Grand Rapids - Turning back the hands on the clock of a healthy life might prove possible with additional cellular research, according to an MSU faculty member.
Dr. Michael Fossel, MSU clinical professor of medicine and an attending physician in the St. Mary's Hospital emergency room in Grand Rapids, will publish this summer his second book advocating for such research.
Fossel's first work, "Reversing Human Aging," was written for the general public in 1996 and examined the ability of clinical science to intervene in aging.
"The bottom line is, as of that moment, and this moment, too, really, nothing that you can buy or do clinically affects aging - period," Fossel said. "There is nothing. You can't reverse aging slowly or anything else. I don't care what you use."
For almost a decade, Fossel has delved further into research for his academic text "Cells, Aging, and Human Disease," scheduled for release in June.
Fossel's texts involve a theory in which the ends of chromosomes might be responsible for the aging of cells. The chromosome caps, called telomeres, shorten as cells divide. Once telomeres reach a certain length, cells no longer divide and enter a state of aging known as senescence. The telomere theory states that lengthening the telomeres will help cells avoid aging.
"Basically, telomeres re-lengthen the gene, and it's the length of the end of the gene that determines the pattern of gene expression for old versus young cells," Fossel said.
Fossel's text describes three ways to re-lengthen telomeres: put in a gene you already have but can't activate, activate the gene you have or put in the protein produced by the gene.
Geron Corp., a California-based biopharmaceutical company, holds most of the intellectual property rights for research into the third method's use of protein. The company has demonstrated that the enzyme telomerase is capable of restoring telomere length when introduced into normal cells.
The telomerase enzyme is not present in normal cells and tissues, but occurs during tumor progression. The company's research has shown telomerase allows cancer cells to maintain telomere length, which allows them to continue to replicate. The company is working to apply the research to age-related degenerative diseases and cancer research.
Critics of the theory argue that lengthening the telomeres also might leave chromosomes at risk for cancer-causing mutations, rather than simply avoiding cell division.
Dr. Norman Sharpless, an assistant professor of medicine and genetics at the University of North Carolina, has studied telomeres as an oncologist. He and Ronald DePinho published "Telomeres, stem cells, senescence, and cancer" in January with the American Society for Clinical Investigation.
Sharpless said there are a lot of road blocks to the theory because lengthening telomeres could have adverse effects.
"Some can be a tumor barrier but others can be a tumor progressor," he said. "The telomere barrier is a large part, a significant component, to not getting cancer."
Dr. Don Ingram, the acting chief of the laboratory of experimental gerontology at the National Institute on Aging, agrees research to prove the theory is important to cell biology, but he isn't sold on telomere lengthening for use in aging.
"I'm not impressed with it," he said. "The process is not an overarching explanation. There is not an aging process; there are many things that could go wrong and several aging processes."
Ingram said more research needs to be done to prove the theory and Fossel agrees.
"The question really is, "What are the chances of affecting aging at the cellular level?", and the answer is we know we can in the lab," he said. "We can do it in the cells and we can do it in what are called reconstituted tissues, but nobody has taken it to clinical testing yet."
Fossel argues most people assume aging is a part of life, but if the telomere theory is applied, age-related diseases will no longer become a burden for people as they age.
"A lot of people still, even in the aging-research community, tend to assume, 'Well, things wear out; what do you expect?'" Fossel said. "No, they're allowed to wear out; that's different."
Criticism comes with any new idea, Fossel said, and he entertains appropriate critiques. His goal of combining cell biology and human pathology into one text is for people to prove or deny the theory.
"Where's the data? Where's the beef? - that's great criticism," he said. "I'm not saying, 'Wow', I'm saying, 'Let's think about it and see what we can do.'"
Tom Tomlinson, director of the MSU Center for Ethics and Humanities in the Life Sciences, said extending the length of human life also might have a large sociological effect.
If people live longer, he said, there are concerns about employment of younger generations, motivation for life goals, and stigmatization of the elderly.
"(There) are issues of concern and we want to think about (them) as this research is pursued," Tomlinson said.
Meghan Gilbert can be reached at gilbe109@msu.edu.
