Cologne Seminars on Ageing "Insights from the Mammalian Methylation Consortium on Maximum Lifespan"

About Steve' s talk:

DNA methylation-based biomarkers, such as epigenetic clocks, are widely used to assess the effectiveness of
rejuvenation interventions. The Mammalian Methylation Consortium was formed with two main objectives: The first was to
develop DNA methylation measures for tracking aging in all mammalian species, culminating in the pan-mammalian
methylation clock (Lu et al., 2023, Nat Aging). The second objective was to investigate DNA methylation profiles
associated with maximum mammalian lifespan, explored in three studies.

In the first study, we developed multivariate predictors of maximum lifespan based on highly conserved cytosines (Li et
al., 2024, Science Advances). This predictor can estimate maximum lifespan directly from a DNA sample even when the
species is unknown.

The second study identified individual CpGs and clusters of CpGs (referred to as modules) that
correlate with maximum lifespan (Haghani et al., 2023, Science), offering new insights into the methylation landscapes
characteristic of long-lived species. Interestingly, there was low overlap between CpGs associated with maximum lifespan
and those linked to chronological age.

The third study (Horvath et al., 2024, Nat Comm) examined the dynamic changes in DNA methylation across selected
chromatin states throughout the lifespan. Our findings highlight two key results: First, there is a reciprocal relationship
between the rate of methylation change in bivalent promoter regions and maximum lifespan. Second, the rate of
methylation change observed in young animals is predictive of changes seen in older animals. Collectively, these studies
reveal that DNA methylation patterns provide a critical link between developmental processes and aging mechanisms.