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Scientific Articles Featured in

The 2015 Muzzle Tour Healthy Longevity Notebook

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1. 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.

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. 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.

4. 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.

5. 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.

6. 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.

7. 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?

8. 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.

9. 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.

10. 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.

11. 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.

12. 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”.

13. 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.

14. 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.

15. 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.

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