DNA methylation signatures of frailty beyond age: a longitudinal study of female and male mice
Zhu, D.; Frost, S.; Griffin, P. T.; McNamara, M.; Sinclair, D. A.; Kane, A. E.
Show abstract
Frailty is an age-related geriatric syndrome with largely unknown mechanisms. We conducted a longitudinal study of aging C57BL/6JNIA mice (females; n = 40, male; n = 49), measured frailty index and derived DNA methylation data from PBMCs. We selected frailty-related differentially methylated CpGs and determined differentially methylated regions (DMRs), focusing on both age-independent and -dependent frailty, and using both mixed-sex and sex-stratified subgroups. We propose a joint set of 925 frailty-related DMRs, perform an association study with frailty outcomes, build epigenetic frailty clocks and validate in mice with interventions. Notably, age-independent frailty DMRs are enriched in nervous and endocrine pathways, distinct from signaling and lipid metabolism pathways identified from age-dependent DMRs. We observe hypermethylation in signaling pathways and hypomethylation in lipid metabolism and cytochrome P450 pathways with frailty progression. 36 DMRs show consistent associations in validation. These findings highlight distinct epigenetic signatures underlying frailty and aging, with potential sex-specific mechanisms.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A Novel Blood-Based Epigenetic Clock for Intrinsic Capacity Predicts Mortality and is Associated with Clinical, Immunological and Lifestyle Factors 97%
- Heterochronic parabiosis reprograms the mouse brain transcriptome by shifting aging signatures in multiple cell types 96%
- Nature of epigenetic aging from a single-cell perspective 95%
Similar papers in this journal
Similar papers in this journal
- Age-Dependent Maturation and Rejuvenation of the Neural 3D Chromatin Interactome in Enriched Environments 96%
- Single-Cell Epigenomics Uncovers Heterochromatin Instability and Transcription Factor Dysfunction during Mouse Brain Aging 95%
- Defining the age-dependent and tissue-specific circadian transcriptome in male mice 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.