DNA methylation rates scale with maximum lifespan across mammals

Crofts, Samuel; Latorre-Crespo, Eric; Chandra, Tamir

doi:10.1101/2023.05.15.540689

Cited by 3 publications

References 40 publications

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Developmental hematopoietic stem cell variation explains clonal hematopoiesis later in life

Kreger,

Mooney,

Shibata

et al. 2024

Nat Commun

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Clonal hematopoiesis becomes increasingly common with age, but its cause is enigmatic because driver mutations are often absent. Serial observations infer weak selection indicating variants are acquired much earlier in life with unexplained initial growth spurts. Here we use fluctuating CpG methylation as a lineage marker to track stem cell clonal dynamics of hematopoiesis. We show, via the shared prenatal circulation of monozygotic twins, that weak selection conferred by stem cell variation created before birth can reliably yield clonal hematopoiesis later in life. Theory indicates weak selection will lead to dominance given enough time and large enough population sizes. Human hematopoiesis satisfies both these conditions. Stochastic loss of weakly selected variants is naturally prevented by the expansion of stem cell lineages during development. The dominance of stem cell clones created before birth is supported by blood fluctuating CpG methylation patterns that exhibit low correlation between unrelated individuals but are highly correlated between many elderly monozygotic twins. Therefore, clonal hematopoiesis driven by weak selection in later life appears to reflect variation created before birth.

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Developmental hematopoietic stem cell variation explains clonal hematopoiesis later in life

Kreger,

Mooney,

Shibata

et al. 2024

Nat Commun

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DNA methylation rates scale with maximum lifespan across mammals

Crofts,

Latorre-Crespo,

Chandra

2023

Nat Aging

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DNA methylation rates have previously been found to broadly correlate with maximum lifespan in mammals, yet no precise relationship has been observed. We developed a statistically robust framework to compare methylation rates at conserved age-related sites across mammals. We found that methylation rates negatively scale with maximum lifespan in both blood and skin. The emergence of explicit scaling suggests that methylation rates are, or are linked to, an evolutionary constraint on maximum lifespan acting across diverse mammalian lineages.

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DNA methylation rates scale with maximum lifespan across mammals

Crofts

Latorre-Crespo

Chandra

2023

Preprint

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DNA methylation rates have previously been found to broadly correlate with maximum lifespan in mammals, yet no precise relationship has been observed. We compared methylation rates at conserved age-related sites across mammals in both skin and blood and found that methylation rates scale with maximum lifespan to the power of negative one. The emergence of an explicit scaling law suggests that methylation rate is either a fundamental limiting factor in maximum lifespan across species or is linked to an underlying universal constraint.

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DNA methylation rates scale with maximum lifespan across mammals

Cited by 3 publications

References 40 publications

Developmental hematopoietic stem cell variation explains clonal hematopoiesis later in life

Developmental hematopoietic stem cell variation explains clonal hematopoiesis later in life

DNA methylation rates scale with maximum lifespan across mammals

DNA methylation rates scale with maximum lifespan across mammals

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