Ancient Viral Remnants Serve as Accurate Aging Clock

Researchers at Weill Cornell Medicine and the epigenetics startup TruDiagnostic have found DNA markers linked to retroelements—remaining pieces of ancient viral genetic material—in human genes.

These markers function as extremely precise epigenetic clocks that predict chronological age. The study provides credence to the theory that specific retroelements in the human genome might have an impact on aging.

Although the impact of retroelements on gene regulation, gene expression, genomic stability, and the course of human diseases has been established, their potential as aging biomarkers has not received much attention.

The study published in Aging Cell concludes that the retroelement clocks integrated into the human genome identify distinct aging signals not identified by other clocks that gauge chronological age. Most aging clocks calculate an individual's biological age using patterns of epigenetic markers, which are chemical tags called methyl groups that are affixed to DNA and influence the expression of certain genes.

As people age, the pattern of methylation on retroelements appears to change. This makes some genes more active and potentially causes inflammation, age-related diseases, and genomic instability.

Building an Aging Clock Based on Retroelements

Aging is a complex process shaped by genetic, environmental, and epigenetic factors, leading researchers to seek reliable markers that can predict biological age—a reflection of a person's age at the biochemical level, which influences health and overall well-being. In contrast, chronological age simply represents the number of years a person has lived, and the two may not always align for an individual.

Researchers utilized a machine learning model from TruDiagnostic to analyze epigenetic data from 12,670 individuals aged 12 to 100. By examining DNA methylation patterns of retroelements, specifically human endogenous retrovirus (HERV) and long interspersed nuclear elements (LINEs), they created a composite retroelement-Age clock named "Retro-Age."

“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,” said first author Dr. Lishomwa Ndhlovu, the 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 discovered that the Retro-Age clock maintained accuracy across various human tissues, complemented existing epigenetic clocks, and extended to other mammalian species. Their findings suggest that retroelement activity could be a fundamental component of aging across different species.

Turning Back the Clock—Impact of Environmental Factors

The researchers also discovered that the DNA methylation patterns they saw were sensitive to external variables like antiretroviral medication taken by HIV-positive individuals, in addition to being predictive of age. Epigenetic aging is accelerated by HIV infection, but antiretroviral therapy seems to partially rewind time.

This implies that retroelement activity affects the biological aging process in HIV-positive individuals by being impacted by the infection and its treatment.

The reactivation of specific retroelements increases with age, potentially leading to biological hallmarks of aging such as inflammation, cellular senescence, and genomic instability.”

Dr. Michael Corley, Corresponding Author and Assistant Professor, Department of Immunology in Medicine, Division of Infectious Diseases, Weill Cornell Medicine

Corley continued, “Our findings indicate that retroelement clocks capture previously undetected facets of biological aging and may open the door to future treatments for these and other age-related conditions.”

According to the researchers, tracking the activity of retroelements may be useful in tracking the efficacy of anti-aging treatments, health outcomes in aging populations, and the influence of lifestyle modifications on biological aging.

Drs. Ndhlovu and Corley hope to investigate novel therapeutic approaches or treatments for age-related diseases by targeting the epigenetic states of particular retroelements in the human genome. The researchers pointed out that this strategy might eventually counteract or lessen the biological effects of aging, extending a person's lifespan and improving their state of health.