Stay dynamic to slow aging

n page 803, Gourlay et al. report the first evidence that the actin cytoskeleton can affect release of reactive oxygen species (ROS) by mitochondria, and thus life span in yeast. Certain mutant Saccharo-myces cerevisiae strains with alleles that reduce actin dynamics possess defective mitochondria. The team O Cells with increased actin dynamics live longer. went on to show that such strains display increased levels of mitochondrially-derived ROS and die early compared with wild-type yeast. In an exciting contrast, mutant yeast with increased actin dynamics had lower levels of ROS and substantially increased longevity. Actin dynamics was increased either via a mutant actin allele or deletion of the gene encoding the actin-stabilizing protein SCP1, which has homology to vertebrate SM22/ transgelin protein. In the latter case, the yeast lived up to 40 generations longer. The function of the actin–ROS connection is unknown. But actin, as a relatively abundant protein with an intrinsic ATPase activity, may be a convenient indicator of cellular excitement. Thus, cells that are metabolically active, producing a lot of ROS, and in need of a vigorous ROS-suppressing machinery may pick up on the dynamics of actin as a proxy for cellular metabolism and respond by dampening pathways that cause ROS release. Alternatively, actin may directly bind to and regulate the opening of mitochondrial channels involved in ROS release. ᭿ Binding to the basement ancer metastasis is often more deadly than the primary tumor. Wang et al. report on page 935 that exposed basement membrane may offer a docking site when tumors spread to the lung—the most common site of metastasis. Some existing metastasis studies have used long time points that may mask several sequential events. Wang et al. targeted the point of initial cell attachment by developing an ex vivo lung perfusion model. After injecting fluorescent tumor cells into rat renal vein, they immediately isolated the lungs allowing them to measure arrest of cells in pulmonary tissue. Prior treatment with a range of integrin antibodies revealed that ␣ 3 ␤ 1 integrin—which is widely expressed in cancerous cells—is the key player in tumor cell attachment. This was confirmed by genetic deletion and restoration of the distinct ␣ 3 and ␤ 1 subunits in a variety of cells. Having found the anchor, the team then needed to know where it came to rest on the blood vessel wall. And here, perhaps, is the most fascinating part of their discovery: …