[Pophealth] stress and aging changes in cells

[Stephen Bezruchka]

A very important way that hierarchy is involved in worsening health status 
in populations is that those lower down suffer more stress.  And now we 
are finding new mechanisms through which stress causes worse health. 
There are a variety of ways of looking at the different processes and 
lower levels of the enzyme telomerase is cutting edge stuff.  Below is a 
piece from the NY Times by a key researcher in this process that talks 
about the new concepts, and after that I'll put the key references.  This 
material represents another way of talking about the biology behind 
population health.  STephen

***
NYT July 3, 2007
A CONVERSATION WITH ELIZABETH H. BLACKBURN; Finding Clues to Aging in the 
Fraying Tips of Chromosomes
By CLAUDIA DREIFUS
When Time magazine named Elizabeth H. Blackburn, a cell biologist, one of 
this year's ''100 Most Influential People in the World,'' it listed her 
age as 44.
''Don't think I'm going to ask for a correction on that one,'' Dr. 
Blackburn, 58, a biochemistry professor at the University of California, 
San Francisco, said in a recent visit to New York City. ''If they want to 
turn back the clock, that's lovely.''

Dr. Blackburn, a winner of the 2006 Albert Lasker Award for Basic Medical 
Research, studies aging and biochemical changes in cells that are related 
to the diseases of old age.
Whatever Dr. Blackburn's own chronologic age, the buzz in scientific 
circles is that she is likely to be the next woman awarded the Nobel Prize 
in Medicine.
Q.What are telomeres and telomerase?
A. Telomeres are the protective caps at the ends of chromosomes in cells. 
Chromosomes carry the genetic information. Telomeres are buffers. They are 
like the tips of shoelaces. If you lose the tips, the ends start fraying.
Telomerase is an enzyme. In cells, it restores the length of the telomeres 
when they get worn. As the ends of the chromosomes wear down, the 
telomerase comes in and builds them back up.
In humans, the thing is that as we mature, our telomeres slowly wear down. 
So the question has always been: did that matter? Well, more and more, it 
seems like it matters.
Q.Is there a link between telomere length and stress?
A. In my lab, we're finding that psychological stress actually ages cells, 
which can be seen when you measure the wearing down of the tips of the 
chromosomes, those telomeres.
A few years ago, Dr. Elissa Epel, a psychologist who studies chronic 
stress, came to see me. She asked, 'Does stress have any effect on cell 
aging?' There's always been this observation that people under great 
stress appear to be care-worn. They look haggard, right?
So Elissa designed this study where we looked at two groups of mothers. 
One had normal, healthy children. The other group had a child with a 
chronic illness. Physiological and psychological measurements were done on 
everyone. With the stressed group, we found that the longer the mothers 
had been caring for their chronically ill child, the less their telomerase 
and the shorter their telomeres.
This was the first time you could clearly see cause and effect from a 
nongenetic influence. Genes play a role in telomerase levels, but this was 
not genes. This was something impacting the body that came from the 
outside and affecting its ability to repair itself. By the way, we found 
similar effects in women who were primary caregivers for partners with 
dementia.
Q.Is this scientific proof of the mind-body connection?
A. It's a proof. There have been others. Researchers have found that the 
brain definitely sends nerves directly to organs of the immune system and 
not just to the heart and the lower gut. In that way, too, the brain is 
influencing the body.
One of the things that came out of our study of these mothers is a link 
between low telomerase and stress-related diseases. We looked at the 
measures for cardiovascular disease -- bad lipid profiles, obesity, all 
that stuff. The women with those had low telomerase.
We also looked at low telomeres and cancer. We wondered if a cell with 
worn down chromosome tips might divide in some abnormal way. Our findings 
have yet to be published, so I can't tell you much here, but we think 
we're onto something.
Q.Is your goal to find a drug to repair the telomeres?
A. Or an intervention. We know that stress is bad for cells. What about 
alleviating it? We've been collaborating on studies looking at the 
telomerase levels in people who practice meditation. We are looking at 
whether or not telomerase changes after a three-month program of 
meditation. We'll know more soon.
One of the really interesting things about doing research these days is 
how interdisciplinary it has become. A few years ago, I never thought that 
I would be collaborating with psychologists. Ten years ago, if you'd told 
me that I would be seriously thinking about meditation, I would have said 
one of us is loco.
Q.How did you develop this specialty: studying the ends of chromosomes?
A. In the 1970s, I did a Ph.D. with Fred Sanger in Cambridge who was in 
the process of inventing ways to map what's inside DNA. He later won the 
Nobel Prize. In his lab, I noticed you could sequence -- or map -- the 
very ends of DNA molecules. However, this was still a difficult task 
because DNA strands are very long and with the limited technology that 
existed then, it was hard to locate the ends.
Later, I did a post-doc at Yale with Joe Gall, who had discovered a class 
of very tiny linear chromosomes in a type of single-celled protozoa. These 
creatures -- they are pond scum, literally -- had lovely, accessible 
chromosomes. And I thought, 'Oh, wonderful. I'll sequence these.' And 
right away, I found these strange molecular features about their ends: 
telomeres.
And over the next few years, things began to emerge from ours and other 
laboratories, saying there's something very important about them. Till 
then, people had thought that only DNA could make other DNA. We -- my 
wonderful then-graduate student Carol Greider and I -- discovered this 
enzyme, telomerase, and it showed it actually made DNA.
Q.How did you get appointed to President Bush's Council on Bioethics?
A. I received a call in the autumn of 2001 from Leon Kass, the chairman. 
He asked if I'd serve. I think he'd already called a lot of people who'd 
turned him down.
This was not too many days after 9/11. In that moment, I wanted to help 
the country, but didn't know how. I thought, 'I certainly know cell 
biology, and that's what I can be useful for.' So I accepted. But I had to 
be vetted by the White House office of personnel first. One question I was 
asked was, 'Who did you vote for?'
Q.Once on it, did you feel the council had a preset political agenda?
A. Oh, yes. Especially about stem cells. Basically it was, 'You don't need 
any of those pesky embryonic stem cells because everything is wonderful 
with adult stem cells.' When one would ask, 'What's the evidence?' you'd 
hear, 'Somebody wrote a review article about adult stem cells.' And I'd 
say, 'That is not the same as primary data. Anyone with a word processor 
can write a review article.'
There was a lot of that, and I was always saying, 'Let's look at the 
science.' My persistence didn't endear me to Leon Kass, I felt. One day, I 
was asked to call the White House personnel office where an official said, 
'Thank you. Thank you for serving.' I asked him, 'Why are you thanking 
me?' 'You will no longer be on the council.' I was one of two members who 
hadn't been reappointed for a second two-year term.
Q.Did the experience anger you?
A. It disappointed. Particularly this closed view on embryonic cells. To 
make a division between them and adult stem cells is foolish because they 
are all on a continuum. To understand how any of these work means 
researchers have to look at and compare them to each other. Why blind 
yourself to this fact?
Q.What's your take on the news recently reported on these pages that 
researchers have been able to insert genes into skin cells of mice and 
give them the qualities of embryonic stem cells?
A. It's an advance. But it will be a while before we know if it will work 
for human cells. Mouse cells have a history of not always being a good 
model for human cells.

*****
Epel, E. S., E. H. Blackburn, et al. (2004). "Accelerated telomere 
shortening in response to life stress." Proc Natl Acad Sci U S A 101(49): 
17312-5.

Epel, E. S., J. Lin, et al. (2006). "Cell aging in relation to stress 
arousal and cardiovascular disease risk factors." Psychoneuroendocrinology 
31(3): 277-87.

Sapolsky, R. M. (2004). "Organismal stress and telomeric aging: an 
unexpected connection." Proc Natl Acad Sci U S A 101(50): 17323-4.