The Implications of Cross-Species Epigenetic Clocks

It is reasonable to think that interventions successfully targeting one or more mechanisms of aging will produce benefits across all higher animals. The underlying mechanisms of aging are quite universal. Equally, it is reasonable to think that different species are impacted to different degrees by any given mechanism of aging, and thus interventions may produce small or sizable benefits, depending on the details. Researchers here comment on the ability to produce cross-species epigenetic clocks, in that there are patterns of epigenetic marks on equivalent sites in the genome in two or more species that correlate to chronological age in the same way. Does this then imply that a therapy that both reverses this pattern and extends healthy life span in one species can be expected to do the same in the other? Perhaps, but I don't think that to be a sure bet.

DNA methylation profiles have been used to develop biomarkers of aging known as epigenetic clocks, which predict chronological age with remarkable accuracy and show promise for inferring health status as an indicator of biological age. Epigenetic clocks were first built to monitor human aging, but their underlying principles appear to be evolutionarily conserved, as they have now been successfully developed for many mammalian species.

Here, we describe reliable and highly accurate epigenetic clocks shown to apply to 93 domestic dog breeds. The methylation profiles were generated using the mammalian methylation array, which utilizes DNA sequences that are conserved across all mammalian species. Canine epigenetic clocks were constructed to estimate age and also average time to death.

We also present two highly accurate human-dog dual species epigenetic clocks, which may facilitate the ready translation from canine to human use (or vice versa) of antiaging treatments being developed for longevity and preventive medicine. These clocks, which measure methylation levels in highly conserved stretches of the DNA, promise to increase the likelihood that interventions that reverse epigenetic age in one species will have the same effect in the other.

Link: https://doi.org/10.1073/pnas.2120887119