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Life Extension by Michael West Feb 2013

Life Extension by Michael West Feb 2013

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Published by Ken Storey
Life Extension by Michael West Feb 2013
Life Extension by Michael West Feb 2013

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Published by: Ken Storey on Feb 01, 2013
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02/01/2013

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http://www.lef.org/ 
 
Life Extension Magazine February 2013
 
 
How Engineered Stem Cells May Enable Youthful Immortality
by Michael D. West, PhD
(Intro by Life Extension) 
What you are about to read is a blueprint by which newly developing technologies may beused to induce biological
immortality
in human beings.This research goes far beyond what is normally published in
Life Extension magazine.
When perfected, the research findings you are about to learn may enable doctors to inject
progenitor cells 
that will
regenerate
every tissue in your body, thus restoring you to youthful
health and vigor.
Some readers will find this article challenging to comprehend, but I encourage everyone to review it several times to understandhow close we may be to achieving meaningful reversal of aging processes.This article also contains new findings about how easy it is to
increase
your
telomere length
, which has been shown to conferlongevity and protect against age
-
related disease.
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 theimplications 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 andcontrol the central mechanisms of the aging
clockwork
. This molecular machinery should be thought of as upstream centralregulators (like telomeres) that subsequently trigger mechanisms further downstream. It is these downstream pathologicalmechanisms, 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 thedynamite 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 theexplosion 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 offhow 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 downstreammay 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 lifeexpectancy 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 agingprocess.But first we should consider the basis for assuming that such a central clockwork exists, or that it would even be feasible tointervene 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 tocombat the deadliest manifestation of cell mortality in the United States, namely,
coronary artery disease..
.the leading cause ofheart attack.
WHAT YOU NEED TO KNOW
Scientists Discover Novel Way to Reset Cellular Aging Clock
 
Pluripotent cells have the power to become a variety of cell types.
Most somatic cells lack sufficient telomerase, and so every time somatic cells replicate,they progressively shorten their telomeres.
Germ
-
line cells retain telomere length appropriate for the beginning of life, due to anabundance of telomerase activity.
Telomerase, is an enzyme that synthesizes telomeres, a repeated sequence of DNA
over and over again at the end of DNA strands needed to maintain cellular viability.
Although telomeres typically shorten with aging, shortening is not inevitable andtelomeres can also lengthen.
Recent scientific studies have shown that reduced plasma levels of omega
-
6 fats coupled with increased omega
-
3sresulted in an increase in telomere lengths.
It is possible to utilize these advances to not only revert a cell in the body (somatic cell) back to the all
-
powerful
pluripotent stem cell state, but also to activate telomerase and reset the clock of cell aging all the way back to the
very beginning of life.
THE FACTS OF LIFE
Let’s begin with the facts of life and remember how an individual human being comes to existin the first place. The union of a sperm and egg cell leads to a unified cell commonly called a
zygote 
, which then divides into two cells, then four, and so on, until a small cluster of cellsform, each of which has the power to become any of the cell types in the human body.Cells that have this power are said to be
pluripotent 
, meaning they have power (
-
potent 
) tobecome a variety (plurality or
pluri 
-)
of cell types. These cells commit to the cell type they willeventually become, that is, each cell will commit to becoming a
reproductive
(sperm or egg)
cell, or one of the body’s many life
-
functioning
cell types such as muscle, blood, or braincells. This process of cellular commitment is called
differentiation 
.If pluripotent cells differentiate into sperm or egg cells, scientists say they are remaining in the
germ 
line 
. The germ
-
line is thatlineage of cells that connects the generations and is the biological basis of the immortality of the species. They are the cellswhose continuous proliferation ensures there are always zebras in Africa. They are the reason why you can go to a localgreenhouse and buy fresh young petunias to plant in your garden every spring, year after year. Germ
-
line cells have the amazingability to spin off new individuals forever, without the limitations of aging.
 
When pluripotent germ
-
line cells commit to become one of the
life
-
functioning cell
types of the body, we say they have
differentiated into
somatic 
cells. This differentiation seals their fate. These somatic cells are now mortal, even though, up to thispoint, they have been proliferating continuously for billions of years as germ
-
line cells. They will now become part of the body thatis programmed to die usually within 100 years. Those cells that went the germ
-
line route have the potential (though not certainty)that they may continue in future generations indefinitely. Because they are not committed to a mortal fate, scientists say thecells are
immortal.
The use of this term does not mean that the individual cells are indestructible, nor does it mean anything in areligious sense. Instead, the term simply refers to the lack of commitment to the mortality that occurs when these cells
differentiate into
somatic 
(functional) cells that have finite lifespans, sometimes measured in maximum amount of doubling timesbefore they die.For the past few decades, scientists have focused on deciphering the molecular mechanisms of the
immortality 
of
germ
-
linecells
in order to find a means of using those insights to restore health to aging
somatic
(life
-
sustaining functional)
cells
. In other
words, we have attempted to find a means to rewind the clock of the
ticking time bomb
in our cells back to the beginning of life.In the past few years, we have learned that, when cells make the decision to become
somatic 
(that is, cells that enable the bodyto
function
as opposed to
reproductive
 
germ 
line 
cells) they turn off
telomerase 
, an enzyme that synthesizes a repeated
sequence of DNA over and over again at the end of DNA strands needed to maintain cellular viability. This region of the
chromosomes is called
telomeres
,
and we refer to it in this article as the
telomere clock of cellular aging
.Most
somatic 
cells lack sufficient
telomerase 
, and so every time
somatic 
cells proliferate, they progressively shorten their
telomeres
. This functions as a clock mechanism not unlike the burning of a fuse. However, in contrast to
somatic 
cells,
germ 
line 
cells retain telomere length appropriate for the beginning of life, due to an abundance of telomerase activity.Since there is currently no known way to safely and effectively extend telomere length in the body, our researchers have insteadsought means to mimic the natural immortality of germ
-
line cells in the laboratory dish to make young and healthy cells of allkinds that could potentially be injected into the body. Using this approach, we might be able to repair tissues afflicted with age
-
related degenerative diseases. The good news is that this technology is now very much operational in the laboratory and is a
focus of intensive research around the world.
 
REDUCED OMEGA
-
6 + INCREASED OMEGA
-
3 = EXTENDED TELOMERE LENGTH
Telomeres are the caps at the ends of chromosomes. Shorter telomeres have been linked with age
-
related disease and earlydeath.
13-16
 Although telomeres typically shorten with aging, shortening is not inevitable and telomeres can also lengthen. Telomerelength is associated with lifestyle behaviors. for instance, women who are obese or smoke cigarettes suffer greater loss oftelomere length, with a corresponding reduction in life span.
17,18
 As this article was being finalized, a new study was published that measured telomere length in humans given
EPA/DHA fish
oil
supplements. The results showed that reduced plasma levels of
omega
-
6 fats
coupled with increased omega
-
3s resultedin an increase in
telomere lengths
.
19
 The scientists attributed this
telomere length
increase to reductions in inflammatory cytokines and oxidative stress broughton by
higher
levels of
omega
-
3s
in relationship to pro
-
inflammatory omega
-
6s.
Omega
-
6
fats to avoid include corn, sunflower, and safflower oils, along with arachidonic acid found in red meat and eggyolks. olive oil, rich in monounsaturated fats, should be substituted for omega
-
6 oils whenever possible. Dietary sources ofomega
-
3s include cold
-
water fish, walnuts, and flax seed.In this human study where
telomeres
were
lengthened
, scientists used between
1,250
and
2,500 mg
of EPA/DHA
fish oil
 daily to boost omega
-
3 plasma levels in relation to omega
-
6s.
19
 
Life Extension
members typically consume
2,400 mg
of
EPA/DHA
daily in their fish oil supplement.
EMBRYONIC STEM CELLS

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