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Abnormal aggregation of amyloid-β protein (1-42) (Aβ(42)) is the primary pathology in Alzheimer's disease (AD). Two types of Aβ(42) fibrils have been identified in the insoluble fraction of diseased human brains. Here, we report that the fraction previously deemed 'soluble' during sarkosyl extraction of AD brains actually harbors numerous amyloid fibrils, with a looser bundling than those in the insoluble fraction. Using cryo-electron microscopy (cryo-EM), we discover a third type (type III) of...

No abstract

Early vascular aging plays a central role in chronic kidney disease (CKD), but its molecular causes remain unclear. Somatic mutations accumulate in various cells with age, yet their functional contribution to aging tissues is not well understood. Here we found progerin, the protein responsible for the premature aging disease Hutchinson-Gilford progeria syndrome, steadily recurring in vascular smooth muscle cells of patients with CKD. Notably, the most common progeria-causing mutation, LMNA...

No abstract

During brain development, synapses are initially formed in excess and are later eliminated in an activity-dependent manner. Weak synapses are preferentially removed, but the mechanism linking neuronal activity to synapse removal is unclear. Here, we show that, in the developing mouse visual pathway, inhibiting synaptic transmission induces postsynaptic activation of caspase-3. Caspase-3 deficiency results in defects in synapse elimination driven by both spontaneous and experience-dependent...

No abstract

Cellular senescence, a major contributor to aging and age-related pathologies, is characterized by irreversible proliferative arrest and a disease-linked, proinflammatory profile known as the Senescence Associated Secretory Phenotype (SASP). A critical unanswered question is whether these properties are regulated by specific enhancer subsets, potentially licensing strategies that selectively block deleterious SASP components. Here, we identify two functionally distinct and independently...

CONCLUSIONS: Depression was prevalent among the oldest-old in India. Appropriate intervention strategies should be applied to prevent MMD among the oldest-old in India.

Advanced age is the most important risk factor for dementia. Measures of biological ageing such as DNA methylation age (DNAmAge) can give more information about the accumulation of age-related molecular damage in different organs than chronological age alone. Using post-mortem brain tissue from Swedish Twin Registry participants, we explored the relationship between lifestyle factors, dementia and DNAmAge measures from prefrontal cortex and cerebellum (n = 27 individuals) and paired blood...