Aging

Summary This study profiles cell-type-specific senescence signatures in circulating blood cells from human longitudinal cohorts and shows that these signatures track distinct dimensions of health status and aging trajectories. The findings establish circulating senescence signatures as high-resolution biomarkers of biological aging with potential utility for monitoring healthspan in humans.

Summary SenCat is a comprehensive multiomic atlas of human cell senescence generated by profiling multiple primary cell types induced to senescence through distinct triggers. Integrated analysis of transcriptome, epigenome, and proteome data across cell types and senescence inducers redefines the core features of the senescent state and identifies cell-type-specific and universal senescence signatures.

Summary This review examines the evidence for senescence in vascular smooth muscle cells (VSMCs) and its contribution to vascular aging and disease. The authors discuss the mechanisms driving VSMC senescence, its downstream consequences for vascular function, and the potential for senolytic and senomorphic interventions.

Summary This study combines single-cell analysis with long-read nanopore sequencing to capture full-length RNA isoforms and uncover temporal changes in RNA transcription, processing, and alternative splicing in the aging mouse cortex and hippocampus.

Summary Spatial transcriptomics profiling of the aging mouse brain reveals that inflammatory gene expression changes during aging are not uniformly distributed but originate preferentially in white matter regions. The findings provide a spatially resolved map of the aging brain transcriptome and identify candidate cellular drivers of neuroinflammation.

Summary This study reveals that senescent cells suppress the canonical integrated stress response (ISR) while activating a remodeled secretory program. The suppression of ISR in senescence is mechanistically linked to altered eIF2α phosphorylation dynamics, and the resulting secretory phenotype differs from the classical SASP, with implications for age-related tissue dysfunction.

Summary This study reveals that 5-hydroxymethylcytosine (5hmC) enrichment in gene bodies acts as an epigenetic mechanism that constrains the amplitude of transcriptional changes occurring during aging. Genes with high 5hmC show attenuated age-related expression changes, identifying DNA hydroxymethylation as a regulator of transcriptional stability in aging tissues.

Summary This review covers the major cellular stress response pathways and how they are altered during aging. Topics include the integrated stress response, heat shock response, oxidative stress, proteostasis, and their connections to age-associated physiological decline and disease.