Reversing Human Aging

MFossel mfossel at
Sat Jul 27 08:05:34 EST 1996

As the author, I thought you might like a few generic comments.

First:  telomere shortening does not (even theoretically) "cause" aging. 
Rather it times the onset and progression of aging in cells, ultimately
resulting in the myriad of disease that we collectively associate with
(and sometimes define as) aging.  The "causes" of aging are the usual
suspects:  free radicals, spontaneous isomerization, and so forth, as well
as the subsequent damage they cause.  Telomere shortening alters gene
expression ("SGE" or senescent gene expression) by limiting a cell's
ability to maintain homeostasis and fulfill its normal physiologic role
vis a vis other cells.

Second:  many normal cells do not divide (postnatally) and therefore do
not show telomere shortening, senescent gene expression, or direct cell
senescence.  Typical cells in this category include neurons (but not the
glia cells which make up 90% of the nervous system by cell numbers) and
muscle cells (but not the fibroblasts in the muscle, nor the endothelial
cells lining the vessels which supply such muscle cells).  The upshot is
that many cells do not directly senescence, but show pathology which is
(only theoretically in the case of dementia; with excellent evidence in
the case of atherosclerosis and secondary heart attacks and strokes)
secondary to senescent changes in cells which DO divide and whose
telomeres shorten.  Neurons depend on glial cells; cardiac muscle cells
depend on endothelial cells that line the vessels.  In both cases,
non-aging cells are the "innocent bystanders" to the pathology of cells
which do age.  It is hard to believe how people STILL confuse cell
division with aging pathology and try to cite neurons and muscle cells as
evidence against the telomere theory of aging when their very lack of
*direct* aging changes supports the theory.  It seems to come up in every
posted note I read.  Aging pathology in non-dividing somatic cells is
secondary.  Aging pathology in non-dividing cells is secondary.  Aging
pathology in non-dividing cells is secondary.  I'll bet I am still
explaining this to people in a hundred years...

Third:  we can *probably* find a therapeutic window between aging and
cancer.  The approach would be to first use a TI (telomerase inhibitor) to
force senescence (and death) of cancer cells, THEN proceed to telomerase
activation in remaining cells.  If we reconstitute youthful immune
function (aged lymphocytes have shorter telomeres), we may enable the
immune system to more effectively recognize and more efficiently kill
remaining early clonal populations of cancer cells whose telomeres were
still sufficiently long to survive initial TI therapy.  Theory...

Fourth:  is it too early to speculate?  Not in my mind:  clearly others
disagree, stating that the book should be banned (seriously) or was
irresponsible.  My own feeling is that:  1) the general public is capable
(on the average) of drawing its own conclusions, and that 2) the social
implications of altering the healthy human lifespan will be so profound
that early discussion is imperative.

Fifth:  telomere shortening does NOT merely correlate with cell aging, but
is causal.  This was true until three years ago and the data was published
only this spring (March 15, 1996 in EMB0 by Jerry Shay, Woody Wright, et
al) when we found that lengthening the telomere pushed back the Hayflick
limit correspondingly.  Causing telomere shortening the "cause" of
cellular senescence is still sloppy:  see point one above.

Sixth:  yes, insects somatic cells are post-mitotic.  The cells are
"terminally differentiated".  Telomere length has -- as far as I know --
no particular relevance to insect aging.  Insects are probably the classic
case of "wear and tear" as the cause of aging.  Humans are not insects. 
In humans, cells continue to divide and telomeres play a role in altering
gene expression, undercutting cell defences (eg against free radical
damage) and cell function, and timing aging and its defining pathology.

Michael Fossel, MD, PhD
Author, "Reversing Human Aging"

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