The number of age predictors based on DNA methylation (DNAm) profile is rising due to their potential in predicting healthspan and application in age-related illnesses, such as neurodegenerative diseases. The cumulative assessment of DNAm levels at age-related CpGs (DNAm clock) may reflect biological aging. Such DNAm clocks have been developed using various training models and could mirror different aspects of disease/aging mechanisms. Hence, evaluating several DNAm clocks together may be the most effective strategy in capturing the complexity of the aging process. However, various confounders may influence the outcome of these age predictors, including genetic and environmental factors, as well as technical differences in the selected DNAm arrays. These factors should be taken into consideration when interpreting DNAm clock predictions. In the current review, we discuss 15 reported DNAm clocks with consideration for their utility in investigating neurodegenerative diseases and suggest research directions towards developing a more optimal measure for biological aging.

x as in both instances a loss of NPC function has been observed [8][9][10][11] . In particular, dividing cells depend on a constant supply of new NPCs, and indeed NPC assembly is compromised in mitotically aged yeast cells 10 .The mechanisms how FG-Nups are protected from making inappropriate interactions during NPC biogenesis are only beginning to liquid-liquid phase separate 5,6 and aggregate 7 , make NPC biogenesis a multi-step and complex event. Appearance of misassembled NPC intermediates or damaged NPCs is a risk to the cell as it could possibly lead to loss of compartmentalization. In ageing, as well as in disease, it becomes clear how NPC function is intricately interwoven with cell physiology, b WT DNAJB6 Lamin B1 Merge

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