Fig. 4: Intermittent fasting-mediated lifespan extension depends on SPD synthesis.
From: Spermidine is essential for fasting-mediated autophagy and longevity
a, Representative microscopy images on day 5 of chronological lifespan experiments of yeast WT and ∆spe1 in control and −N medium, stained with propidium iodide (PI). Scale bar, 5 µm. b, PI-negative (live) cells during chronological aging of yeast WT and ∆spe1 in control and −N medium. n = 36 (WT), 26 (∆spe1 CTL), 24 (∆spe1 −N) biologically independent samples (yeast cultures). c, PI-negative (live) cells during chronological aging yeast WT and ∆spe2, ∆spe3 and ∆spe4 cells grown to the log phase and shifted to CTL or −N. n = 8 biologically independent samples (yeast cultures). d, Lifespan of female w1118 flies fed standard food with or without 10 mM DFMO and subjected to IF12:12. n = 315 (ad lib), 313 (IF), 327 (ad lib + DFMO), 348 (IF + DFMO) flies. e, Flies from d were assessed for their climbing ability, measured as covered walking distance after a negative geotaxis stimulus, between days 53–60. n = 11 biologically independent samples. f, Flies from d were assessed for their climbing ability, measured as speed after a negative geotaxis stimulus, between days 53–60. n = 11 biologically independent samples. g, Lifespan of C. elegans N2 fed control (CTL) or odc-1(RNAi) expressing bacteria during IF48:48. The worms were transferred every other day. IF groups were transferred to agar plates without bacteria every second day. Note that the statistics and experiments were performed together with the groups depicted in i and Fig. 6p. n = 913 (CTL ad lib), 750 (CTL IF), 794 (odc-1(RNAi) ad lib), 779 (odc-1(RNAi) IF) worms. h, The susceptibility of worms to heat stress is reduced by IF48:48 in control, but not in worms fed odc-1(RNAi) expressing bacteria. Young worms (after the first round of fasting) were placed at 37 °C for 6 h. Survival was assessed after overnight recovery at 20 °C. n = 5 biologically independent experiments. i, Lifespan of C. elegans N2 fed bacteria expression control (CTL) or RNAi against argn-1, spds-1 or smd-1 during IF48:48. Note that the experiments and statistics were performed together with the groups depicted in g and Fig. 6p. n = 913 (CTL ad lib), 750 (CTL IF), 899 (argn-1(RNAi) ad lib), 797 (argn-1(RNAi) IF), 820 (smd-1(RNAi) ad lib), 803 (smd-1(RNAi) IF), 881 (spds-1(RNAi) ad lib), 746 (spds-1(RNAi) IF) worms. Statistics used were two-way ANOVA with Holm-Šídák’s multiple comparisons test (b,c,e,f,h) and log-rank test with Bonferroni correction (d,g,i). Bar graphs show the mean ± s.e.m. Source numerical data are available in source data. AUC, area under the curve.
