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Recurrent somatic mutation and progerin expression in early vascular aging of chronic kidney disease

4 months 3 weeks ago
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...
Gwladys Revêchon

Activity-dependent synapse elimination requires caspase-3 activation

4 months 3 weeks ago
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...
Zhou Yu

Ligand-specific regulation of a binary enhancer code dictating cellular senescence

4 months 3 weeks ago
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...
Thomas Suter

Brain DNA Methylation Age, Lifestyle Factors and Dementia in the Swedish Twin Registry

4 months 3 weeks ago
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...
Christopher E McMurran