Telomeric Theory - Implications

Excelife excelife at earthlink.net
Fri Nov 6 17:41:58 EST 1998

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 

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. 


1) Butler MG, Tilburt J, DeVries A, Muralidhar B, Aue G, Hedges L, Atkinson 
J, Schwartz H, Cancer Genet Cytogenet 1998 Sep;105(2):138-144, Comparison of 
chromosome telomere integrity in multiple tissues from subjects at different 

2) Vaziri H, Benchimol S, Exp Gerontol 1996 Jan;31(1-2):295-301, From 
telomere loss to p53 induction and activation of a DNA-damage pathway at 
senescence: the telomere loss/DNA damage model of cell aging.

3) Nishimura F, Terranova VP, Braithwaite M, Orman R, Ohyama H, Mineshiba J, 
Chou HH, Takashiba S, Murayama Y, Oral Dis 1997 Sep;3(3):162-6, Comparison of 
in vitro proliferative capacity of human periodontal ligament cells in 
juvenile and aged donors.

4) Osiewacz HD, Hamann A, Biochemistry (Mosc) 1997 Nov;62(11):1275-84, DNA 
reorganization and biological aging. A review.

5) Boulton SJ, Jackson SP, EMBO J 1998 Mar 16;17(6):1819-28, Components of 
the Ku-dependent non-homologous end-joining pathway are involved in telomeric 
length maintenance and telomeric silencing.

6) Counter CM, Meyerson M, Eaton EN, Ellisen LW, Caddle SD, Haber DA, 
Weinberg RA, Oncogene 1998 Mar 5;16(9):1217-22, Telomerase activity is 
restored in human cells by ectopic expression of hTERT (hEST2), the catalytic 
subunit of telomerase.

7)  Shay JW, J Cell Physiol 1997 Nov;173(2):266-70, Telomerase in human 
development and cancer.

8) Sedivy JM, Proc Natl Acad Sci U S A 1998 Aug 4;95(16):9078-9081, Can ends 
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.

13) Vaziri H, Benchimol S, Curr Biol 1998 Feb 26;8(5):279-282, Reconstitution 
of telomerase activity in normal human cells leads to elongation of telomeres 
and extended replicative life span.

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