Unlocking the Secrets of Aging: New Epigenetic Clocks Provide Insights

Harvard researchers pioneer an epigenetic clock predicting biological age through DNA structure. Using innovative machine-learning models, they identify genetic factors that both accelerate and counteract aging.

New Update

In a groundbreaking development, researchers at Harvard-affiliated Brigham and Women’s Hospital have unveiled innovative epigenetic "clocks" designed to unravel the mysteries of aging. The study, published in Nature Aging, introduces a machine-learning model that goes beyond predicting biological age from DNA patterns. Instead, it distinguishes between genetic variations that either accelerate or counteract aging, offering a profound understanding of the factors influencing our aging process.

Unlocking the Secrets of Aging | In Shorts 

    • Harvard-affiliated researchers develop an epigenetic clock predicting biological age from DNA structure.
    • Innovative machine-learning models distinguish genetic factors that influence aging.
    • Clocks distinguish between changes that speed up and counteract aging, offering unprecedented insights.
    • Researchers create a map of human CpG sites causing biological aging, aiding in intervention evaluation.
    • DamAge and AdaptAge clocks show associations with adverse outcomes and protective changes.
    • Application of clocks on reprogrammed stem cells reveals reduction in age-related damage.
    • Clocks consistently reflect age-related damage in conditions and capture protective adaptations.

Lead investigator Vadim Gladyshev explains, "Our clocks distinguish between changes that accelerate and counteract aging to predict biological age and assess the efficacy of aging interventions."

The traditional approach to understanding aging involved examining the relationship between methylation patterns and known aging-related features. However, this new clock surpasses its predecessors by not only predicting biological age but also pinpointing the factors causing the body to age at different rates.

Decoding the Language of DNA: Brigham and Women's Hospital's Breakthrough

The study emphasizes the impact of DNA methylation, alterations in genetic structure shaping gene function, on the aging process. Lifestyle choices and genetic inheritance play crucial roles, as demonstrated by the fact that individuals with similar lifestyles may age at different rates.

The research team, led by Gladyshev and graduate student Kejun Ying, employed epigenome-wide Mendelian Randomization (EWMR) on a vast genetic dataset. This technique, used to establish causation between DNA structure and observable traits, focused on 20,509 CpG sites associated with eight aging-related characteristics.

The study's three models—CausAge, DamAge, and AdaptAge—were trained on data from 2,664 individuals. By analyzing blood samples from over 7,000 participants, researchers developed a map identifying human CpG sites influencing biological aging. This map serves as a tool to identify biomarkers causative to aging and evaluate interventions promoting longevity or accelerating aging.

EWMR Unveils Causation: A Deep Dive into Aging-related DNA Structures

Testing the validity of their clocks on data from the Framingham Heart Study and the Normative Aging Study, the researchers found DamAge correlated with adverse outcomes, including mortality, while AdaptAge correlated with longevity.

In a bold move, the team assessed biological age by reprogramming stem cells. DamAge decreased, indicating a reduction in age-related damage during reprogramming, while AdaptAge displayed intriguing patterns.

Furthermore, the clocks demonstrated efficacy in samples from patients with chronic conditions and those influenced by lifestyle choices like smoking. DamAge consistently increased in conditions associated with age-related damage, while AdaptAge decreased, capturing protective adaptations.

Gladyshev highlights the significance of their findings, stating, "Our findings present a step forward for aging research, allowing us to more accurately quantify biological age and evaluate the ability of novel aging interventions to increase longevity."

While Gladyshev and Ying are inventors on a patent application related to the research, the study opens up exciting possibilities for future interventions in the complex process of aging.

Disclaimer: Originally from The Harvard Gazette, this news has been rewritten by our research team to enhance awareness and knowledge dissemination