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.

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:

Methylation, as evidenced by the epigenetic “marks” it leaves, bears a substantial correlation with maximum life span across mammalian species. Looking at methylation profiles on the DNA molecule as terrain with peaks and troughs, Horvath commented that species with long lives have prominent peaks and valleys, developed during extended gestation and development periods. In contrast, short-lived species have short gestation periods and rapid development, resulting in cells with a flatter, less-defined methylation landscape.
Maximum life span of a species is associated with specific developmental processes, as suggested by the involvement of certain genes and genetic transcription factors.
Cytosines whose methylation levels correlate with maximum life span differ from those that change with chronological age, suggesting that molecular pathways pertaining to average life span within a species are distinct from those determining the species’ maximum life span.
Evolution acts not only at the genetic level, but also at the epigenetic level. “Our results demonstrate that DNA methylation is subjected to evolutionary pressures and selection,” said the authors, whose database has been made public for other researchers.

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.

Source: https://www.uclahealth.org/news/ucla-researchers-lead-groundbreaking-studies-mammalian-aging