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Aging is accompanied by widespread DNA methylation changes, yet their full genomic scope and parent-of-origin dynamics remain poorly understood. Here, we apply nanopore long-read sequencing to 7,284 whole blood samples enabling methylation measurements of 17,959,684 high-quality CpG units. Over 20% of the measured high quality CpG units undergo age-associated changes, predominantly hypomethylation. From these data, we construct a methylation aging clock from 1,373 high-quality CpG units, with...

The cholinergic system is central to attention, learning, and neuroplasticity and undergoes progressive degeneration with aging. Neuroplasticity-based computerized cognitive training is a scalable, non-pharmacological strategy to support cognitive health in older adults, yet its neurobiological mechanisms remain unclear. [18F]Fluoroethoxybenzovesamicol (FEOBV) positron emission tomography (PET) quantifies presynaptic cholinergic terminals via vesicular acetylcholine transporter (VACht) binding,...

Microtubules are well-researched components of the cytoskeleton, yet we lack a holistic understanding that bridges molecular and cellular details with the broader functions of the microtubule cytoskeleton in development, ageing and disease. For example, how microtubule properties and functions are affected by tubulin post-translational modifications, disease-related mutations or variation of the microtubule lattice remains unexplored. In this Roadmap, we argue that integrating various...

Breast cancer is among the leading causes of cancer mortality worldwide, with aging as a major risk factor. Caloric restriction (CR) is a well-established non-pharmaceutical intervention that extends healthspan and delays tumorigenesis, yet the systemic molecular mechanisms remain elusive. Both chronic and intermittent CR influence metabolic homeostasis, but their long-term effects on circulating miRNAs in breast cancer predisposition are unclear. Here, we examined how chronic and intermittent...

Secreted proteins are essential to modulate homeostasis in the extracellular space and facilitate communication to distal cells or tissues. Yet, the identity and functional importance of extracellular proteins in aging have been understudied. Here we use proximity labeling followed by quantitative proteomics to systematically characterize proteins along the intestinal secretory pathway in C. elegans, focusing on secreted proteins. We identify intestine-secreted proteins that are modulated with...

Can the skin microbiome shape healthy aging?

Endolysosomal dysfunction is a hallmark of Alzheimer's disease and related tauopathies, yet underlying mechanisms remain poorly understood. This study investigates the role of sphingolipid metabolism in maintaining endolysosomal membrane integrity and its impact on tau aggregation and toxicity in Caenorhabditis elegans and human cell culture models. Fluorescence recovery after photobleaching and C-Laurdan dye imaging revealed that silencing sphingolipid metabolism genes reduced endolysosomal...

Science, Ahead of Print.

Scientists created smart nanoparticles that can both illuminate hidden glioblastoma cells during surgery and destroy microscopic cancer left behind afterward. In mice, the treatment prevented recurrence and led to 100% survival at 60 days, though it has not yet been tested in humans.

Researchers discovered a brain-based “brake” that can shut down chronic nerve pain in mice by calming an overactive pain circuit. Targeting this system more precisely could one day lead to powerful pain relief without affecting opioid receptors throughout the entire body.

Discovery in hamsters suggests path toward inducing hibernation in mammals that don’t do it naturally

1000-year archive from the Galápagos portends greater weather disruptions from the Pacific climate cycle