About Negligible Vascular Senescense

"Strategies for Engineered Negligible Senescence" (SENS) means, in plain non-scientific terms," a proposed way to develop a cure for aging. Scientists know more than enough to get started on the development of working anti-aging medicine - therapies that can halt or reverse the root causes of age-related degeneration. Dr. Tapp is working directly with the top researchers in this field and will readily provide all approved learning and techniques to his patients.

"Senescence" refers to the biological processes of a living organism approaching an advanced age (i.e., the combination of processes of deterioration which follow the period of development of an organism). The word senescence is derived from the Latin word senex, meaning "old man" or "old age" or "advanced in age".

"Vascular" means "related to blood vessels", which are part of the circulatory system. Researchers in the Linus Pauling Institute at Oregon State University have discovered a fundamental mechanism that causes aging blood vessels to lose their elasticity – a literal “hardening of the arteries” that is often a prelude to high blood pressure and cardiovascular disease.

An understanding of this mechanism, scientists say, provides an important new target for both drugs and dietary changes that might help prevent or treat atherosclerosis and heart disease. This is a leading cause of death around the world that, in some form, affects about 80 percent of older Americans.

Blood vessels in humans, like those of other animals, have vascular “smooth muscles” that can alternatively relax and contract to accommodate fluctuations in blood flow and volume. A thin layer of “endothelial cells” in the vessels serves, in part, as a sensor mechanism to help regulate this process. And proper function of the endothelial cells, in turn, is driven by specific enzymes and signaling pathways.

What has been known for some time is that blood vessels, as they age, lose much of their capacity to relax – according to the OSU research, about half of that capacity, even in healthy vessels. If the vessels are narrowed by atherosclerotic lesions the problem is further exacerbated. High blood pressure is often the result, which in turn can lead to heart attacks, strokes, and death.

Some of the most common high blood pressure medications, in fact, function by helping to address this loss of elasticity in blood vessels. The nitroglycerin pills used by many people with unstable angina provide an immediate boost of nitric oxide, which serves to relax blood vessels.

What has not been known is exactly why this “hardening” of the blood vessels occurs with age. The new OSU study answers much of that question. “Basically, we’ve learned that in older blood vessels, the cellular signaling process is breaking down,” said Hagen. “The vessels still have the ability to relax much as they did when they were younger, but they are not getting the message.”

A complex enzymatic process outlined in the new study explains how this “failure to communicate” occurs. An enzymatic reaction called “phosphorylation,” which is essential to the signaling process, loses about half of its effectiveness in aging blood vessels. This loss of phosphorylation is due to less activity in one enzyme, AKT, that facilitates the process, and excess activity of phosphatases, that reverse it.

The researchers also discovered that ceramides, one type of lipid, or fat, are primarily responsible for the excessive activity of phosphatases. And in laboratory experiments with blood vessels from rats, they were able to inhibit ceramide synthesis.

Tory Hagen, Burgess and Elizabeth Jamieson Chair in Healthspan Research said, “The laboratory studies were very compelling,” he said. “We were able to make aging blood vessels behave as if they were young again.”

Biomedical gerontologist Aubrey de Grey proposes that there are most likely only seven categories of biological process that lead to degenerative aging and age-related disease, and that all have been known for almost twenty years. That no new categories have been discovered since the late 1980s - over a time of great progress in all fields of biology and medicine - strongly suggests that there are no other significant causes of age-related degeneration and disease.

In principle, scientists can already describe potential therapies that could address each of these processes. The basic tools required for these therapies have in many cases already been demonstrated in the laboratory or in trials for more limited uses.

  • Some tissues lose cells with advancing age, like the heart and areas of the brain. Stem cell research and regenerative medicine are already providing very promising answers to degeneration through cell loss.
  • We must eliminate the telomere-related mechanisms that lead to cancer. de Grey suggests selectively modifying our telomere elongation genes by tissue type using targeted gene therapies.
  • Mitochondrial DNA is outside the cellular nucleus and accumulates damage with age that impairs its critical functions. de Grey suggests using gene therapy to copy mitochondrial DNA into the cellular nucleus. Other strategies for manipulating and repairing damaged mitochondrial DNA in situ were demonstrated for the first time in 2005.
  • Some of the proteins outside our cells, such as those vital to artery walls and skin elasticity, are created early in our life and never recycled or recycled very slowly. These long-lived proteins are susceptible to chemical reactions that degrade their effectiveness. Scientists can search for suitable enzymes or compounds to break down problem proteins that the body cannot handle.
  • Certain classes of senescent cell accumulate where they are not wanted, such as in the joints. We could in principle use immune therapies to tailor our immune systems to destroy cells as they become senescent and thus prevent any related problems.
  • As we age, junk material known as amyloid accumulates outside cells. Immune therapies (vaccines) are currently under development for Alzheimer's, a condition featuring prominent amyloid plaques, and similar efforts could be applied to other classes of extracellular junk material.
  • Junk material builds up within non-dividing, long-life span cells, impairing functions and causing damage. The biochemistry of this junk is fairly well understood; the problem lies in developing a therapy to break down the unwanted material. de Grey suggests searching for suitable non-toxic microbial enzymes in soil bacteria that could be safely introduced into human cells.

Making gains in SENS science in unrelated bits and pieces is likely to be a slow path for progress towards meaningful healthy life extension, however. Curing any one age-related condition is a wonderful thing for sufferers, but it will not increase healthy life span for anyone else - nor will it lead directly to therapies that can extend healthy life span without further investment and work. It would be much more cost-effective to directly address the root cause of aging and age-related disease.

Thirty years ago, few biologists thought that it would be possible to increase the maximum life span characteristic of each species over the variety of environmental conditions in which they live, whether in nature or in the laboratory. But the evolutionary theory of aging suggested otherwise. Accordingly, experiments were performed with fruit flies, Drosophila melanogaster, which showed that manipulation of the forces of natural selection over a number of generations could substantially slow the rate of aging, both demographically and physiologically.

After this first transgression of the supposedly absolute limits to life extension, it was suggested that mammals too could be experimentally evolved to have greater life spans and slower aging. And further, it was argued that such postponed-aging mammals could be used to reverse-engineer a slowing of human aging. The subsequent discovery and theoretical explanation of mortality-rate plateaus revealed that aging was not due to the progressive physiological accumulation of damage. Instead, aging is now understood by evolutionary biologists to arise from a transient fall in age-specific adaptation, a fall that does not necessarily proceed toward ineluctable death. This implies that SENS must be based on re-tuning adaptation, not repairing damage. As evolutionary manipulation of model organisms shows us how adaptation can be focused on engineering negligible senescence, there are thus both scientific and practical reasons for making SENS evolutionary

Progress in any one area of SENS science is likely to lead to therapies for a class of age-related diseases. It is not unreasonable to expect the research community - motivated as it is to seek cures for specific diseases - to slowly fill in the gaps in SENS as time moves on.
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