Aging is characterized by progressive loss of molecular fidelity that compromises stem-cell function and tissue homeostasis. Aging transcriptomes show widespread disruption of RNA processing, including increased intron retention, cryptic splice-site usage, and altered RNA quality control. These changes arise from somatic mutations as well as accumulated transcriptional, metabolic, and proteostatic stress. Importantly, similar splicing abnormalities are observed in age-associated diseases such as clonal hematopoiesis and neurodegeneration, overlapping with physiological aging states. Here, we synthesize mechanistic, stem-cell, and longevity studies to define declining RNA-processing fidelity as a unifying contributor to aging across systems. We propose the ‘splicing axis of aging’ as a framework linking RNA-processing dysfunction to tissue decline and outline emerging therapeutic strategies to restore spliceosome integrity and RNA homeostasis.

Aging is characterized by progressive loss of molecular fidelity that compromises stem-cell function and tissue homeostasis. Aging transcriptomes show widespread disruption of RNA processing, including increased intron retention, cryptic splice-site usage, and altered RNA quality control. These changes arise from somatic mutations as well as accumulated transcriptional, metabolic, and proteostatic stress. Importantly, similar splicing abnormalities are observed in age-associated diseases such as clonal hematopoiesis and neurodegeneration, overlapping with physiological aging states. Here, we synthesize mechanistic, stem-cell, and longevity studies to define declining RNA-processing fidelity as a unifying contributor to aging across systems. We propose the ‘splicing axis of aging’ as a framework linking RNA-processing dysfunction to tissue decline and outline emerging therapeutic strategies to restore spliceosome integrity and RNA homeostasis.

Seq-Scope maps skeletal muscle transcriptomes at high spatial resolution while preserving histological context, revealing distinct responses of myofibers, neuromuscular junctions, and stromal cells t...

Autism spectrum disorder (ASD) is associated with more than 1,200 risk genes, raising a fundamental question: Do these diverse genetic changes affect the brain in entirely different ways, or do they converge on shared biological mechanisms?

To define the effects of IFNα on WT and neoplastic hematopoiesis, we leveraged genotyping of transcriptomes (GoT) that simultaneously captures the mutation status and whole transcriptomes in thousands of single cells24. We focused on CALR-MUT ET25 due to heterogeneous molecular response despite clinical response in most patients13,26. To overcome interpatient variabilities, we applied GoT to fluorescence-activated cell sorting (FACS)-isolated CD34+ hematopoietic stem and progenitor cells (HSPCs) from serial (that is, baseline and treated) bone marrow biopsies from patients who were treated weekly with a pegylated form of IFNα for at least one year in clinical trials MPN-RC-111 and MPN-RC-112 (refs. 27,28) (Fig. 1a, Extended Data Fig. 1a,b and Supplementary Table 1; n = 8 baseline samples, 13 treated samples; additional 3 baseline samples from previous work24; 72% cells genotyped for CALR mutations). We incorporated time-point-specific barcoded antibodies29 to multiplex serial baseline and treated samples into the same experiments (Fig. 1b). We advanced GoT by incorporating immunophenotyping30 (GoT-IM). GoT-IM provided somatic genotyping, whole transcriptomes, immunophenotyping and treatment status for thousands of HSPCs. We integrated across the 24 samples, clustered the cells based on scRNA-seq and annotated the clusters31,32 based on canonical cell markers (Fig. 1c, Extended Data Fig. 1b–j and Supplementary...

Drosophila olfactory sensory neurons tend to express a single ligand-specific receptor, following a one-receptor-per-neuron rule expected to apply broadly across insects. Recent work challenges this view by showing that some neurons in the mosquito Aedes aegypti coexpress multiple receptors. However, the full extent and nature of coexpression in Ae. aegypti remains unclear. We sequenced the transcriptomes of 46,000 female antennal neurons to resolve all olfactory neuron subtypes and identify...

This Community Page presents the 100 Diatom Genomes Project, which aims to sequence the genomes and transcriptomes of 100 diatom species across major lineages, life forms and ecological strategies. Th...