Page 7 - A. Aging
P. 7

A      2.0                                                                                                                B                                              C
                                                                                                                                                                                                                                                                 Relative Cellular Proliferation
                                                                                                                                                                                                                                                                                                               AKT inhibitors                                                                   125                                           125



                                                                                                                                                                                                                                                                            **
                                                                                                                                                                                                                                                                    1.5                                                                                                                         100                                           100

                                                                                                                                                                                                                                                                                                                                                                                          Lysosomal Mass  (Relative to DMSO)  50       Autofluorescence  (Relative to DMSO)



                                                                                                                                                                                                                                                                    1.0                                                                                                                           75               **                          75               **







                                                                                                                                                                                                                                                                    0.5                                                                                                                           25                                           50

                                                                                                                                                                                                                                                                                                                                                                                                                                               25



                                                                                                                                                                                                                                                                    0.0                                                                                                                            0                                            0
                                                                                                                                                                                                                                                                               GDC-0068  AZD5363  GSK690693  PF-04691502  TIC10  Triciribine  Honokiol  PHT-427  AT7867  A-674563  MK-2206 2HCl  CCT128930  DMSO     GDC0068                            DMSO       GDC0068

























































                                                                                                                                                                                                                                                              A                                      B                                      C                                          D

                                                                                                                                                                                                                                                                         1 2 5            *                     125                                      125                                                                                     Rotenone+




                                                                                                                                                                                                                                                                         1 0 0
                                                                                                                                                                                                                                                                                                                100
                                                                                                                                                                                                                                                                                                                                                         100
                                                                                                                                                                                                                                                                                                                                                                                                          Senescent (GDC0068)
                                                                                                                                                                                                                                                                                                                                                                                                80
                                                                                                                                                                                                                                                                                                                                                                                                           Oligomycin
                                                                                                                                                                                                                                                                   MMP (Relative to GDC0068)  7 5          ROS (DHR123)  (Relative to DMSO)  75  *  ROS (MitoSOX)  (Relative to DMSO)  75  *  OCR(pmol/min)  100  Senescent (DMSO) FCCP          Antimycin
                                                                                                                                                                                                                                                                                                                                                                                                60
                                                                                                                                                                                                                                                                          5 0
                                                                                                                                                                                                                                                                                                                                                          50
                                                                                                                                                                                                                                                                                                                 50
                                                                                                                                                                                                                                                                                                                                                                                                40
                                                                                                                                                                                                                                                                          2 5




                                                                                                                                                                                                                                                                           0                                     25                                       25                                    20
                                                                                                                                                                                                                                                                                                                                                                                                 0
                                                                                                                                                                                                                                                                                                                                                           0
                                                                                                                                                                                                                                                                                                                   0
                                                                                                                                                                                                                                                                                   DMSO     GDC0068                       DMSO     GDC0068                         DMSO     GDC0068            -20       10     20      30     40 Time(min)  60     70     80     90    100
                                                                                                                                                                                                                                                                                                                                                                                                                                      50


















































                                                                                                                                                                                                                                                                                                                                                                                               with Chloroquine
                                                                                                                                                                                                                                                             A                            LC3B         Mitochondria        Merged         B                           C                                                                                  D
                                                                                                                                                                                                                                                                                                                                                                                               10 μm LC3B          Mitochondria       Merged

                                                                                                                                                                                                                                                                  YOUNG                                                                         1.2           **             YOUNG                                                                          100





                                                                                                                                                                                                                                                                               10μm  10μm             10μm             10μm                     0.8                            10μm              10μm             10μm             10μm                      80


                                                                                                                                                                                                                                                                  DMSO                                                                        CYTO-ID Green                  DMSO                                                                         Mitochodrial Mass  60  **


                                                                                                                                                                                                                                                              SENESCENT  10μm        10μm             10μm             10μm                     0.4                      SENESCENT  10μm         10μm             10μm             10μm                      20
                                                                                                                                                                                                                                                                                                                                                                                                                                                             40



                                                                                                                                                                                                                                                                  GDC0068                                                                       0.0                          GDC0068                                                                          0





                                                                                                                                                                                                                                                                   10μm              10μm             10μm             10μm                              DMSO   GDC0068       10 μm              10μm             10μm             10μm                              DMSO   GDC0068
                                                                                                                                                                                                                                                                                                                                                                              10μm
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