In the paper, "Living and Dying for Sex: A Theory of Aging Based on the Modulation of Cell Cycle Signaling by Reproductive Hormones," published in the August issue of the journal, Gerontology (2004;50:265-290), the authors provide both a new definition and a new theory of aging.
"Besides an evolutionarily credible reason for why and how we age, this new theory explains many phenomena known to be associated with aging," said Dr. Atwood. "These include: what determines the ultimate size of an organism, what regulates the initiation of puberty, why organisms with predator evading attributes such as birds and turtles live so long and how caloric restriction extends longevity."
"The fundamental principle of the theory is that the hormones controlling reproduction also control aging by regulating cell division," said Dr. Bowen. "By controlling cell division, these hormones are responsible for our growth and development when we are young in order to achieve reproduction. However, as fertility begins to decrease in our early 30's, in an attempt to maintain fertility, these hormones become imbalanced. This imbalance causes changes in cell division that lead to the diseases and frailty of old age."
The authors state that it was the new definition of aging -- any change in an organism over time -- that allowed them to make the connection between these hormones and cell division. They also emphasize that the new definition provides for a very different perspective on the aging process. They believe this new perspective will allow for new insights on aging and new treatments for diseases associated with the aging process.
"For example, under the old definition of aging -- loss of function over time -- all research has focused on slowing the rate of aging," noted Dr. Bowen. "However, with the change over time definition, it becomes clear that in the case of a premature infant it would be good to increase the rate of aging. At Voyager Pharmaceutical Corp., we are currently pursuing research in this area."
"The theory of aging developed by Drs. Bowen and Atwood is striking in its novelty," said Andrzej Bartke, Ph.D., professor and director of geriatric research at Southern Illinois University School of Medicine. "In particular, the age-related increase in the release of gonadotropins is viewed as a potentially important mechanism of aging rather than a mere secondary consequence of reduced output of gonadal hormones. The authors use this new and different way of looking at endocrine changes that accompany aging to suggest novel therapeutic interventions."
Other examples of the immediate practical implications of this theory are the two Alzheimer's disease Phase II clinical trials that Voyager Pharmaceutical Corp. is currently conducting. These studies are evaluating the efficacy of the gonadotropin releasing hormone analogue, leuprolide acetate, for the treatment of Alzheimer's disease.
"We believe that the age-related increases in pituitary gonadotropins, (luteinizing hormone and follicle stimulating hormone) seen in older men and during menopause in women, cause the brain changes that characterize Alzheimer's disease," said Dr. Bowen. "Leuprolide acetate, a drug that has been used extensively for numerous hormone related disorders, eliminates these hormones. We are testing the idea that this drug can halt or significantly slow the course of this devastating disease."
ALADDIN I (Anti-gonadotropin Leuprolide in Alzheimer's Disease Drug INvestigation) is a 90-patient women's study that is fully enrolled and ALADDIN II is a similar study that is currently enrolling 105 men. The trial sites are located in Fort Lauderdale, Miami, Boca Raton, St. Petersburg and Tampa, FL along with Lafayette and Rancho Mirage, CA, Boston, MA, Charleston, SC, Madison, WI., Hamden, CT and Alexandria, VA. Information about the study can be obtained by calling 919-846- 4880.
In addition to its work in Alzheimer's disease and premature infants, Voyager has begun research into Parkinson's disease and has applied for intellectual property protection for the treatment of over 150 other age- related diseases.