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Biology subjects

Fornero, G.

Publications and source records attributed to Fornero, G..

2 recordsLinked to original sources

Genome-wide multi-layered epigenomic profiling across human aging

Aging is characterized by highly reproducible alterations across multiple layers of the epigenetic landscape, including DNA methylation, chromatin accessibility, and histone modifications. However, it remains unclear to what extent these age-associated changes are interconnected and coordinated coherently. To investigate the genome-wide distribution and interplay of age-associated epigenetic alterations, we generated whole-genome bisulfite sequencing (WGBS) data from blood samples of 120 healthy donors. Integration with ATAC-seq data revealed no clear relationship between age-related changes in DNA methylation and chromatin accessibility. We further examined the association of these alterations with age-dependent changes in CTCF occupancy and histone modifications, including H3K27ac, H3K27me3, H3K4me1, H3K4me3, and H3K9me3, but observed very little corresponding changes in chromatin states. Collectively, our integrative genome-wide analysis revealed only limited association between age-associated epigenetic alterations in DNA methylation, chromatin accessibility, and histone modifications, arguing against a broadly coordinated remodeling of the aging epigenome.

genomics↗

Multimodal single-cell analysis uncovers transcription factor networks underlying T-cell aging

Aging of the immune system is associated with chronic inflammation and impaired immune function, yet the regulatory mechanisms underlying these changes remain incompletely understood. Here, we generated paired single-cell transcriptomic and chromatin accessibility profiles from peripheral blood mononuclear cells of young and old healthy donors to characterize immune aging at single-cell resolution. Using an integrative computational framework for multi-omic single-cell analysis, we detected pronounced age-associated changes in T cells, including loss of naive CD8+ T cells and expansion of differentiated memory and effector populations. Aging was accompanied by increased inflammatory signaling and reduced oxidative phosphorylation programs. Enhancer-based gene regulatory network analyses identified a reduced role of TCF7 and increased activity of inflammatory regulators, including FOSL2, in aged T cells. Integration with genetic association and eQTL datasets further supported the functional relevance of age-associated regulatory regions and their target genes.

bioinformatics↗