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.