Research Paper Volume 2, Issue 7 pp 393—414

Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes

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Figure 1. The pex5Δ mutation shortens chronological life span (CLS), alters cell morphology and remodels lipid metabolism in CR yeast. (A) Outline of subcellular localization of the Fox1p, Fox2p and Fox3p enzymes of fatty acid ß-oxidation in WT and pex5Δ cells. (B - F) Survival and the mean life spans of chronologically aging WT and pex5Δ yeast cultured in medium initially containing 0.2%, 0.5%, 1% or 2% glucose. Data are presented as means ± SEM (n = 16-38; ***p < 0.001; **p < 0.01). (G - I) Levels of free fatty acids (FFA), diacylglycerols (DAG) and triacylglycerols (TAG) in WT and pex5Δ cells grown on 0.2% glucose and taken for analyses at the indicated time-points. FFA and TAG were measured by quantitative mass spectrometry. The levels of DAG were quantitated by densitometric analysis of TLC plates. Data are presented as means ± SEM (n = 3-8; ***p < 0.001; **p < 0.01; *p < 0.05). (J and K) Transmission electron micrographs (J) and spectra of lipids extracted from purified endoplasmic reticulum (ER) and lipid bodies (LB) and analyzed by TLC (K) for WT and pex5Δ (Δ5) yeast grown on 0.2% glucose and taken for analyses at the indicated time-points. Abbreviations: Cta1p, peroxisomal catalase; D, diauxic growth phase; EE, ethyl esters; ERG, ergosterol; FA-CoA, CoA esters of fatty acids; L, logarithmic growth phase; M, mitochondrion; N, nucleus; PD, post-diauxic growth phase; ST, stationary growth phase.