Testing Two Evolutionary Theories of Human Aging with DNA Methylation Data.

Area of Science:

• Evolutionary biology
• Genetics
• Gerontology

Background:

• Theories of aging, including mutation accumulation (MA) and disposable soma (DS), propose mechanisms for senescence.
• DNA methylation patterns change with age and are heritable, offering a potential molecular marker for aging processes.
• Understanding the genetic and epigenetic underpinnings of aging is crucial for addressing age-related diseases.

Purpose of the Study:

• To differentiate between mutation accumulation (MA) and disposable soma (DS) aging theories using genomic DNA methylation data.
• To investigate how the heritability of age-differentially methylated sites changes with age.
• To identify specific genomic sites consistent with MA or DS predictions.

Main Methods:

• Utilized familial DNA methylation data from 610 individuals across 176 families.
• Analyzed 48,601 age-differentially methylated sites across the genome.
• Applied variance components models to assess changes in methylation heritability with age.

Main Results:

• Identified 102 age-differentially methylated sites showing increasing heritability with age, consistent with mutation accumulation (MA).
• Identified 2266 age-differentially methylated sites showing decreasing heritability with age, consistent with disposable soma (DS).
• The majority of observed DNA methylation changes align with epigenetic drift, but targeted changes also exist.

Conclusions:

• Both mutation accumulation (MA) and disposable soma (DS) theories likely contribute to human aging.
• Epigenetic drift plays a significant role in age-related DNA methylation changes.
• Specific age-related methylation changes may be mediated by aging-related genes.