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Traumatic brain injury (TBI) is a significant public health concern, particularly in aging populations. While advanced age and frailty affect outcomes after TBI, the independent effect of frailty on long-term outcomes in geriatric TBI patients remains poorly understood. We hypothesized that higher disease-specific frailty is independently associated with poor long-term outcomes and quality of life following TBI. To determine whether a TBI-specific frailty index assessed at presentation is...

Host-associated microbiomes often display host specificity and heritability, yet the evolutionary processes under which such structured communities first emerge are still unclear. In particular, the conditions by which intergenerational (i.e., vertical) transmission of microbes can evolve and generate host-specific microbiomes are still unresolved. Here, we present an eco-evolutionary theory of microbiome assembly under minimal assumptions of microbial dynamics (i.e., neutrally driven by...

Among the more than 90 identified genetic risk loci for late-onset Alzheimer's disease (AD) and related dementias, the apolipoprotein E (APOE) gene ɛ2/ɛ3/ɛ4 polymorphisms remain the longstanding benchmark for genetic disease risk with a consistently large effect across studies^(1-10). Despite this massive signal, the exact mechanisms by which ɛ4 increases and ɛ2 decreases dementia risk remain poorly understood. Notably, recent trials of anti-amyloid therapies suggest less efficacy and higher...

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...

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