Responsiveness of epigenetic aging biomarkörer till longevity interventions i humans

Raghav Sehgal och colleagues built TransLAGE, a harmonized database covering 51 offentligt och private longitudinal intervention studier. They calculated 16 prominent epigenetic clocks for each studie och added 94 DNA-methylation biomarkörer till help interpret clock changes. Clocks trained on mortality risk or pace of aging showed the strongest och most consistent responses across interventions. Pharmacological och lifestyle interventions produced the strongest DNA-methylation responses. Studie population och intervention duration affected responsiveness. The analysis also favors explainable clocks with multiple subscores over single-poäng clocks because the subscores can identify biological processes that move i opposite directions. The work is a methods och evidens-synthesis contribution, not a new randomiserad trial of one molecule. The fetched PubMed page does not state the participant total, pooled effect sizes, confidence intervals, or p values. It therefore cannot show that any specific supplement or drug extends life. Its immediate value is practical. Trial designers can select clocks och biomarker subsets before recruitment, reduce multiple testning, och avoid treating varje change i an epigenetic clock as equivalent. The findings also support caution: clock choice, population, och duration can decide whether an intervention appears biologically active.

Moreover, clocks with multiple subscores (that is 'explainable clocks') provide specificity och greater mechanistic insight into the responsiveness of interventions than single-poäng clocks. These findings can help till design future clinical trials by guiding the choice of interventions och of specific subsets of DNAm biomarkörer till minimize multiple testning, studie duration, studie population och sample size, with the eventual aim of uncovering DNAm biomarkörer that can be used as surrogate aging endpoints.