Question:
Hmm, remember that line about harassing someone to make them "gray
before their time"?
http://www.sciam.com/article.cfm?chanID=sa003&articleID=0005525A-9A84...
Apparently, mental stress has been linked to shortened telomeres. Is
it a case of all that adrenaline and other stress hormones simply
speeding up your metabolism and forcing cells to multiply more often?
Or does stress also disrupt the normal circadian rhythm/metabolism and
somehow shorten the telomeres that way?
What exactly is the underlying mechanism here?
Answer:
Free radicles shorten telomeres and are caused to some extent by
stress so they may be involved. Either way telomere shortening is not
good at all. Its involvement in aging in at least some systems can now
be considered a given. The paper I post below is just one of several
recent ones that lead to this conclusion.
We have read with interest the work by Lesgards et al. (1) on the
effect of different lifestyle factors on their test system, which
measures the resistance of red blood cells to an oxidative challenge.
Their study showed that psychologic stress is a major factor
influencing antioxidant status. This finding encouraged us to share
our experiences of a earlier study that resulted in similar
conclusions using an enzyme, 5´-ectonucleotidase (NT), located on the
external surface of lymphocytes (2,3). NT is significant because it
has a role in lymphocyte maturation; newborns with persistently low
activities have multiple infections, whereas with normalization of NT,
their infections resolved (4). We previously showed that NT activities
decreased, by then-unknown mechanism(s), as the course of HIV (human
immunodeficiency virus) infection progressed (5). Later, we carried
out this study in psychologically stressed patients to see if stress
itself could lower the activity of this enzyme and thereby contribute
to the immune deficiency reported for stressed/depressed patients (6).
In one aspect of this study, honors students in psychology were
monitored at different times of the year when their stress levels were
low (after holidays) and high (exams/thesis writing). These students
were psychologically assessed for stress using the Profile of Mood
Score (POMS). The POMS scores were significantly correlated with NT,
which was significantly lower (30%) at high stress periods and
normalized when the stress resolved (after holidays), indicating the
reversibility of the effect of stress on NT.
In another group of chronically stressed/depressed patients, NT values
were also found to be very low; however, in a subgroup of these
patients taking vitamins A, C, and E and coenzyme Q10, the NT values
were equivalent to those of an unstressed healthy population (2).
Subsequent in vitro studies showed that NT was inhibited within 5 min
after exposure to superoxide anions and that this effect could be
reversed either by ascorbate added to the in vitro system at
physiologic levels present in serum (100 µM) or by oral administration
of the same antioxidant mix to volunteers for about 6 weeks (3,7).
Measurement of tissue ascorbate also showed that this metabolite, like
NT, decreased significantly at high-stress periods and resolved when
the stress dissipated. Our earlier findings of low NT in HIV-positive
patients further confirmed our oxidant mechanism when these patients
were later shown to have a high prooxidant state (8).
Besides stress, we also studied another prooxidant
state--diabetes--and showed that with poor management of this
condition, as measured by hemoglobin A1C (HbA1C), NT decreased
significantly (7). That is, NT correlated negatively and significantly
with HbA1C. These studies, taken together, confirmed that NT is a good
indicator of a high prooxidant state, whether through HIV infection,
psychologic stress, or diabetes.
In summary, psychologic stress gives rise to a prooxidant state that
is reflected by low NT and increased red blood cell sensitivity to
oxidative insult. Why stress should cause a prooxidant state is not
known. We hypothesize that stress by increasing cortisol favors the
development of an innate immune response (2,3). In normal
circumstances the innate response would abate as the adaptive immune
system takes over. However, with chronic stress the high prooxidant
nature of the innate response persists, because of chronically
elevated cortisol, and NT and probably other important extracellular
proteins of lymphocytes are inhibited, resulting in an attenuated
adaptive immune response and subsequent immunodeficiency. That an
innate or pro-inflammatory process persists in stressed patients is
evidenced by persistent increased blood concentrations of acute phase
proteins seen in these patients (9,10).
