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Chapter 3

The Science of Aging: Surprising Truths about Dogs and Their Factors for Disease

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many theories about aging: To access a library of resources and studies on aging, go to the National Institute on Aging and visit their page on Advances in Aging Research at

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David Sinclair’s study of one particular family of proteins called “sirtuins” has been particularly revealing: To access all of Dr. David Sinclair’s academic papers, go to his lab’s website at Also see his book Lifespan: Why We Age―and Why We Don’t Have To (New York: Atria 2019).

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It’s really no surprise . . . that the rise in obesity among dogs (a rise of around 20 percent since 2007): To track pet obesity and access pet obesity data, go to the Association for Pet Obesity Prevention at

Almost one-third of eleven- to twelve-year-old dogs and 70 percent of fifteen- to sixteen-year-old dogs show cognitive disturbances: See J. C. Neilson, B. L. Hart, K. D. Cliff, and W. W. Ruehl, “Prevalence of Behavioral Changes Associated with Age-related Cognitive Impairment in Dogs,” J Am Vet Med Assoc 218, no. 11 (June 2001): 1787–91. doi: 10.2460/javma.2001.218.1787.

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There is a huge variation in mean life span across the different breeds of dogs: See Lisa J. Wallis, et al., “Demographic Change Across the Lifespan of Pet Dogs and Their Impact on Health Status,” Front Vet Sci 5 (August 2018): 200. doi: 10.3389/fvets.2018.00200. eCollection 2018.

studies zeroing in on so-called zombie cells, which are senescent cells: See Katarina Zimmer’s review article, “Can Destroying Senescent Cells Treat Age-Related Disease?” The Scientist, March 2020,–67136.

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Animal studies have also shown a more direct tie between zombie cells and aging: Ibid. Also see Megan Scudellari’s article “To Stay Young, Kill Zombie Cells,” Nature 550 (October 2017): 448–50,

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a natural plant compound (polyphenol) called “fisetin” reduces the level of these damaged zombie cells in the body: See Matthew J. Yousefzadeh, et al., “Fisetin Is a Senotherapeutic that Extends Health and Lifespan,” EBioMedicine 36 (October 2018): 18–28. doi: 10.1016/j.ebiom.2018.09.015. Epub 2018 Sep 29.

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Studies show that body weight is more predictive of lifespan than height, breed, or breed group: See Lisa J. Wallis, et al., “Demographic Change Across the Lifespan of Pet Dogs and Their Impact on Health Status,” Front Vet Sci 5 (August 2018): 200. doi: 10.3389/fvets.2018.00200. eCollection 2018.

was among the first scientists to connect serum IGF-1, body size, and age in the domestic dog more than a decade ago: Kimberly A. Greer, Larry M. Hughes, and Michal M. Masternak, “Connecting Serum IGF-1, Body Size, and Age in the Domestic Dog,” Age (Dordr) 33, no. 3 (September 2011): 475–83. doi: 10.1007/s11357-010-9182-4. Epub 2010 Sep 24.

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The condition is known as Laron syndrome, named after Zvi Laron: See Zvi Laron, “Lessons from 50 Years of Study of Laron Syndrome,” Endocr Pract 21, no. 12 (December 2015): 1395–402. doi: 10.4158/EP15939.RA. Epub 2015 Sep 24.

Larger dogs also tend to grow faster, which could result in what scientists at the Dog Aging Project call “jerry-built bodies”: Go to

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Studies also indicate that the earlier a puppy is spayed or neutered, the greater the likelihood of health problems: See Benjamin L. Hart, Lynette A. Hart, Abigail P. Thigpen, and Neil H. Willits, “Assisting Decision-Making on Age of Neutering for 35 Breeds of Dogs: Associated Joint Disorders, Cancers, and Urinary Incontinence,” Front Vet Sci 7 (July 2020): 388. doi: 10.3389/fvets.2020.00388. eCollection 2020.

Elinor Karlsson, PhD, is among the scientists participating: Go to

Over at the National Human Genome Research Institute in Maryland, the Dog Genome Project: Go to the National Human Genome Research Institute to access the NHGRI Dog Genome Project at

a mutation in the dog genome that causes narcolepsy: See Ryan K. Tisdale, Akihiro Yamanaka, and Thomas S. Kilduff, “Animal Models of Narcolepsy and the Hypocretin/Orexin System: Past, Present, and Future,” Sleep (December 2020): zsaa278. doi: 10.1093/sleep/zsaa278. Online ahead of print.

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resulting in lipid peroxidation, the production of toxic substances called “advanced lipoxidation end products” (ALEs), which also bind to the same receptors, inciting more RAGE:  See Marco Mol, et al., “Advanced Lipoxidation End Products (ALEs) as RAGE Binders: Mass Spectrometric and Computational Studies to Explain the Reasons Why,” Redox Biol 23 (May 2019): 101083. doi: 10.1016/j.redox.2018.101083. Epub 2018 Dec 18.

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from pancreatitis and liver dysfunction to immune dysregulation: See Martina Podborska, et al., “Increased Markers of Oxidative Stress in Plasma of Patients with Chronic Pancreatitis,” Neuro Endocrinol Lett 30, Suppl 1 (2009): 116–20. Also see: Carolina M. Perdomo, Gema Frühbeck, and Javier Escalada, “Impact of Nutritional Changes on Nonalcoholic Fatty Liver Disease,” Nutrients 11, no. 3 (March 2019): 677. doi: 10.3390/nu11030677. Also see: Saja, et al., “Triglyceride-Rich Lipoproteins Modulate the Distribution and Extravasation of Ly6C/Gr1low Monocytes,” Cell Reports (September 2015). doi: 10.1016/j.celrep.2015.08.020.

dogs consume up to 122 times the AGEs in their diets as humans: See Malgorzata Teodorowicz, Wouter H. Hendriks, Harry J. Wichers, and Huub F. J. Savelkoul, “Immunomodulation by Processed Animal Feed: The Role of Maillard Reaction Products and Advanced Glycation End-Products (AGEs),” Front Immunol 9 (September 2018): 2088. doi: 10.3389/fimmu.2018.02088. eCollection 2018.

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with scary results that have sometimes resulted in pet food recalls: See Lisa Fletcher’s “FDA to Investigate After ABC7 Exposes Euthanasia Drug in Dog Food,” February 6, 2018,

Take a look at the graphic below, which shows the pet food recalls: See Susan Thixton, “When Second Place Is Very Bad” at, May 14, 2019,

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James Spratt was the first to manufacture a dried dog biscuit food: The internet is ablaze with stories about James Spratt. One place to start is at, “The History of Commercial Pet Food: A Great American Marketing Story,” March 1, 2017, You can also read about the history of pet food at the Pet Food Institute (

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if it worked for dentists and toothpaste, why not vets and dog food?: For a great read on the “doctor-approved” dog food brands, see Tara Parker-Pope’s piece (“Colgate Gives Doctors Treats For Plugging Its Food Brands”) for The Wall Street Journal, November 3, 1997.

The go to NRC reference has been updated once, in 2006: See Also see:

All sorts of corporate marriages and divorces have occurred since the budding pet food industry was born a little over one hundred years ago: keeps track of revenue from leading pet food companies.

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One of the most intriguing areas of research today is in epigenetics: For a primer on epigenetics, go to,

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We can change the expression of many genes
: See Payel Sen, et al., “Epigenetic Mechanisms Regulating Longevity and Aging,” Cell 166, no. 4 (August 2016): 822–39. doi: 10.1016/j.cell.2016.07.050.

three stages of healing called the “cell danger response” (CDR): See Robert K Naviaux, “Metabolic Features of the Cell Danger Response,” Mitochondrion 16 (May 2014): 7–17. doi: 10.1016/j.mito.2013.08.006. Epub 2013 Aug 24.

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One genetic nutrient-sensing “switch” that has been a center of attention in research circles lately is mTOR: For a comprehensive read about mTOR and autophagy see James Clement, The Switch: Ignite Your Metabolism with Intermittent Fasting, Protein Cycling, and Keto (New York: Gallery, 2019).

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The “R” in mTOR represents, as noted above, represents rapamycin, a compound that’s actually produced by a bacterium: Again, for a comprehensive read about mTOR and autophagy see James Clement, The Switch: Ignite Your Metabolism with Intermittent Fasting, Protein Cycling, and Keto (New York: Gallery, 2019).

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Dogs manifest a broad range of cancers: See Brian W. Davis and Elaine A. Ostrander, “Domestic Dogs and Cancer Research: A Breed-based Genomics Approach,” ILAR J 55, no. 1 (2014): 59–68. doi: 10.1093/ilar/ilu017.

Cancer is a complex disease in both humans and dogs: Go to

if you transplant the mitochondria from a cancerous cell into a normal cell, the cell becomes cancerous: See Thomas N. Seyfried, “Cancer as a Mitochondrial Metabolic Disease,” Front Cell Dev Biol 3 (July 2015): 43. doi: 10.3389/fcell.2015.00043. eCollection 2015.

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A Finnish study shows 72.5 percent of dogs display at least one form of anxiety: See Milla Salonen, et al., “Prevalence, Comorbidity, and Breed Differences in Canine Anxiety in 13,700 Finnish Pet Dogs,” Sci Rep 10, no. 1 (March 2020): 2962. doi: 10.1038/s41598-020-59837-z.

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8 percent of dog owners and 6 percent of cat owners gave medications to their pets for anxiety: See Packaged Facts, “Pet Medications in the U.S., 5th Edition,” August 5, 2017, pub ID: LA15184172. Also see: Nathanial Morris, “Does Your Pet Really Need Prozac?” The Washington Post, April 28, 2018,

A 2019 UK survey of dog owners revealed 76 percent of people wanted to change one or more of their dogs’ behaviors: See Jane Katherine Murray, et al., “ ‘Generation Pup’ – Protocol for a Longitudinal Study of Dog Behavior and Health,” BMC Vet Res 17, no. 1 (January 2021): 1. doi: 10.1186/s12917-020-02730-8.

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Most charts that show a dog’s age also factor size into the equation: See “How to Calculate Dog Years to Human Years,” American Kennel Club, November 20, 2019,

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Pioneered by geneticist Dr. Steve Horvath at UCLA, the epigenetic clock relies on the body’s epigenome: See Steve Horvath and Kenneth Raj, “DNA Methylation-based Biomarkers and the Epigenetic Clock Theory of Ageing,” Nat Rev Genet 19, no. 6 (June 2018): 371–84. doi: 10.1038/s41576-018-0004-3.

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Top Epigenome Triggers: To access a library of research and reviews on epigenomics, see Nature’s entry on the subject at

A 2019 study by researchers at the University of California, San Diego, proposed this new clock: See Heather Buschman, “How Old Is Your Dog in Human Years? Scientists Develop Better Method than ‘Multiply by 7,’ ” UC San Diego News Center, July 2, 2020. Also see Tina Wang, et al., “Quantitative Translation of Dog-to-Human Aging by Conserved Remodeling of the DNA Methylome,” Cell Systems (2020). doi: 10.1016/j.cels.2020.06.006.

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Amyloid and Aging: See C. C. Rowe, et al., “Imaging Beta-amyloid Burden in Aging and Dementia,” Neurology 68, no. 20 (May 2007): 1718–25. doi: 10.1212/01.wnl.0000261919.22630.ea. Also see: Victor L Villemagne, et al., “Aβ-amyloid and Tau Imaging in Dementia,” Semin Nucl Med 47, no. 1 (January 2017): 75–88. doi: 10.1053/j.semnuclmed.2016.09.006. Epub 2016 Oct 13.

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Single nucleotide polymorphisms (SNPs) represent variations in DNA sequences: For a general review of SNPs, go to and search for “What are single nucleotide polymorphisms (SNPs)?”