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Aging, Genetics, Men's Health, Neuroscience, Research, Stanford News, Women's Health

Having a copy of ApoE4 gene variant doubles Alzheimer’s risk for women but not for men

Having a copy of ApoE4 gene variant doubles Alzheimer's risk for women but not for men

brain cactus - smallSince the early 1990s, when Duke University neurologist Allen Roses, MD, first broke the news, it’s been known that a person carrying the gene variant known as ApoE4 is at elevated risk of getting Alzheimer’s disease. To this day ApoE4 is the strongest known single genetic risk factor for Alzheimer’s, a progressive neurological syndrome that robs its victims of their memory and reasoning ability.

But only now is it looking certain that the increased Alzheimer’s risk ApoE4 confers is largely restricted to women. Men’s fates don’t seem to be altered nearly as much by the genetic bad penny that is ApoE4, according to a new Annals of Neurology study led by Mike Greicius, MD, medical director of the Stanford Center for Memory Disorders.

Accessing two huge publicly available national databases, Greicius and his colleagues were able to amass medical records for some 8,000 people and show that initially healthy ApoE4-positive women were twice as likely to contract Alzheimer’s as their ApoE4-negative counterparts, while ApoE4-positive men’s risk for the syndrome was barely higher than that for ApoE-negative men.

What the heck is ApoE4 for, anyway? In my release on the new study, I wrote:

The ApoE gene is a recipe for a protein important for shuttling fatty substances throughout the body. This is particularly important in the central nervous system, as brain function depends on rapid rearrangement of such fatty substances along and among nerve cell membranes. The ApoE gene comes in three varieties — ApoE2, ApoE3 and ApoE4 — depending on inherited variations in the gene’s sequence. As result, the protein that the gene specifies also comes in three versions, whose structures and fatty-substance-shuttling performance differ. Most people carry two copies of the ApoE3 gene variant (one from each parent). But about one in five people carries at least one copy of ApoE4, and a small percentage have two ApoE4 copies. Numerous studies … have confirmed that ApoE4 is a key risk factor for Alzheimer’s disease, with a single copy of ApoE4 increasing that risk twofold or fourfold. Carrying two copies confers 10 times the risk of Alzheimer’s.

Early hints in the medical literature that the ApoE4 variant exerted differential effects on women’s versus men’s brains were largely ignored until now, says Greicius. He says that’s because most of the seminal ApoE4/Alzheimer’s genetics research was conducted as case-control studies: The ApoE4 gene version’s frequency in people with Alzheimer’s was compared to its frequency in people without the disease. (About half of those with Alzheimer’s, but only about 15 percent without it, are positive for ApoE4.)

But that method has limitations, says Greicius: “About 10-15 percent of ‘normal’ 70-year-olds will develop Alzheimer’s if you wait five or ten years.” Their lurking in the “normal” group dilutes the results. Moreover, Greicius says,“these kinds of genetic studies are looking for needles in a haystack, so they require large numbers of subjects – thousands – to achieve statistical significance. If you want to further examine male/female differences, you have to double the sample size.” That’s costly.

And that’s how come the large government- and industry-supported repositories to which Greicius and his team resorted are such a great idea.

Previously: Estradiol – but not Premarin – prevents neurodegeneration in women at heightened dementia risk, Common genetic Alzheimer’s risk factor disrupts healthy older women’s brain function, but not men’s, Hormone therapy halts accelerated biological aging seen in women with Alzheimer’s genetic risk factor and A one-minute mind-reading machine? Brain-scan results distinguish mental states
Photo by Sean Michael Ragan

Aging, Stanford News, Technology

Stanford Center of Longevity announces dementia-care design challenge winners

Stanford Center of Longevity announces dementia-care design challenge winners

Winners have been announced for Stanford Center on Longevity‘s first Design Challenge, which launched last fall. As previously written about on Scope, 52 teams representing 31 universities in 15 countries submitted entries, all of them centered on improving the daily lives for people with dementia as well as their families and caregivers.

Stanford News reports:

There were seven finalists, including one student team from Stanford.

Sha Yao from the Academy of Art University in San Francisco won the $10,000 first place prize for her project, “Eatwell,” which involved the design of tableware specifically for people with Alzheimer’s.

For example, blue was chosen as the color of the insides of bowls because dementia sufferers can become confused when food and bowl have similar colors, according to Smith. As spills are common when bowls are tipped to get the final bits out, Yao designed a slanted bottom that eliminates the need to tip. The cups have low centers of gravity and are difficult to knock over.

The piece describes runner-up prize winners and the center’s new design contest, themed “enabling personal mobility across the life span.”

Previously: Finalists announced for Stanford Center on Longevity’s Design Challenge and Soliciting young minds to help older adults

Aging, Genetics, Stanford News, Videos

Unlocking the secrets to human longevity

Unlocking the secrets to human longevity

Does the key to extending life lie within our genetic code? In this Stanford+Connects micro lecture, Stuart Kim, PhD, a professor of developmental biology and genetics, explains why he believes the answer is yes.

In his lab at Stanford, Kim and colleagues study functional genomics and aging and the search for genes that can either speed up or slow down aging, in particular with respect to the kidney. During this talk, he shares some of his lab’s advances in developmental biology in doubling the lifespan of a nematode, which is the world’s fastest-aging animal.

Previously: Male roundworms shorten females’ lifespan with soluble compounds, say Stanford researchers, Key to naked mole rat longevity may be related to their body’s ability to make proteins accurately, Longevity gene tied to nerve stem cell regeneration, say Stanford researchers and California’s oldest person helping geneticists uncover key to aging

Aging, Medicine and Society, Stanford News

Stanford Distinguished Careers Institute encourages “personal reflection and intellectual exploration”

Stanford Distinguished Careers Institute encourages "personal reflection and intellectual exploration"

PizzoStanford University announced today a new center to support highly accomplished leaders who are mid-career in public or private sector positions and seeking new resources and influences to prepare for their next steps. The Stanford Distinguished Careers Institute (DCI) will offer 20 participants access to faculty and classes in all seven of Stanford’s schools, including the School of Medicine. Additionally, the DCI Fellows will participate in specially designed programs including a core program of weekly seminars and discussions, one-to-two day meetings on key issues, and monthly dinners with faculty scholars and Stanford and Silicon Valley community leaders.

Philip Pizzo, MD, former dean of the medical school, is founding director of the institute, which is a partnership with the Stanford Center on Longevity.

From a Stanford News article:

“We know what role universities play in early life and in stimulating the first phase of careers,” said [Pizzo], who returned to teaching in 2012 after serving as dean of Stanford School of Medicine for 12 years. “What is their role in mid- to later-career life transitions and journeys?”

“Life should be filled with new journeys and new opportunities, and shouldn’t be affixed to traditional stopping points that are no longer relevant,” said Pizzo, who is the David and Susan Heckerman professor of pediatrics, and of microbiology and immunology at Stanford. “We need to recalibrate the way we think about the life journey, and recognize that individuals have different things to offer and to gain at different stages in life.”

Pizzo said the institute will serve as a transition to new ventures for participants, allowing them to build on their life experiences to create something unique that will improve themselves and the world.

“The new way forward that emerges from participating in the institute can be one long-anticipated and hoped-for, or one not yet imagined,” he said.

Previously: The legacy of Stanford’s Philip Pizzo and Phil Pizzo, the marathon man, moves on
Photo by L.A. Cicero

Aging, Genetics, Neuroscience, Research, Sleep, Stanford News

Restless legs syndrome, most common in old age, appears to be programmed in the womb

Restless legs syndrome, most common in old age, appears to be programmed in the womb

Restless legsWhile the sleep disorder called “restless legs syndrome” is more typical of older than younger people, it looks as though it’s programmed in the womb. And a group led by Stanford neurologist Juliane Winkelmann, MD, has pinpointed for the first time the anatomical region in the brain where the programming takes place.

Restless legs syndrome, or RLS, is just what it sounds like: a pattern of unpleasant sensations in the legs and the urge to move them. It has been described as a feeling similar to the urge to yawn, except that it’s situated in the legs or arms instead of the upper torso and head.

Estimates vary, but something on the order of one in ten Americans has RLS. Women are twice as likely as men, and older people more likely than young people, to have it. This urge to move around comes in the evening or nighttime, and can be relieved only by – wait for it – moving around. Needless to say, that can cause sleep disturbances. In addition, RLS can lead to depression, anxiety and increased cardiovascular risk.

Very little is known about what actually causes RLS, although it’s known to be highly heritable. Although a number of gene variants (tiny glitches in a person’s DNA sequence) associated with the condition have been discovered, each by itself appears to contribute only a smidgeon of the overall effect, and nobody knows how.

Winkelmann has been exploring the genetic underpinnings of RLS at length and in depth. In a just-published paper in Genome Research, she and her colleagues have shown that one gene variant in particular depresses the expression of a protein involved in organ development and maintenance. The DNA abnormality Winkelmann’s team zeroed in on occurs not on the gene’s coding sequence – the part of the gene that contains the recipe for the protein for which the gene is a blueprint – but rather on a regulatory sequence: a part of the gene that regulates how much of that protein (in this case, the one involved in organ development and maintenance) gets made, and when.

The kicker (pardon my pun) is that the regulatory sequence in question seems to be active only during early brain development and only in a portion of brain that is destined to become the basal ganglia, a brain region well known to be involved in movement.

“Minor alterations in the developing forebrain during early embryonic development are probably leading to a predisposition in the [basal ganglion],” Winkelmann says. “Later in life, during aging, and together with environmental factors, these may lead to the manifestation of the disease.”

(Wondering if you’ve got RLS? Check this out.)

Previously: National poll reveals sleep disorders, use of sleeping aids among ethnic groups, Caucasian women most likely to have restless leg syndrome
Photo by Maxwell Hamilton

Aging, Stanford News, Stem Cells

Elderly muscle stem cells from mice rejuvenated by Stanford scientists

Elderly muscle stem cells from mice rejuvenated by Stanford scientists

dumbbellsI’ve been pretty good about my gym workouts lately. But I’ve realized that it’s a lot more difficult to build muscle mass now than it was during my 20s. That’s because, as we age, muscle stem cells become less able to repair injury and generate new muscle fibers.

Now a report in Nature Medicine outlines some interesting findings from the laboratory of Stanford microbiologist and immunologist Helen Blau, PhD, suggesting it may be possible to perk up a population of elderly stem cells through a combination of biophysical and biochemical cues.

As I describe in our release:

Blau and her colleagues also identified for the first time a process by which the older muscle stem cell populations can be rejuvenated to function like younger cells. “Our findings identify a defect inherent to old muscle stem cells,” she said. “Most exciting is that we also discovered a way to overcome the defect. As a result, we have a new therapeutic target that could one day be used to help elderly human patients repair muscle damage.”

Blau, who directs Stanford’s Baxter Laboratory for Stem Cell Biology, and postdoctoral scholar Ben Cosgrove, PhD, found that growing muscle stem cells from elderly laboratory mice (a 24-month-old mouse is roughly equivalent to an 80-year-old human, based on average lifespans) in a specialized matrix called hydrogel, coupled with a drug treatment to block an inhibitory pathway, caused the cells to divide rapidly. When implanted into elderly mice with a muscle injury, the cultured cells sprang to work.

“We were able to show that transplantation of the old treated muscle stem cell population repaired the damage and restored strength to injured muscles of old mice,” Cosgrove said. “Two months after transplantation, these muscles exhibited forces equivalent to young, uninjured muscles. This was the most encouraging finding of all.”
The researchers plan to continue their research to learn whether this technique could be used in humans. “If we could isolate the stem cells from an elderly person, expose them in culture to the proper conditions to rejuvenate them and transfer them back into a site of muscle injury, we may be able to use the person’s own cells to aid recovery from trauma or to prevent localized muscle atrophy and weakness due to broken bones,” Blau said. “This really opens a whole new avenue to enhance the repair of specific muscles in the elderly, especially after an injury. Our data pave the way for such a stem cell therapy.”

Previously: Making iPS cells safer for use in human through the study of a cellular odd fellow, New mouse model of muscular dystrophy provides clues to cardiac failure and Mouse model of muscular dystrophy points finger at stem cells
Photo by Positively Fit

Aging, Stanford News, Technology

Finalists announced for Stanford Center on Longevity’s Design Challenge

Finalists announced for Stanford Center on Longevity's Design Challenge

OLYMPUS DIGITAL CAMERAStanford Center on Longevity launched a design challenge last September to put student minds to the task of improving the daily lives of people with dementia and their caregivers and families. Now, Forbes reports, seven finalists have been named from among the 52 teams in 15 countries that submitted ideas for products and services that would help people with cognitive impairment live independently longer. From Forbes:

“Cognitive impairment affects people in such a personal way, the challenge brought out a lot of creativity,” says Ken Smith, Director of Mobility at the Stanford Center on Longevity.

The students who entered weren’t just studying design and engineering. They also came from fields such as nursing, psychology, fine arts and computer science. Dementia affects patients, families caregivers and health providers in a multitude of ways, so the inventions addressed the disease from a variety of angles.

The Design Challenge winner and runners-up will be announced on April 10, when the theme of next year’s challenge will be revealed.

Previously: Soliciting young minds to help older adults and A look at the benefits of an aging society
Photo by Kevin Poh

Aging, In the News, Patient Care, Technology

Helping older adults live independently using mobile-health technology

Helping older adults live independently using mobile-health technology

oldcoupleHow much privacy would you be willing to give up to maintain your independence? If you’re confused by the question, consider this Washington Post article discussing home-use medical devices that track behavior and vital signs in older adults to share with their doctors. Keeping tabs remotely could let an aging population stay in their homes longer.

From the piece:

Their medicine bottles will alert their doctor when they miss a dose. Pressure-sensing floor mats can sense when they have fallen or let caregivers know when a patient hasn’t showered for a while.

The devices often mean adding “sensor platforms in what have traditionally been protected spaces — your home, your office,” said Joseph Lorenzo Hall, [PhD,] chief technologist at the Center for Democracy and Technology. “Even something like a temperature sensor can be revealing . . . it can easily tell if you’re home.”

The effort also pushes traditional telemedicine, including video conferencing with your doctor, into a more intimate space.

But receiving such data from a patient can make it easier for doctors to monitor their health, said David Lindeman, [PhD,] a gerontologist and director for the Center for Technology and Aging. Also, he said, monitoring someone while they are in their natural environment rather than a clinical setting can also lead to more accurate diagnoses.

But with great data comes great responsibility to protect it. The article continues:

…widespread use of such technology can raise questions about whether patient’s personal details are being properly protected. More companies are entering the market that haven’t traditionally dealt with health information, said Hall of the Center for Democracy and Technology.

It is also unclear how data breach, security and other laws apply to the growing ecosystem of new devices, and how companies will set their own standards to protect the influx of data.

Previously: Eat a carrot and exercise – or your iBird dies and Research shows remote weight loss interventions equally effective as face-to-face coaching programs
Photo by Martin

Aging, Chronic Disease, Health and Fitness, Men's Health, Research, Women's Health

More evidence that prolonged inactivity may shorten life span, increase risk of chronic disease

More evidence that prolonged inactivity may shorten life span, increase risk of chronic disease

sitting_deskIf you have a lengthy daily commute, spend hours at a desk clacking on the computer, or sit for a prolonged period for other reasons, a pair of recent studies may have you leaping to your feet.

The first study, conducted by researchers at Cornell University, examined the effects of sitting for a long period of time each day over a 12-year period. Results showed that individuals who were inactive for more than 11 hours had a 12 percent higher mortality rate than those who sat for four hours or less. And don’t think you’re not at risk because you occasionally hit the gym. Cornell researcher Rebecca Seguin, PhD, explained in a Futurity post:

The assumption has been that if you’re fit and physically active, that will protect you, even if you spend a huge amount of time sitting each day… In fact, in doing so you are far less protected from negative health effects of being sedentary than you realize.

While this study focused on postmenopausal women, additional research from Kansas State University shows that the health risks of being sedentary affect both both genders. The study analyzed data on nearly 200,000 men and women ages 45 to 106 taken from a large Australian study of health and aging. The research showed that both exercising and reducing sitting time were key to improving health. MedicalXPress reports:

Even standing throughout the day—instead of sitting for hours at a time—can improve  and quality of life while reducing the risk for  such as , diabetes, heart disease, stroke, breast cancer and colon cancer, among others.

Sitting for prolonged periods of time—with little muscular contraction occurring—shuts off a molecule called lipoprotein lipase, or LPL, [Sara Rosenkranz, PhD,] said. Lipoprotein lipase helps to take in fat or triglycerides and use it for energy.

“We’re basically telling our bodies to shut down the processes that help to stimulate metabolism throughout the day and that is not good,”  [Rosenkranz] said. “Just by breaking up your , we can actually upregulate that process in the body.”

Previously: Exercise is valuable in preventing sedentary deathIs standing healthier than sitting?How sedentary behavior affects your health and Stanford hosts conference on the science of sedentary behavior 
Photo by Danny Choo

Aging, Applied Biotechnology, Technology

Treating common forms of blindness using tissue generated with ink-jet printing technology

Treating common forms of blindness using tissue generated with ink-jet printing technology

eyes_011414The possibility of printing organs or tissues to treat a range of medical conditions is one that continually fascinates me. So I was interested to read about a new approach using a standard ink-jet printer to build tissue for repairing retinal damage.

Technology Review reports on why printing eye cells could be more effective than the conventional method of generating cells:

Scientists can grow single layers of cells in cultures, but printing may be a more effective way to engineer new tissues and organs, which are made of multiple different cell types positioned in intricate three-dimensional orientations. The retina, for example, is a highly organized, multilayered structure composed of various types of neurons and non-neuronal cells. The new ink-jet technique makes it possible to place retinal cells in “very precise and special arrangements,” says [University of Cambridge professor Keith Martin, who led the research].

Rebuilding the retina is an extremely difficult challenge, because “you have to reconstruct what is basically a small computer” whose function arises from a very complicated architecture in which multiple cell layers are connected in a number of different ways, says Joel Schuman, chairman of the department of ophthalmology at the University of Pittsburgh. If this architecture could be re-created using a printer, “you would be so many steps ahead of trying to grow the layers individually and then put them together,” he says.

The piece goes on to explain how printed eye cells could be used in treating common forms of blindness including macular degeneration, which is the leading cause of blindness.

Previously: Stanford researchers develop solar-powered, wireless retinal implantAustralian scientists implant early prototype of a “bionic eye” into a patient, Stanford-developed retinal prosthesis uses near-infrared light to transmit images and Developing a prosthetic eye to treat blindness
Photo by Scinern

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