Summary: Researchers have developed “Retro-Age”, an epigenetic clock that predicts biological age by analyzing DNA markers of ancient viral remnants in the human genome. The study highlights how reactivation of retroelements such as HERVs and LINEs impacts aging, inflammation, and genome stability.
The findings suggest that monitoring these markers could help guide anti-aging therapies and improve health outcomes, especially in diseases such as HIV. The study also paves the way for the exploration of potential therapeutic approaches to reverse the biological effects of aging.
Key Facts:
A new epigenetic clock: “RetroAge” predicts biological age using DNA markers of ancient viral elements Impact on ageing: Retroelement activity is linked to inflammation and genomic instability in ageing Therapeutic potential: Findings could help guide anti-ageing treatments and monitor their effectiveness.
Source: Weill Cornell University
Researchers at Weill Cornell Medicine and epigenetics company True Diagnostics have discovered DNA markers in our genes linked to retroelements – remnants of ancient viral genetic material – that act as highly accurate epigenetic clocks that predict our chronological age.
The results support the idea that specific retroelements in the human genome may be involved in aging.
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 August 2 in the journal Aging Cell, concludes that these retroelement clocks embedded in the human genome capture a unique signal of aging that has not previously been recognized by 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 affect gene expression.
Methylation patterns of retroelements appear to change with age, with some genes becoming more active, potentially leading 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 used TruDiagnostic’s machine learning models 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 is accurate when examined in a range of human tissues, complements existing epigenetic clocks, and extends to other mammalian species. Their findings suggest that retroelement activity may be a fundamental aspect of aging 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 retroelement activity is influenced by both infection and its treatment, affecting the biological ageing process in HIV-infected individuals.
“Reactivation of certain retroelements increases with age and may lead to the 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 and may pave the way for future treatments for these and other age-related conditions.”
The researchers said monitoring retroelement activity could help track the effectiveness of anti-aging therapies, the health of ageing populations, and the impact of lifestyle changes on biological ageing.
Drs. Ndhlovu and Corley plan to explore new therapies and interventions for age-related diseases by targeting the epigenetic state of specific retroelements in the human genome. They note that this approach may ultimately reverse or mitigate the biological effects of aging, potentially extending an individual’s health and lifespan.
Funding: Research reported in this article was funded by National Institutes of Health grants R01AG082056, R01HL160392, R01MH134391, and UM1AI164559 (ACEL14288).
About this Genetics and Aging Research News
Author: Corinne Esposito
Source: Weill Cornell University
Contact: Corinne Esposito – Weill Cornell University
Image: This image is provided by Neuroscience News
Original research: Open Access.
“Retroage: A unique epigenetic aging biomarker captured by DNA methylation status of retroelements” by Lishomwa Ndhlovu et al., Aging Cell
Abstract
RETROAGE: A unique epigenetic biomarker of aging captured by DNA methylation status of retroelements
Reactivation of retroelements in the human genome has been linked to aging, but it is unclear whether the epigenetic state of specific retroelements can predict chronological age.
We provide evidence that locus-specific retroelement DNA methylation can be used to create a retroelement-based epigenetic clock that accurately measures chronological age in the immune system, across human tissues, and across mammalian species.
We also developed a high-precision retroelement epigenetic clock compatible with EPICv.2.0 data, constructed from CpGs that do not overlap with existing first- and second-generation epigenetic clocks, suggesting a unique signal of the epigenetic clock that has not been captured previously.
We found that the retroelement-based epigenetic clock is reversed during transient epigenetic reprogramming and accelerated in HIV-1-infected individuals and responds to antiretroviral therapy.
Our findings highlight the utility of retroelement-based aging biomarkers and support a renewed emphasis on the role of retroelements in aging science.
