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DNA methylation and chromatin accessibility predict age in the domestic dog

Title: DNA methylation and chromatin accessibility predict age in the domestic dog
Authors: Jin, Kelly; McCoy, Brianah M.; Goldman, Elisabeth A.; Usova, Viktoria; Tkachev, Victor; Chitsazan, Alex D.; Kakebeen, Anneke; Jeffery, Unity; Creevy, Kate E.; Wills, Andrea; Snyder‐Mackler, Noah; Promislow, Daniel E. L.
Contributors: National Institute of Child Health and Human Development; National Institute of Neurological Disorders and Stroke; National Institute on Aging
Source: Aging Cell ; volume 23, issue 4 ; ISSN 1474-9718 1474-9726
Publisher Information: Wiley
Publication Year: 2024
Collection: Wiley Online Library (Open Access Articles via Crossref)
Description: Across mammals, the epigenome is highly predictive of chronological age. These “epigenetic clocks,” most of which have been built using DNA methylation (DNAm) profiles, have gained traction as biomarkers of aging and organismal health. While the ability of DNAm to predict chronological age has been repeatedly demonstrated, the ability of other epigenetic features to predict age remains unclear. Here, we use two types of epigenetic information—DNAm, and chromatin accessibility as measured by ATAC‐seq—to develop age predictors in peripheral blood mononuclear cells sampled from a population of domesticated dogs. We measured DNAm and ATAC‐seq profiles for 71 dogs, building separate predictive clocks from each, as well as the combined dataset. We also use fluorescence‐assisted cell sorting to quantify major lymphoid populations for each sample. We found that chromatin accessibility can accurately predict chronological age (R 2 ATAC = 26%), though less accurately than the DNAm clock (R 2 DNAm = 33%), and the clock built from the combined datasets was comparable to both (R 2 combined = 29%). We also observed various populations of CD62L+ T cells significantly correlated with dog age. Finally, we found that all three clocks selected features that were in or near at least two protein‐coding genes: BAIAP2 and SCARF2 , both previously implicated in processes related to cognitive or neurological impairment. Taken together, these results highlight the potential of chromatin accessibility as a complementary epigenetic resource for modeling and investigating biologic age.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1111/acel.14079
Availability: https://doi.org/10.1111/acel.14079; https://onlinelibrary.wiley.com/doi/pdf/10.1111/acel.14079
Rights: http://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.C2A538C7
Database: BASE