Fig. 6: Hypodermal DAF-2 degradation in aging worms slows cognitive decline through CREB-dependent pathway via Notch ligand OSM-11.
From: Body-to-brain insulin and Notch signaling regulates memory through neuronal CREB activity
a, Hypodermis-specific DAF-2 degradation in old adult animals improves STAM. b, Neuron-specific DAF-2 degradation in old adult animals does not increase STAM. a,b, Auxin started on day 5, while STAM was performed on day 6. c, Comparison of 1-h memory in young (day 2) versus old (day 6) adult animals with hypodermis-specific or neuron-specific DAF-2 degradation. Only hypodermis-specific DAF-2 degradation improves old (day 6) adult memory. d, osm-11 expression decreases with age26. c,d, In the box plots, the center line denotes the median, box range indicates the 25th–75th percentile, and whiskers denote minimum–maximum values. e,f, OSM-11 overexpression increases memory in aged (day 5) adults. CI (e) and learning index (f) are shown. g, Memory was evaluated by calculating the rate of change in CI between the learning and 0.5-h time points across replicates. h,i, Aged (day 6) daf-2(e1370);crh-1(n3315) learning and STAM is impaired relative to daf-2 worms. CI (h) and learning index (i) are shown. j, Slope analysis as in g using learning and 1-h time points. a,b,e,f,h,i, Representative experiment from three biological replicates. Mean ± s.e.m. Two-way repeated-measures ANOVA using data. Bonferroni post hoc tests. n ≥ 4 chemotaxis plates at each time point, where each dot represents an individual assay plate with ~80 worms. Representative experiment for three biological replicates. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001. c,d,g,j, Two-sided unpaired t-test.
