III CURRENT RESEARCH INTO TELOMERES
C) OTHER TELOMERE RESEARCH
The research into cancer, telomeres and telomerase and Gerons numerous
research programs are exciting but there is a lot of other research into the
telomeric theory of aging being conducted around the world.
Dr R. Effros at U.C.L.A. is researching the effects of telomeric shortening
on the T-Cells in the immunological systems of the elderly. Her observations
include the dominance of senescent "memory" T-cells in aged individuals which
may "prevent renewal of the T-cell pool with more functional T-cells". The
implications being that the restoration of replicative capacity in those
T-cells that are approaching senescence could have the effect of restoring
functioning of some parts of the immunological system in the elderly.
Rawes V, Kipling D, Kill IR and Faragher RG at The University of Brighton,
UK, have demonstrated results that "suggest that the process of senescence is
a common feature of different cell lineages but that the specific rate can
differ between them." Thus the cell lines constituting the endothelial cells
in the vascular system may be experiencing telomeric loss faster than other
cell lines in the body. This may be a factor underlying age-related
"disease" progression in some systems of the body.
Yui J, Chiu CP and Lansdorp PM at Terry Fox Laboratory, Canada, have
"observed telomerase activity in candidate stem cells is either expressed in
a minor subset of stem cells or, more likely, is not sufficient to prevent
telomere shortening." This demonstrates that even cells normally expressing
the enzyme telomerase can experience telomeric loss and eventually enter
senescence. Since many of these stem cells are the source of cells to
maintain various cellular systems their entrance into senescence may be a
factor in the "aging" of these systems.
Martens UM, et al, also at Terry Fox Laboratory, Canada, made observations
that "provide evidence of chromosome-specific factors regulating the number
of T2AG3 repeats in individual telomeres". This is important in
understanding how cells respond to telomeric shortening. Since the telomeres
on different chromosomes can be of different lengths those with the shortest
telomeric repeats will be lost earlier than those with longer telomeres.
Depending on the genes located on a particular chromosome its loss can either
be catastrophic for the cell or possibly of no consequence, (this will become
important in the discussion of aging in mice in the next section).
Tahara H, et al, at Hiroshima University School of Medicine, Japan,
demonstrated that "a significant proportion of WRN, (Werner's syndrome), cell
strains showed drastic shortening or lengthening of telomere lengths during
cell passages compared with normal cell strains" This confirms earlier
studies that Werner's syndrome and the childhood aging disease progeria
result from errors in the system(s) that maintain telomeric length.
Horikawa I, Oshimura M and Barrett JC of The National Institute of
Environmental Health Sciences in North Carolina report that their "results
suggest that a senescence-inducing gene on chromosome 3 controls hEST2/hTRT
gene expression", (the gene encoding the catalytic subunit of telomerase).
This research may provide the understandings of telomerase production in
human cells necessary for any possible intervention.
Ulaner GA and Giudice LC at Stanford Univ. demonstrated "tissue-specific and
developmental regulation of telomerase in the human fetus, suggesting an
important role for this ribonucleoprotein in human fetal tissue
differentiation and development." Determining how telomeres are produced
during normal embryonic development may provide us with the methods to
effectively intervene later in life.
These are but a few examples of the research into telomeres going on around
the world. Each of them add a piece to the puzzle and move us forward in our
attempts to understand and utilize the telomeric theory of aging.
(Next: Criticisms and negative findings)
Thomas Mahoney, Pres.
Lifeline Laboratories, Inc.