Published by
Stanford Medicine

Category

Aging

Aging, Immunology, Infectious Disease

Found: A molecule mediating memory meltdown in aging immune systems

Found: A molecule mediating memory meltdown in aging immune systems

persistence of memoryEven perfectly healthy older people don’t always remember names as quickly as they did when they were younger. So what. They also don’t walk as fast. Big deal.

A bigger deal: Older immune systems don’t respond as quickly or as well to invasions by pathogens. That’s in large part because they fail to remember previous encounters with pathogens (or their defanged doppelgängers, which we call vaccines). Why do they forget? Stanford immunologist Jorg Goronzy, MD, may have a handle on part of the reason.

In a study published in Cell Reports, Goronzy and his colleagues have shown that immune cells of a particular type are more likely to be marked, in older people, by a surface protein that sparks apoptosis, or cellular suicide. As a result, the immune system’s memory of pathogens or vaccinations of yore gets cloudy, leaving the door open to a repeat attack by intruders that a more adept immune system would have summarily squelched.

A healthy immune system bulks up vigorously in response to pathogens or vaccines. Different types of immune cells that are skilled at recognizing and/or warring with the foreign body start to multiply and morph. Many of these cells effectively become front-line warriors, throwing themselves into battle against the invading pathogen (or its harmless vaccine lookalike). Others are more like archers lobbing darts that can knock off the bad guys while sparing innocent bystanders (the body’s own tissues). Still others, known as CD4 cells, coordinate the whole counterattack, sending chemical signals to other cells, or rubbing up against them at close range to whisper secret instructions.

Continue Reading »

Aging, In the News, Medicine and Society, Palliative Care, Patient Care

End-of-life discussions the focus of PBS piece

End-of-life discussions the focus of PBS piece

For many, end-of-life discussions are either unpleasant, brief, or unlikely to happen at all. But, as a recent episode of PBS’ Religion and Ethics NewsWeekly emphasized, it is critically important that patients have open and honest conversations on the topic with their family members and doctors.

The piece featured Philip Pizzo, MD, former dean of Stanford’s medical school and co-author of the 2014 Institute of Medicine’s 500-page report titled “Dying in America,” and VJ Periyakoil, MD, director of Stanford’s Palliative Care Education and Training. Through the Stanford Letter Project, Periyakoil is on a quest to empower patients and help stimulate a broad national discussion on what matters most at life’s end. She says in the piece:

I think the biggest challenge is people don’t want to make plans and have discussions because the topic is so threatening to them. So what happens is because they don’t plan for it, they are subjected to treatments that are A, not helpful and B, not what they want.

I helped facilitate the interviews with Periyakoil and Pizzo last October; coincidentally around that time, my older sister suddenly fell ill and died unexpectedly. One of the things that came up was whether or not she had an advance directive and, fortunately for my family, my sister (who was just 46 years old) had written down her wishes and no one was left wondering or tasked to make a difficult decision. I know firsthand how beneficial the work of Periyakoil and others can be.

Previously: No one wants to talk about dying, but we all need toStudy: Doctors would choose less aggressive end-of-life care for themselvesHow would you like to die? Tell your doctor in a letter, Stanford doctor on a mission to empower patients to talk about end-of-life issues and Medicare to pay for end-of-life conversations with patients

Aging, Chronic Disease, Neuroscience, Patient Care, Research, Stanford News, Stroke

Stanford study: Commonly used sleeping pill may boost stroke recovery

Stanford study: Commonly used sleeping pill may boost stroke recovery

sleeping pillIf what works in mice works in people, a widely popular sleeping pill could someday start seeing action as an aid to stroke recovery, according to a study carried out by Stanford neuroscientists Gary Steinberg, MD, PhD, and Tonya Bliss, PhD, and published in Brain.

Count to 40. Chances are that sometime between when you start and when you finish, someone in the United States will experience a stroke. That’s how common they are: about 800,000 strokes every year in the U.S., and – far from being confined to rich countries – around 35 million worldwide.

But that’s just the number of new strokes annually. Unfortunately, a stroke isn’t something you just get and then get over. Few people fully recover, leaving some 5.4 million Americans currently saddled with stroke-caused disabilities.

The main way for anyone incurring a stroke to minimize its damage is to get to a treatment center right away. As I wrote in a news release summarizing the study’s findings:

A stroke’s initial damage, which arises when the blood supply to part of the brain is blocked, occurs within the first several hours. Drugs and mechanical devices for clearing the blockage are available, but to be effective they must be initiated within several hours of the stroke’s onset. As a result, fewer than 10 percent of stroke patients benefit from them.

I repeat: Get to a treatment center right away. Don’t wait “to see if it blows over.” But since even in the best-case scenario many stroke sufferers will sustain some brain damage, the next best thing is a treatment that could help undo that damage – if only there were one.

Sad to say, no effective treatments during the recovery phase exist other than physical therapy, which has been shown to be only marginally successful. So anything that could enhance patients’ recovery during the  three- to six-month post-stroke period when 90 percent of whatever recovery a patient’s going to experience occurs, as a rule, would be a home run.

In their study, Steinberg, Bliss and their colleagues swung for the fences. They induced strokes in animal models, then waited for a few days to make sure that what they planned to do next, if it helped, was working during the recovery phase rather than the rush-rush damage-control phase.

Then they gave some of the mice the FDA-approved insomnia drug zolpidem (better known by the trade name Ambien) and others a control solution that did not contain the drug. Over the next month, they compared the mice’s performance on various tests of sensory and motor-coordination ability. By several measures, the zolpidem-treated mice were back at their pre-stroke levels within a few days of treatment; the control mice took the entire month. (Unlike humans, mice do eventually recover from strokes even when untreated.)

Mice are mice, and humans are humans. But Zolpidem’s already-on-the-market status greatly improves the prospects for clinical trials of the drug. And wouldn’t it be ironic if faculties slumbering under a stroke’s spell could be awakened by a pill designed to put us asleep?

Previously: Targeted brain stimulation of specific brain cells aids 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 Guian Bolisay

Aging, Big data, Genetics, Research, Science, Stanford News

Genetic links to healthy aging explored by Stanford researchers

Genetic links to healthy aging explored by Stanford researchers

Old man with babyIs the secret to a long life written in your genes? Or will your annual merry-go-rides around the sun be cut short by disease or poor health? The question is intriguing, but difficult to answer. But that hasn’t stopped researchers from looking for genes or biological traits that may explain why some people live to be very old while others sicken and die at relatively young ages.

Today, developmental biologist Stuart Kim, PhD, published some very interesting research in PLoS Genetics about regions of the human genome that appear to be associated with extreme longevity  (think upper 90s to over 100 years old).

One, a gene called APOE, is associated with the development of Alzheimer’s disease. It’s been previously been implicated in longevity. However, the other four regions identified by the study are new. They are involved in biological processes such as cellular senescence or aging, autoimmune disease and signaling among cells.

As explained in the journal’s press release:

Previous work indicated that centenarians have health and diet habits similar to normal people, suggesting that factors in their genetic make-up could contribute to successful aging. However, prior genetic studies had identified only a single gene (APOE, known to be involved in Alzheimer’s disease) that was different in centenarians versus normal agers.

As we’ve explained here before, studying the very old is difficult, in part because there are so few of them. That makes it hard to come up with statistically significant results when comparing them to others. For this study, Kim and his colleagues devised a new technique to identify regions of the genome associated with longevity by linking it to the likelihood of developing other common diseases or disease-related traits, including type 2 diabetes, bone density, blood pressure and coronary artery disease.

Continue Reading »

Aging, Evolution, Genetics, Research, Science, Stem Cells

The war within: In our aging bodies, the “fittest” stem cells may not be the ones that ensure our survival

The war within: In our aging bodies, the "fittest" stem cells may not be the ones that ensure our survival

ageAnti-aging research has been in the news lately: for instance, here, here and (less recently and less frivolously) here.

Albert Einstein College of Medicine researcher Nir Barzilai, MD, who’s spearheading the groundbreaking anti-aging trials referred to in these articles, is far from frivolous. I remember really liking a talk he gave at Stanford a few years ago about his ongoing study of super-old Ashkenazis, at a symposium sponsored by Stanford’s Glenn Laboratories for the Biology of Aging.

Now, Tom Rando, MD, PhD, the director of Glenn Labs at Stanford, has co-authored a thought-provoking review in Science that advances a theory of why we age.

It’s not the only theory. Judy Campisi of the Buck Institute for Research on Aging, for example, has explored the detrimental activities of differentiated cells gone wrong within our tissues. The older the tissue, the wronger the cells in it go.

Rando and his co-author, Baylor College of Medicine regenerative-medicine expert Margaret Goodell, PhD, come at aging from the opposite end of the spectrum: stem cells, the least-differentiated cells in the body. In particular, Rando and Goodell target the aging-associated actions of so-called somatic stem cells, which reside in virtually all (and, probably, actually all) of our tissues and whose fates are restricted to spawning only cell types that belong in those tissues. While we’re growing up, those somatic stem cells are the reason why: They divide to generate the differentiated cells that bulk us up. Once we’ve matured, they mostly hang back, springing into action to replace tissue lost to injury or to wear and tear.

Radiation, noxious foreign substances, and plain old existence wreaks sporadic damage on somatic stem cells by triggering genetic mutations or by altering the cells’ epigenetic settings, the patterns of chemical stop-and-go signs that variously switch the 20,000-odd genes in each cell’s genome on or off. These insults pile up as life’s pages turn. Eventually, Rando and Goodell write, a curious, Darwin-like natural selection occurs among our tissue-resident stem cells.

Continue Reading »

Aging, Genetics, Research, Science, Stanford News

A tiny fish helps solve how genes influence longevity

A tiny fish helps solve how genes influence longevity

Nothobranchius_furzeri_GRZ_thumb_wikimedia_UgauA tiny, short-lived fish may help solve one of the largest mysteries: how do genes influence longevity?

The African turquoise killifish has evolved as the shortest-lived known vertebrate — driven by its survival in the hot climate of Mozambique and Zimbabwe in seasonal ponds that only exist for a few months during the wet season. This compressed life span makes the killifish an ideal organism for genetic studies on aging and longevity.

To help researchers study this intriguing animal model, Stanford geneticist Anne Brunet, PhD, and her colleagues have now fully mapped the genome of the African turquoise killifish. Their initial insights into the genetic determinants of the killifish’s life span were published today in Cell.

Brunet’s team sequenced short segments of the killifish DNA and then assembled them using specialized software to create a complete map of the turquoise killifish genome.

Brunet explains in a news release:

The range of life spans seen in nature is truly astonishing, and really we have very little insight into how this has evolved or how this works. By having the genome of this fish and comparing it to other species, we start seeing differences that could underlie life span differences both between species and also within a species.

Continue Reading »

Aging, Events, Stanford News, Videos

Former medical school dean discusses learning and longevity at Stanford 125 event

Former medical school dean discusses learning and longevity at Stanford 125 event

The year-long celebrations for Stanford University’s 125th anniversary are in full swing, and Philip Pizzo, MD, former dean of Stanford’s medical school, recently helped kick off the festivities. Earlier this month, he and experts in the fields of psychology, computer science, education, physics and the humanities drew a crowd of more than 550 people to Stanford’s Cemex Auditorium to discuss the theme “Thinking Big About Learning.”

In his talk, Pizzo, founding director of the Stanford Distinguished Careers Institute, explored the topics of learning, aging and longevity and how traditional views of education and career (learn when young and do the same job for life) no longer apply now that people are living and working longer than ever.

If you missed the event, you can watch video of Pizzo’s talk here. Other videos from the symposium, including talks from Stanford psychology professor Carol Dweck, PhD, and Jeremy Bailenson, PhD, director of the Virtual Human Interaction Lab, are available on the Stanford 125 website.

Previously: Living long and living well: A conversation on longevity at Medicine XA look at aging and longevity in this “unprecedented” time in history and Living loooooooonger: A conversation on longevity

 

Aging, Behavioral Science, Neuroscience, Stanford News, Videos

Decisions, decisions: How our decision making changes with age

Decisions, decisions: How our decision making changes with age

Research in neuroscience, psychology, business and economics tells us that a plethora of influences can alter the decisions we make. The author explored some of these factors in a Worldview Stanford course and wrote about them in a Stanford story package, Decisions, Decisions. This post is part of a series on what she learned. 

Without revealing my age, I will simply say that I am beyond the teenage years, when risks fail to register and decisions are dominated by reward. But it turns out the person I was then shaped how my brain makes decisions today.

Kathleen Fitzpatrick, MD, a child psychiatrist, says that during our teenage years dramatic changes take place in the brain. Wiring we don’t use dies off and wiring we use heavily flourishes and multiplies, creating new connections and with it new behaviors.

In my story about how age alters decision-making I write:

During this time of brain circuit upheaval, adolescents weigh the pros and cons of decisions differently from adults. They overestimate the rewards of a decision (Fun! Friends!) but don’t accurately estimate possible risks (grounding, police).

Our teenage behaviors shape which of those new connections remain. If a behavior is rewarded, those pathways are strengthened. A failed behavior fades into a distant, embarrassing memory.

Read the story for more about both the teenage brain and also the way our decision-making shifts as we get older. Hint: we become less worried, which is something to look forward to.

Previously: Exploring the science of decision making and Exploring the intelligence-gathering and decision-making processes of infants
Video courtesy of Worldview Stanford

Aging, Medical Apps, Stanford News, Technology

Stanford Letter Project, which helps users have end-of-life discussions, now available for mobile devices

Stanford Letter Project, which helps users have end-of-life discussions, now available for mobile devices

Stanford_LetterFor many of us, the topic of how we want to spend our final days rarely comes up in discussions with our family members or doctors. And a big reason why is that we think of reflecting on how we want to die as highly emotional and unpleasant.

But there are some compelling reasons to take the time to clarify what matters to you most in your waning days of life: It can reduce stress on your loved ones and help your physician provide a better quality of care.

Earlier this year, VJ Periyakoil, MD, director of palliative care education and training at Stanford, launched the Stanford Letter Project, a campaign to empower all adults to take the initiative to talk to their doctor about what matters most to them at life’s end.

Recently, Periyakoil released mobile app versions of the Stanford Letter Project for both the iPhone and Android. The apps, which offer templates comprised of simple questions aimed at getting the end-of-life conversation rolling, are free and can be downloaded from the iTunes and Google Play stores. Templates are available in Spanish, English, Italian, Taglog, Russian and Hindi.

As Periyakoil explained in a recent 1:2:1 podcast, “2.6 million Americans die every year, and very few of them get to talk to their doctor about their end of life wishes.” She urges every adult to tell their doctors about how they want to spend their last days; she suggests engaging in end-of-life discussions each time you reach a milestone in your life such as getting married, having a baby or being diagnosed with a chronic illness.

Previously: How would you like to die? Tell your doctor in a letter, Stanford doctor on a mission to empower patients to talk about end-of-life issues, Medicare to pay for end-of-life conversations with patients and “Everybody dies – just discuss it and agree on what you want

Aging, Events, Medicine and Society, Medicine X, Stanford News

Living long and living well: A conversation on longevity at Medicine X

Living long and living well: A conversation on longevity at Medicine X

Beskind

There were big-time laughs, and the expected misty eye or two, at today’s Medicine X session on aging and longevity. Natrice Rese, a retired personal support worker, began the conversation with a moving ePatient Ignite! talk about how life for many older adults is less than “golden.” She told the audience how difficult time spent in a nursing home or care facility can be: “So many people wait to be fed, wait to be dressed, wait to be undressed, wait to be taken outside… When you’re dependent on care from others, your life is reduced to a waiting game.”

Her mother found herself in one such place at the age of 85, and Rese recalled how her mom pulled her aside one day and said, “Don’t come near these places – it’s not good here.” Her mother was in the throes of Alzheimer’s and unable to offer further details, but “her words stay with me today,” Rese somberly told the audience.

Rese said her mom’s comments ultimately reinforced her desire to work to make sure older adults feel appreciated and are able to “create memories that matter.”

Fellow panelist Barbara Beskind is certainly doing that – and more. The 91-year-old former occupational therapist made headlines when she landed a job at Silicon Valley design firm IDEO. Appearing at the conference alongside Dennis Boyle, a partner and founding member of the firm, she goes to the office every Thursday and is now working on a variety of projects related to aging – including a redesigned walker.

Younger designers “can’t put themselves in the shoes of the elderly,” Beskind told USA Today earlier this year. “People who design for the elderly think they need jeweled pill boxes or pink canes. We need functional equipment.”

“I admire you,” Rese told Beskind during a panel discussion, after hearing about Beskind’s contributions. “You shouldn’t be one of a few – you should be one of many.”

Continue Reading »

Stanford Medicine Resources: