Researchers Identify Gene Variation that Protects Against Alzheimer’s Disease

Todd Hollingshead wrote . . . . . . .

Brigham Young University (BYU) researcher published in Genome Medicine details a novel and promising approach in the effort to treat Alzheimer’s disease.

BYU professors Perry Ridge and John Kauwe have discovered a rare genetic variant that provides a protective effect for high-risk individuals — elderly people who carry known genetic risk factors for Alzheimer’s — who never acquired the disease.

In other words, there’s a specific reason why people who should get Alzheimer’s remain healthy. Study authors believe this genetic function could be targeted with drugs to help reduce the risk of people getting the disease.

“Instead of identifying genetic variants that are causing disease, we wanted to identify genetic variants that are protecting people from developing disease,” said Ridge, assistant professor of biology at BYU. “And we were able to identify a promising genetic variant.”

That former approach to Alzheimer’s disease has been generally effective in producing a list of genes that might impact risk for the disease, but it leaves researchers without sufficient data on what to do next. In this new approach, Ridge and Kauwe develop the biological mechanism by which a genetic variant actually impacts Alzheimer’s disease.

Using data from the Utah Population Database — a 20-million-record database of the LDS Church’s genealogical records combined with historical medical records from Utah — Ridge and Kauwe first identified families that had a large number of resilient individuals: those who carried the main genetic risk factor for Alzheimer’s (E4 Allele) but remained healthy into advanced age.

Using whole genome sequencing and a linkage analysis methodology, they then looked for the DNA that those resilient individuals shared with each other that they didn’t share with loved ones who died of Alzheimer’s. They discovered the resilient subjects shared a variant in the RAB10 gene while those who got the disease did not share the genetic variant.

Once the researchers identified the potentially protective gene variant, they over expressed it in cells and under expressed it in cells to see the impact on Alzheimer’s disease related proteins. They learned that when this gene is reduced in your body, it has the potential to reduce your risk for Alzheimer’s.

“There are currently no meaningful interventions for Alzheimer disease; no prevention, no modifying therapies, no cure,” Kauwe said. “The discoveries we’re reporting in this manuscript provide a new target with a new mechanism that we believe has great potential to impact Alzheimer’s disease in the future.”

BYU was the lead institution on this research effort and collaborated with the University of Utah, Utah State University, the Mayo Clinic and the Washington University School of Medicine.

Source: Brigham Young University

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Study: Compound Found in Berries and Red Wine can Rejuvenate Cells

Richard Faragher, Lizzy Ostler and Lorna Harries wrote . . . . .

By the middle of this century the over 60s will outnumber the under 18s for the first time in human history. This should be good news, but growing old today also means becoming frail, sick and dependent. A healthy old age is good for you and a remarkably good deal for society. Improving the overall health of older Americans could save the US alone enough money to pay for clean drinking water for everyone on Earth for the next 30 years.

But if we want people to be healthy in old age we have to understand the mechanisms underlying the deterioration of our bodies over time. Doing so – and learning how we can prevent it – has been the goal of ageing research for more than 60 years.

There has been astonishing progress made over the last decade. In 2009, it was shown that the drug rapamcyin extended the lifespans of mice by 10-15%. Two years later a landmark study showed that experimental clearance of “senescent” cells – dysfunctional cells which build up as we age and cause damage to tissue – improved healthy lifespan in laboratory mice. These results delighted those of us who had argued for decades that senescent cells were a major cause of late life problems and should therefore be therapeutic targets.

Research on both living human cohorts and isolated cells have looked at the types of genes which change in expression levels (the process by which information from a gene is used to make the tens of thousands of proteins needed by a cell during ageing. This has revealed that the largest changes occur in genes which regulate how “messenger RNAs” are made. These transfer the information stored in DNA to the cellular machinery which turns it into proteins.

In the human cell, proteins known as “RNA splicing factors” determine which messenger RNA can be made from RNA building blocks in a process known as RNA splicing. The ability of our cells to do this is restricted with ageing. But it was unclear whether this loss is a result of senescent cells accumulating in ageing tissue or something new, occurring in parallel with senescence until now.

New evidence

Now our latest study, published in BMC Cell Biology shows that a natural substance can actually rejuvenate senescent cells by targeting RNA splicing.

In our experiments, we treated such cells with compounds we synthesised based on resveratrol, a natural product found in red wine, berries and other foods, reported to alter RNA splicing in cancer cells. Resveratrol – which can be found in many natural foods – is a blunt tool that affects multiple cellular pathways. But our synthetic variants are actually much more precise and we picked ones that preferentially affected RNA splicing.

Senescent human cells treated with our products showed remarkable effects, which we called “rejuvenation”. RNA splicing patterns were rapidly reset to that seen in young cells and then the senescent cultures began to grow again. Variations of this basic experiment showed that splicing factor restriction is separate from senescence but interacts with it.

Restoring RNA splicing rejuvenates senescent cells in part because our cells are normally rendered senescent through telomere shortening, the gradual loss of the DNA at the ends of chromosomes that occurs with repeated cell division. Some RNA splicing factors that decline with age are capable of helping to repair telomeres and so, if you restore them, they lengthen telomeres back up and stop the cell being senescent.

Restricted splicing has serious implications beyond the capacity of cells to divide and how tissues deal with stress. It limits cell responses, potentially contributing to the increased frailty that is a hallmark of ageing in many organisms including humans.

Following our discoveries the area of RNA splicing is now ripe for detailed study, not least because cells from old individuals that have not become senescent probably still have compromised splicing. Restricted splicing may prove to be a critical mechanism in the development of a wide range of age-associated diseases.

Drugs and diet

Our compounds have allowed us to begin to identify the key molecular pathways that mediate splicing factor restriction and may have a future as a platform for anti-degenerative drugs. But when only one or two in tens of thousands of compounds become medicines none of us are quitting work just yet.

As resveratrol and similar molecules are found in food, our work may have revealed an unsuspected link between diet and RNA splicing. Many groups have shown the beneficial effects of diets containing these foods – altered splicing may be one, but not the only, way in which they mediate their effects. However you’d need to drink some 30 litres of red wine a day to achieve the doses of analogues of resveratrol we used in tissue culture.

Pure resveratrol already exists as a dietary supplement. However, we do not recommend taking it just yet. One of the reasons we made the novel compounds was that resveratrol, like many natural products, has a whole range of activities, some that appear beneficial and some less so.

Our emphasis on achieving health in later life without undue concern for its extension chimes closely with the popular view. Something in excess of 60% of the population do not want thousand-year lifespans, even when given a guarantee of perfect health.

The challenge now is to convert this basic scientific discovery into the benefits people want, and as quickly as possible. Until then, there’s always blueberries …

Source : The Conversation

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Hong Kong Researchers Create Tomatoes with Anti-ageing Properties

Danny Mok wrote . . . . . . .

The research team led by Professor Chye Mee-len from the university’s School of Biological Sciences identified a new strategy to simultaneously enhance health-promoting compounds vitamin E, provitamin A, lycopene, as well as phytosterols and squalene, in tomatoes, becoming the first in the world to do so.

Her team members, HKU associate professor Wang Mingfu and postdoctoral fellow Liao Pan, modified a gene isolated from Indian mustard and introduced it into ordinary tomatoes.

The genetically modified tomatoes contained 494 per cent more vitamin E than ordinary tomatoes. Provitamin A and lycopene content was also 169 per cent and 111 per cent higher, respectively. These substances are all anti-ageing antioxidants.

There were no differences in the appearance and size of the altered tomatoes, compared to normal tomatoes.

Professor Chye said: “Our transgenic tomatoes can be processed to give tomato juice and tomato paste that are enriched with many healthy components.”

And she said the extracts with enriched phytosterols, vitamin E and carotenoids could be used in the production of anti-ageing cream, sun-care lotion or face masks. These compounds have excellent anti-inflammatory and antioxidant activity, she said.

Her team planned to further the research by testing these tomatoes on animals to examine the health benefits in detail.

Source : SCMP

Smell Tests Identify Patients for Treatment before Development of Alzheimer’s

Researchers at Columbia University Medical Center (CUMC) and the New York State Psychiatric Institute (NYSPI) may have discovered a way to use a patient’s sense of smell to treat Alzheimer’s disease before it ever develops. Having an impaired sense of smell is recognized as one of the early signs of cognitive decline, before the clinical onset of Alzheimer’s disease. The researchers at CUMC and NYSPI have found a way to use that effect to determine if patients with mild cognitive impairment may respond to cholinesterase inhibitor drugs to treat Alzheimer’s disease.

The findings were published online this week in the Journal of Alzheimer’s Disease.

Cholinesterase inhibitors, such as donepezil, enhance cholinergic function by increasing the transmission of the neurotransmitter acetylcholine in the brain. Cholinergic function is impaired in individuals with Alzheimer’s disease. Cholinesterase inhibitors, which block an enzyme that breaks down acetylcholine, have shown some effectiveness in improving the cognitive symptoms of Alzheimer’s disease. However, they have not been proven effective as a treatment for individuals with mild cognitive impairment (MCI), a condition that markedly increases the risk of Alzheimer’s disease.

“We know that cholinesterase inhibitors can make a difference for Alzheimer’s patients, so we wanted to find out if we could identify patients at risk for Alzheimer’s who might also benefit from this treatment,” said D.P. Devanand, MBBS, MD, professor of psychiatry, scientist in the Gertrude H. Sergievsky Center at CUMC, and co-director of the Memory Disorders Clinic and the Late Life Depression Clinic at NYSPI. “Since odor identification tests have been shown to predict progression to Alzheimer’s, we hypothesized that these tests would also allow us to discover which patients with MCI would be more likely to improve with donepezil treatment.”

In this year-long study, 37 participants with MCI underwent odor identification testing with the University of Pennsylvania Smell Identification Test (UPSIT). The test was administered before and after using an atropine nasal spray that blocks cholinergic transmission.

The patients were then treated with donepezil for 52 weeks, and were periodically reevaluated with the UPSIT and with memory and cognitive function tests. Those who had a greater decline in UPSIT scores, indicating greater cholinergic deficits in the brain, after using the anticholinergic nasal spray test saw greater cognitive improvement with donepezil.

In addition, short-term improvement in odor identification from baseline to eight weeks tended to predict longer-term cognitive improvement with donepezil treatment over one year.

“These results, particularly if replicated in larger populations, suggest that these simple inexpensive strategies have the potential to improve the selection of patients with mild cognitive impairment who are likely to benefit from treatment with cholinesterase inhibitors like donepezil,” said Dr. Devanand.

Source: EurekAlert!

How to Prevent Falls in Older Adults

Hallie Levine wrote

Regular exercise and vision screenings are among the strategies that significantly reduce older adults’ risk of injuries from falls, according to a review of 54 studies published in the Journal of the American Medical Association (JAMA).

This is important because every 20 minutes in the U.S., someone age 65 or older dies from a fall. In fact, falls are the most frequent source of injury for seniors, with more than one in four people 65 or older taking a spill each year, according to the Centers for Disease Control and Prevention (CDC). Seniors had more than 29 million falls in 2014 alone. And about 20 percent of falls cause a serious health issue such as a broken bone or head injury.

“A fall is often a life-changing event, the start of a downward spiral of increasing frailty and dependency,” says Eric Larson, M.D., M.P.H., executive director of the Kaiser Permanente Washington Health Research Institute, who wrote an editorial accompanying the study. And those who fall once are twice as likely to fall again, according to the CDC. So reducing the risk of falling is essential, Larson says.

In the new study, researchers looked at the effects of 39 fall-prevention interventions in previously published research involving almost 42,000 people. They found that four single or combination strategies were most effective.

“The greatest reduction—38 percent—was seen in people who exercised and had vision assessment and treatment to correct any vision issues,” says the study’s author, Andrea Tricco Ph.D., an associate professor at the Dalla Lana School of Public Health at the University of Toronto. “But our study also shows that other strategies, such as environmental assessments and modifications, patient education, and taking calcium and vitamin D supplements also help.”

In addition, the researchers found that some of the interventions they looked at, including cognitive behavior therapy, dietary modifications, electromagnetic field therapy, and podiatry assessment and treatment, seemed to have little positive effect.

Here, what to know to prevent falls:

Know What Hikes Your Fall Risk

Advancing age is the most significant risk factor for falling, but several others can also increase susceptibility, Larson says. These include:

Poor vision. Age-related vision changes and eye diseases such as macular degeneration, diabetic retinopathy, glaucoma, and cataracts can affect your ability to navigate safely while walking.

Medication side effects. Almost one-third of older adults in the U.S. take over-the-counter (OTC) or prescription sleep aids, which can cause next-day drowsiness, dizziness, and balance problems, and more than double the risk of falls and hip fractures. A number of other drugs may also raise fall risk, including anti-anxiety medications such as diazepam (Valium and generic) and lorazepam (Ativan and generic), and OTC diphenhydramine (Benadryl Allergy and generic). A May 2016 study of 90,127 older adults found a 36 percent increase in serious falls during the first 15 days after starting blood pressure medication.

Medical conditions. Anemia, inner-ear disorders, and low blood pressure can throw off your balance. Other conditions that may hike your fall risk include Parkinson’s disease, dementia, a history of stroke, and arthritis.

Protect Yourself From Dangerous Falls

According to the new study and to other experts, the following steps can improve your overall balance and help lower the likelihood of a potentially devastating fall.

Stay active. The new review found that all types of exercise help to prevent falls, possibly because most activity strengthens legs and enhances balance, Tricco says. One activity to consider is tai chi. Practicing this Chinese form of gentle exercise one to three times a week may slash your fall risk by half, according to a study published in July in the Journal of the American Geriatrics Society.

Maintain good balance. If you have difficulty doing heel-to-toe walking (taking steps with one foot directly in front of the other) or you’re unable to stand on one leg for at least 30 seconds, you may be at increased risk for falls, cautions Marvin M. Lipman, M.D., Consumer Reports’ chief medical adviser. Have your doctor assess you for health conditions that can affect balance, like those mentioned in “Know What Hikes Your Fall Risk,” above. He or she may also prescribe physical therapy to strengthen your muscles and improve your balance, flexibility, and endurance. (Here are basic balancing exercises from the National Institute of Aging.)

Take care of your vision. See an ophthalmologist or optometrist for a complete eye exam every year or two after the age of 65 to check for age-related eye diseases. If you’ve recently gotten multifocal eyeglass lenses, be aware that they can impair depth perception; you’ll need to take extra care to prevent falls until you get used to your prescription. The same goes for the first few weeks after cataract surgery. Your eyesight will improve, but it will take a bit of time to adjust to your new level of vision.

Assess your home. More than 75 percent of falls take place in or near the home, according to the National Council on Aging. The new review found that the combined strategy of assessing (and, when necessary, modifying) living environments for older adults, along with exercise and vision assessment and treatment was useful in reducing fall risk. Some quick and simple changes—such as fixing a broken handrail or removing throw rugs that may cause slips and trips—can enhance safety significantly. Find a whole-home hazard checklist here.

Bone up on calcium and vitamin D. The JAMA review found that getting sufficient amounts of these nutrients appeared to help reduce fall risk. “They have been linked to stronger bones, which may in turn lower chances of having a fall,” Larson explains. Adults between age 50 and 70 should get 1,000 mg of calcium and 600 IU of vitamin D each day. Those over the age 70 need 1,200 mg of calcium daily and 800 IU of vitamin D.

The best way to get calcium is through foods that are rich in the mineral, such as dairy products (a cup of plain low-fat yogurt or low-fat milk has around 300 mg), fortified foods such as oatmeal, and leafy greens like broccoli. Good sources of vitamin D include fatty fish such as salmon (with 447 IU in a 3-ounce serving, cooked), fortified milk, orange juice, and soy beverages. Because our bodies also make vitamin D when we’re exposed to sunlight, our experts suggest getting 10 minutes of sunshine per day.

Review medications carefully. If you’re taking sleeping pills or anti-anxiety drugs regularly, or other medication that leaves you feeling groggy or off-balance, speak to your physician about how to safely wean yourself from them. If your doctor recommends any new medication, ask about side effects that could cause grogginess or balance problems.

Wear sturdy shoes. Opt for shoes with a heel collar and firm (not cushy) sole, which will help you feel the ground beneath you better and thus improve balance, even at home. “I bought my own parents slippers with hard soles like a tennis shoe to wear when they got up in the middle of the night to go to the bathroom, since that’s a prime time for falls,” Larson says. During the winter when it’s icy, consider slip-on ice cleats when you go outdoors for added traction that may prevent falls.

Source : Consumer Reports

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