The Raelian Movement
for those who are not afraid of the future : http://www.rael.org
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What Makes Us Age? Ticking of Cellular Clock Promotes Seismic Changes
in Chromatin Landscape Associated With Aging
http://www.sciencedaily.com/releases/2010/10/101003205928.htm
ScienceDaily (Oct. 4, 2010) — Like cats, human cells have a finite
number of lives: once they divide a certain number of times
(thankfully, more than nine) they change shape, slow their pace, and
eventually stop dividing -- a phenomenon called "cellular senescence."
Biologists know that a cellular clock composed of structures at the
chromosome end known as telomeres records how many "lives" a cell has
expended. Up to now, investigators have not yet defined how the
clock's ticking signals the approach of cellular oblivion.
In a study published in the Oct. 3, 2010, issue of Nature Structural
and Molecular Biology, a team led by Jan Karlseder, Ph.D., at the Salk
Institute for Biological Studies reports that as cells count down to
senescence and telomeres wear down, their DNA undergoes massive
changes in the way it is packaged. These changes likely trigger what
we call "aging."
"Prior to this study we knew that telomeres get shorter and shorter as
a cell divides and that when they reach a critical length, cells stop
dividing or die," said Karlseder, an associate professor in the
Molecular and Cell Biology Laboratory. "Something must translate the
local signal at chromosome ends into a huge signal felt throughout the
nucleus. But there was a big gap in between."
Karlseder and postdoctoral fellow Roddy O'Sullivan, Ph.D., began to
close the gap by comparing levels of proteins called histones in young
cells-cells that had divided 30 times-with "late middle-aged" cells,
which had divided 75 times and were on the downward slide to
senescence, which occurs at 85 divisions. Histone proteins bind linear
DNA strands and compress them into nuclear complexes, collectively
referred to as chromatin.
Karlseder and O'Sullivan found that aging cells simply made less
histone protein than do young cells. "We were surprised to find that
histone levels decreased as cells aged," said O'Sullivan, the study's
first author. "These proteins are required throughout the genome, and
therefore any event that disrupts this production line affects the
stability of the entire genome."
The team then undertook exhaustive "time-lapse" comparisons of
histones in young versus aging cells and confirmed that marked
differences in the abundance and variety of histones were evident at
every step as cells moved through cell division.
O'Sullivan calls the "default" histone pattern displayed by young
cells "happy, healthy chromatin." By contrast, he says, aging cells
appear to undergo stress as they duplicate their chromosomes in
preparation for cell division and have difficulty restoring a
"healthy" chromatin pattern once division is complete.
Comparisons of histone patterns in cells taken from human subjects-a
9- versus a 92-year-old-dramatically mirrored histone trends seen in
cell lines. "These key experiments suggest that what we observe in
cultured cells in a laboratory setting actually occurs and is relevant
to aging in a population," says Karlseder.
The initiation of diseases associated with aging, such as cancer, is
largely attributed to DNA, or genetic, damage. But this study suggests
that aging itself is infinitely complex: that progressive telomere
shortening hastens chromosomal aging by changing the way genes entwine
with histones, so-called "epigenetic" changes. How DNA interacts with
histones has enormous impact on whether genes are expressed-hence the
current intense interest in the relationship of the epigenomic
landscape to disease states.
Rescue experiments in which the team cosmetically enhanced aging cells
confirmed that signals emitted by eroding telomeres drove epigenetic
changes. When aging cells were engineered to express telomerase, the
enzyme that restores and extends stubby telomeres, those rejuvenated
cells showed histone levels reminiscent of "happy, healthy chromatin,"
and a partial return to a youthful chromatin profile.
Lest you sink your savings into schemes to elongate your telomeres,
beware. "The flip side of elongating telomeres is that you enable
cells to grow for much longer periods and can generate what are called
"immortal" cells," says Karlseder. "That takes you one step closer to
cancer cell development."
Up to now, the Karlseder lab has mostly focused on interactions
between telomeres and DNA repair mechanisms. This paper now pushes
them into the field of epigenetics. "We will continue to examine
epigenetic changes in cells at different ages," says Karlseder. "We
now want to determine if histone changes follow a linear process or
whether they kick in as we age."
Also contributing to this work were Stuart Schreiber, Ph.D., of the
Broad Institute of Harvard and MIT and Howard Hughes Medical Institute
and his postdoctoral fellow Stefan Kubicek, Ph.D.
The study was funded by the National Institutes of Health, the George
E. Hewitt Foundation for Medical Research, and the Ernst Schering
Research Foundation and the European Union.
Story Source:
The above story is reprinted (with editorial adaptations by
ScienceDaily staff) from materials provided by Salk Institute, via
EurekAlert!, a service of AAAS.
Journal Reference:
1. Roderick J O'Sullivan, Stefan Kubicek, Stuart L Schreiber & Jan
Karlseder. Reduced histone biosynthesis and chromatin changes arising
from a damage signal at telomeres. Nature Structural and Molecular
Biology, 03 October 2010 DOI: 10.1038/nsmb.1897
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"Ethics" is simply a last-gasp attempt by deist conservatives and
orthodox dogmatics to keep humanity in ignorance and obscurantism,
through the well tried fermentation of fear, the fear of science and
new technologies.
There is nothing glorious about what our ancestors call history,
it is simply a succession of mistakes, intolerances and violations.
On the contrary, let us embrace Science and the new technologies
unfettered, for it is these which will liberate mankind from the
myth of god, and free us from our age old fears, from disease,
death and the sweat of labour.
Rael
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