Abstract
Biological ageing and its mechanistic underpinnings are of immense biomedical and ecological significance. Ageing involves the decline of diverse biological functions and places a limit on a species’ maximum lifespan. Ageing is associated with epigenetic changes involving DNA methylation. Furthermore, an analysis of mammals showed that the density of CpG sites in gene promoters, which are targets for DNA methylation, is correlated with lifespan. Using 252 whole genomes and databases of animal age and promotor sequences, we show a pattern across vertebrates. We also derive a predictive lifespan clock based on CpG density in a selected set of promoters. The lifespan clock accurately predicts maximum lifespan in vertebrates (R2 = 0.76) from the density of CpG sites within only 42 selected promoters. Our lifespan clock provides a wholly new method for accurately estimating lifespan using genome sequences alone and enables estimation of this challenging parameter for both poorly understood and extinct species.
Highlights
Biological ageing and its mechanistic underpinnings are of immense biomedical and ecological significance
We have shown that CpG density correlates strongly with lifespan across the five most speciose vertebrate classes
Our results enabled the construction of a model that can predict lifespan accurately from only a small number of genomics features
Summary
Biological ageing and its mechanistic underpinnings are of immense biomedical and ecological significance. The lifespan clock accurately predicts maximum lifespan in vertebrates (R2 = 0.76) from the density of CpG sites within only 42 selected promoters. DNAm of cytosine-phosphate-guanosine (CpG) sites, involves a covalent modification to cytosine to form 5-methylcytosine This modification to DNA has the potential to regulate gene expression, including of genes critical for longevity, without altering the underlying sequence. It’s often reported, maximum lifespan for a species is difficult to define It is frequently the highest reported value for captive animals because of the difficulty in estimating age for wild individuals. CpG sites are prone to mutation[32] and their function in regulating gene expression may make them prime targets for evolutionary pressures to vary lifespans This hypothesis was strongly supported in an investigation showing that CpG density is correlated with lifespan among a set of conserved mammalian promoters[26]. Many studies have explored using the predictive power of methylation at specific CpG sites, no such study has investigated the predictive power of CpG density to estimate lifespan
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