Project description:In order to uncover mechanisms of hBMSC senescence, we performed high-throughput RNA-seq using young and senile human bone MSC (hBMSC).
Project description:Age-related cell loss underpins many senescence-associated diseases. Senile cataract is a primary blindness-causing age-related ocular disease. Apoptosis of lens epithelial cells (LECs) is the common cellular basis of senile cataract resulted from prolonged exposure to oxidative stress, the mechanism of which remains elusive. Here we reported the concomitance of increased autophagy and apoptosis in the same LEC from senile cataract patients. Oxidative stress triggered autophagy preceded apoptosis, while blocking autophagy by ablation of Atg7 or Atg3 gene remarkably suppressed apoptosis in HLE-B3 cell line. We identified autophagy adaptor SQSTM1/p62 as the critical scaffold protein to sustain a pro-survival signaling PKCι-NF-κB cascades, which antagonized the pro-apoptotic signaling in LECs. Importantly, prolonged autophagy in human senescent LECs responding to oxidative stress induced extensive degradation of p62 protein and therefore facilitated apoptosis. Moreover, pharmacological inhibitor of autophagy, 3-MA, significantly rescued apoptosis of human senescent LECs challenged by oxidative stress. Collectively, our data demonstrated that hyperactivation of autophagy aggravates age-related apoptotic cell death via inhibiting the p62-PKCι-NF-κB pro-survival axis in human senescent LECs. This work expands the understanding of the etiology of senile cataract and provides insight for mechanisms of age-related cell death in senescence-associated diseases.
Project description:Analysis of LCM samples isolated from the inner (subgranular zone-side, neurogenic site) and outer (molecular zone-side) granule cell layer of either young adult or senile dentate gyrus. Results provide insight into the molecular signatures of young and old granule cells.
Project description:Comparative evaluation of the aqueous humor proteome of primary angle closure and primary open angle glaucomas and senile cataract eyes
Project description:DNA methylation data from vervet cerebral cortex, blood, and liver using highly conserved mammalian CpGs represented on the mammalian methylation array (HorvathMammalMethylChip40). We selected a total of 240 samples representing the entire vervet lifespan, from neonatal to senile stages: 144 samples from the peripheral blood, 48 samples from the liver, and 48 samples from the cortical brain area BA10.
