Posts tagged with "Alzheimer’s Disease"

Harnessing the Nine Hallmarks of Aging: to live your healthiest life by Greg Macpherson for use by 360 Magazine

Reversing the Aging Process At A Cellular Level

By: Greg Macpherson, pharmacist, author, “Harnessing the Nine Hallmarks of Aging

You might think that the occasional gray hair, fine line and wrinkle starting to stare back at you in the mirror is a sign that time is starting to have its impact felt, but these visible changes as we age are just a symptom of what has been going on at a cellular level inside your body for decades. We all know that you can’t change time, but recent advances in our understanding of aging at a cellular level mean that in the not too distant future we will be able to change the impact that time has on our cells.

And it’s about time. Right now, despite the decades and billions of dollars that have gone and continue to go into attempting to understand and solve the diseases associated with advancing age like Alzheimer’s disease, Parkinson’s disease and cardiovascular disease, we have not made the progress we should.

Researchers are now starting to ask the question – what if we change track and seek to understand the aging process? By slowing aging, we not only spend decades longer in good health, but we push the diseases associated with old age down the road–possibly avoiding them all together.

 Why We Decline with Age

With better questions come better answers, progress, and breakthroughs. Nearly a decade ago, in the absence of a single theory regarding aging, scientists reached a consensus on nine key areas of our cells that decline in function as we age. These key areas are called the nine hallmarks of aging, and they all have something in common. If you make them worse, you age faster. If you make them better, you slow the aging process down.

Identifying the hallmarks of aging has given researchers cellular targets to focus on, and has unleashed an incredible amount of human capital focused on solving, or at least reducing, the ravages of aging on our bodies. Researchers armed with tens of billions of dollars in research grants and private equity are now racing to find the answers. And the prize is huge–resolving the aging process, deferring the diseases of older age and extending the time we spend in middle age in good health by decades will transform humanity and will both disrupt and create a trillion dollar industry overnight.

Progress is being made at an accelerating rate, and there are now therapies that have  been proven in mice models that are now making their way into clinical studies. Rapamycin, a pharmaceutical that is typically used for organ transplant recipients, because of its ability to help the body avoid rejecting the organ, is now understood to extend life in mice by up to 60%. Senolytics, molecules that help the body identify and remove senescent cells that increasingly accumulate as we age and literally poison the healthy cells that surround them, have extended life in mice by up to 30%. Metformin, a drug used to treat Type 2 diabetes has been identified to significantly reduce cancer rates and extend life.

And these are just a few of the compounds that have been identified that shift the effect of time on our bodies. These and more molecules being developed right now, plus strategies for healthy aging that have been identified from the blue zones around the world where people live to 100 and beyond at a much higher rate than the rest of us, are amongst the many healthy aging strategies that I featured in my book, “Harnessing the Nine Hallmarks of Aging, to Live Your Healthiest Life.”

As a pharmacist with 30 years of experience, I have spent the last decade working in the biotechnology arena associated with anti-aging, translating the complex world of anti-aging science to make it available for the rest of us. By understanding the nine hallmarks of aging­–adopting simple strategies from the blue zones, and sharing the breakthrough molecules that have not been available to humans in previous generations– I’ve put together a step-by-step, healthy aging strategy. We can all adopt  this strategy and, in the process, significantly alter our aging trajectory and making healthy aging much more of a certainty.

Why DNA Matters

One example of a hallmark of aging is “genomic instability,” which is another way of saying that the negative changes to our DNA in our cells that happen as we age. Your DNA is your cellular instruction set and defines what it means to be a human versus every other living species on our planet. Your DNA is responsible for the difference between a skin cell and a heart cell, a neuron and an insulin producing cell.

Your DNA are molecules that sit at the center of almost every single cell in your body, helping it function, live and thrive. Your DNA does this in an incredibly hostile environment as it deals with the external stress of pollution, mutagenic foods and chemicals, UV light and X-rays, and the internal insults of oxidative stress. Due to these factors your DNA is damaged between 50,000 and 100,000 times per day, per cell.

Because of the importance of having a healthy instruction set, your cells spend a huge amount of resource on the repair and maintenance of your DNA and as we age, and this process starts to decline, which has significant effect on the health of your cells. Take a quick look at the back of your hand compared to the skin on the inside of your wrist to get a sense of the difference between cells exposed to UV damage that hits your DNA.

DNA damage is happening right now in every cell in your body, and over time it affects the ability of your cells to function effectively. Starting as early as your 30s, by supporting DNA repair and maintenance through making lifestyle changes and by taking molecules, like hobamine, NMN and apigenin, as outlined in my book, it can help your body keep your DNA and the other hallmarks of aging in good shape. By following the roadmap of this breakthrough strategy in a healthy aging, you will age better than previous generations have ever been able to achieve.

Biography

Greg Macpherson is a pharmacist, entrepreneur and author of, “Harnessing the Nine Hallmarks of Aging: To Live Your Healthiest Life.” For more than a decade, he has been working in the biotechnology sector, specifically focusing on the aging process at the cellular level. This work led him to discover ways to harness the nine identified, scientific hallmarks of aging, which is the premise of his book that addresses the natural aging process, how to age more favorably and simple strategies to slow the aging process and build a functional longevity plan. Beyond theory and concept, Macpherson has used his entrepreneurial spirit to further develop solutions to this new paradigm of aging, described in his book, by launching SRW Laboratories, a science and research based company that curates the latest biotechnology research to formulate natural products designed to help slow the onset of aging and disease, and develop evidence based solutions for those who are experiencing age-related health concerns. SRW, which stands for Science, Research and Wellness, is Macpherson’s natural world laboratory that will develop the preventative formulas from nature required to slow down the aging process based on the nine hallmarks of aging, which include mitochondrial dysfunction, telomere attrition and cellular senescence, to name a few. With aging being the single biggest risk factor for developing disease, Macpherson’s mission to slow the aging process at a cellular level could help millions of people delay the onset of diseases associated with advanced aging like Alzheimer’s and heart disease.
greg macpherson headshot for use by 360 Magazine

Dentistry illustration by Kaelen Felix for 360 Magazine

Cold Sore Flareup Triggers

Virus Highjacks Important Immune Response, UVA Discovery Reveals

Researchers at the University of Virginia School of Medicine have shed light on what causes herpes simplex virus to flare up, explaining how stress, illness and even sunburn can trigger unwanted outbreaks.

The discovery could lead to new ways to prevent cold sores and recurrent herpes-related eye disease from reoccurring, the researchers report.

“Herpes simplex recurrence has long been associated with stress, fever and sunburn,” said researcher Anna R. Cliffe, PhD, of UVA’s Department of Microbiology, Immunology and Cancer Biology. “This study sheds light on how all these triggers can lead to herpes simplex-associated disease.”

About Herpes Simplex Recurrence

Once you’re infected with herpes simplex virus (HSV) – and more half of Americans are – the virus never really goes away. Instead, it lurks inside neurons, waiting for the right moment to strike again, a process known as reactivation.

Cold sores, also known as fever blisters, are one of the most common symptoms of HSV reactivation. Recurrent reactivation in the eye leads to herpes keratitis, which, if left untreated, can result in blindness. HSV infection has also been linked to the progression of Alzheimer’s disease.

Recurrences of HSV are typically associated with stress, illness or sunburn, but doctors have been uncertain exactly what causes the virus to reactivate. Cliffe and her collaborators found that when neurons harboring the virus were exposed to stimuli that induce “neuronal hyperexcitation,” the virus senses this particular change and seizes its opportunity to reactivate.

Working in a model developed by the Cliffe lab using mouse neurons infected with HSV, the researchers determined that the virus highjacks an important immune response within the body. In response to prolonged periods of inflammation or stress, the immune system releases a particular cytokine, Interleukin 1 beta. This cytokine is also present in epithelial cells in the skin and eye and is released when these cells are damaged by ultraviolet light.

Interleukin 1 beta then increases the excitability in the affected neurons, setting the stage for HSV to flare up, the UVA researchers discovered.

“It is really remarkable that the virus has hijacked this pathway that is part of our body’s immune response,” Cliffe said. “it highlights how some viruses have evolved to take advantage of what should be part of our infection-fighting machinery.”

The scientists say that more research will need to be done to fully understand the potential factors which play into herpes simplex disease. It may vary depending on the virus strain or the type of neuron infected, even. And it is still unknown if the virus alters how neurons respond to cytokines such as Interleukin 1 beta. But the new insights help doctors better understand what is happening in neurons and the immune system, and that could lead to ways to prevent unwanted outbreaks, the researchers hope.

“A better understanding of what causes HSV to reactivate in response to a stimulus is needed to develop novel therapeutics,” Cliffe said. “Ultimately, what we hope to do is target the latent virus itself and make it unresponsive to stimuli such as Interleukin 1 beta.”

Findings Published

The researchers have published their findings in the scientific journal eLife. The research team consisted of Sean R. Cuddy, Austin R. Schinlever, Sara Dochnal, Philip V. Seegren, Jon Suzich, Parijat Kundu, Taylor K. Downs, Mina Farah, Bimal N. Desai, Chris Boutell and Cliffe.

The work was supported by the National Institutes of Health’s National Institute of Neurological Disorder and Stroke, grant R01NS105630; the National Institute of Allergy and Infectious Diseases, grant T32AI007046; the National Eye Institute, grant F30EY030397; the National Institute of General Medical Sciences, grants T32GM008136, T32GM007267, GM108989 and GM007055and Medical Research Council grant MC_UU_12014/5.

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog.

Appropriate Protein Intake

Okayama University research: Estimating appropriate protein intake

In a recent study published in eLife scientists at Okayama show how proteins can hamper an organism’s growth

Biochemists have shown that very high protein levels can be harmful to cells in the human body. However, exactly which proteins fall under this category remains a mystery. Mr.Yuichi Eguchi (graduate student) and Associate Professor Hisao Moriya’s research team at Okayama University recently reported a framework for discriminating between which proteins are toxic at excessive levels and which are not.

The theory behind this phenomenon, also known as the protein burden, is that accumulation of excessive protein within the cell will deplete the cell of resources, such as energy. The limit required to reach this burden though, is not the same for all proteins. Green fluorescent protein (GFP) is a harmless protein artificially introduced into cells for visualizing the insides of the cell. When GFP levels were increased within yeast cells, they found that GFP up to 15% of total protein content was harmless to the cells. Using this measure as a standard, Associate Professor Hisao Moriya’s team set out to estimate the burden limit of functional proteins in the cells. 29 proteins essential for energy production were subsequently over-produced.

While many of these proteins also had limits close to 15%, suggestive of their harmless nature, some of the proteins showed growth retardation and other unpleasant effects at lower levels. One such protein was found to accumulate within the mitochondria. Clogging the mitochondria prevents cells from producing oxygen. Another protein was found to undergo structural changes and aggregate into big pieces. Another reason for some of these proteins having a low burden limit, was due to metabolic disturbances induced when they were produced even slightly higher than usual. When these proteins were inactivated by mutations, their burden limit increased. Lastly, the researchers also found that certain proteins showed growth retardation, even at very low levels. Further investigation revealed that such proteins are programmed to remain at inherently low levels. Therefore, even small changes to their concentrations can be dangerous.

This study paved a framework for biologists to make distinctions between proteins based on how toxic they are when present in abnormal amounts. These differences could be attributed to the function, structure or genetic programming for that protein. Scientists can hope to use this framework to investigate proteins that are associated with diseases such as Alzheimer’s disease or Parkinson’s disease.

Background

The protein burden: Each protein has a distinct function within cells. Proteins are found in millions within the cell, and are synthesized or increased when required. Their levels subside when the cell doesn’t require them anymore. In certain conditions, such as neurodegenerative disorders, the levels of some proteins inherently remain high. Because the cell is not used to this, a battle to reduce these proteins ensues. This not only uses up the cell’s energy but damages the cell in the process.

By measuring the expression level that causes growth defect (expression limit), Eguchi and Moriya established a framework to distinguish harmful proteins from harmless proteins upon overexpression. They also found that some proteins were harmful upon overexpression because; they form aggregation through cysteine residues (S-S bond), they are transported into mitochondria, and they trigger metabolic perturbation.

About Okayama University

Okayama University is one of the largest comprehensive universities in Japan with roots going back to the Medical Training Place sponsored by the Lord of Okayama and established in 1870. Now with 1,300 faculty and 13,000 students, the University offers courses in specialties ranging from medicine and pharmacy to humanities and physical sciences. Okayama University is located in the heart of Japan approximately 3 hours west of Tokyo by Shinkansen.

Seth Rogen’s Hilarity for Charity

It was a night to remember in Los Angeles as Seth Rogen, along with a star-studded cast, came together to raise funds for treatment for Alzheimer’s Disease at his 6th annual Hilarity for Charity variety show (On Mar 24). Thought you could use in any weekend celebrity round-ups you may be working on.

As the premier spirit of the event, comedians and guests alike were able to sip and savor a variety of Crown Royal cocktails while kicking back and enjoying a few laughs – all while doing some good. Crown Royal also gifted their generous host, Seth Rogen with a custom embroidered bag and bottle of Crown Royal XR.

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