Researchers at Weill Cornell Medicine, in collaboration with the epigenetics company TruDiagnostic, have identified specific DNA markers within retroelements—ancient viral sequences integrated into our genome—that serve as highly accurate predictors of chronological age. This study, published in Aging Cell, suggests that these retroelements may play a significant role in the aging process, a possibility that had previously been underexplored.
Retroelements and Aging
Retroelements, known for influencing gene regulation, expression, and genomic stability, have now been linked to the aging process through their potential as biomarkers. The study introduces a new type of aging clock based on the methylation patterns of retroelements, which change as individuals age. These changes may drive genomic instability, inflammation, and age-related diseases by altering gene activity.
Most aging clocks estimate biological age by analyzing epigenetic markers—methyl groups attached to DNA that influence gene expression. However, this new research demonstrates that retroelement-based clocks, termed "Retro-Age," capture aging signals that have been missed by traditional methods.
Developing the Retro-Age Clock
The research team employed a machine learning model from TruDiagnostic to analyze epigenetic data from 12,670 individuals, aged 12 to 100. They focused on two specific types of retroelements: human endogenous retroviruses (HERVs) and long interspersed nuclear elements (LINEs). The composite clock they developed, Retro-Age, uses these methylation patterns to provide a novel and precise measure of biological age.
Lishomwa Ndhlovu, the study's first author and a professor of immunology at Weill Cornell Medicine, highlighted the potential of this new tool, stating, "Now, with Retro-Age, we have greater insight and a fresh perspective into the aging process and a potentially powerful tool to predict biological age."
Testing and Implications
The Retro-Age clock showed high accuracy across various human tissues and even extended its relevance to other mammalian species. This finding suggests that retroelement activity might be a fundamental aspect of aging not only in humans but across different species.
Environmental Factors and Epigenetic Aging
The study also explored how external factors, such as antiretroviral therapy in people living with HIV, influence retroelement methylation patterns. HIV infection accelerates epigenetic aging, but antiretroviral therapy can partially reverse this effect. This suggests that retroelement activity—and consequently, biological aging—can be modulated by environmental factors.
Michael Corley, a co-author of the study and an assistant professor of immunology at Weill Cornell Medicine, noted, "The reactivation of specific retroelements increases with age, potentially leading to biological hallmarks of aging such as inflammation, cellular senescence, and genomic instability." He added that retroelement clocks could capture previously undetected aspects of biological aging, offering potential avenues for future therapeutic interventions.
Future Directions
The researchers plan to explore therapeutic strategies targeting the epigenetic states of retroelements to potentially reverse or mitigate the effects of aging. This approach could lead to new treatments for age-related diseases and contribute to extending both the health span and lifespan of individuals.
Original Publication
Ndhlovu, L. C., Bendall, M. L., Dwaraka, V., Pang, A. P. S., Dopkins, N., Carreras, N., Smith, R., Nixon, D. F., & Corley, M. J. (2024). Retro-age: A unique epigenetic biomarker of aging captured by DNA methylation states of retroelements. Aging Cell, 00, e14288. https://doi.org/10.1111/acel.14288
Retroelements and Aging
Retroelements, known for influencing gene regulation, expression, and genomic stability, have now been linked to the aging process through their potential as biomarkers. The study introduces a new type of aging clock based on the methylation patterns of retroelements, which change as individuals age. These changes may drive genomic instability, inflammation, and age-related diseases by altering gene activity.
Most aging clocks estimate biological age by analyzing epigenetic markers—methyl groups attached to DNA that influence gene expression. However, this new research demonstrates that retroelement-based clocks, termed "Retro-Age," capture aging signals that have been missed by traditional methods.
Developing the Retro-Age Clock
The research team employed a machine learning model from TruDiagnostic to analyze epigenetic data from 12,670 individuals, aged 12 to 100. They focused on two specific types of retroelements: human endogenous retroviruses (HERVs) and long interspersed nuclear elements (LINEs). The composite clock they developed, Retro-Age, uses these methylation patterns to provide a novel and precise measure of biological age.
Lishomwa Ndhlovu, the study's first author and a professor of immunology at Weill Cornell Medicine, highlighted the potential of this new tool, stating, "Now, with Retro-Age, we have greater insight and a fresh perspective into the aging process and a potentially powerful tool to predict biological age."
Testing and Implications
The Retro-Age clock showed high accuracy across various human tissues and even extended its relevance to other mammalian species. This finding suggests that retroelement activity might be a fundamental aspect of aging not only in humans but across different species.
Environmental Factors and Epigenetic Aging
The study also explored how external factors, such as antiretroviral therapy in people living with HIV, influence retroelement methylation patterns. HIV infection accelerates epigenetic aging, but antiretroviral therapy can partially reverse this effect. This suggests that retroelement activity—and consequently, biological aging—can be modulated by environmental factors.
Michael Corley, a co-author of the study and an assistant professor of immunology at Weill Cornell Medicine, noted, "The reactivation of specific retroelements increases with age, potentially leading to biological hallmarks of aging such as inflammation, cellular senescence, and genomic instability." He added that retroelement clocks could capture previously undetected aspects of biological aging, offering potential avenues for future therapeutic interventions.
Future Directions
The researchers plan to explore therapeutic strategies targeting the epigenetic states of retroelements to potentially reverse or mitigate the effects of aging. This approach could lead to new treatments for age-related diseases and contribute to extending both the health span and lifespan of individuals.
Original Publication
Ndhlovu, L. C., Bendall, M. L., Dwaraka, V., Pang, A. P. S., Dopkins, N., Carreras, N., Smith, R., Nixon, D. F., & Corley, M. J. (2024). Retro-age: A unique epigenetic biomarker of aging captured by DNA methylation states of retroelements. Aging Cell, 00, e14288. https://doi.org/10.1111/acel.14288