Here's the dilemma.
At a fundamental level, we age because our cells stop dividing and multiplying.
So why shouldn't medical science try to extend our lifespans and improve our health in old age by making sure our cells keep proliferating?
The answer is cancer. Any measures we take to keep tissues growing might raise the odds of cancer, which is characterized by cells that never stop dividing.
Patricia Opresko lives at the intersection of this quandary.
A researcher at the University of Pittsburgh's Graduate School of Public Health, Dr. Opresko studies the basic mechanisms of why cells age, partly by specializing in a rare premature aging malady known as Werner syndrome.
Werner strikes only about 1 in a million people, and the genetic defect that causes it is particularly prevalent in Japanese people, who account for about 800 of the world's 1,000 living patients. People with Werner syndrome develop baldness, wrinkles, cataracts, osteoporosis and other aging maladies in their teens or early 20s and often die in their 40s.
- Position: Assistant professor, environmental and occupational health, University of Pittsburgh.
- Age: 36
- Residence: Squirrel Hill
- Education: Bachelor's in chemistry and biology, DeSales University, Center Valley, Pa., 1994; Ph.D., biochemistry and molecular biology, Penn State University College of Medicine, 2000.
- Previous positions: Postdoctoral fellow, National Institute on Aging, Baltimore, 2000-2005.
- Professional honors: Young investigator's award, National Institute of Environmental Health Sciences, 2006; Ellison Medical Foundation New Scholar in Aging Research, 2006.
- Publications: Twenty-eight articles in professional journals, four book chapters.
It turns out, she said, that the genetic location for Werner syndrome may be the same one involved in a link between some forms of chromium and lung cancer, which has shown up in welders who work on stainless steel. Dr. Opresko has received a young investigator's award from the National Institute of Environmental Health Sciences to examine the chromium-cancer link.
Welding-fume chromium can attack the body's chromosomes, which are the 23 pairs of packaged DNA we inherit from our mothers and fathers and which exist inside each of our cells. When that occurs, one protein that tries to fix the damage is the same one that is missing in Werner patients, she said.
In both cases, the destruction seems to occur in specialized cells at the ends of chromosomes called telomeres (pronounced TEA-lo-meers).
"The telomeres are really a very special area of the genome," Dr. Opresko said, "because their job is to tell the cell I'm a natural, normal, protected chromosome end and not a broken chromosome. They've sort of been likened to the plastic cap on the end of a shoelace. They make the end of the chromosome look like the end of a shoelace instead of a frayed end."
Telomeres also play a key role in aging, because in most cases, every time a cell divides, its telomeres shorten up slightly. Human cells start out with 1,600 to 2,500 repeat sequences at the ends of their telomeres, and each time a cell divides, the chromosomes lose 8 to 25 repeats.
Eventually, when the telomeres get short enough, the cell goes into senescence and stops dividing, which is how old age plays out on a molecular level.
The only cells that maintain their telomere length are egg and sperm cells, she said. "In these germ cells," she said, "we don't ever lose repeats, and this is really important, because otherwise we would pass on shorter telomeres to our children and their children would have shorter telomeres and eventually the species would run out of telomeres."
Many human tissues also have adult stem cells, which are designed to replenish our tissues as we grow older, and those stem cells don't lose telomere repeats as fast as other cells do.
Eventually, though, most human cells will stop dividing, she said, and one theory for why that happens is that it's "a mechanism that protects our cells against cancer, so if they senesce, they no longer divide and can't become malignant."
If it's that simple, though, why are people more likely to get cancer as they age?
There are at least two possibilities, Dr. Opresko said.
Studies at the Lawrence Berkeley National Laboratory have suggested that senescent cells secrete substances that can disrupt the normal tissue around them, making it easier for cancer cells to get a foothold and spread. And sometimes, she said, senescent cells that have stopped dividing undergo chromosome disruptions that eventually can make them cancerous and kick them back into high gear.
A key substance that helps repair telomeres is the enzyme telomerase, which is very active in reproductive and stem cells. Unfortunately, it also can be hijacked by cancer cells to keep them thriving and multiplying.
Some scientists are exploring whether telomerase could be used to enhance people's health as they age, Dr. Opresko said, but there is always the risk it could trigger more cancers. "It's a double-edged sword."
She has been focused on biology since her first encounter with the subject at age 13, when she learned about DNA. "I was just so amazed that we understood the blueprint of life and what puts together a cell and so I was really hooked ever since then."
After growing up in New Jersey, she moved to Eastern Pennsylvania and attended DeSales University, then Penn State University's medical school, where she earned a doctorate in biochemistry and molecular biology. She joined Pitt's department of environmental and occupational health three years ago.
While her main mission is to understand the underlying processes of cellular aging, she hopes her work will one day help people live healthier lives in their later years.
Researchers already know that short telomeres are associated with heart disease, diabetes, pulmonary fibrosis and osteoporosis, she said.
If they could figure out how to keep the chromosome ends from getting so stubby, they might delay or prevent those conditions, she said.
"The idea is if you could prevent these diseases, people might die of natural causes" instead of suffering through chronic illnesses and pain.
Mark Roth can be reached at firstname.lastname@example.org or 412-263-1130