Biology subjects

The Dog Aging Project Consortium,

Publications and source records attributed to The Dog Aging Project Consortium,.

3 recordsLinked to original sources

bioRxiv2024

DNA methylation of transposons pattern aging differences across a diverse cohort of dogs from the Dog Aging Project

Within a species, larger individuals often have shorter lives and higher rates of age-related disease. Despite this well-known link, we still know little about underlying age-related epigenetic differences, which could help us better understand inter-individual variation in aging and the etiology, onset, and progression of age-associated disease. Dogs exhibit this negative correlation between size, health, and longevity and thus represent an excellent system in which to test the underlying mechanisms. Here, we quantified genome-wide DNA methylation in a cohort of 864 dogs in the Dog Aging Project. Age strongly patterned the dog epigenome, with the majority (66% of age-associated loci) of regions associating age-related loss of methylation. These age effects were non-randomly distributed in the genome and differed depending on genomic context. We found the LINE1 (long interspersed elements) class of TEs (transposable elements) were the most frequently hypomethylated with age (FDR < 0.05, 40% of all LINE1 regions). This LINE1 pattern differed in magnitude across breeds of different sizes- the largest dogs lost 0.26% more LINE1 methylation per year than the smallest dogs. This suggests that epigenetic regulation of TEs, particularly LINE1s, may contribute to accelerated age and disease phenotypes within a species. Since our study focused on the methylome of immune cells, we looked at LINE1 methylation changes in golden retrievers, a breed highly susceptible to hematopoietic cancers, and found they have accelerated age-related LINE1 hypomethylation compared to other breeds. We also found many of the LINE1s hypomethylated with age are located on the X chromosome and are, when considering X chromosome inactivation, counter-intuitively more methylated in males. These results have revealed the demethylation of LINE1 transposons as a potential driver of intra-species, demographic-dependent aging variation.

genomics↗

bioRxiv2024

Aging at scale: Younger dogs and larger breeds from the Dog Aging Project show accelerated epigenetic aging.

Dogs exhibit striking within-species variability in lifespan, with smaller breeds often living more than twice as long as larger breeds. This longevity discrepancy also extends to health and aging-larger dogs show higher rates of age-related diseases. Despite this well-established phenomenon, we still know little about the biomarkers and molecular mechanisms that might underlie breed differences in aging and survival. To address this gap, we generated an epigenetic clock using DNA methylation from over 3 million CpG sites in a deeply phenotyped cohort of 864 companion dogs from the Dog Aging Project, including some dogs sampled annually for 2-3 years. We found that the largest breed size tends to have epigenomes that are, on average, 0.37 years older per chronological year compared to the smallest breed size. We also found that higher residual epigenetic age was significantly associated with increased mortality risk, with dogs experiencing a 34% higher risk of death for each year increase in residual epigenetic age. These findings not only broaden our understanding of how aging manifests within a diverse species but also highlight the significant role that demographic factors play in modulating the biological mechanisms underlying aging. Additionally, they highlight the utility of DNA methylation as both a biomarker for healthspan-extending interventions, a mortality predictor, and a mechanism for understanding inter-individual variation in aging in dogs.

genomics↗

bioRxiv2022

Dog Size and Patterns of Disease History Across the Canine Age Spectrum: Results from the Dog Aging Project

Age in dogs is associated with the risk of many diseases, and canine size is a major factor in that risk. However, the size effect is not as simple as the age effect. While small size dogs tend to live longer, some diseases are more prevalent among small dogs. Utilizing owner-reported data on disease history from a substantial number of companion dogs, we investigate how body size, as measured by weight, associates with the prevalence of a reported condition and its pattern across age for various disease categories. We found significant positive associations between weight and prevalence of skin, bone/orthopedic, gastrointestinal, ear/nose/throat, cancer/tumor, brain/neurologic, endocrine, and infectious diseases. Similarly, weight was negatively associated with the prevalence of eye, cardiac, liver/pancreas, and respiratory disease categories. Kidney/urinary disease prevalence did not vary by weight. We also found that the association between age and disease prevalence varied by dog size for many conditions including eye, cardiac, orthopedic, ear/nose/throat, and cancer. Controlling for sex, purebred/mixed breed, and geographic region made little difference in all disease categories we studied. Our results align with the reduced lifespan in larger dogs for most of the disease categories but suggest potential avenues for further examination.

physiology↗