Body weight and high-fat diet are associated with epigenetic aging in female members of the BXD murine family.

Autor: Sandoval-Sierra JV; Department of Preventive Medicine, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA., Helbing AHB; Department of Preventive Medicine, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA., Williams EG; Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg., Ashbrook DG; Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA., Roy S; Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA., Williams RW; Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA., Mozhui K; Department of Preventive Medicine, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA.; Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2020 Sep; Vol. 19 (9), pp. e13207. Date of Electronic Publication: 2020 Aug 12.
DOI: 10.1111/acel.13207
Abstrakt: DNA methylation (DNAm) is shaped by genetic and environmental factors and modulated by aging. Here, we examine interrelations between epigenetic aging, body weight (BW), and life span in 12 isogenic strains from the BXD family of mice that exhibit over twofold variation in longevity. Genome-wide DNAm was assayed in 70 liver specimens from predominantly female cases, 6-25 months old, that were maintained on normal chow or high-fat diet (HFD). We defined subsets of CpG regions associated with age, BW at young adulthood, and strain-by-diet-dependent life span. These age-associated differentially methylated CpG regions (age-DMRs) featured distinct genomic characteristics, with DNAm gains over time occurring in sites such as promoters and exons that have high CpG density and low average methylation. CpG regions associated with BW were enriched in introns, tended to have lower methylation in mice with higher BW, and were inversely correlated with gene expression (i.e., higher mRNA levels in mice with higher BW). CpG regions associated with life span were linked to genes involved in life span modulation, including the telomerase reverse transcriptase gene, Tert, which had both lower methylation and higher expression in long-lived strains. An epigenetic clock defined from age-DMRs revealed accelerated aging in mice belonging to strains with shorter life spans. Both higher BW and the HFD were associated with accelerated epigenetic aging. Our results highlight the age-accelerating effect of heavier BW. Furthermore, we demonstrate that the measure of epigenetic aging derived from age-DMRs can predict genotype and diet-induced differences in life span among female BXD members.
(© 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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