VI. Discussion
C. Implications of the Telomeric Theory of Aging
The research into the telomeric theory is going to have a significant
influence on our lives in the years to come. That telomeres are
significantly shorter in replicating cells of the elderly(1) is evidence that
telomeric shortening is related to aging. That critically shortened
telomeres are likely causative of cells entering senescence(2) suggests a
mechanism by which telomeres could be a cause of some of the declines in
functioning noted during aging.(3) The negative effects of differential
genetic expression with age(4) also appear to be related to telomeric control
of some transcriptional silencing mechanisms.(5)
Procedures to maintain telomeric length in replicating cells(6) could,
therefor, have some significant effects in avoidance of these age related
declines.
Additionally, the immortalization of many cancers is thought to involve the
re-activation of the enzyme telomerase.(7) Cancer appears to be a two step
process.(8) First of bypassing of senescence and then the escape from or the
avoidance of crisis. Telomerase appears to be the major factor in the latter
stage, although alternative process of telomeric lengthening are implicated
in some cancers.(9)
Thus, the de-activation of telomerase functioning in cancerous tissues(10)
may stop the progression of cancerous growth in many tissues.
Finally, the research findings of Wright, et.al, at The University of Texas
Southwestern Medical Center,(11) Bodnar, et.al. of the Geron Corp.(12) and
Vaziri et.al. at The Ontario Cancer Institute(13) show that telomeric
lengthening can maintain normal human cells in a phenotypically youthful
state with an increased replicative life span.
These findings, among others, suggest that telomeric lengthening could have a
positive effect on human life span.
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Chou HH, Takashiba S, Murayama Y, Oral Dis 1997 Sep;3(3):162-6, Comparison of
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restored in human cells by ectopic expression of hTERT (hEST2), the catalytic
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justify the means?: Telomeres and the mechanisms of replicative
senescence and immortalization in mammalian cells.
9) Bryan TM, Reddel RR, Eur J Cancer 1997 Apr;33(5):767-73, Telomere dynamics
and telomerase activity in in vitro immortalised human cells.
10) Kondo S, Tanaka Y, Kondo Y, Hitomi M, Barnett GH, Ishizaka Y, Li, FASEB J
1998 Jul;12(10):801-11, Antisense telomerase treatment: induction of two
distinct pathways, apoptosis and differentiation.
11) Wright WE, Brasiskyte D, Piatyszek MA, Shay JW, EMBO J 1996 Apr
1;15(7):1734-41, Experimental elongation of telomeres extends the lifespan of
immortal x normal cell hybrids.
12) Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB,
Shay JW, Lichtsteiner S, Wright WE, Science 1998 Jan 16;279(5349):349-352,
Extension of life-span by introduction of telomerase into normal human cells.
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