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Monday, January 20, 2014



How Engineered Stem Cells May Enable Youthful Immortality

by Michael D. West, PhD

(Intro by Life Extension)

Targeting the Clockwork of Cell   Immortality: A Progress Report

There appears to be a consensus among gerontologists that a significant extension of the healthy human lifespan will require targeting of the clockwork mechanisms that cause aging. We will therefore attempt to explain what this means and what the implications may be for reversing biological aging.
Modern gerontology research can be divided into two camps. In the first camp, researchers are on a quest to understand and control the central mechanisms of the aging “clockwork”. This molecular machinery should be thought of as upstream central regulators (like telomeres) that subsequently trigger mechanisms further downstream. It is these downstream pathological mechanisms, such as chronic inflammation, that inflict age-related changes in specific tissues. 1-3
The second camp of researchers is focused on targeting molecules involved in these downstream mechanisms, as these factors (such as pro-inflammatory cytokines) are the “hatchet men” that directly trigger disease processes. 4,5
If we were to think of the individual mortal human as a ticking time bomb, the upstream mechanisms would be the clocking mechanism of the bomb, perhaps a ticking alarm clock or a burning fuse, and the downstream mechanisms would be the dynamite that is the most direct cause of the damage that follows. The first camp’s approach would therefore be to prevent the explosion itself by stopping the clock, whereas the second camp’s solution would be to let it explode but blunt the force of the explosion by covering it with a dump truck full of sand.
In humans, an example of an upstream clockwork mechanism would be the telomere clock of cellular aging, which counts off how many times a cell has divided and hence determines how old a cell really is. An example of a downstream mechanism would be an inflammatory process that leads to activation of damaging molecules in the coronary arteries as seen in atherosclerosis. 6-8
Many of the downstream processes are those typically addressed in Life Extension articles. This emphasis on the downstream may in part reflect the fact that our current understanding of many of the downstream mechanisms predates our understanding of the “upstream” clocking mechanisms. In addition, interventions into in these downstream events have favorably impacted the severity of age-related diseases.
However, most gerontologists agree that targeting the downstream mechanisms will not sufficiently extend human life expectancy to meet the objectives of those who seek aggressive solutions to pathological aging. By targeting upstream-biology—never before attempted in the practice of medicine—we could potentially create the most powerful impact on the aging process.
But first we should consider the basis for assuming that such a central clockwork exists, or that it would even be feasible to intervene in the inexorable progress of this ticking clock.
In this short progress report, we will attempt to describe the shortest path to a proof-of-principle by referring to a natural type of cellular immortality recently captured in the laboratory dish. This line of reasoning is now taking off in the scientific community.
We will then describe research funded in part by the Life Extension Foundation® that has potential clinical application to combat the deadliest manifestation of cell mortality in the United States, namely, coronary artery disease...the leading cause of heart attack.

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