Fundamental equations linking methylation dynamics to maximum lifespan in mammals

We describe a framework that addresses concern that the rate of change in any aging biomarker displays a trivial inverse relation with maximum lifespan. We apply this framework to methylation data from the Mammalian Methylation Consortium. We study the relationship of lifespan with the average rate...

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Bibliographic Details
Published in:Nature communications 2024-09, Vol.15 (1), p.8093-17
Main Authors: Horvath, Steve, Zhang, Joshua, Haghani, Amin, Lu, Ake T., Fei, Zhe
Format: Article
Language:English
Subjects:
631/114/2409
631/114/2415
631/136/7
631/181
631/208/176/1988
Age
Aging
Aging - genetics
Aging - physiology
Animals
Biomarkers
Chromatin
Chromatin - genetics
Chromatin - metabolism
Context
DNA Methylation
Dogs
Humanities and Social Sciences
Humans
Life span
Longevity - genetics
Mammals
Mammals - genetics
multidisciplinary
Promoter Regions, Genetic - genetics
Science
Science (multidisciplinary)
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Summary:We describe a framework that addresses concern that the rate of change in any aging biomarker displays a trivial inverse relation with maximum lifespan. We apply this framework to methylation data from the Mammalian Methylation Consortium. We study the relationship of lifespan with the average rate of change in methylation (AROCM) from two datasets: one with 90 dog breeds and the other with 125 mammalian species. After examining 54 chromatin states, we conclude three key findings: First, a reciprocal relationship exists between the AROCM in bivalent promoter regions and maximum mammalian lifespan: AROCM ∝ 1/MaxLifespan. Second, the correlation between average methylation and age bears no relation to maximum lifespan, Cor(Methyl,Age) ⊥ MaxLifespan. Third, the rate of methylation change in young animals is related to that in old animals: Young animals’ AROCM ∝ Old AROCM. These findings critically hinge on the chromatin context, as different results emerge in other chromatin contexts. The mystery of mammalian lifespan is examined through DNA methylation dynamics, revealing an inverse relationship between lifespan and average methylation rate changes in bivalent promoter regions. Results vary depending on chromatin context.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-51855-z