Translation of Dog Years Into Human Years Updated With Epigenetic Analysis
10.07.2020For every year a human ages, a dog is said to age seven, but an epigenetics study by researchers from the University of California, San Diego has found that the relationship between the two is not linear.
By analyzing the DNA methylomes of about 100 dogs and comparing them to human methylomes, the researchers developed a new formula to gauge aging in dogs based on epigenetic changes that arise over time, with many of the changes affecting developmental genes. As they reported in Cell Systems on Thursday, they found that humans and dogs don't age at the same rate, as dogs age more quickly while young than people do.
"I have a six-year-old dog — she still runs with me, but I'm now realizing that she's not as 'young' as I thought she was," senior author Trey Ideker from UCSD said in a statement.
He and his colleagues developed an approach they dubbed synteny bisulfite sequencing (SysBS) to characterize CpGs within the dog genome that are syntenic with CpGs captured by Illumina human methylome arrays. SysBS, they reported, captures 90,000 CpGs out of the 232,000 conserved CPGs in the Illumina array.
Using this approach, the researchers characterized the methylomes of 104 dogs, mostly Labrador retrievers, that ranged in age from 0.1 to 16 years. At the same time, they amassed previously published methylation profiles derived from the blood of 320 humans between the ages of 1 and 103 years old.
The methylomes of young dogs and young humans and the methylomes of older dogs and older humans were most similar, suggesting conservation of methylation changes across species.
However, the epigenetic changes that occur in both dogs and humans take place more quickly in dogs, the researchers noted, with dogs aging more rapidly in their early years but then more slowly in their later years.
The relationship between human and dog ages follows a natural logarithmic function, the researchers found.
The formula they developed corresponds with different developmental milestones. For instance, an eight-week-old puppy is equivalent to a nine-month-old baby, which is about when both begin to lose their baby teeth, and a 12-year-old dog is equivalent to a 70-year-old human, reflecting the expected life spans of both Labrador retrievers and humans worldwide.
The methylation of nearly 400 genes changes over time and clusters into network modules enriched for developmental functions. Four of these modules accumulated increased methylation with age and were associated with synapse assembly, neuroepithelial cell differentiation, and anatomical patterning.
The researchers cautioned, though, that their analysis focused on one dog breed and that analyzing other breeds with different expected life spans could yield slightly different clocks. But as they also extended this formula to predict age in mice, they suspect it may work across dog breeds.
They plan to next test other dog breeds as well as other sample types like saliva, rather than the whole-blood samples they analyzed in this study.
In the future, this could help efforts aimed at combating aging. "There are a lot of anti-aging products out there these days — with wildly varying degrees of scientific support," Ideker added. "But how do you know if a product will truly extend your life without waiting 40 years or so? What if you could instead measure your age-associated methylation patterns before, during, and after the intervention to see if it's doing anything?"
