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Moving Closer to a Vaccine for Atherosclerosis – Article by Steve Hill

Moving Closer to a Vaccine for Atherosclerosis – Article by Steve Hill

Steve Hill


Editor’s Note: The U.S. Transhumanist Party features this article by our guest Steve Hill, originally published by the Life Extension Advocacy Foundation (LEAF) on April 13, 2018. In this article, Mr. Hill reviews a study published by the La Jolla Institute for Allergy and Immunology, in which the study authors successfully vaccinated atherosclerotic mice. In fact, this method supported Dr. Aubrey de Grey’s early insight – his claim that we must attack plaque altogether.

~ Bobby Ridge, Assistant Editor, July 5, 2019

Scientists could be one step closer to a solution to atherosclerosis by preventing the buildup of plaques that clog the arteries and lead to strokes and heart attacks.

What is atherosclerosis?

Atherosclerosis is the accumulation of cholesterol-containing plaques in the walls of arteries; this causes them to narrow, leading to reduced blood flow, higher blood pressure, and an increased risk of a heart attack or stroke. Atherosclerosis is the number one cause of death globally, and, by far, the highest risk factor for this disease is aging, although there are lifestyle factors, such as poor diet, smoking, obesity, and being sedentary.

Drugs such as statins attempt to manage the symptoms but are not truly effective in combating this disease, as they do not address the underlying cause: the formation of the sticky plaques that clog the arteries. Scientists such as Dr. Aubrey de Grey from the SENS Research Foundation have long been advocating for therapies that remove or prevent the formation of plaques altogether, as this would address the problem directly.

One step closer to a solution

In the journal Circulation, researchers at the La Jolla Institute for Allergy and Immunology have published a new study that supports the possibility that there are ways to prevent the formation of plaques in the first place [1]. The team has reported the successful vaccination of atherosclerotic model mice by using a small piece of protein cut from “bad cholesterol”, which facilitates the formation of plaques.

The vaccine was shown to reduce plaque in the mice, and the team also identified the T cells most likely responsible for positive outcomes in human blood samples as part of the same study. The researchers suggest that this technique could form the basis of a vaccine for people.

The vaccine works by boosting the activity and numbers of a type of T cell responsible for reducing inflammation, which leads to a reduction of plaque formation. We have talked about therapies that modulate the immune system and change the ratio of immune cells multiple times, and it is looking like an increasingly promising avenue of research.

“Bad cholesterol” is an amalgam of cholesterol, which is a lipid, and its carrier, low-density lipoprotein (LDL). In order to create the vaccine, the team engineered a peptide that represents a short section of LDL.

The team mounted this peptide on a scaffold called a tetramer and exposed it to immune cells to see which ones became activated in its presence. They tested human blood from two groups of women, one with plaques and one without, to see which immune cells responded to the presence of the peptide.

They observed that a type of regulatory T cell (Tregs) was activated in both groups, although the numbers of Tregs was much lower in subjects with plaques than subjects without, as were the presence of other types of T cells. This suggests that the function of Tregs is somehow hampered by the inflammation that atherosclerosis causes.

The next generation of vaccines that offer greater utility

As well as having the potential to address atherosclerosis, this research spotlights the utility of next-generation vaccines. The immunogenic component of traditional vaccines is a cocktail of molecules harvested from dead or weakened pathogens, but this approach does not work against non-infectious diseases like cancer and atherosclerosis; these next-generation vaccines are much more specific, as they can regulate the immune response using just a single peptide. This means vaccines that target non-infectious diseases are now possible, and, as they are highly targeted, they should have fewer unwanted side effects.

The results presented in this paper show that an effective vaccine against atherosclerosis is now potentially possible. However, the researchers do caution that there is more research to be done before this vaccine can be translated to human use.

Conclusion

While statins simply try to treat the symptoms, a therapy that prevents the buildup of plaques in the first place would be a very welcome step in the battle against age-related diseases and the suffering they bring. If the therapy can be translated to people, it would make strokes and heart attacks practically a thing of the past, and that day cannot come soon enough.

Literature

[1] Kimura, T., Kobiyama, K., Winkels, H., Tse, K., Miller, J., Vassallo, M., … & Jenkins, M. K. (2018). Regulatory CD4+ T Cells Recognize MHC-II-Restricted Peptide Epitopes of Apolipoprotein B. Circulation, CIRCULATIONAHA-117.

Steve Hill serves on the LEAF Board of Directors and is the Editor-in-Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ Magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Keep Me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.

What It Will Be Like to Be an 85-Year-Old in the 2070s – Article by Scott Emptage

What It Will Be Like to Be an 85-Year-Old in the 2070s – Article by Scott Emptage

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Scott Emptage


I will be 85 sometime in the early 2070s. It seems like a mirage, an impossible thing, but the future eventually arrives regardless of whatever you or I might think about it. We all have a vision of what it is to be 85 today, informed by our interactions with elder family members, if nothing else. People at that age are greatly impacted by aging. They falter, their minds are often slowed. They are physically weak, in need of aid. Perhaps that is why we find it hard to put ourselves into that position; it isn’t a pleasant topic to think about. Four decades out into the future may as well be a science-fiction novel, a faraway land, a tale told to children, for all the influence it has on our present considerations. There is no weight to it.

When I am 85, there will have been next to no senescent cells in my body for going on thirty years. I bear only a small fraction of the inflammatory burden of older people of past generations. I paid for the products of companies descended from Oisin Biotechnologies and Unity Biotechnology, every few years wiping away the accumulation of senescent cells, each new approach more effective than the last. Eventually, I took one of the permanent gene therapy options, made possible by biochemical discrimination between short-term beneficial senescence and long-term harmful senescence, and then there was little need for ongoing treatments. Artificial DNA machinery floats in every cell, a backup for the normal mechanisms of apoptosis, triggered by lingering senescence.

When I am 85, the senolytic DNA machinery will be far from the only addition to my cells. I underwent a half dozen gene therapies over the years. I picked the most useful of the many more that were available, starting once the price fell into the affordable-but-painful range, after the initial frenzy of high-cost treatments subsided into business as usual. My cholesterol transport system is enhanced to attack atherosclerotic lesions, my muscle maintenance and neurogenesis operate at levels far above what was once a normal range for my age, and my mitochondria are both enhanced in operation and well-protected against damage by additional copies of mitochondrial genes backed up elsewhere in the cell. Some of these additions were rendered moot by later advances in medicine, but they get the job done.

When I am 85, my thymus will be as active as that of a 10-year-old child. Gene and cell therapies were applied over the past few decades, and as a result my immune system is well-gardened, in good shape. A combination of replacement hematopoietic stem cells, applied once a decade, the enhanced thymus, and periodic targeted destruction of problem immune cells keeps at bay most of the age-related decline in immune function, most of the growth in inflammation. The downside is that age-related autoimmunity has now become a whole lot more complex when it does occur, but even that can be dealt with by destroying and recreating the immune system. By the 2030s this was a day-long procedure with little accompanying risk, and the price fell thereafter.

When I am 85, atherosclerosis will be curable, preventable, and reversible, and that will have been the case for a few decades. There are five or six different viable approaches in the marketplace, all of which basically work. I used several of their predecessors back in the day, as well. Most people in the wealthier parts of the world have arteries nearly free from the buildup of fat and calcification. Cardiovascular disease with age now has a very different character, focused more failure of tissue maintenance and muscle strength and the remaining small portions of hypertension that are still problematic for some individuals. But that too can be effectively postponed through a variety of regenerative therapies.

When I am 85, there will be an insignificant level of cross-linking in most of my tissues, as was the case since my early 60s. My skin has the old-young look of someone who went a fair way down the path before being rescued. Not that I care much about that – I’m much more interested in the state of my blood vessels, the degree to which they are stiff and dysfunctional. That is why removal of cross-links is valuable. That is the reason to keep on taking the yearly treatments of cross-link breakers, or undergo one of the permanent gene therapies to have your cells produce protective enzymes as needed.

When I am 85, I will have a three-decade patchwork history of treatments to partially clear this form of amyloid or that component of lipofuscin. I will not suffer Alzheimer’s disease. I will not suffer any of the common forms of amyloidosis. They are controlled. There is such a breadth of molecular waste, however: while the important ones are addressed, plenty more remain. This is one of the continuing serious impacts to the health of older individuals, and a highly active area of research and development.

When I am 85, I will be the experienced veteran of several potentially serious incidences of cancer, all of which were identified early and eradicated by a targeted therapy that produced minimal side-effects. The therapies evolve rapidly over the years: a bewildering range of hyper-efficient immunotherapies, as well as treatments that sabotage telomere lengthening or other commonalities shared by all cancer cells. They were outpatient procedures, simple and quick, with a few follow-up visits, so routine that they obscured the point that I would be dead several times over without them. The individual rejuvenation technologies I availed myself of over the years were narrowly focused, not perfect, and not available as early as I would have liked. Cancer is an inevitable side-effect of decades of a mix of greater tissue maintenance and unrepaired damage.

Do we know today what the state of health of a well-kept 85-year-old will be in the 2050s? No. It is next to impossible to say how the differences noted above will perform in the real world. They are all on the near horizon, however. The major causes of age-related death today will be largely controlled and cured in the 2050s, at least for those in wealthier regions. If you are in your 40s today, and fortunate enough to live in one of those wealthier region, then it is a given that you will not die from Alzheimer’s disease. You will not suffer from other common age-related amyloidosis conditions. Atherosclerosis will be reliably controlled before it might kill you. Inflammatory conditions of aging will be a shadow of what they once were, because of senolytic therapies presently under development. Your immune system will be restored and bolstered. The stem cells in at least your bone marrow and muscles will be periodically augmented. The cross-links that cause stiffening of tissues will be removed. Scores of other issues in aging process, both large and small, will have useful solutions available in the broader medical marketplace. We will all live longer and in better health as a result, but no-one will be able to say for just how long until this all is tried.

Scott Emptage is an anti-aging activist in the United Kingdom.