1.
As far as any scientist can tell, Lobsters show no signs of aging and when they
die, it seems to be of extrinsic causes like predation.
In his encyclopedic work,
Longevity, Senescence, and the Genome, Finch
(1990) devotes an entire chapter to "negligible senescence" in lobsters, Quahog
clams, tortoises and bristlecone pines. Of course, we are not suggesting that lobsters are impervious
to death,and in fact their
constant growth probably limits their lifespan at some point. But for dramatic
effect we choose the word 'immortal', and think the term is not too inappropriate:
Single cell lines which do not age are refferred to as 'immortal', as is the more
primitive multi-cellular organism
Hydra.
See also:
Cellular senescence not
observed in sponges, corals and lobsters.
Animals that are
immortal or long-lived animals with "negligible senescence"
2.
This excellect explanation of the Telomere Position Effect and its role
in human aging is offered by the Telomolecular team at this URL:
http://www.telomolecular.com/case_studies.asp
Position effect is a term used to describe an event in which a gene's behavior is
affected by its location on the chromosome. The changes in behavior can be expressed
in various ways, such as differences in the appearance and function of cells (phenotype),
relay of instructions from the gene, and in doubling time of the dividing cells.
Position effects have been reported in insects, plants, yeast and mice, and more
recently in human cells. The findings that TPE exists in human cells offer clues
to cellular aging. In the experiments reported in Science magazine, investigators
used a human cancer cell line called HeLa to investigate TPE and the relation between
gene activity and telomere length. HeLa cells, which are "immortal," contain telomerase
that lengthens the telomere, enabling the cells to keep dividing. In the experiments,
investigators introduced into the cell a gene called luciferase (the gene that makes
fire flies glow), linked to DNA. Luciferase, called a reporter gene whose location
is identified in the cell by its luminescence, was inserted near a telomere. Its
luminescence compared to that of the reporter inserted at internal sites of the
chromosome. To test if telomere length influences gene silencing, the investigators
then elongated the telomere by telomerase, and examined telomere positional effect
on luciferase. The results showed that luciferase near the telomere produced 10
times less luminescence than luciferase located at internal sites in the chromosome.
Increasing the length of the telomere further increased TPE, resulting in an additional
two- to 10-fold decrease in luminescence. These experiments showed that the proximity
of a telomere to a gene silences the gene: when the telomere is lengthened, and
the gene is located further away from the critical end of the telomere, it is silenced
even more. TPE is meaningful and consistent with experimentation. Old cells fail
to produce key enzymes and proteins essential in tissue repair, they divide very
slowly, and eventually reach cell senescence and die. However, cells treated to
produce the telomerase enzyme divide indefinitely in an energetic fashion, produce
the proteins that young cells produce, and repair internal cell damage while preventing
genomic instability. Young cells show an incredible resistance to oxidative damage,
glycation, and cell mutations of all kind that old cells do not. Because young cells
replicate vigorously, demonstrate superior cell signaling, produce important proteins
(such as collagen and elastin in the skin), and have more rapid cell function, they
are able to maintain tissues and vital organs in a way that old cells cannot.
4.
Matsumura, Hayflick. Senescent human diploid cells in culture:
survival, DNA synthesis and morphology. 1979.
Matsumura, Hayflick. DNA Synthesis in the human diploid cell strain WI-38 during in-vitro aging: an autoradiography study. 1979.
5.
We believe that this will first arrive in the form of a drug or natural supplement
- a molecule small enough to penetrate the somatic cell walls in the human body,
which has the ability to activate the dormant gene which lies in each of our somatic
cells and codes for hTERT, the catalytic component of telomerase. This was
the gene that Geron used (by inserting an extra, non-dormant copy) to immortalize
the now famous cells. The challenge of delivering that small molecule to every
single cell in the body would be conveniently met by the cardiovascular system -
a system designed to carry out just that type of delivery. Its perfection will come in the far more advanced ability to
periodically extend telomeres to precise lengths appropriate to the tissue those cells inhabit.
6.
Aging selected for its own sake
Aging is a specific biological function rather than the result
of a disorder in complex living systems: biochemical evidence in support of Weismann’s hypothesis
The programmed death phenomena, aging and the Samurai law of biology
The Evolution of Aging
7.
So could HGPS be 'cured' with telomerase activation of cells throughout the body?
Not really in the sense that this would not address the underlying, and devastating,
failure of each cell to build a secure membrane inside the nucleus. But, in
theory it should greatly ameliorate the symptoms in as much as it was successfull
in allowing the compensating cells to hyperproliferate without aging, that is, without
losing telomere length. Even better would be the development of a viral gene
therapy technique one day that could somehow fix the mutation or override it with a healthy
copy of the LMNA gene.
8.
In this case, however, it might also be attributed to some cells whose DNA damage
has triggered a senescence response, which is a damage control cell response similar
to the p53 'aptopsis' response intended at haulting the division lest the damage
spread further.
9.
See also:
Opresko PL et al.,
Coordinate action of the helicase and 3' to 5' exonuclease of Werner
syndrome protein
Orren DK et al.,
The Werner syndrome helicase/exonuclease (WRN) disrupts and degrades
D-loops in vitro