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Dogs, Materials and Methods
•24 privately owned healthy mid-sized middle-aged dogs
(>16 kg, >6 years)
•Placebo-controlled double-blind randomized trial
•0.1 and 0.05 mg/kg rapamycin orally, 3 times per week for 10 weeks
•Full bloodwork at weeks 0, 3 and 11
•Heart ultrasound at weeks 0 and 11
Results
•Mild transient increase in water consumption reported
in some dogs in both the treatment and placebo groups.
•Rapamycin-treated dogs showed an improved E/A Ratio (P=0.026).
The E/A Ratio is known to deteriorate with age. [11,12]
•Rapamycin-treated dogs showed significantly improved fractional
shortening (FS; P=0.036) and improved ejection fraction(P=0.058),
which reflects findings in mice. [13]
•Observed changes in blood tests remained within normal limits.
•Blood tests were consistent with increased red blood cell survival:
•MCV was decreased in treatment vs. placebo (P=0.012); however,
RBC increased and HCT remained stable.
•Indications of metabolic changes:
•AST increased in the treatment group (P=0.032); however, ALT did
not, which points to changes in mitochondrial metabolism.
•TRI increased in low and decreased in high rapamycin (P=0.028).
•Indicators of immune function modulation:
•EOS (P=0.015) and LYM (P=0.01) decreased, WBC and PMN did not.
1Dog Aging Project, University of Washington Medicine Pathology, Seattle, WA, USA
2Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, USA
Discussion
•Rapamycin caused no significant side effects at the doses we used.
•Changes in blood parameters remained within normal limits.
•Rapamycin-treated dogs showed improved heart function.
•Pending full funding, we will conduct a longer term study on a larger
cohort of privately owned dogs that will allow us to compare mortality
between treatment and placebo groups.
•We expect rapamycin to show beneficial effects on healthy aging
similar to those documented for dietary restriction in dogs. [8]
•A 2 to 5 year increase in healthy lifespan in dogs is a realistic goal.
Rapamycin
•FDA approved immune modulator [2]
•Potent anti-aging effects in various model
organisms (yeast, worms, flies, mice) [3-6]
•Inhibits mTOR, which is also inhibited by reduced calorie intake [7,8]
•All lifespan studies thus far performed under laboratory conditions
The Domestic Dog
•Lives in the same environment as humans
•Receives comparable medical care [9]
•Shows lifespan and healthspan extension under dietary restriction [8]
•Gets many of the age-related diseases that we see in humans [9,10]
•Life- and healthspan extension in dogs would have multiple benefits:
•Delaying aging and age-related diseases in companion dogs is
beneficial and desirable in and of itself.
•Findings from a study in privately owned dogs are more
applicable to a human environment than studies in lab animals.
•Keeping working dogs in good health for longer would result in
substantial financial savings.
Aging
•Complex process involving many different
pathways and mechanisms, resulting in
loss of normal organ function
•Aging is the single most important risk
factor for a variety of diseases (cancer, heart
and kidney disease, cognitive decline etc.)
•Thus, Healthy Aging is the Ultimate Preventive
Medicine. [1]
Silvan R. Urfer1, Kate E. Creevy2, Tammi Kaeberlein1, Daniel E. Promislow1 and Matt Kaeberlein1
The Dog Aging Project
Rapamycin as a Potential Aging Modulator in Dogs
Aging
Cognitive
decline
Immune system
decline
Type 2
diabetes
Autoimmune
disease
Alzheimer’s
disease
Cancer
Heart
disease
Kidney
disease
Abstract
•Rapamycin reliably extends healthy lifespan in a wide
variety of model organisms.
•Dogs live in the same environment as humans and are a
better model than laboratory animals.
•We gave 24 privately owned dogs rapamycin (n=16) or
placebo (n=8) for 10 weeks:
•No substantial clinical side effects
•Improved heart function
•Signs of longer red blood cell survival
•We will study rapamycin in a larger cohort for a longer
time to test its effects on aging in dogs.
AST Difference
MCV Difference EOS Difference
RBC Difference ALT Difference LYM Difference
dogagingproject.com
urfers@uw.edu
Week 11
Baseline
TRI Difference
Baseline & Week 11
E/A Ratio Difference Baseline & Week 11
Green: Placebo
Orange: Rapa 0.05 mg/kg
Red: Rapa 0.1 mg/kg
FS Difference
Baseline & Week 11