Définition
DNA methylation is the addition of methyl groups to cytosine bases in DNA, typically at CpG sites. It is the most studied epigenetic modification and forms the basis of the most accurate biological age tests. Methylation patterns shift with aging, lifestyle, and environmental exposures.
DNA methylation is catalyzed by DNA methyltransferase (DNMT) enzymes, which transfer methyl groups from S-adenosylmethionine (SAM) to the carbon-5 position of cytosine in CpG dinucleotides. When CpG sites in gene promoters are methylated, the associated gene is typically silenced. Demethylation of previously silenced sites can activate gene expression. This system allows the same DNA sequence to produce different gene expression patterns in different cell types, developmental stages, and environmental contexts.
Across aging, DNA methylation changes in predictable patterns — some sites gain methylation (progressive silencing of certain genes), others lose it. These age-associated methylation changes are the basis for epigenetic clocks. The Horvath clock uses 353 CpG sites; the GrimAge clock uses a different set predictive of mortality and disease. Commercial tests measure these patterns in DNA extracted from saliva or blood.
The SAM required for methylation reactions is synthesized through the one-carbon cycle, which depends on methylfolate (5-MTHF), methylcobalamin (B12), vitamin B6, choline, and betaine (TMG) as co-factors. This links dietary intake directly to methylation capacity — deficiencies in these nutrients impair the one-carbon metabolism that supports methylation. Elevated homocysteine is the most accessible marker of inadequate methylation support.
Factors associated with accelerated DNA methylation age (epigenetic aging): smoking (the single strongest environmental signal), excess visceral adiposity, chronic psychological stress, sleep deprivation, sedentary behavior, and high processed food intake. Factors associated with slower epigenetic aging: aerobic fitness, Mediterranean-style diet, adequate sleep, stress management, and social connection.
Termes associés
Ava Longevity · Built on the Ava Method · MMXXV