New Research Highlights Role of DNA Expression Regulation in Longevity Across Mammal Species

Published: Monday, October 18, 2021, 2:30 p.m. U.S. Eastern Time

Media Contact: Kara Flynn, 202.257.8424,

ROCKVILLE, MD – Small changes in the regulatory mechanisms of DNA expression show correlations with chronological age, sex, and lifespan, according to new research presented at the American Society of Human Genetics 2021 Annual Meeting.  These findings open new avenues for studying longevity and further our understanding of the role of epigenetics in mammalian evolution and biologic processes involved in aging and lifespan.

Epigenetic changes, unlike genetic changes, affect the way genes work without changing the DNA sequence. One common epigenetic mechanism used by cells to control gene activity involves the methylation of specific DNA letters. DNA methylation levels change with age and have been linked to longevity in many animal models. Now, a team led by Amin Haghani, PhD, a geneticist at the University of California, Los Angeles, reports the results of an investigation into DNA methylation across more than 200 mammalian species, ranging from the small and short-lived to the massive and long-lived. Analyses of this dataset allowed the researchers to identify correlations between DNA methylation and various traits within and across species of mammals, such as chronological age, sex, and maximum lifespan.

Dr. Haghani and his colleague Steve Horvath, PhD, profiled DNA methylation patterns from more than 14,000 tissue samples of different age ranges from 200 mammalian species. The species included animals with short lifespans (mice and rats) as well as longer-lived species (bats and whales). Machine learning analysis of this dataset allowed the researchers to identify methylation patterns that correlated with various traits within and across species, such as chronological age, sex, maximum lifespan, and adult body weight.

The researchers also identified new epigenetic biomarkers of longevity that were changed by known anti-aging interventions in mice (such as caloric restriction or removal of the growth hormone receptor). Future research could elucidate the role of these biomarkers in longevity and mortality risk in mammals.

In addition, similar to phylogenetic trees that diagram the evolutionary relationships among different species, Drs. Haghani and Horvath constructed phyloepigenetic trees that incorporate this epigenetic information. The phyloepigenetic trees illustrated stable and consistent differences in DNA methylation levels and paralleled the evolutionary distances among types of species established genetically for phylogenetic trees. The high similarity between the phyloepigenetic and phylogenetic trees indicates that the conservation and divergence of DNA methylation profiles closely parallels that of genetics through evolution.

“This new cross-species epigenetic analysis has uncovered important targets for future experimental studies of aging and longevity,” said Dr. Haghani. “Our ultimate goal is to understand the mechanisms of aging and to translate this knowledge to humans.

“How can we break the lifespan barrier in humans? What anti-aging interventions could actually increase our lifespan? The DNA methylation patterns we have identified form a roadmap to addressing many fundamental questions about evolution and aging.”

Media Interest: To learn more about Dr. Haghani’s work or set up an interview, please contact to coordinate.

Reference: Haghani, A. and Horvath, S. (October 18, 2021). Abstract: DNA methylation patterns underlying lifespan differences in mammals. Presented at the American Society of Human Genetics 2021 Annual Meeting.

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Founded in 1948, the American Society of Human Genetics is the primary professional membership organization for human genetics specialists worldwide. Its nearly 8,000 members include researchers, academicians, clinicians, laboratory practice professionals, genetic counselors, nurses, and others with an interest in human genetics. The Society serves scientists, health professionals, and the public by providing forums to: (1) share research results through the ASHG Annual Meeting and in The American Journal of Human Genetics and Human Genetics and Genomics Advances; (2) advance genetic research by advocating for research support; (3) educate current and future genetics professionals, health care providers, advocates, policymakers, educators, students, and the public about all aspects of human genetics; and (4) promote genetic services and support responsible social and scientific policies. For more information, visit:

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