The conventional wisdom that every year in a dog’s life equates to seven human years is wrong, according to a paper published in the journal Cell Systems. The study authors have devised a formula to calculate a dog’s age based on the chemical changes in DNA as organisms grow old.
Wang et al created an oligo-capture system to characterize the dog DNA methylome, targeting syntenic regions of the genome conserved across all mammals. Image credit: Ideker Lab, University of California, San Diego.
Dogs share the same environment as their owners and receive almost the same standard of health care as humans, providing a unique opportunity for scientists to understand aging across species.
Like humans, dogs follow similar developmental trajectories that lead them to grey and become more susceptible to age-related diseases over time.
However, how they age on a molecular level is more complicated — aging rapidly at first and slowing down later in life.
“In terms of how physiologically mature a one-year-old dog is, a 9-month-old dog can have puppies. Right away, you know that if you do the math, you don’t just times seven,” said study senior author Dr. Trey Ideker, a researcher at the University of California, San Diego.
“What’s surprising is exactly how old that one-year-old dog is — it’s like a 30-year old human.”
Human and dog DNA don’t change much throughout the course of life, but chemical marks on DNA, called methylation marks, do.
Dr. Ideker and colleagues considers these marks like wrinkles in the genome.
“I tend to think of it very much like when you look at someone’s face and guess their age based on their wrinkles, gray hair, and other features. These are just similar kinds of features on the molecular level,” Dr. Ideker said.
The researchers studied 104 Labrador retrievers spanning a 16-year age range and compared the changes in the methylation pattern to humans.
The comparison revealed a new formula that better matches the canine-human life stages:
Human age = 16 ln(dog age) + 31
Based on the new function, an 8-week-old dog is approximately the age of a 9-month-old baby, both being in the infant stage where puppies and babies develop teeth.
The average 12-year lifespan of Labrador retrievers also corresponds to the worldwide life expectancy of humans, 70 years.
In both species, the scientists found that the age-driven methylation largely happens in developmental genes that are hotly fired up to create body plans in utero and regulating childhood development.
“By the time one becomes an adult and stops growing, you’ve largely shut off these genes, but they’re still smoldering,” Dr. Ideker said.
“If you look at the methylation marks on those developmental genes, they’re still changing.”
Focusing on the smoldering developmental genes, the authors developed a clock that can measure age and physiological states across different species, while other methylation-quantifying age-predicting methods only do well in one species.
“Future investigation in different dog breeds with various lifespans could provide more insight into the new clock,” Dr. Ideker said.
“The clock may not only serve as a tool to understand cross-species aging but also apply as clinical practice for veterinarians to take proactive steps to treat animals.”
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Tina Wang et al. 2020. Quantitative Translation of Dog-to-Human Aging by Conserved Remodeling of the DNA Methylome. Cell Systems 11: 1-10; doi: 10.1016/j.cels.2020.06.006
