December 1, 2009

Message for women and dogs: keeping ovaries is linked to longevity

Research published Tuesday (Dec. 1) shows female dogs that keep their ovaries longer also live longer. The study, exploring the factors that favor successful aging in pet dogs, was conducted by a research team led by David J. Waters, a doctor of veterinary medicine.

Waters' work is the first investigation to look for a link between retaining ovaries and reaching exceptional longevity in mammals. Waters is executive director of the Gerald P. Murphy Cancer Foundation, based at the Purdue Research Park of West Lafayette. The Murphy Foundation is home to the Center for Exceptional Longevity Studies, which tracks the oldest living pet dogs in the United States.

The researchers collected and analyzed lifetime medical histories, ages and causes of death for 119 canine "centenarians" - exceptionally long-lived Rottweiler dogs living in the United States and Canada that survived to 13 years, which is 30 percent longer than average Rottweilers. These exceptionally long-lived dogs were compared to a group of 186 Rottweilers that had usual longevity, approximately nine years.

"A female survival advantage in humans is well-documented - women outnumber men by 4:1 among those who reach 100," said Waters, who is associate director of Purdue University's Center on Aging and the Life Course and a professor in the Department of Veterinary Clinical Sciences. "Like women, female dogs in our study had a distinct survival advantage over males. But taking away ovaries during the first four years of life completely erased the female survival advantage. We found that female Rottweilers that kept their ovaries for at least six years were four times more likely to reach exceptional longevity compared to females who had the shortest lifetime ovary exposure.

"Clearly, we have tapped into a unique resource with our Exceptional Longevity Database. We like to think of it as the pet dog equivalent of the New England Centenarian Study. We want to better understand the biology of aging. Our quest to validate pet dogs as a model for the study of healthy human aging is at the core of this research."

Murphy Foundation scientists think it is time to tackle a new set of research questions relevant to the biology behind aging. At the top of the list are identifying ovary-sensitive processes that may influence the rate of aging and defining the critical window of ovary exposure that optimizes longevity.

The pet dog research published in Aging Cell mirrors the findings of the Nurses' Health Study published this summer by Dr. William Parker and colleagues from the John Wayne Cancer Institute in Santa Monica, Calif.

Parker's group studied more than 29,000 women who underwent a hysterectomy for benign uterine disease. The findings showed that the upside of ovary removal - protection against ovarian, uterine and breast cancer - was outweighed by increased mortality from other causes. As a result, longevity was cut short in women who lost their ovaries before the age of 50 compared with those who kept their ovaries for at least 50 years.

"For the last 35 years, most doctors have been routinely advising women undergoing hysterectomy to have their ovaries removed to prevent ovarian cancer," Parker said. "We believe that such an automatic recommendation is no longer warranted."

Waters believes it boils down to systems thinking.

"Nobody would argue that taking the caterpillars out of an environment does not change that environment in unforeseen ways," he said. "You're not simply left with the old environment minus caterpillars. Likewise, we are dealing with an ovarian ecology that urges us to pause and consider the long-term health consequences of taking out ovaries."

Taken together, the emerging message for dogs and women seems to be that when it comes to longevity, it pays to keep your ovaries.

"What we have here is a compelling convergence," Waters said. "The data from women and dogs, together with reported longevity benefits from ovary transplants in mice, are pointing in the same direction - the notion that a network of processes regulating longevity is under ovarian control."

Parker believes the results point to a need for a new conversation between patient and doctor, framed by the patient's specific risk factors and personal concerns. Waters concurs.

"In this era of personalized medicine, it seems only fitting that we should be directing the conversation about elective ovary removal in women and dogs toward a more forward-looking, individualized script," Waters said.

About the Center for Exceptional Longevity Studies

The Center for Exceptional Longevity Studies seeks to identify important genetic and environmental determinants of healthy longevity and to better understand the complex relationship between aging and cancer. While the scientific community looks for reliable research approaches to verify exciting scientific leads, we see enormous value in studying pet dogs living with their owners as a virtual aging laboratory. There is a big payoff for validating this kind of innovative thinking - an opportunity to promote healthy longevity in both pets and people. The center and its research are supported by P&G Pet Care, makers of Iams and Eukanuba, and the Rottweiler Health Foundation. The research is conducted jointly by the Murphy Cancer Foundation and Purdue University.

About Purdue Research Park

The 725-acre Purdue Research Park has the largest university-affiliated business incubation complex in the country. The park is home to more than 160 companies. About 100 of these firms are technology-related and another 39 are incubator businesses. The park is owned and managed by the Purdue Research Foundation, a private, nonprofit foundation created to assist Purdue University in the area of economic development. In addition to the Purdue Research Park in West Lafayette, the foundation has established technology parks in other locations around Indiana including Indianapolis, Merrillville and New Albany.

To the Purdue Research Park, https://www.purdueresearchpark.com

To move closer to understanding the mechanistic underpinnings of sex differences in human longevity, we studied pet dogs to determine whether lifetime duration of ovary exposure was associated with exceptional longevity. This hypothesis was tested by collecting and analyzing lifetime medical histories, age at death, and cause of death for a cohort of canine 'centenarians' – exceptionally long-lived Rottweiler dogs that lived more than 30 percent longer than average life expectancy for the breed. Sex and lifetime ovary exposure in the oldest-old Rottweilers (age at death, ≥ 13 years) were compared to a cohort of Rottweilers that had usual longevity (age at death, 8.0-10.8 years). Like women, female dogs were more likely than males to achieve exceptional longevity (OR, 95 percent CI = 2.0, 1.2–3.3; P = 0.006). However, removal of ovaries during the first 4 years of life erased the female survival advantage. In females, a strong positive association between ovaries and longevity persisted in multivariate analysis that considered other factors, such as height, body weight, and mother with exceptional longevity. A beneficial effect of ovaries on longevity in females could not be attributed to resistance against a particular disease or major cause of death. Our results document in dogs a female sex advantage for achieving exceptional longevity and show that lifetime ovary exposure, a factor not previously evaluated in women, is associated with exceptional longevity. This work introduces a conceptual framework for designing additional studies in pet dogs to define the ovary-sensitive biological processes that promote healthy human aging.

Purdue Research Park contact:
Steve Martin, 765-588-3342, sgmartin@prf.org

Source:
David J. Waters, 765-775-1009, waters@purdue.edu