Scientists at UCLA David Geffen School of Medicine and UCLA Health led an international research team that published two articles detailing changes in DNA -- changes that researchers found are shared by humans and other mammals throughout history and are associated with life span and numerous other traits.
"We've discovered that the life spans of mammals are closely associated with chemical modifications of the DNA molecule, specifically known as epigenetics, or more accurately, methylation. In essence, mammals with longer life spans exhibit more pronounced DNA methylation landscapes, whereas those of shorter-lived species have more subdued, flatter methylation patterns," said the senior author of both articles, Steve Horvath, PhD, ScD, an expert on the aging process and a professor in human genetics and biostatistics at UCLA at the time the studies were conducted.
Jason Ernst, a professor of biological chemistry, computer science, and computational medicine at UCLA, said, "The technology we designed to measure DNA methylation levels across mammals along with the tissue sample contributions from a large consortium of researchers led to the production of a highly unique data set, which, when analyzed with advanced computational and statistical tools, unveiled a deeper understanding of the relationship between DNA methylation, life span, aging, and other biological processes across mammals."
The studies, one published in Science and the other in Nature Aging, focus on DNA methylation, or cytosine methylation, a chemical modification of cytosine, one of the four building blocks of the DNA molecule.
DNA methylation is a mechanism by which cells can control gene expression -- turning genes on or off. In these studies, the researchers focused on DNA methylation differences across species at locations where the DNA sequence is generally the same.
To study the effects of DNA methylation, the nearly 200 researchers -- collectively known as the Mammalian Methylation Consortium -- collected and analyzed methylation data from more than 15,000 animal tissue samples covering 348 mammalian species. They found that changes in methylation profiles closely parallel changes in genetics through evolution, demonstrating that there is an intertwined evolution of the genome and the epigenome that influences the biological characteristics and traits of different mammalian species.
Among the Science study's findings:
Horvath and the consortium researchers used a subset of the database to study the methylation profiles of 185 species of mammals. Identifying changes in methylation levels that occur with age across all mammals, they developed a "universal pan-mammalian clock," a mathematical formula that can accurately estimate age in all mammalian species. Results of this study are published in Nature Aging.
Horvath and a UCLA team introduced the concept of an epigenetic clock for age measurement, using human saliva samples, in 2011. Two years later, Horvath demonstrated that cytosine methylation enables the creation of a mathematical model for estimating age across all human tissues. The new work, which describes universal clocks, demonstrates that a single formula can accurately estimate age across mammalian tissues and species.
Among the Nature Aging study's findings:
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