Scientists have recreated the “retro-age” clock using old viral DNA Markers for predicting biological age that provide new insights into aging. This discovery could lead to novel anti-aging therapies.

Researchers at Weill Cornell Medicine, in collaboration with epigenetics company TruDiagnostic, have identified DNA markers linked to retroelements – ancient viral genetic remnants in our genes – that serve as highly accurate epigenetic clocks to predict chronological age. These findings suggest that certain retroelements in the human genome may play a role in the aging process.

Retroelements are known to influence gene regulation, gene expression, genomic stability and the progression of various human diseases, but their potential as biomarkers for aging has been largely unexplored.

The study was published in the journal Ageing cellconcluded that these retroelement clocks embedded in the human genome capture unique signals of aging that have not previously been detected by other clocks used to measure chronological age. Most aging clocks estimate a person’s biological age based on patterns of epigenetic markers – chemical tags called methyl groups that are attached to DNA and affect the expression of genes. The methylation pattern of retroelements appears to change with age, causing some genes to become more active, which may lead to genomic instability, inflammation, and age-related diseases.

Aging is a complex process influenced by genetic, environmental and epigenetic factors. Researchers are looking for reliable markers that can predict biological age – a snapshot of a person’s age at the biochemical level that impacts health and overall well-being. Chronological age, on the other hand, indicates the number of years a person has lived. Depending on the person, the two may not correlate.

Construction of an aging clock based on retro elements

The researchers used a machine learning TruDiagnostic’s model for analyzing epigenetic data from 12,670 individuals between the ages of 12 and 100. Using the resulting DNA methylation patterns of retroelements, specifically human endogenous retrovirus (HERV) and long interspersed nuclear elements (LINEs), they developed a composite retroelement age clock called “Retro-Age.”

“With Retro-Age, we now have a deeper insight and a new perspective on the aging process, as well as a potentially powerful tool for predicting biological age,” said lead author Dr. Lishomwa Ndhlovu, Herbert J. and Ann L. Siegel Distinguished Professor of Medicine and professor of immunology in medicine in the Division of Infectious Diseases at Weill Cornell Medicine.

The researchers found that the retro-age clock remained accurate when examining various human tissues, complemented existing epigenetic clocks, and even extended to other mammalian species. speciesTheir results suggest that retroelement activity may be a fundamental aspect of aging in different species.

Turning back time – influence of environmental factors

The researchers also found that the DNA methylation patterns they observed not only predicted age but also responded to external factors such as antiretroviral therapy in HIV-infected individuals. HIV infection accelerates epigenetic aging, while antiretroviral therapy appears to turn back the clock to some extent. This suggests that retroelement activity is influenced by both the infection and its treatment, and impacts the biological aging process in HIV-infected individuals.

“Reactivation of certain retroelements increases with age, potentially leading to biological hallmarks of aging such as inflammation, cellular senescence and genomic instability,” said corresponding author Michael Corley, PhD, assistant professor of immunology in medicine in the Division of Infectious Diseases at Weill Cornell Medicine. “Our findings suggest that retroelement clocks capture previously undiscovered aspects of biological aging and could open the door to future treatments for this and other age-related diseases.”

Monitoring retroelement activity could help track the effectiveness of anti-aging therapies, the health status of the aging population and the impact of lifestyle changes on biological aging, the researchers said.

Dr. Ndhlovu and Dr. Corley aim to explore new treatments or therapeutic interventions for age-related diseases by targeting the epigenetic states of specific retroelements in the human genome. This approach, they noted, could ultimately reverse or mitigate the biological effects of ageing, thereby improving a person’s healthspan and lifespan.

Reference: “Retro-age: A unique epigenetic biomarker of aging captured by DNA methylation states of retroelements” by Lishomwa C. Ndhlovu, Matthew L. Bendall, Varun Dwaraka, Alina PS Pang, Nicholas Dopkins, Natalia Carreras, Ryan Smith, Douglas F. Nixon and Michael J. Corley, August 02, 2024, Ageing cell.
DOI: 10.1111/acel.14288

The research reported in this article was funded by the National Institutes of Healthwith grants R01AG082056, R01HL160392, R01MH134391 and UM1AI164559​(ACEL14288)​.