Diabetes Drug Metformin Has Unexpected, Broad Implications for Healthy Aging

Metformin is the most commonly prescribed type 2 diabetes drug, yet scientists still do not fully know how it works to control blood sugar levels. In a collaborative effort, researchers from the Salk Institute, The Scripps Research Institute and Weill Cornell Medical College have used a novel technology to investigate why it functions so well. The findings, which identified a surprising number of biochemical “switches” for various cellular processes, could also explain why metformin has been shown to extend health span and life span in recent studies. The work was published in Cell Reports on December 3, 2019.

“These results provide us with new avenues to explore in order to understand how metformin works as a diabetes drug, along with its health-span-extending effects,” says Professor Reuben Shaw, co-corresponding author of the paper and the director of Salk’s NCI-designated Cancer Center. “These are pathways that neither we, nor anyone else, would have imagined.”

Previously, the only biochemical pathway that was known to be activated by metformin was the AMPK pathway, which Shaw discovered stalls cell growth and changes metabolism when nutrients are scarce, as can occur in cancer. But the scientists believed more pathways than AMPK might be involved.

The scientists developed a novel screening platform to examine kinases, the proteins that transfer phosphate groups, which are critical on/off switches in cells and can be rapidly flipped by metformin. Using this technology, the researchers were able to decode hundreds of regulatory “switch-flipping” events that could affect healthy aging.

“Being mentored by John Yates, one of the top mass spectrometry investigators in the world, and Reuben Shaw, an expert in the field of metabolism, enabled me to both develop and apply a novel technology to a critical biological question: What pathways are regulated by metformin in the liver?” says Ben Stein, first author and postdoctoral associate at Weill Cornell Medical College.

The results revealed that metformin turns on unexpected kinases and pathways, many independent of AMPK. Two of the activated kinases are called Protein Kinase D and MAPKAPK2. These kinases are poorly understood, but are known to have some relation to cellular stress, which could connect them to the health-span- and life-span-extending effects observed in other studies. In fact, metformin is currently being tested in multiple large-scale clinical trials as a health-span- and life-span-extending drug, but the mechanism for how metformin could affect health and aging has not been clear. The current study indicates that Protein Kinase D and MAPKAPK2 may be two players in providing these therapeutic effects, and identifies new targets and cellular processes regulated by AMPK that may also be critical to metformin’s beneficial effects.

“We never imagined these two kinases would have anything to do with metformin,” says Shaw, holder of the William R. Brody Chair. “The results broaden our understanding of how metformin induces a mild stress that triggers sensors to restore metabolic balance, explaining some of the benefits previously reported such as extended healthy aging in model organisms taking metformin. The big questions now are what targets of metformin can benefit the health of all individuals, not just type 2 diabetics.”

Next, the researchers plan to examine the new signaling pathways they discovered in more detail to better understand the beneficial effects of metformin.

Source: Salk


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Treating More than Just the Heart is Critical for Geriatric Patients

Geriatric conditions such as frailty and cognitive impairments may inadvertently worsen when older patients are treated in cardiac intensive care units – even as they receive excellent care for their heart attack, heart failure, valvular heart disease or pulmonary embolism, according to a new scientific statement from the American Heart Association, published today in the Association’s premier journal Circulation.

In addition to their cardiovascular conditions, many older patients often have additional health conditions, take multiple medications for these conditions, may be frail or have cognitive impairment. Caring for older adults in the cardiac intensive care unit is markedly different than caring for younger patients, according to the statement, which provides an overview of how geriatric conditions may influence acute cardiovascular care.

“Treating the whole patient – considering their entire health profile, rather than focusing only on their acute cardiovascular event – is essential for achieving the best possible outcomes among geriatric patients with acute cardiovascular disease,” said Abdulla A. Damluji, M.D., M.P.H., chair of the writing group for the statement, assistant professor of medicine at Johns Hopkins University School of Medicine in Baltimore, Maryland, and interventional cardiologist at the Inova Heart and Vascular Institute, Falls Church, Virginia.

While in a cardiac intensive care unit, older patients often experience factors that are emotionally and physically disorienting – such as bright lights, excessive noise, new medications, urinary catheters, dietary shifts, sleep disruptions and toileting challenges. “For vulnerable older adults who may already be experiencing cognitive decline, the environment in the cardiac intensive care unit may deplete already limited coping skills and could lead to delirium,” said Damluji.

Delirium is a state of an acute disturbance in awareness and attention. It commonly occurs during critical illness, and it contributes to a higher risk of dying in the hospital. “Reducing the level of sedation used in older patients may help mitigate delirium, however, more research needs to be done to fully understand how best to treat this condition in the context of acute cardiovascular illness,” said Damluji.

Extended bedrest, often necessary in an intensive care unit, is detrimental to patients of all ages. For older, critically ill patients, who are often frail when admitted to the cardiac intensive care unit, bedrest can significantly worsen their frailty. Further deterioration in muscle strength and bone density often occurs with prolonged immobility, which can also lead to poor medication tolerance, an increased risk of falling, weakened heart function and pressure ulcers (bed sores).

Early mobilization – getting the patient out of bed as soon as appropriate, may be helpful for some patients to address frailty. Encouraging appropriate physical movement may result in less weakness, an improved ability to walk and less time in the cardiac intensive care unit, among other benefits.

Another issue faced by older adults admitted to the cardiac intensive care unit is that they take an average of 12 different prescription medications, raising the risk of adverse side effects, drug-to-drug and drug-to-disease interactions. Patients may benefit by having some of their medications discontinued or deprescribed, if appropriate.

“In recent years, there has been a strong emphasis by the American Heart Association and other organizations to integrate geriatric syndromes into cardiovascular care for older patients, although implementation is slow. Strategies to achieve a wholistic care approach for each patient remains an important goal to improve care of older patients in the cardiac intensive care unit,” said Damluji.

Most clinical trials on how to treat acute cardiovascular conditions were performed on younger populations, however, their findings may not be accurate for older patients. Yet, most people over age 85 years have a cardiovascular disease and are likely to be admitted to a cardiac intensive care unit for treatment of an acute event, according to the statement.

Source: American Heart Association


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Aerobic Exercise And Heart-Healthy Diet May Slow Development Of Memory Problems

Cognitive impairment without dementia (CIND), or mild cognitive impairment, is a condition that affects your memory and may put you at risk for Alzheimer’s disease and dementia. According to the U.S. National Library for Medicine, signs of mild cognitive impairment may include frequently losing things, forgetting to go to events and appointments, and having more trouble coming up with words than other people of your age.

Sine experts believe that risk factors for heart disease also are risk factors for dementia and late-life cognitive decline and dementia. Recently, researchers examined two potential ways to slow the development of CIND based on what we know about preventing heart disease. They published the results of their study in the Journal of the American Geriatrics Society.

The research team had a theory: That the healthy lifestyle behaviors that slow the development of heart disease could reduce heart disease risk and also slow cognitive decline in older adults with CIND. These behaviors include regular exercise and a heart-healthy diet, such as the DASH (Dietary Approaches to Stop Hypertension) diet.

In order to investigate their theory, the researchers designed a study titled “Exercise and NutritionaL Interventions for coGnitive and Cardiovascular HealTh EnhaNcement” (or ENLIGHTEN for short). The goal of the study was to examine the effects of aerobic exercise (sometimes known as “cardio” or “cardiovascular” exercise because it involves activities that increase the circulation of oxygen through the blood) and the DASH diet on cognitive functioning in older adults with CIND.

The ENLIGHTEN study examined 160 adults 55-years-old or older. The study participants were older adults who didn’t exercise and had memory problems, difficulty thinking, and making decisions. They also had at least one additional risk factor for heart disease, such as high blood pressure (also known as hypertension), high cholesterol, diabetes, or other chronic conditions.

Participants took a number of tests to measure their heart disease risk factors and cognitive ability. Researchers also assessed participants’ dietary habits and ability to perform daily activities. The participants were then randomly assigned to one of four groups: a group doing aerobic exercise alone, a group following the DASH diet alone, a group doing aerobic exercise and following the DASH diet combined, or a group receiving standard health education.

People in the exercise group did 35 minutes of moderate intensity aerobic exercise (including walking or stationary biking) three times per week for six months. They were supervised for three months and then exercised unsupervised at home for three months. Participants in the exercise group did not receive any counseling in the DASH diet and were encouraged to follow their usual diets for six months.

People in the DASH eating plan group received instruction about how to meet DASH guidelines in a series of weekly sessions for three months and then bi-weekly for the remaining three months. Participants in the DASH group were asked not to engage in regular exercise until the completion of the six-month study.

People in the exercise and DASH group followed the exercise and DASH programs for six months. The participants who were enrolled in the health education group received weekly educational phone calls for three months and then bi-weekly calls for three months. Phone calls were conducted by a health educator on health topics related to heart disease. Participants were asked to maintain their usual dietary and exercise habits for six months until they were re-evaluated.

At the conclusion of the six-month intervention and assessment, participants were free to engage in whatever activity and dietary habits they desired, with no restrictions.

The results of the research team’s study showed that exercise improved the participants’ ability to think, remember, and make decisions compared to non-exercisers, and that combining exercise with the DASH diet improved the ability to think, remember, and make decisions, compared to people who didn’t exercise or follow the diet—even though they didn’t perfectly follow the programs they were assigned to during the six-month interventions.

The researchers concluded that their findings are promising proof that improved ability to think, remember, and make decisions can last one year after completing a six-month exercise intervention. They suggested that further studies would be needed to learn more.

Source: Health in Aging


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Coenzyme Q10 (CoQ10)

Jamie Eske wrote . . . . . . . . .

Coenzyme Q10, or CoQ10, is a naturally occurring chemical that exists in almost every cell of the human body. CoQ10 carries out several vital roles, including promoting energy production and neutralizing harmful particles called free radicals.

A deficiency in CoQ10 can adversely affect a person’s health. People can get CoQ10 through foods and supplements.

What is CoQ10?

CoQ10 is an essential nutrient present in almost every cell of the human body. The following foods also contain CoQ10:

  • oily fish
  • organ meats
  • eggs
  • nuts
  • whole grains

CoQ10 plays a vital role in energy production and DNA replication and repair. It also acts as an antioxidant, neutralizing harmful free radicals.

Several factors can lower CoQ10 levels in the body. These include:

  • aging
  • taking statins, which are cholesterol-lowering medications
  • genetic mutations that affect the production of CoQ10
  • disorders of the mitochondria, which are the parts of the cell that generate energy
  • CoQ10 deficiency is associated with numerous diseases, including:
    • heart disease
    • cancer
    • Alzheimer’s disease

How does it work

For the body to use CoQ10, it must convert it from its inactive form, ubiquinone, into it its active form, ubiquinol.

Mitochondria are responsible for powering the body’s cells. To do this, they use CoQ10 to produce the chemical adenosine triphosphate (ATP). This process is known as ATP synthesis. ATP is the primary source of energy for the body’s cells.

However, mitochondria produce free radicals during ATP synthesis.

Under normal conditions, free radicals regulate communication between cells and defend the body against infectious microbes. However, excess free radicals cause DNA damage, which can lead to the following:

  • inflammation
  • DNA mutations
  • tissue damage

CoQ10 acts as an antioxidant by neutralizing free radicals. In this way, CoQ10 helps protect cells from the harmful effects of DNA damage.

What is the correct dosage?

The exact recommended dose of CoQ10 will vary according to the following factors:

  • a person’s age
  • a person’s health
  • the condition receiving treatment

Standard daily doses of CoQ10Trusted Source range from 60 milligrams (mg) to 500 mg. The highest recommended dose is 1,200 mg. However, clinical trials have used dosages as high as 3,000 mg per day.

Different types of CoQ10 supplements may also require different dosages. Most supplements contain the inactive form of CoQ10, ubiquinone, which is harder to absorb than ubiquinol.

A 2018 randomized trial compared the effects of 200 mg daily doses of ubiquinone and ubiquinol supplements on CoQ10 levels in older men. Ubiquinol supplementation led to a 1.5-fold increase in the amount of CoQ10 in the blood. Supplements containing ubiquinone did not have a significant effect on CoQ10 levels.

Benefits of CoQ10

CoQ10 protects cells against oxidative damage. It also plays a vital role in producing the body’s primary source of energy, ATP. CoQ10 could, therefore, provide a range of health benefits. Some examples include:

Improving heart health

The heart contains some of the highest concentrations of CoQ10 in the body. The vast majority of people with heart disease also have low CoQ10 levels. ResearchersTrusted Source now consider low CoQ10 levels to be an indicator of the severity and long term outcome of various heart diseases.

In one 2018 pilot studyTrusted Source, ten children with cardiac muscle dysfunction received 110–700 mg of liquid ubiquinol per day. At weeks 12 and 24 of treatment, the children had significantly higher CoQ10 plasma levels and improved heart function.

Reducing muscle pain from statin use

Cardiovascular disease (CVD) is an umbrella term for conditions that affect the heart or blood vessels. Doctors often prescribe statins to treat CVD. These drugs work by reducing the cholesterol production that can contribute to the disease.

Although statins reduce cholesterol production, they also lower CoQ10 levels. Reduced CoQ10 levels can lead to mitochondrial dysfunction, which can cause muscle painTrusted Source, or myopathy.

CoQ10 supplements may help relieve muscle pain related to statin use.

A 2019 randomized controlled trialTrusted Source investigated the effect of CoQ10 on statin-related muscle pain. The study involved 60 participants who had previously reported muscle pain while taking statins. Over 3 months, each participant received daily doses of either 100mg of CoQ10 supplement or a placebo.

The participants who took the CoQ10 supplements had significantly reduced statin-related muscle pain. Those who received the placebo reported no change in muscle pain.

However, the authors of a 2015 meta-analysis evaluated the efficacy of CoQ10 supplementation for treating statin-related muscle pain. The meta-analysis included six studies with a combined total of 302 patients. The authors found no evidence that CoQ10 significantly improves statin-related muscle pain.

Further large-scale RCTs are necessary to determine whether CoQ10 is a viable treatment for people experiencing statin-related muscle pain.

Treating migraines

Chronic migraines may be due to inflammation of neurons and cells in a part of the brain called the trigeminovascular system.

A 2018 clinical trial investigated whether coQ10 supplements could reduce inflammation in 45 women with episodic migraines. The women took 400 mg daily doses of either a CoQ10 supplement or a placebo. The women who took the CoQ10 supplements had fewer and less intense migraines when compared to the placebo group.

Women who took the CoQ10 supplements also showed lower levels of certain inflammatory biomarkers. Inflammatory biomarkers are substances in the blood that indicate the presence of inflammation somewhere in the body.

A 2018 meta-analysis reexamined five studies investigating the use of CoQ10 supplements for migraines. The meta-analysis concluded that CoQ10 is more effective than a placebo at reducing the duration of migraines. However, CoQ10 did not appear to affect migraine severity or frequency.

Protecting against age-related diseases

Mitochondrial function decreases as the body’s CoQ10 levels naturally deplete with age.

ResearchTrusted Source suggests that mitochondrial dysfunction can contribute to age-related neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. These diseases are associated with free radical damage.

A 2015 study investigated the effect of a Mediterranean diet combined with CoQ10 supplementation on metabolism in elderly adults. This combination led to an increase in antioxidant biomarkers in the urine.

The authors concluded that taking CoQ10 and eating a diet low in saturated fat may help protect against diseases caused by free radical damage.

In another 2015 studyTrusted Source, older adults received CoQ10 and selenium supplements for 48 months. The participants reported improvements in vitality, physical performance, and overall quality of life.

Risks of too much CoQ10

CoQ10 supplements appear to be safe, and most people tolerate them even at high doses. However, CoQ10 supplements can cause the following side effects:

  • nausea
  • stomach pain
  • heartburn
  • headache
  • dizziness
  • fatigue
  • light sensitivity
  • insomnia
  • skin rash

CoQ10 supplements may interfere with certain medications, including:

  • blood-thinners, such as warfarin
  • insulin
  • some types of chemotherapy medication

People should consult a doctor before taking any new medications or dietary supplements, including CoQ10.

Source: Medical News Today

How Well Are You Aging? A Blood Test Might Tell

Imagine a blood test that could spot whether you are aging too quickly.

New research suggests it’s not the stuff of science fiction anymore.

The scientists analyzed plasma — the cell-free, fluid part of blood — from more than 4,200 people between the ages of 18 and 95, and found a link between 373 proteins and aging.

“We’ve known for a long time that measuring certain proteins in the blood can give you information about a person’s health status — lipoproteins for cardiovascular health, for example,” said study senior author Tony Wyss-Coray. He’s co-director of the Alzheimer’s Disease Research Center at Stanford University in California.

“But it hasn’t been appreciated that so many different proteins’ levels — roughly a third of all the ones we looked at — change markedly with advancing age,” he added in a university news release.

The study was published Dec. 5 in the journal Nature Medicine.

“Proteins are the workhorses of the body’s constituent cells, and when their relative levels undergo substantial changes, it means you’ve changed, too,” Wyss-Coray explained. “Looking at thousands of them in plasma gives you a snapshot of what’s going on throughout the body.”

The findings suggest that physical aging doesn’t occur at a steady pace, but is uneven and has three distinct surges — ages 34, 60 and 78.

At those ages, there are spikes in levels of specific proteins in the blood with noticeable changes, according to the researchers.

Eventually, a blood test for these proteins might be able to identify people who are aging more rapidly than normal and at increased risk for age-related conditions such as Alzheimer’s disease or heart disease.

Such a test might also help identify drugs or other factors that slow or speed aging, the study authors said.

However, any clinical use of such a blood test is at least five to 10 years away, the researchers noted.

“Ideally, you’d want to know how virtually anything you took or did affects your physiological age,” Wyss-Coray said.

Source: HealthDay


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