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Cellular senescence is a fundamental biological process contributing to aging, often accompanied by extensive chromatin remodeling. Dynamic alterations of three-dimensional (3D) genomic spatial structure, driven by chromatin reorganization, play a critical role in cell fate determination, but their relevance in therapy-induced senescence (TIS) remains underexplored. Here, we perform an integrative multi-omics analysis of Hi-C, ATAC-seq, CUT&RUN, and RNA-seq in primary human fibroblasts...

Chronic stress has been linked to mitochondrial dysfunction and impaired telomere maintenance, yet the mechanistic relationships connecting these pathways in humans remain poorly resolved. Using longitudinal findings from the Guillén-Parra cohort as a motivating human example, this Perspective offers a reinterpreted framework that proposes a unifying energetic interpretation in which bioenergetic insufficiency-defined as a mismatch between stress-induced energetic demand and mitochondrial...

TAR DNA-binding protein 43 (TDP-43) dysfunction is a hallmark of several neurodegenerative diseases, including frontotemporal dementia, amyotrophic lateral sclerosis, and Alzheimer's disease. Although cryptic exon inclusion is a well-characterized consequence of TDP-43 loss of function, emerging evidence reveals broader roles in RNA metabolism, notably in the regulation of alternative polyadenylation (APA) of disease-relevant transcripts. In the present study, we examined 3' untranslated region...

Based mainly on rodents studies, forty-hertz (40-Hz) physical stimulation has been regarded as a potential noninvasive treatment for Alzheimer's disease (AD). Considering the brain differences between rodents and humans, the effects of 40-Hz physical stimulation need to be further validated using nonhuman primates before its clinical application. Here, we took advantage of a rare opportunity to expose nine aged rhesus monkeys (26 to 31 y old) to 40-Hz auditory stimulation. Given the strong...

Blood biomarkers have emerged as accurate tools for detecting Alzheimer's disease (AD) pathology, offering a minimally invasive alternative to traditional diagnostic methods such as imaging and cerebrospinal fluid (CSF) analysis. Yet, the logistics surrounding venipuncture for blood collection, although considerably simpler than the acquisition of imaging and CSF, require precise processing and storage specific to AD biomarkers that are still guided by medical personnel. Consequently,...

Sequence alignment is essential for genomic research and clinical diagnostics, yet detecting complex rearrangements such as inversions, duplications, and gene conversions remains challenging due to allele complexity and limitations of current methods. We introduce VACmap, a non-linear mapping approach to enhance the detection and representation of all genetic variations. VACmap improves duplication detection from 20% to 90% in the Challenging Medically-Relevant Genes (CMRG) benchmark and...

Reprogramming of somatic cells into induced pluripotent stem cells through the introduction of transcription factors Oct3/4, Sox2, Klf4, and c-Myc (OSKM) represents a landmark advance in regenerative biology. Building on this foundation, partial reprogramming can help reset epigenetic age. It further opens opportunities to treat degenerative diseases without the tumorigenic risks associated with full pluripotency. The review advances the field in three ways: it links lineage-preserving partial...

CONCLUSIONS AND IMPLICATIONS: Our equation appears to have high predictive power. With rapid and simple measurement of anthropometric and demographic indices, the equation can be used to evaluate ASM in primary care facilities lacking specialized equipment.

The Greenland shark (Somniosus microcephalus) is the longest-living vertebrate and inhabits the exceptionally dim and cold waters of the Arctic deep sea. Due to its extreme lifespan, harsh environmental conditions, and prevalent corneal parasitisation, the Greenland shark has previously been thought to have impaired or degenerated vision. Here, we present genomic, transcriptomic, histological and functional evidence that the Greenland shark retains an intact visual system well-adapted for life...

Resistance training (RT) is an effective intervention for improving muscle health and metabolism in ageing, but the degree of responsiveness (hypertrophy) to RT varies substantially. We examined muscle metabolomic profiles before and after 10-weeks RT in older adults classified into upper (UPPER) and lower (LOWER) tertiles of hypertrophy to identify key metabolic adaptation differences. Fifty older adults (23 males, 27 females, mean 68.2 years old) completed 10 weeks of RT combined with whey...

Clonal haematopoiesis of indeterminate potential (CHIP) is an ageing-related condition associated with a substantial fraction of circulating leukocytes having descended from a single somatically mutated haematopoietic stem cell (HSC). CHIP increases the risk of haematological malignancies and several chronic diseases (for example, cardiovascular pathologies) and contributes to persistent, low-grade inflammation or inflammageing. Inflammageing, in turn, promotes functional impairment of normal...

Brain health is closely linked to bone homeostasis. Skeletal aging is characterized by inadequate bone formation and marrow adiposity, but whether the brain contributes to this imbalance remains unknown. This study shows that aged brain neurons, mainly those in the hippocampus and cerebral cortex, produce excess WD repeat and FYVE domain containing 1 (WDFY1) protein and transfer it to the bone via extracellular vesicles (EVs), leading to bone-fat imbalance and osteoporosis. Increasing brain...

Replacing volatile methylammonium (MA^(+)) with formamidinium (FA^(+)) or cesium (Cs^(+)) cations in mixed Pb-Sn perovskite compositions improves thermal resilience. Nevertheless, the low-solubility Cs-based perovskite tends to preferentially crystallize into a dense Cs-rich surface layer during the AS-assisted crystallization process, which impedes the AS to extract the internal solvent. Here, we introduce a multi-Lewis-base modulator to maintain sustained solvent-extraction channels (SSC) open...

Study adds to evidence that sleep likely evolved among ancient animals as a means of repairing neurons