Age-related changes in gene regulation explain biological clock signals but respond differently to lifespan treatments, growth, and cell identity loss

Epigenetic clock loci are enriched in regions that both accumulate and lose disorder with age.

• Changes in DNA methylation with age are observed across various species.
• A computational approach was developed to analyze variability or 'disorder' in DNA methylation patterns.
• Age-associated changes in DNA methylation disorder may contribute to the signals used in epigenetic clocks.
• Epigenetic clocks based on regional disorder were created and compared to traditional epigenetic clocks.
• Common responses and key differences were identified between standard epigenetic clocks and those based on disorder.
• These findings suggest a complex relationship between DNA methylation disorder and the processes of epigenetic aging.

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