Age-associated epigenetic drift trajectory and cross-national disparities in accelerated aging in domestic dogs

• 成果类型: Article
• 署名作者: Jang, Subin; Kim, Seong Jun; Kang, Dayeon; Hong, Chae-yeon; Bok, Eun-yeong; Lee, Sung-Lim; Choe, Yong-Ho; Kim, Jaemin
• 署名单位: Gyeongsang National University; Gyeongsang National University; Gyeongsang National University; Gyeongsang National University; National Institute of Animal Science, Republic of Korea; Rural Development Administration (RDA), Republic of Korea; Gyeongsang National University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2528874123
• 发表日期: 2026-07-21
• 页码: e2528874123
• 关键词: Aging; dog; acceleration; epigenetic clock; longevity; women; EVEN

摘要

Aging is accompanied by both increasing interindividual heterogeneity and systematic, age-associated alterations in DNA methylation (DNAm). Here, we investigated these complementary dimensions of epigenetic aging in dogs using global and locus-specific measures of epigenetic drift alongside clock-based estimates of biological aging. We observed pervasive, yet genomically structured epigenetic instability throughout the canine lifespan. The extent of age-associated epigenetic drift further varied by body size, suggesting biological stratification of methylation instability. Cross-national comparison of clock-derived epigenetic age acceleration (EAA) between South Korea and the United States revealed consistently higher EAA in Korean dogs, with sex-associated differences detected within the Korean cohort. We further identified CpGs with cohort-specific age-associated methylation patterns, indicating that population-level differences in epigenetic aging extend beyond clock-based estimates to locus-specific methylation dynamics. Together, these findings highlight population-level diversity in canine epigenetic aging and support dogs as a tractable model for investigating biological and environmental determinants of age-related epigenetic change.