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A hallmark of Alzheimer's disease (AD), the most common form of dementia, is the progressive accumulation of amyloid-beta (Aβ) peptides across distinct brain regions. Anti-Aβ antibodies (Aβ-Abs) targeting specific Aβ variants are essential tools for AD research, diagnostics, and therapy. The monoclonal antibodies Aducanumab, Lecanemab, and Donanemab have recently been approved as the first disease-modifying treatments for early AD, highlighting the clinical importance of their exact binding...

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With increasing global life expectancy, the prognostic significance of kidney function in centenarians and supercentenarians should be clarified. The conventional estimated glomerular filtration rate (eGFR) threshold of < 60 mL/min/1.73 m² may not accurately reflect chronic kidney disease (CKD) in this population, highlighting the need for age-adapted definitions. This study investigated the association of kidney function with all-cause mortality across three age groups. Data from the Tokyo...

Thirteen-year-old Okinawa Institute of Science and Technology hopes to become a global science leader

Nicotinamide adenine dinucleotide (NAD⁺) declines with age, motivating "NAD⁺-boosting" strategies ranging from lifestyle interventions to supplementation with NAD⁺ precursors (e.g., nicotinamide riboside [NR], nicotinamide mononucleotide [NMN]) and, in some wellness settings, parenteral NAD⁺ administration. We conducted a PRISMA-guided systematic review of peer-reviewed human and rodent intervention studies (January 2010-October 2025) evaluating NAD-related compounds administered orally or...

Ageing is a multidimensional and heterogeneous process that progresses asynchronously across organ systems. Advances in multi-omics technologies have led to the development of diverse ageing clocks, including epigenetic, proteomic, metabolomic, and imaging-based models, which extend beyond estimating crude biological age to more precisely capture organ-specific ageing trajectories and predict age-related diseases and mortality risk. Population-scale studies demonstrate substantial...

Golgi fragmentation is a prominent early hallmark of neurodegenerative diseases such as Alzheimer disease (AD) and amyotrophic lateral sclerosis (ALS), yet the shared molecular mechanisms underlying this phenomenon remain poorly understood. Here we identify the E3 ubiquitin ligase ITCH as a central regulator of Golgi integrity and proteostasis. Elevated ITCH disrupts both cis- and trans-Golgi networks, dislocates lysosomal hydrolase sorting factors, and impairs maturation of hydrolases. The...

Centenarians exhibit remarkable longevity and compression of morbidity making them an ideal population for uncovering proteins associated with successful aging. Using proteomics, we characterized the immune and cardiometabolic profiles of centenarians' plasma from the SWISS100 cohort. We identified 583 differentially expressed proteins (DEPs) by centenarians when compared with hospitalized geriatric patients (age 80-90 years) and younger healthy participants (age 30-60 years). We replicated the...

Senescent fibroblasts accumulate in the connective tissue of all organs and promote organ aging and aging-related diseases. The underlying mechanisms for the accumulation of senescent fibroblasts are poorly understood. Natural killer (NK) cells of innate immunity play a critical role in the removal of tissue resident senescent cells. We here show that NK cells from old adults and old mice fail to efficiently remove senescent fibroblasts. This is due to severely reduced perforin and granzyme B...

Alzheimer's disease (AD) is a neurodegenerative disorder characterised by progressive memory loss and cognitive decline. With the global population ageing, the prevalence of AD continues to rise, posing a significant public health challenge. Historically, AD research has centred on two hallmark pathological features: β-amyloid (Aβ) deposition and tau protein hyperphosphorylation. However, repeated failures of therapeutic strategies targeting these pathways in clinical trials have prompted a...

A 'gut-brain axis' is an intricate bidirectional connection between the gut and the central nervous system, serving as a key pathway for signal exchange. However, current in vitro models do not fully capture these dynamic interactions, limiting mechanistic insight and therapeutic testing. Here, we show a 3D human gut-brain-vascular microphysiological platform that integrates lumenized villus-like intestinal barrier, blood vascular-astrocyte interactions, and brain tissue to model...

Vestibular dysfunction becomes increasingly prevalent with aging and it is estimated that more than 80 % of people over 80 years old experience balance problems linked to vestibular dysfunction. Within the peripheral vestibular organs, sensory hair cells transform hair bundle motion into receptor potentials and information is next relayed to the brain by electrical activity in vestibular afferent nerves. There are three types of vestibular afferents: calyx-only afferents innervate one or more...

The nematode Caenorhabditis elegans is a favorable model for studying cell-surface protein interactomes, given its well-defined and stereotyped intercellular contacts. Here, we report an extracellular interactome dataset for C. elegans. Most of these interactions were unknown, despite recent datasets for flies and humans, as our collection contains a larger selection of protein families. We uncover interactions for all four major axon guidance pathways, including ectodomain interactions between...

Recent advances in biogerontology show that ageing is malleable, opening the possibility of delaying chronic disease and extending healthspan. Ethical debate has been dominated by consequentialist framings, balancing potential benefits against fears of overpopulation, inequality, or loss of meaning. We seek to further this discussion by grounding the case for longevity research not only in outcomes but also in respect for autonomy, self-ownership, and the intrinsic value of life itself. On this...

Alzheimer's disease (AD) is a neurodegenerative disorder characterised by progressive memory loss and cognitive decline. With the global population ageing, the prevalence of AD continues to rise, posing a significant public health challenge. Historically, AD research has centred on two hallmark pathological features: β-amyloid (Aβ) deposition and tau protein hyperphosphorylation. However, repeated failures of therapeutic strategies targeting these pathways in clinical trials have prompted a...

Identification of ground contact timings (GCT) is critical for monitoring mobility in older adults. Laboratory methods are precise but limited to controlled environments, restricting their applicability in real-world settings. Treadmills allow extended measurements but fail to reflect the variability of overground walking. We evaluated the performance of deep learning models trained on treadmill data from young adults and their generalizability to treadmill and outdoor walking in older adults....