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. Biogerontologists are actively exploring a potential health trade-off important to mothers: Whether the production of offspring comes at a maternal cost, the consequence of a diversion of physiological resources that could lead to accelerated aging and increased late-life frailty. New research in aging dogs exploring the linkage between reproduction and aging shows production of live offspring did not increase late-life frailty. Instead of harboring a hidden penalty, females with live offspring exhibited elevated robustness later in life.
The study conducted by scientists at the Gerald P. Murphy Cancer Foundation's Center for Exceptional Longevity Studies was published today in the peer-reviewed The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences.
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.
Life history theory predicts a physiological cost of reproduction, with diversion of resources away from body maintenance leading to accelerated senescence, deficit accumulation, and diminished longevity. However, in human studies using longevity as the study endpoint, a reproduction-longevity trade-off has not been consistently demonstrated. In fact, a systematic analysis of parity (the condition of having given birth) and all-cause mortality in women revealed a J-shaped relationship, suggesting a moderate level of parity is associated with lower mortality.
Reasoning that longevity might be a measure insensitive to the cost of reproduction, investigators have begun to evaluate whether late-life frailty, as an indicator of cumulative health deficits, is influenced by production of live offspring. Results of such frailty studies in women have been mixed, with only a fraction of investigators reporting a detrimental association between higher parity and higher late-life frailty. In these studies, however, it remains unclear whether the frailty cost of high reproduction was the consequence of biological or non-biological influences.
"We enlisted companion dogs as a large animal model of frailty with the intent of circumventing many of the sociobehavioral determinants of human frailty, such as engagement in caregiving, education level, inclination to seek medical help, and smoking behavior that can complicate the interpretation of studies in humans," said David J. Waters, DVM, PhD, Director of the Murphy Foundation's Center for Exceptional Longevity Studies. "We sought to expose a dormant vulnerability in females who had completed reproduction that could manifest itself years or decades later. But our approach utilizing a clinical frailty index to register late-life deficit accumulation provided no evidence to support the thesis that the physiological cost of producing live offspring is associated with higher later-in-life frailty."Instead, the investigators found parity was associated with lower late-life frailty – a result that aligns with some studies in women.
"Women and companion dogs share the same environment and are protected species — free of predators, benefiting from disease prevention practices such as vaccination, and receiving life-saving medical and surgical care. Perhaps this renders the two species less likely to manifest any physiological cost of reproduction," Waters commented. This line of reasoning is supported by the findings of a 2025 study that showed the relationship between contraception/sterilization and longevity in female pet dogs and women was uniquely different from other vertebrate species.
Waters' research is important because it melds together results from these two species suggesting that parous females may actually have the capacity to dampen the development of later-in-life frailty.
The mechanistic pathways responsible for the observed relationship remain unclear. But emerging evidence suggests that pregnancy may exert long-standing beneficial impact on some health outcomes, and these effects are not solely attributable to temporary changes in gestational hormones, but rather a mechanism that is durable.
"The epigenetic reprogramming of gene expression in a wide array of target tissues provoked by pregnancy could provide a dynamic yet durable long-term memory able to persist long after the provoking stimulus of pregnancy is no longer present," said Waters, who is also a Faculty Associate in Purdue University's Center on Aging and the Life Course.
The pursuit of mechanistic linkages between pregnancy and subsequent health outcomes, including frailty, in companion dogs would appear to be an area ripe for inquiry by One Health-minded investigators.
The uniqueness of the study was articulated by Rong Fu, PhD, co-author of the study. "Investigators have been working to decipher the cryptic relationship between reproduction and longevity — attempting to disentangle the bidirectional, competing factors that situate reproductive success as a physiological cost and at the same time an upsided surrogate of high maternal fitness. Here, in geriatric companion dogs, we applied a frailty tool — a 34-item clinical frailty index called EARS-FI — to measure lifetime deficit accumulation in females that differed in physiological investment in reproduction. The research sidesteps many of the sociobehavioral determinants of human frailty," said Dr. Fu, who is Associate Professor of Sociology at Siena University.
"With our work in dogs, we believe we are getting a clearer look at the biology," Dr. Fu continued.
The motivation to pursue this line of inquiry, challenging the conventional life history theory-based stance that reproduction should come at a physiological cost, was spurred by a seminal study published by Gordon and colleagues in 2020. Their report presented a compelling finding: Higher frailty associated with six or more children occurred equally in both mothers and fathers. The authors concluded their results were more likely the consequence of sociobehavioral factors, such as economic strain, disruption of occupational attainment, and psychological stress of childrearing, rather than caused by the physiological toll of producing live offspring.
"We took the hint and put our female dogs to work, hopeful that our frailty tool could help to elucidate the biological underpinnings of frailty development," said Waters. "With this frailty tool, we are mapping healthspan."
The new dog study was selected for publication in a prominent aging journal's Special Issue on Animal Models of Frailty, which features other cutting-edge work in rodents and non-human primates.
To explore the frailty-reproduction linkage in dogs, the investigators utilized late-life robustness as the primary study outcome, defined as the lowest quintile of frailty values in the study population. Compared to nulliparous females, females with live offspring were 3 times more likely to retain late-life robustness, a relationship that was not attenuated after adjusting for covariates such as lifetime ovary exposure, overweight body condition, and birth cohort. Moreover, a dose-response analysis revealed females with the largest reproductive effort — largest number of litters — had the highest likelihood of late-life robustness. The pattern held.
Because the exposure variable (parity versus nulliparity) was not randomized in this observational study, investigators explored the possibility that selection bias could result in individuals of lower earlier-in-life health/fitness landing in the nulliparous group, which could account for the higher late-life frailty observed among nulliparous females.
"One of the notable features of the study is our use of two measures of early life fitness — earlier-in-life health deficits in nulliparous females and lifetime morbidity profiles in the entire cohort — which showed our main findings could not be readily explained based upon selection," said Andres Carrillo, PhD, Professor in the College of Health Sciences at Chatham University, and co-author of the study.
The work is also notable for opening the door to a new research methodology: Enlisting the oldest-living dogs as our greatest teachers , a strategy laid out by Waters in a 12-minute TEDx talk. Waters leads the team conducting the first systematic study of exceptional longevity in 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 structured veterinary interviews with dog owners. To capture an even more detailed picture of these exceptional dogs, Waters has conducted in-home scientific visits of 130 of these dogs living in 40 U.S. states and Canada.
"In the new study, we extend work in the field of frailty research by introducing a new application of the dog model of frailty as a large animal model for the study of reproduction and deficit accumulation," Waters said. "The work is timely, representing the first test of evolutionary theory of trade-offs in companion dogs as it pertains to reproductive investment and subsequent physical frailty."
As an emerging model of human healthspan, canines have been employed by investigators to generate important insights into identifying specific early-life events (e.g. gonad retention in males) that may mitigate the mortality consequences of late-life frailty. Such recently published work is challenging conventional thinking about the health consequences associated with spaying or neutering companion dogs.
"These exceptional dogs offer a unique opportunity to explore the numerous ways that healthy life span can be extended by taking a life course approach," said Waters.
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 maternal investment in reproduction means to healthy aging makes perfect sense.
"We engaged a cohort of aged companion dogs as a well-nourished, predator-free, protected population living in the same environment as humans, whose access to high quality medical care rivals that of human populations," stated Waters, who is Professor Emeritus, Department of Veterinary Clinical Sciences in Purdue's College of Veterinary Medicine. "Congruent with results from several studies in women, the work signals an important contribution to the maternal cost of reproduction debate suggesting some parous females may have the capacity to dampen development of later-in-life frailty, which should be further investigated at the genetic and epigenetic level."
The current work, which is of interest to investigators exploring novel approaches to prevent, delay, or even reverse frailty, is also of interest to scholars and practitioners in the field of veterinary reproduction. Dr. Waters will share the study results during a podium presentation at Therio 2026, the annual meeting of the Society for Theriogenology, American College of Theriogenologists, and Theriogenology Foundation, which convenes July 22-24, 2026 in Pittsburgh, PA.
Waters points to the growing scientific interest in harnessing the domesticated dog population to pursue these kinds of underexplored research questions in the field of geroscience.
"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 straightforward one: Come closer. We're ready to listen now more intently to your life narratives, illuminating our scientific progress, feeding innovation, and enriching our lives."
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 Murphy Foundation's One Health approach recognizes the interconnectedness of human, animal, and environmental health, aiming to optimize health outcomes across these domains. The Gerald P. Murphy Cancer Foundation is a 501 (c)(3) not-for-profit research institute. For more details, visit our website . For more details on frailty research, visit our frality research page.
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 healthspan from cells to societies.
