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Understanding the molecular basis of neurodegeneration requires a comprehensive map of the genome's protein-coding output. Although thousands of small open reading frames (ORFs) are translated in the human brain, proteomic evidence for their encoded microproteins (MPs) (≤150 amino acids (aa)) remains limited. Here, we present a brain MP atlas that integrates transcriptomics, mass spectrometry and deep-learning-predicted spectra across more than 600 postmortem frontal cortex samples with and...

Somatic mosaicism is increasingly recognized as a pervasive feature of the human brain and a potential contributor to neurological disease across the lifespan. Unlike germline variants, somatic variants arise post-zygotically and are unevenly distributed across regions, cell types and even individual neurons, enabling focal biological effects that can scale to network-level dysfunction. In this Review, we synthesize current evidence that developmental timing, clonal architecture and...

Sleep is increasingly recognised as a potentially modifiable factor in cognitive ageing, but evidence is often limited by cross-sectional designs, single sleep measures and global cognitive outcomes. This study examined whether multiple sleep characteristics (device-based and self-report) were associated with domain-specific cognitive function across repeated observations in community-dwelling adults aged 55 years and older. Adults aged ≥ 55 years were assessed at three time points over 2 years...

Tobacco smoking is a critical modifiable risk factor for age-related diseases and mortality. Although smoking cessation is known to improve health outcomes, whether smoking-induced biological aging is reversible upon cessation remains unclear. We investigated the associations of smoking status and cessation duration with epigenetic age acceleration (EAA) using multi-generational DNA methylation clocks. We analyzed data from 1,911 adults aged 50-84 years in the National Health and Nutrition...

Chronic occupational stress is increasingly recognized as a modifiable accelerator of biological aging, yet it remains underappreciated as a target of geroscience-informed public health intervention. This review reframes workplace stress as a life-course determinant of aging trajectories and introduces a translational framework that positions occupational environments as platforms for promoting healthy aging. Drawing on insights from the Semmelweis Study, a large longitudinal occupational...

Clinical researchers will probe complications that can arise after immunization, but some worry about political influence

A major analysis of 139 clinical trials involving nearly 10,000 people suggests that some of the simplest treatments may work best for knee osteoarthritis. Knee braces ranked highest overall for reducing pain, stiffness, and mobility problems, while water-based therapy was especially effective for pain and regular exercise consistently improved both pain and physical function. More high-tech approaches, including ultrasound, generally performed worse.