How to Slow down the Ticking Clock: Age-Associated Epigenetic Alterations and Related Interventions to Extend Life Span
Round 1
Reviewer 1 Report
The authors provide here an excellent review about the various aspects of age-associated epigenetic changes. Starting from a description of DNA and histone modifications (mainly methylations & acetylations) during aging, the development and use of epigenetic (methylation) clocks, the connection of DNA methylation and hallmarks of aging to the use of epigenetic changes as biomarkers for predicting various diseases and to possible ways to influence the rate of epigenetic aging (life-style, diet, pharmacological and gene therapy intervention). The review is well written and structured and pleasant to read. Furthermore, with more than 350 citations it provides a comprehensive overview of the literature.
As minor comment it might be interesting if the authors include and discuss recent publications that developed epigenetic clocks for naked mole rats. It seems that NMR age at the epigenetic level without showing any physiological decline (PMID 35039495 & doi.org/10.1038/s43587-021-00152-1). What does this mean for the causal involvement of DNA methylation in the aging process?
In summary this is an excellent review that I recommend for publication in Cells
Reviewer 2 Report
In their review, Galow et al. extensively discuss epigenetic modification during aging. The histone modifications associated with aging are described and the bidirectional connection between metabolism and epigenetics is emphasized. Particular importance is given to DNA methylation, its physiological importance and its association with the stage of life. The involvement of epigenetics in important diseases is also discussed and the main risk factors influencing the acceleration of epigenetic aging are considered. The environmental, therapeutic and pharmacological impact on epigenetic mechanisms in the extension of the life span is also evaluated. Globally, the topics are covered comprehensively and effectively. Particular appreciation goes to the figures.
