Scientists use ancient virus to create ‘retroage’ clock DNA The discovery of markers that can predict biological age has provided new insight into aging, which may lead to new anti-aging therapies.
Researchers at Weill Cornell Medicine, in collaboration with epigenetics company TruDiagnostic, have identified DNA markers linked to retroelements, ancient viral genes that persist in our genes and act 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 affect gene regulation, gene expression, genomic stability, and the progression of various human diseases, but their potential as biomarkers of aging has been largely unexplored.
The study, published in the journal Aging Cell, concludes that these retroelement clocks embedded in the human genome capture unique signals of aging that have not previously been recognized in other clocks that measure chronological age. Most aging clocks estimate a person’s biological age based on patterns of epigenetic markers – chemical tags called methyl groups that attach to DNA and influence gene expression. The methylation patterns of retroelements appear 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, and researchers are seeking reliable markers that can predict biological age. Biological age is a snapshot of a person’s age at a biochemical level that impacts health and overall well-being, while chronological age represents the number of years a person has lived. Depending on the individual, the two may not correlate.
Constructing an aging clock based on retroelements
The researchers Machine Learning The researchers used TruDiagnostic’s model to analyze epigenetic data from 12,670 individuals aged between 12 and 100 years old. They used the resulting DNA methylation patterns of retroelements, specifically human endogenous retroviruses (HERVs) and long interspersed nuclear elements (LINEs), to develop a composite retroelement age clock they called “Retro-Age.”
“Retro-Age provides deeper insight and a new perspective on the aging process, creating a potentially powerful tool for predicting biological age,” said lead author Lishomwa Ndlovu, PhD, the Herbert J. and Anne L. Siegel Professor Emeritus in the Department of Infectious Diseases at Weill Cornell College of Medicine.
The researchers found that the retroage clock was accurate when examined across a range of human tissues, complemented existing epigenetic clocks, and could be extended to other mammals. seedTheir findings suggest that retroelement activity may be a fundamental aspect of ageing in a range of species.
Turning back the clock – the impact 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 the antiretroviral therapy that HIV-infected individuals receive. HIV infection accelerates epigenetic aging, while antiretroviral therapy appears to turn back the clock to some extent. This suggests that the activity of retroelements is influenced by both the infection and its treatment, influencing the biological aging process in HIV-infected individuals.
“Reactivation of certain retroelements increases with age and can lead to biological hallmarks of aging, such as inflammation, cellular senescence and genomic instability,” said corresponding author Michael Corey, PhD, assistant professor of medicine and immunology in the Department of Infectious Diseases at Weill Cornell Medical College. “Our findings indicate that the retroelement clock captures a previously undetected aspect of biological aging that may pave the way for future treatments for these and other age-related diseases.”
The researchers said that monitoring retroelement activity could help track the effectiveness of anti-aging therapies, the health status of older adults, and the impact of lifestyle changes on biological ageing.
Dr. Ndhlovu and Dr. Corley plan to explore new therapies and interventions for age-related diseases by targeting the epigenetic state of specific retroelements in the human genome. This approach, they note, may ultimately reverse or mitigate the biological effects of aging, improving an individual’s healthspan and lifespan.
Reference: “RetroAGE: A unique epigenetic biomarker of aging captured by DNA methylation status of retroelements” by Lishomwa C. Ndhlovu, Matthew L. Bendall, Varun Dwaraka, Alina PS Pang, Nicholas Dopkins, Natalia Carreras, Ryan Smith, Douglas F. Nixon, Michael J. Corley, August 2, 2024, Aging Cell.
DOI: 10.1111/acel.14288
The study reported in this article National Institutes of Healthand received grants R01AG082056, R01HL160392, R01MH134391, and UM1AI164559 (ACEL14288).
