Subhash Katewa (Kapahi lab, Buck Institute) talked about the metabolic adaptations that occur in flies whose lifespan is being extended by dietary restriction (DR). Katewa is studying translational control in DR using a method called translational profiling, which uses the number of ribosomes bound to each mRNA as an index of translational activity (more ribosomes = more translation). He found that DR increases translation of messages that encode a variety of mitochondrial functions; this observation led to some interesting findings about the differential turnover of triglycerides in DR vs ad libitum flies.

Adam Freund (Campisi lab, Buck Institute) spoke about the sources of age-related inflammation, focusing on the senescence-associated secretory phenotype (SASP). Freund has elucidated mechanisms of SASP control that intermediate between the most upstream events in senescence (DNA damage) and its downstream effects (secretion of inflammatory factors). I have it on good authority that he has a completed manuscript on the subject, hopefully to be publshed soon, so I won’t say more about his story here. (Mr. Freund happens to be my baymate.)

Dario Valenzano (Brunet lab, Stanford University) is studying the genetic architecture of longevity in a short-lived fish Nothobranchius furzeri, the shortest-living vertebrate that can be reared in captivity. As a graduate student, Valenzano developed a system of biomarkers for tracking the progress of aging in skin, brain and other tissues – not only physical markers like the senescence-associated beta-galactosidase but also behavioral markers that change over the lifespan. He is now proceeding to map the longevity-associated genes in N. furzeri and testing the sufficiency of the genes he finds. Early results indicate that short-lived and long-lived fish are dying from different causes, as evidenced by a bimodal distribution of death rate vs. age.

Adolfo Sánchez-Blanco (Kim lab, Stanford University Medical School) described the “molecular odometer” for aging in the worm C. elegans. He began with the observation that lifespan is variable, even among clonally identical individuals kept under identical conditions. With genetics and environment taken out of the picture, what makes some individuals live longer than others? In order to address this question, SB had to develop a molecular marker (e.g., promoter activity of some gene) that measures physiological age (as opposed to chronological age), and then determine whether the expression level of that marker in individual worms is predictive of lifespan. SB has identified several such genes whose expression at middle age strongly predicts remaining lifespan. He is now actively looking for interventions that abolish the correlation between marker expression and longevity: if the marker gene’s activity is serving to overcome the life-shortening effect of some stress, then removing that stress will not necessarily abolish the variability in the marker, but will eliminate the correlation between marker levels and lifespan. (This is a subtle but important logical issue; I would have thought that one should look for interventions that drove the population distribution of marker levels toward the favorable side of the distribution. It was clear from questions that a lot of audience members had trouble with this logic, and I’m still not sure I understand it myself.)

(next session)