Gerald P Murphy masthead

Scientific Articles Featured in

The Muzzle Tour Healthy Longevity Notebook

In category of Cancer; Ovary and Longevity; Selenium; and Education.
Click on publication titles below to download them.

On Cancer

1. Cancer clues from pet dogs.
    Scientific American 2006; 295: 94-101.

This article introduced readers to the field of comparative oncology – the study of the similarities and differences between the naturally-occurring cancers of humans and animals. When it comes to cancer and aging, pet dogs and people are in the same boat. The article benchmarked progress in studying the cancers of pet dogs, highlighting promising lines of inquiry to accelerate progress in cancer treatment and prevention.

2. Exceptional longevity in pet dogs is accompanied by cancer resistance and delayed onset of major diseases.
    Journal of Gerontology: Biological Sciences 2003; 58: B1078-1084.

This report contained the first detailed description of pet dogs who had reached exceptional longevity. Similar to human centenarians who live to be 100, oldest-old Rottweiler dogs showed a delayed onset of major life-threatening diseases, including cancer. This paper introduced the scientific community to pet dogs living in the same households as humans as an attractive mammalian model of human aging to study the factors that regulate longevity and cancer resistance.

3. Endogenous gonadal hormone exposure and bone sarcoma risk.
    Cancer Epidemiology Biomarkers Prevention 2002; 11:1434-1440.

This was the first study published in the scientific literature to focus on the role of sex hormones and bone cancer. Results showed that male and female Rottweilers who had their testes or ovaries removed during
the first 12 months of life had a 3 to 4-fold increased risk for bone sarcoma.

On Ovary and Longevity

4. Life course analysis of the impact of mammary cancer and pyometra on age-anchored life expectancy in female
Rottweilers: Implications for envisioning ovary conservation as a strategy to promote healthy longevity in pet dogs.

      The Veterinary Journal 2017; 224(1):25-37.

Mammary cancer and pyometra are widely recognized as important, ovary-driven health hazards of pet dogs. Early ovariohysterectomy (spay) can reduce the incidence (occurrence) of these two diseases. In this manuscript, Dr. Waters reported results of the first-ever breed-specific, life course analysis of the impact of mammary cancer and pyometra on life expectancy and premature mortality in dogs. The analysis shows that at no time points during the life course was the current or future diagnosis of mammary cancer or pyometra associated with shortened survival compared to females who never developed these conditions.

5. Longevity in pet dogs: Understanding what’s missing.
      The Veterinary Journal 2014; 200(1):3-5.

In this invited editorial published in a top European veterinary journal, Dr. Waters urges us to take a closer look at longevity research in dogs so we can gain an understanding of what’s missing. It summarizes: Although the biology of successful aging is unquestionably complex, solid progress in successful aging hinges on closer attention to two concepts: life course perspective and whole organism thinking.

6. Caught in an act of convenience: Disentangling our thinking about the influence of ovariohysterectomy (spaying)
on healthy longevity in dogs.

    In: Domestication History, Genetics, Behavior and Implications for Health. Nova Science
    Publishers Inc.; 2013; 115-120.

Ovaries are endocrine organs, not just reproductive units. When we remove endocrine organs, we can expect to re-set the system, impact overall health. This essay uses accessible language to describe how we might direct our re-thinking and shift the dialogue to illuminate the longevity benefits of ovaries.

7. Exceptional longevity in female Rottweiler dogs is not encumbered by investment in reproduction.
    AGE 2013; 35(6):2503-2513.

This was the first study in the scientific literature to explore the potential trade-off between investment in reproduction and longevity in dogs. In a detailed evaluation of reproductive histories of Rottweilers that captured both reproductive intensity (number of offspring) and tempo of reproductive effort (age at first and last reproduction), we found no evidence that a bitch’s physiological investment in offspring is associated with disadvantaged longevity. Instead, independent of reproductive investment, longer duration of ovary exposure was significantly associated with highly successful aging.

8. In search of a strategic disturbance: Some thoughts on the timing of spaying.
    Clinical Theriogenology 2011; 3: 433-437.

The purpose of this paper was to provoke a thoughtful re-examination of our assumptions regarding the health consequences of early, elective ovariohysterectomy in dogs. Ovaries are endocrine organs so ovary removal is a physiological disturbance. This line of reasoning raises a new set of questions. If we refocus our thinking on optimizing the timing of spaying (rather than debating whether spaying is good or bad), can we make spaying a strategic physiological disturbance?

9. Probing the perils of dichotomous binning: how categorizing female dogs as spayed or intact can misinform
our assumptions about the lifelong health consequences of ovariohysterectomy.

    Theriogenology 2011; 76:1496-1500.

Previous studies on spaying and longevity had categorized bitches as spayed or intact based on gonad status at time of death. In this paper we showed this common method of categorizing our study subjects – ignoring the timing of spaying in each bitch – distorts the real relationship between number of years of ovary exposure and longevity. Our conclusion: Continuing to categorize bitches based upon whether they are spayed or intact at time of death is an inadequate method for representing important biological differences in lifetime ovary exposure, which can lead to misleading assumptions about the overall health consequences of ovariohysterectomy.

10. Aging research 2011: Exploring the pet dog paradigm.
      ILAR Journal 2011; 52(1):97-105.

Dr. Waters was invited by the National Academies of Sciences to write this paper as part of a special collection of scientific articles describing emerging animal models of human aging. This paper explores the opportunities and challenges of harnessing pet dogs as biogerontology’s new workhorse. Move over worms and flies … make room for man’s best friend to teach us about the aging process.

11. Exploring mechanisms of sex differences in longevity: Lifetime ovary exposure and exceptional longevity in dogs.
      Aging Cell 2009; 8: 752-55.

This study, published in the world’s top impact aging research journal, was the first to analyze the relationship between the number of years of ovary exposure (age at spay) and likelihood of exceptional longevity in dogs. Results showed that female Rottweilers were twice as likely to reach exceptional longevity than male Rottweilers, but taking away ovaries during the first 4 years of life completely erased the female longevity advantage. Evidence from this landmark study, along with data from women and mice, point in the same direction: Ovaries are part of a system that promotes longevity.

On Selenium

12. A matter of context: How an understanding of redox homeostasis informs the consideration of pro-oxidant
strategies to target tuberculosis, HIV, and cancer metastasis.

      Acta Scientific Nutritional Health 2019; 3:81-86.

This manuscript probes the consequences of reactive oxygen species and oxidative damage through the lens of redox homeostasis.

13. Prostate cancer risk reduction achievable through selenium supplementation: Looking back to move forward.
      Acta Scientific Nutritional Health 2019; 3:45-50.

This is a perspective on selenium supplementation and prostate cancer prevention.

14. Five threads: How U-shaped thinking weaves together dogs, men, selenium, and prostate cancer risk.
      Free Radical Biology & Medicine 2018; 127:36-45.

This paper summarizes two decades of Dr. Waters' research team’s work on advancing the understanding of the cancer-fighting action of the essential trace mineral selenium. It was first presented at the Se 2017 Conference in Stockholm, Sweden.

15. Homeostatic housecleaning effect of selenium:Evidence that noncytotoxic oxidant-induced damage sensitizes
prostate cancer cells to organic selenium-triggered apoptosisInsights from the U-shaped.

      Biofactors 2013; 39:575-588.

Guided by the selenium feeding trial in eldery dogs, this paper investigates how selenium protects prostate cancer by "homeostatic housecleaning" — selectively sweeping away of damaged cells. In petri dish, prostate cancer cells are exposed to oxidative stress to be DNA-damaged and then treated with organic selenium to study the critical cellular signaling pathways which determine the fate of damaged cells — death or survival.

16. Defining the optimal selenium dose for prostate cancer risk reduction: Insights from the U-shaped
relationship between selenium status, DNA damage, and apoptosis.

      Dose Response 2009; 8:285-300.

This paper summarizes our work on the cancer-fighting trace mineral selenium as a strategy to decrease risk of prostate cancer in men. It proposes that a clearer interpretation of the results from human studies could benefit from U-shaped thinking — the idea that more of good things is not always better.

17. Effects of dietary selenium supplementation on DNA damage and apoptosis in canine prostate.
      Journal of the National Cancer Institute 2003; 95(3):237-241.

The goal of this study was to advance the field of human prostate cancer prevention. Our results showed that dogs supplemented with the trace mineral selenium had a significant reduction in genetic damage in the prostate. The results provoked a re-thinking of just how selenium might be beneficial — through the selective sweeping away of damaged cells, rather than the protection of cells from damage. Later, we named this cancer-clearing process “homeostatic housecleaning”.

On Education

18. A pedagogical strategy addressing an unmet need: Making the biology of aging an accessible part of interdisciplinary gerontology education.
      Gerontology & Geriatrics Education 2017; 40:55-70.

Dr. Waters was selected to serve as Chair of a Session on Innovations in Graduate Education at the 2017 Association for Gerontology Higher Education Conference in Miami, Florida. At the conference, Dr. Waters was invited to submit a manuscript capturing his 15-year experience teaching the Biology of Aging to Dual Title PhD in Gerontology candidates at Purdue University.

19. As if blackbirds could shape scientists: Wallace Stevens takes a seat in the classroom of interdisciplinary science.
      The Wallace Stevens Journal 2017; 41:259-269.

Wallace Stevens, one of the most revered American poets of the 21st century, wrote a famous poem titled “Thirteen Ways of Looking at a Blackbird”, which explored the role that the observer plays in imagining and interpreting aspects of the World. Dr. Waters examines how providing students of science with portals to the genius of Stevens can help scientists-in-training explore the limits of perception, language, and thought, thereby opening a new gateway to achieving the imagino-analytical balance of the skillful discoverer. This manuscript is published in the journal's special issue, Teaching Stevens.

20. On cultivating an attitude of precision with language: An uncommon prescription for conditioning creative excellence.
      TEXT 2017 April; Special Issue 40.

Dr. This is an invited paper on creativity in scientific discovery and education. It introduces several Dr. Waters' original ideas such as "The Failure Hinges", which describes an unexpected linkage between language precision and successful failure.

21. The biology of successful aging: Watchful progress at biogerontology’s known-unknown interface.
      In: Gerontology: Perspectives and Issues, 4th Edition. Springer; 2013; 19-48.

This textbook chapter is about the biology of aging. It offers an insightful perspective on the kinds of ideas that biogerontologists wonder about. This published work situates its subject – the biology of successful aging – as a moving target, a field in flux, as it underscores the substantial advances and critical gaps in our understanding.

22. The paradox of tethering: Key to unleashing creative excellence in the research-education space.
      Informing Science 2012; 15:229-245.

This paper is the product of a keynote address delivered by Dr. Waters at an international conference on research, education, and communication. It explores ways that we can move closer to achieving the goal of situational excellence — reaching our full potential as discoverers and educators.

23. On the self-renewal of teachers.
      Journal of Veterinary Medical Education 2011; 38(3):235-241.

This paper was the first in the veterinary profession to address the subject of self-renewal. Renewal is critical for everyone, not just teachers. Therefore, this paper, which provides a prescription for self-renewal that hinges upon establishing your own collection of intellectual heroes, can benefit reader from all walks of life.

Selected Articles Published

by Murphy Foundation Scientists

The Murphy Foundation’s goal is to make significant scientific contributions that will advance the fields of cancer detection, prevention, and treatment. The breadth and depth of this commitment are illustrated by this collection of selected peer-reviewed scientific publications authored by Dr. Murphy and Dr. Waters.

Click on one of the subject headings below to see related articles.

Aging Anticancer Drug Discovery
Cancer Biology Comparative Oncology
Prognostic Factors / Neural Networks Tumor Imaging
Prostate Cancer & Health Breast Cancer
Other Cancers Nutrition and Cancer Prevention
Renal Physiology Miscellaneous
Bone Cancer