Functional restoration of lysosomes and mitochondria through modulation of AKT activity ameliorates senescence

Senescence is a phenomenon defined by alterations in cellular organelles and is the primary cause of aging and aging-related diseases. Recent studies have shown that oncogene-induced senescence is driven by activation of serine/threonine protein kinases (AKT1, AKT2 and AKT3). In this study, we evaluated twelve AKT inhibitors and revealed GDC0068 as a potential agent to ameliorate senescence. Senescence-ameliorating effect was evident from the finding that GDC0068 yielded lysosomal functional recovery as observed by reduction in lysosomal mass and induction in autophagic flux. Furthermore, GDC0068-mediated restoration of lysosomal function activated the removal of dysfunctional mitochondria, resulting in restoration of mitochondrial function. Together, our findings revealed a unique mechanism by which senescence is recovered by functional restoration of lysosomes and mitochondria through modulation of AKT activity.

Automated summary

Senescence is caused by alterations in cellular organelles and is the primary cause of aging and aging-related diseases. Recent studies have revealed that oncogene-induced senescence is driven by activation of serine/threonine protein kinases (AKT1, AKT2, and AKT3). In this study, GDC0068 was found to have a senescence-ameliorating effect by restoring lysosomal and mitochondrial function through modulation of AKT activity.