortex and a significant supply of a neuron called von Economo, which is linked to higher social intelligence.

Previously: What brain scans reveal about “super agers”, The secret to living longer? It’s all in the ‘tude and Healthy aging the focus of Stanford study
Photo by Fiona Shields

Aging, Immunology, Neuroscience, Research, Stanford News, Stroke

Can immune cells’ anomalous presence in brain explain delayed post-stroke dementia?

Can immune cells' anomalous presence in brain explain delayed post-stroke dementia?

bees in the bonnetAbout every 40 seconds, someone in the United States has a stroke. About one in three of those people will eventually suffer from dementia if they live long enough, even if there’s been no initial damage to brain structures involved in memory and cognition. That’s a mystery.

In a recent study in The Journal of Neuroscience, Stanford neurologist and stroke expert Marion Buckwalter, MD, PhD, points a bony scientific finger at a major likely reason why having a stroke doubles a person’s risk of incurring dementia within the next decade.

The culprit, surprisingly, seems to be a type of normally very beneficial immune cells that under ordinary circumstances have no business being in the brain. These trespassers, called B cells, are best known for generating antibodies that fight off invading pathogens. As I wrote in my release on the new study:

The antibodies that B cells produce are normally of great value to us. They circulate throughout blood and lymph, and bind to microbial invaders, gumming up the pathogens’ nefarious schemes and marking them for destruction by other immune cells. Occasionally, B cells wrongly begin generating antibodies that bind to the body’s own healthy tissues, causing certain forms of autoimmune disease, such as rheumatoid arthritis. Rituxan, a drug approved by the Food and Drug Administration for this condition, is actually an antibody itself: Its target is a protein found on the surface of every B cell. Use of this drug depletes B cells in the body, relieving the symptoms of rheumatoid arthritis and other B-cell-mediated disorders.

The blood-brain barrier, which tightly controls what enters and what leaves the brain, can be disrupted by a stroke, permitting the anomalous appearance of B cells there. Buckwalter and her colleagues showed that in mice experiencing strokes, the affected brain region – immune-cell-free at least one week later – started filling up with B cells until, at seven and twelve weeks post-stroke, there were “tons” of them, she told me. Around the same time, these mice started showing signs of dementia that hadn’t been at all evident a mere week after the stroke.

But in mice of a strain that is genetically incapable of producing B cells, no such cognitive loss occurred. Not only that, but giving plain old ordinary mice Rituxan five days after a stroke prevented this post-stroke dementia.

Then Buckwalter and her team looked at preserved, autopsied brain-tissue samples from people who had had stroke and dementia. Once again, they observed inordinate numbers of B cells in the majority of these brains, suggesting that humans, too, can experience late but lasting infiltration of rampaging B cells into our brains after a stroke.

So maybe giving a Rituxan-like B-cell-depleting compound to these people within that first week after their stroke could stave off dementia.

This wouldn’t by advisable for all stroke patients. You don’t want to wipe out somebody’s B cells (usually, they’re good guys) unless they are causing trouble. And, as seen in the autopsied tissue samples, not all stroke sufferers’ brains fall into that category.

But, Buckingham noted, Rituxan or something like it could work a double shift as both a therapeutic and a diagnostic. Rituxan pretty much binds only to B cells (a prelude to killing them), so tagging the drug with an imaging agent that could be picked up by, say, an MRI scan might tell clinicians which stroke patients have, or don’t have, B’s in their bonnets.

Previously: Targeted stimulation of specific brains cells boosts stroke recovery in mice, Calling all pharmacologists: Stroke-recovery mechanism found, small molecule needed and Brain sponge: Stroke treatment may extend time to prevent brain damage
Photo by _annamo

Aging, Neuroscience, Stanford News, Stroke, Videos

Bio-X undergraduate student finds direction through research

Bio-X undergraduate student finds direction through research

Richie Sapp arrived to Stanford as an undergraduate already interested in studying neuroscience. After talking with several faculty members, he ended up working in the lab of Carla Shatz, PhD, director of Stanford Bio-X.

I interviewed Sapp recently for a series of stories I was working on about undergraduate research opportunities at Stanford. He had participated in a terrific summer program run by Bio-X. I was struck by a few things when we talked, one of which was Sapp’s sincere interest in helping people. He had grown up with a twin brother who had been born with hydrocephaly and as a result had learning delays and is on the autism spectrum. That experience shaped his interest in helping people with similar challenges.

Sapp said that through his experience in the lab he got more out of his undergraduate classes and learned a lot about where he wants to go with his life. He loves the research and discovery, but also wants to go the medical school before pursuing research. Without the experience provided by the Bio-X summer program he might not have known which direction to go.

“The experience of designing experiments and seeing a project through to the end is going to be important for me in whatever I do next,” he said.

Here is the full profile about Sapp, with more about his research experiences.

Previously: Drug helps old brains learn new tricks, and heal

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