Researchers have discovered DNA markers linked to retroelements, which are vestiges of ancient viral DNA, within our genetic material. These markers function as precise epigenetic clocks, allowing for the prediction of an individual’s chronological age. The findings bolster the notion that certain retroelements in our genome may play a role in the aging process.
Scientists at Weill Cornell Medicine, alongside the epigenetics firm TruDiagnostic, have identified DNA markers tied to retroelements—traces of old viral genetic material—found in our genes. These markers serve as remarkably accurate epigenetic clocks, enabling predictions of chronological age. This research supports the hypothesis that specific retroelements in the human genome may contribute to the aging process.
Retroelements are known to influence various aspects, such as gene regulation, gene expression, genomic stability, and the progression of numerous human diseases. However, their potential as aging markers has largely gone unexplored.
The study, published on August 2 in Aging Cell, concluded that these retroelement clocks in the human genome capture distinct signals of aging that previous chronological age clocks did not recognize. Most existing aging clocks estimate biological age based on specific patterns of epigenetic markers—chemical tags known as methyl groups that are added to DNA and impact gene expression. The methylation patterns on retroelements appear to alter as individuals age, resulting in enhanced activity of certain genes, which may contribute to genomic instability, inflammation, and age-related health issues.
Aging is a multifaceted process influenced by genetic, environmental, and epigenetic factors. Researchers seek dependable markers that can accurately predict biological age—a measure of an individual’s age at a biochemical level that affects their health and overall well-being. In contrast, chronological age simply counts the number of years a person has lived. The two measures may not always align for different individuals.
Creating an Aging Clock with Retroelements
Utilizing a machine learning model provided by TruDiagnostic, scientists analyzed epigenetic information from 12,670 individuals aged between 12 to 100 years. By examining the resulting DNA methylation patterns in retroelements, particularly human endogenous retrovirus (HERV) and long interspersed nuclear elements (LINEs), they crafted a composite aging clock known as “Retro-Age.”
“With Retro-Age, we gain deeper insights and a renewed perspective on the aging process, along with a potentially effective tool for predicting biological age,” stated lead author Dr. Lishomwa Ndhlovu, the Herbert J. and Ann L. Siegel Distinguished Professor of Medicine and immunology professor in the Division of Infectious Diseases at Weill Cornell Medicine.
The researchers found that the accuracy of the Retro-Age clock persisted across different human tissues, supplemented existing epigenetic clocks, and even proved applicable to other mammalian species. Their findings suggest that retroelement activity could be a fundamental component of aging across various species.
Reversing the Effects of Aging—The Role of Environmental Factors
The researchers also noted that the observed DNA methylation patterns were not only indicative of age but also responsive to external factors, such as antiretroviral therapy used by individuals living with HIV. The presence of HIV accelerates epigenetic aging, whereas antiretroviral therapy seems to partially reverse the effects of aging. This indicates that retroelement activity is shaped by both the infection and its treatment, influencing the biological aging process in HIV-positive individuals.
“The reactivation of specific retroelements increases with age, potentially causing biological signs of aging such as inflammation, cellular senescence, and genomic instability,” explained corresponding author Dr. Michael Corley, assistant professor of immunology in medicine within the Division of Infectious Diseases at Weill Cornell Medicine. “Our research suggests that retroelement clocks capture previously unrecognized aspects of biological aging, which may pave the way for future therapies targeting these and other age-related issues.”
The monitoring of retroelement activity could aid in evaluating the effectiveness of anti-aging treatments, assessing health outcomes in aging populations, and understanding how lifestyle changes affect biological aging, the researchers advised.
Drs. Ndhlovu and Corley aim to investigate new treatments or therapeutic approaches for age-related diseases by focusing on the epigenetic states of specific retroelements in the human genome. They believe this strategy could eventually reverse or lessen the biological impacts of aging, enhancing both health span and longevity for individuals.
