Curcumin-like Drug Slows Aging, Reverses Memory Deficits


Drug Slows Aging, Reverses Memory Deficits

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Possible Alzheimer’s & Parkinsons Drug

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Roll over and click on BOLD links above and below to open article – unable to indicate color blue.

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“…potential Alzheimer’s drug works by reducing the rate of aging at the molecular level, according to a new study led by Salk Institute scientists.

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The study explains how the drug both improves cognition and reduces the rate of aging, when given to very old mice.

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Study authors say a drug that inhibits aging may succeed where drugs specifically aimed at Alzheimer’s have failed.

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Getting the drug into human clinical trials will require a little over $1 million.”

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 The study was published in the journal Aging Cell….

The mitochondrial ATP synthase is a shared drug target for aging and dementia

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 Salk Institute News

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….“This really glues together everything we know about J147 in terms of the link between aging and Alzheimer’s,” says Dave Schubert, head of Salk’s Cellular Neurobiology Laboratory and the senior author on the new paper. “Finding the target of J147 was also absolutely critical in terms of moving forward with clinical trials.”

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Schubert’s group developed J147 in 2011, after screening for compounds from plants with an ability to reverse the cellular and molecular signs of aging in the brain. J147 is a modified version of a molecule (curcumin) found in the curry spice turmeric. In the years since, the researchers have shown that the compound reverses memory deficits, potentiates the production of new brain cells, and slows or reverses Alzheimer’s progression in mice. However, they didn’t know how J147 worked at the molecular level.

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In the new work, led by Schubert and Salk Research Associate Josh Goldberg, the team used several approaches to home in on what J147 is doing. They identified the molecular target of J147 as a mitochondrial protein called ATP synthase that helps generate ATP—the cell’s energy currency—within mitochondria. They showed that by manipulating its activity, they could protect neuronal cells from multiple toxicities associated with the aging brain. Moreover, ATP synthase has already been shown to control aging in C. elegans worms and flies.

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“We know that age is the single greatest contributing factor to Alzheimer’s, so it is not surprising that we found a drug target that’s also been implicated in aging,” says Goldberg, the paper’s first author.

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Further experiments revealed that modulating activity of ATP synthase with J147 changes the levels of a number of other molecules—including levels of ATP itself—and leads to healthier, more stable mitochondria throughout aging and in disease.

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“I was very surprised when we started doing experiments with how big of an effect we saw,” says Schubert. “We can give this to old mice and it really elicits profound changes to make these mice look younger at a cellular and molecular level.”

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The results, the researchers say, are not only encouraging for moving the drug forward as an Alzheimer’s treatment, but also suggest that J147 may be useful in other age-associated diseases as well.

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“People have always thought that you need separate drugs for Alzheimer’s, Parkinson’s and stroke” says Schubert. “But it may be that by targeting aging we can treat or slow down many pathological conditions that are old-age-associated.”

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Metformin

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From WebMD, March 29, 2017:

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“Doctors have prescribed metformin, the most common drug to treat type 2 diabetes, for about 60 years. But it’s received new attention as a possible anti-aging drug after researchers in Britain found that people with diabetes who took it outlived some of their peers who did not have the disease by 15%.

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“They compared them to a whole bunch of people who were matched for weight and smoking and [other factors] but who didn’t have diabetes,” says Steven Austad, PhD, chairman of the biology department at the University of Alabama at Birmingham. “It turned out the diabetics on metformin were living longer than the non-diabetics who were not on metformin. … It was very, very intriguing.”

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Austad is a bio-gerontologist and scientific director of the American Federation for Aging Research….

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Scientists believe the drug works in the mitochondria, the powerhouses in the body’s cells that convert sugars like glucose into energy. Austad says metformin makes those powerhouses run more efficiently, reducing the release of substances known as free radicals. Free radicals can damage cells, hurting their ability to reproduce and causing defects.”

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….Resveratrol, a compound found in grapes and nuts, may reduce stress that leads to cell aging. Research shows it can extend life span in yeast, worms, and fish, but these effects haven’t been demonstrated in humans yet.”

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The material on this site is for informational purposes only.

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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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Comments are welcome.

This site is not for email, not for medical questions, and not for appointments.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please IGNORE THE ADS BELOW. They are not from me.

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CurcuVIVA reduces joint pain, helps Alzheimers – Oxycodone use much lower


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Rheumatoid arthritis pain is much better in a 54 year old female. She had half the month’s supply of oxycodone left at end of month for breakthrough pain – a big surprise! She had begun CurcuVIVA one daily for that month. It is a dietary supplement available without prescription.

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PJ’s Prescription Shoppe carries it to make it easier for patients though it is available elsewhere.

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CurcuVIVA is a capsule taken once daily. You will see the name Longvida on its label and in the literature. It is the same thing.

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It is curcumin, the active ingredient in turmeric. It differs from turmeric because this form does cross the blood brain barrier to reach brain. Turmeric does not reach the brain, therefore turmeric has no effect on Alzheimers Disease or tauopathies (accumulation of tau proteins). Tau in Alzheimers Disease and frontotemporal dementia and parkinsonism has been linked to chromosome 17.

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UCLA Alzheimers research unit developed this form of curcumin under the direction of Sally A. Frautschy and Greg Cole. On December 2012 they published in the Journal of Biological Chemistry showing Curcumin corrects molecular, synaptic and behavioral deficits in aged human tau transgenic mice.

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For more information on other actions of curcumin such as pain, etc, see a detailed review on the website of Memorial Sloan Kettering Cancer Center Herbs and Botanicals. I link to them on my website (bottom right column) as it is difficult to find. Curcumin has antiplatelet properties that may increase risk of bleeding. I recommend reading the details of mechanism of action and drug interactions.

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Do not combine with other over-the-counter pain medications without checking this link for interactions.

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It “exhibits neuroprotective, choleretic, anti-inflammatory, immunomodulatory, anti-proliferative and chemopreventive effects.” It was “found to be safe and equally effective as a non-steroidal anti-inflammatory drug for the treatment of osteoarthritis of the knee.”

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Caution: “Patients with gastrointestinal disorders or predisposed to kidney stone formation should…use this supplement with caution.”

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Contraindications: “Patients with bile duct obstruction, gallstones, and GI disorders including stomach ulcers and hyperacidity disorders should not take this supplement.”

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The material on this site is for informational purposes only.
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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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This site is not for email and not for appointments.

If you wish an appointment, please telephone the office to schedule.

 

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please ignore the ads below. They are not from me.

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Vitamin D – A Steroid Hormone, Anti-inflammatory


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The Sunshine Vitamin Controversy

What should normal values  be for calcium homeostasis?

My attention was drawn to Vitamin D several years ago when a review appeared in the journal Neurology, published by the Academy of Neurology, that linked low levels of Vitamin D to Multiple Sclerosis.  The article was unusual for its length and the breadth of research cited over several decades.  More recently, a Johns Hopkins article published “the most conclusive evidence to date” that Low Vitamin D Levels Pose Large Threat to Health.

New publications on Vitamin D seem to appear every week with the focus on levels of 25-hydroxyvitamin D, also written as 25(OH)D. Its half life in serum is ~ 10 days to 3 weeks.

The biologically active form 1,25-dihydroxyvitamin D, written as 1,25(OH)D²,  is made in the kidneys and has a much shorter serum half-life of ~ 4-6 hours, thus making it less useful as a serum marker for measuring.

Sources & Metabolism: Vitamin D is a fat soluble vitamin that’s absorbed in the small intestine from  foods such as egg yolks, fatty fish, fish liver oils, fortified milk, margarine, and cereals.  Bile salts are required for absorption.  Sunlight stimulates the skin to synthesize vitamin D, but exposure of hands and face as little as 15 minutes may not be sufficient and it is not as effective for everyone.  It won’t work in winter months, it won’t work for the aged, for those who have pigmented skin, and it won’t work for those who cover their skin.

Vitamin D Metabolism - click to enlarge

Vitamin D Metabolism

The Controversy –  How Do We Determine Normal Values?

Surprisingly, in a well designed multicenter study of healthy young Hawaiians in their 20’s who were exposed to at least 29 hours of sun per week, 51% were found to have vitamin D deficiency using the usual cut off of 30 ng/ml for normal.  This study from 2007 found the mean concentration of 31.6 ng/ml, and the highest of 62 ng/ml.  It raises the question whether

“it seems prudent to use this value [60 ng/ml] as an upper limit when prescribing vitamin D supplementation,”

rather than the generally published normal range of 30 to 80 ng/ml or even 100 ng/ml quoted in some labs.  This study is important in discussing the controversial question of what normal values should be for calcium homeostasis and reviews several possible explanations for inadequate production of D3 including genetic differences.

They note the highest reported values in “Nebraska outdoor workers… were between 81 and 84 ng/ml” but the assay system differed compared to theirs and results in a higher value.   Reviewing this study that was published in the Journal of Clinical Endocrinology & Metabolism has allowed me just now to readjust my own patient practice.

Laboratory Testing:  results can differ from one laboratory to another.  My hospital sends specimens to ARUP for testing, whereas Quest has acknowledged errors in laboratory testing and problems with standardization as reported by the New York Times here.

Function:  It is important for absorption of calcium and phosphorous from the small intestine, for bone health, osteoporosis, risk of falls, certain cancers(colon, breast, prostate), and possibly 6 to 7 years of longevity.  Deficiency of vitamin D is associated with suboptimal health and possibly increased pain; it is linked to infections, gum disease, hypertension, diabetes, coronary disease, neurological diseases such as Multiple Sclerosis, Parkinson’s Disease, dementia and Alzheimer’s Disease though it may not be causal. Its receptor is found all over the body including the brain.

I recommend this review by one of the best web resources at Memorial Sloan Kettering Cancer Center Herbs & Botanicals.

They quote a reference showing it reduces postmenopausal weight gain and “In adults with impaired fasting blood glucose, giving calcium and vitamin D reduced increases in plasma glucose and insulin resistance….”

It is the only vitamin that is a steroid hormone, and my interest increased on learning that it functions as an anti-inflammatory.  But as I tested blood levels for 25(OH) vitamin D and parathyroid hormone (PTH), I discovered more than 90% of my patients had vitamin D deficiency and a few had hyperparathyroidism.  There are four parathyroid glands next to the thyroid, and for some reason doctors have rarely tested their hormone levels.

***Persons with hyperparathyroidism should NOT take calcium or vitamin D.

It may lead to kidney stones and bone pain:  stones, bones and groans.***

Evidence for Optimizing Vitamin D Concentrations

On the other hand, if vitamin D is low, there is some evidence that replacement with vitamin D3 so that blood levels are in the high normal range, may help pain.  That is, it may raise the pain threshold and possibly have other benefits for health and longevity. It is desirable to avoid toxic levels of D as it causes hypercalcemia with depression, drowsiness, weakness, headache, polydipsia,  bone loss, and metastatic calcifications of many organs, soft tissues and blood vessels.  The generally quoted range of normal for 25(OH) vitamin D is 30 to 80, that varies with the lab.

great-western-divide-wp1

Doesn’t that photo of the Great Western Divide make you want to get outside into the sun?

Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes was reviewed by Heike Bischoff-Ferrari et al, in 2006,  though it has been superseded by much additional work since then.

To quote from their article:

This review summarizes the evidence for optimal serum  25(OH)D concentrations. The endpoint selection for this review was based the strongest evidence to date—ie, that from RCTs [randomized controlled trials], consistent evidence from prospective and cross-sectional epidemiologic studies, and strong mechanistic evidence or dose response relations.  BMD [bone mineral density], fracture prevention, lower-extremity function, falls, oral health, and colorectal cancer met these criteria. Weaker evidence exists of a beneficial effect of vitamin D on other diseases, including multiple sclerosis (15), tuberculosis (16), insulin resistance (17, 18), cancers other than colorectal (19 –22), osteoarthritis (23, 24), and hypertension (25–27), but these diseases are not considered here.

They did not review pain studies.  I would add that “weaker” evidence merely means that it must be confirmed by more studies, not that it excludes those conditions.  There is an epidemic of vitamin D deficiency in the country, and the incidence is very high in pain clinics as reported in several studies.

A new multi-center epidemiology study  “Demographic Differences and Trends of Vitamin D Insufficiency in the US Population, 1988-2004”  by Ginde, et al, in 2006,  “demonstrate a marked decrease in serum 25(OH)D levels from the 1988-1994 to the 2001-2004 NHANES data collections.”  And like others before them, they point out:

“Current recommendations for vitamin D supplementation are inadequate to address the growing epidemic of vitamin D insufficiency.”

Summary:

Make sure your doctor checks both your 25(OH)Vitamin D and parathyroid hormone level (PTH) – not thyroid – to determine if you have hyperparathyroidism or if you have normal or low vitamin D.  That will determine if you need replacement or if you should stop using calcium and D as it will cause kidney stones and calcium deposits on your bones leading to pain.

If vitamin D levels are low it may result in increased physical pain and may cause or aggravate many medical conditions.

If PTH levels are high indicating hyperparathyroidism it will cause new painful conditions.

Intake does vary with the patient, the season, the age, but the recommended daily allowance may perhaps be double what it is now.  It is unclear when the federal government will adjust that dosage.   As always, your physician’s recommendation will be based upon blood levels of 25(OH)D and PTH.

Do not make changes in your dosage without careful evaluation.

Could this possibly be one of the most important areas of research this century?

The material on this site is for informational purposes only, and

is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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