The late Sherwin Nuland in his 1995 book How We Die
described the process of extreme old-age death very eloquently: “Whether it is
the anarchy of disordered biochemsitry or the direct result of its opposite-a
carefully orchestrated genetic ride to death-we die of old age because we have
been worn and torn and programmed to cave in. The very old do not succumb to
disease-they implode their way into eternity.”
The most persuasive argument for the biology of death is the
Hayflick Limit. In 1961, going against the thinking at the time, biologists Leonard
Hayflick and Paul Moorhead noticed that their cell cultures were dying after
replicating a certain number of times. At the time Alex Carrel—a Nobel prize
winner in surgery—held the thinking at that time, that cells are naturally
immortal. We do bad things to them to kill them. Taking a direct leaf from the
biblical story of Adam and Eve, we are held responsible for our own mortality.
In contrast, Hayflick demonstrated that normal human fibroblasts
cells divide about 70 times in 3% oxygen—which is the same as human internal
conditions—before stopping replicating. Refuting
the idea that normal cells are immortal. The mechanism was not yet known at the
time of this observation. But a Russian scientist Alexey Olovnikov hypothesized
in 1971, and later confirmed in 1984 by Nobel prize winners Elizabeth Blackburn and
Carol Greider for the necessity of proteins called telomeres at the end of
the DNA which get shorter with every division until they get too short to allow
for more replication.
Although this is an eloquent theory, there is large variance
in correlating telomere length with aging. The telomeres are not proportional
to longevity. Nuno Gomez from the University of Texas Southwestern Medical
Center and his colleagues, undertook the largest comparative study involving
over 60 mammalian species, reported that telomere length inversely correlates
with lifespan, while telomerase (an enzyme that promotes the growth of
telomeres) correlates with size of the species.
Assuming human fibroblasts endure 70 divisions—as Hayflick
says in his 1994 book How and Why We Age—there are more than enough
cells for several lifetimes. Biologically it is feasible that individual cells
in our body can maintain their level of division and renewal for at least 150 years. And yet no
one has lived beyond 122 years.
In addition, it seems that telomeres do not provide us with
a complete picture. The Italian
biologist Giuseppina Tesco and her colleagues in 1998—refuting earlier studies—found
that fibroblast taken from centenarians showed no difference in the number of
replications compared to cells from younger donors. It could be that within the body, cells can be
replaced with new ones—rather than simply renewed.
Adult stem cells have been identified in many organs and tissues
of older adults, including brain, bone marrow, peripheral blood, teeth, heart,
gut, liver, blood vessels, skeletal muscle, skin, ovarian epithelium, and
testis. They are thought to reside in a “stem cell niche" which is a specific
area within each tissue. We all have these and yet some of us seem to use them
up quickly, perhaps we started with fewer stem cells, or perhaps the
environment that we live in degraded them faster.
Older people are more likely to have experienced more
environmental stressors that damage stem cells, and utilized more of their stem
cells. Once they run out or become disabled, stem cells cannot be replaced.
And then this might be the symphony that Sherwin Nuland
talks about. Because dying cells secrete
chemicals that disrupt other cells in their immediate environment even a small
percentage dying cells, can have a much broader domino effect on neighboring
cells. There is a tipping point before an implosion into eternity.
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