West Lafayette, Ind. – Frailty threatens older individuals because it increases their vulnerability to detrimental health outcomes, such as falling, longer hospitalization, or even shortened life expectancy. New research exploring the linkage between frailty and mortality risk points to retaining gonad function as a potent strategy to fight late-life frailty.
The study conducted by scientists at the Gerald P. Murphy Cancer Foundation's Center for Exceptional Longevity Studies was published last week in the peer-reviewed scientific journal Scientific Reports.
The Gerald P. Murphy Cancer Foundation is a not-for-profit research institute focused on cancer and aging. It is based at the Purdue Research Park of West Lafayette.
To date, research on physical frailty has focused mainly on understanding factors that lead to frailty development to discover strategies that might prevent or postpone frailty. In contrast, relatively little attention has focused on factors that might influence frailty resilience, so that fewer adverse health consequences take place once frailty occurs. The results of the new study suggest that the HPG axis — the body's system of regulating production of the hormone testosterone — can significantly impact the lethality of late-life frailty.
"Our work provides the first description of the relationship between HPG axis integrity and the mortality risk associated with late-life frailty," said David J. Waters, DVM, PhD, Director of the Murphy Foundation's Center for Exceptional Longevity Studies. "Male dogs with the shortest duration of testis exposure had a very high mortality risk associated with late-life frailty, whereas the mortality consequence of increasing frailty was erased in males with the longest gonad exposure."
The work is important because it directly addresses a critical question: What factors shape the critical aspects of physiology – the critical context – that can reduce the adverse impact of increasing frailty on health outcomes, including mortality?
"On the basis of our findings, we propose that HPG axis function is an important regulator of the impact of late-life frailty," said Waters, who is also a Faculty Associate in Purdue University's Center on Aging and the Life Course.
The uniqueness of the study was articulated by Markus H. Schafer, PhD, co-author of the study. "The research applies a life course approach to determine whether early-life events, such as endocrine hormone disruption, can buffer against late-life challenges," said Schafer, who is Professor of Sociology at Baylor University, and whose academic work includes describing the buffering role that social connections can exert on the loneliness of people living alone.
"The research results extend current interest in the role that gonadal hormones play in the development of frailty in older men to include a separate, yet complementary consideration — the significant influence gonad function exerts on the adverse consequences of frailty," Schafer continued.
Cutting edge investigations of frailty and other integrated measures of health demand expertise in multiple disciplines. "Dr. Waters has assembled an interdisciplinary team with expertise in veterinary medicine, sociology, nutritional science, exercise science, and comparative medicine to confront this knowledge gap," remarked Kenneth Ferraro, PhD, Distinguished Professor and Founding Director of Purdue's Center on Aging and the Life Course (CALC). "Four of the co-authors of this published study working at four different institutions received their Dual-Title PhD from Purdue CALC, the first university in the United States to award a multidisciplinary Dual-Title PhD in Gerontology."
The work is also notable for opening the door to a new research methodology: Enlisting the oldest-living dogs as our greatest teachers . Waters leads a team conducting the first systematic study of exceptional longevity of companion dogs living in North America.
The Exceptional Aging in Rottweilers Study seeks to better understand highly successful aging and disease resistance through the study of the oldest-living Rottweilers. From this cohort of dogs who have lived 30% longer than breed average — physiologically equivalent to 100-year-old humans — investigators construct lifetime medical histories using questionnaires, medical records, and phone interviews with dog owners. "In the new study, we capitalize on this lifetime cohort to test our hypothesis on gonad function fighting frailty by generating a frailty score in geriatric male dogs with a broad range of lifetime testis exposure and then following them from frailty scoring until time of death," Waters said.
"These exceptional dogs offer a unique opportunity to explore the numerous ways that healthy life span can be extended," said Waters.
The work in canines has already generated important insights into the linkage between ovaries and longevity and the relationship between early endocrine disruption and risk of cruciate ligament rupture . The new findings extend the investigators' recently published work on frailty that are challenging conventional thinking about the health consequences associated with spaying or neutering companion dogs.
Waters put the Exceptional Aging in Rottweilers Study in perspective, noting that for centuries dogs have enriched people's lives in important ways as our pets and our companions. Now, for the first time, the oldest-living dogs are being investigated with the hope that their extreme natural biology will offer up fresh scientific clues.
To Waters, dogs stepping up to contribute a deeper understanding of what hormones mean to healthy aging makes perfect sense.
"Historically, dogs have played a pivotal role in endocrine hormone research, including the discoveries of insulin and the ability to shrink prostate cancers using androgen ablation," stated Waters, who is Professor Emeritus, Department of Veterinary Clinical Sciences in Purdue's College of Veterinary Medicine. "Our work signals an important step toward better understanding frailty resilience, advancing the prospect that by avoiding HPG axis deterioration we might retain an internal hormonal environment that buffers the adverse impact of frailty."
Waters points to the growing scientific interest in harnessing the domesticated dog population to pursue these kinds of underexplored research questions.
"We've identified a special group of dogs that can help to inform us about the future research directions that will benefit companion dogs and people," said Waters. "Our message to these dogs should be a simple one: We're ready to listen."
About the Center for Exceptional Longevity Studies
The Center for Exceptional Longevity Studies seeks to identify important genetic, lifestyle, and environmental determinants of healthy longevity and to better understand the complex relationship between aging, cancer, and cancer avoidance. 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's a big payoff for validating this kind of innovative thinking — an opportunity to promote healthy longevity in both pets and people. The Gerald P. Murphy Cancer Foundation is a 501 (c)(3) not-for-profit research institute.
About the Purdue University Center on Aging and the Life Course
The Purdue University Center on Aging and the Life Course (CALC) is a university-wide entity created to strengthen interdisciplinary inquiry on aging. The central aims of CALC are to advance research to optimize the aging experience of diverse populations and prepare future leaders in the field of gerontology. Created in 2003 and drawing upon the expertise of faculty associates from more than 20 academic departments, the Center emphasizes the advantage of taking a life course approach to analyze aging and health span from cells to societies.
