Aging
Reduced adhesion of aged intestinal stem cells contributes to an accelerated clonal driftAnalysis of clonal dynamics of intestinal stem cells supports an accelerated clonal drift upon aging, likely because of reduced adhesion of aged ISCs because of reduced canonical Wnt signaling.
Loss of SET1/COMPASS methyltransferase activity reduces lifespan and fertility in Caenorhabditis elegansContrary to prior reports, this study shows that a loss of COMPASS components or SET1 activity reduces Caenorhabditis elegans lifespan, suggesting that as in yeast, H3K4 methylation is essential for normal longevity.
β-arrestin1 promotes tauopathy by transducing GPCR signaling, disrupting microtubules and autophagyGPCRs regulator, β-arrestin1, is increased in FTLD-tau patients, is required for β2-adrenergic receptor and metabotropic glutamate receptor 2-induced tau phosphorylation, promotes tau aggregation by impairing autophagy, and destabilizes microtubule dynamics, whereas genetic reduction in β-arrestin1 mitigates tauopathy and cognitive impairments.
Activation of mitochondrial unfolded protein response protects against multiple exogenous stressorsThis work highlights the importance of the mitochondrial unfolded protein response in allowing organisms to survive external stressors through up-regulation of other stress response pathways.
TPC2 promotes choroidal angiogenesis and inflammation in a mouse model of neovascular age-related macular degenerationThis study identifies the endolysosomal two-pore channel TPC2 as a potential novel drug target for age-related macular degeneration (AMD). Inhibition of TPC2 reduces two key clinical hallmarks of the AMD, retinal inflammation and formation of leaky choroi.
Concomitant gain and loss of function pathomechanisms in C9ORF72 amyotrophic lateral sclerosisAxonal trafficking deficits and neurodegeneration in C9ORF72 motoneurons are mediated by GOF and LOF mechanisms with RNA foci and DPRs as upstream events, whereas DNA damage appears downstream.
Reduced RNA turnover as a driver of cellular senescenceRNAs originating from transcription upstream and downstream of genes accumulate in the cytoplasm of a subset of senescent cells, suggesting an RNA alternative to cytoplasmic DNA in the triggering of senescence.
PGE2 accounts for bidirectional changes in alveolar macrophage self-renewal with aging and smokingDysregulation of self-renewal contributes to alterations in alveolar macrophages (AMs). In this study, Penke et al identify PGE2 as a suppressor of AM proliferation, whose divergent bioavailability in aged and cigarette smoke-exposed mice could explain opposite effects on AM numbers.
Profiles of histidine-rich glycoprotein associate with age and risk of all-cause mortalityAffinity-based proteomics assays identify particular profiles of the circulating histidine-rich glycoprotein to increase with age and elevated levels to indicate a higher risk of all-cause mortality.
USP30 sets a trigger threshold for PINK1–PARKIN amplification of mitochondrial ubiquitylationA new inhibitor of the deubiquitylase USP30, an actionable target relevant to Parkinson’s Disease, is introduced and characterised for parameters related to mitophagy.