(previous session)

Craig Skinner (Lin Lab, UC Davis): Identification of potential calorie restriction mimics in yeast using a nitric oxide-based screen. Yeast are an important model system in biogerontology, useful not only for genetic studies of longevity control but also for discovery of bioactive compounds. Calorie restriction (CR) in yeast causes increased levels of nitric oxide (NO) — somewhat surprising in that yeast cells lack a homolog of nitric oxide synthase — and elevated NO is sufficient to extend yeast lifespan. These observations led Skinner to screen a yeast deletion library for elevated NO levels, yielding several genes that extend lifespan.

Mark Lucanic (Lithgow Lab, Buck): Endocannabinoid signaling mediates the effect of diet on lifespan in C. elegans. Mutants in the dauer pathway in C. elegans often influence longevity; the daf-2 mutation, which causes constitutive dauer formation at elevated temperatures, extends lifespan by several fold. Lucanic discovered that endocannabinoids are involved in the regulation of the dauer pathway — and therefore, of longevity — either independently of or far downstream of daf-2 and daf-16. Endocannabinoids are upregulated under well-fed conditions, and shorten lifespan.

Delia David (Kenyon Lab, UCSF): Widespread protein aggregation is an inherent part of aging in C. elegans. Protein aggregates are a hallmark of many age-related neurodegenerative diseases, leading to the hypotheses that the cellular mileu changes with age in a manner that causes native, aggregation-prone proteins to form aggregates. David used mass spectrometry to identify a subset of normal worm proteins aggregate as a function of age. As with the proteins associated with neurodegeneration, specific proteins aggregate in specific cell types. Mutations that extend lifespan (such as daf-2) decrease aggregation, and tend to downregulate the expression of genes encoding aggregation-prone proteins. Curiously, regulators of protein homeostasis tend to aggregate themselves, leading to a destructive positive feedback loop in which the very factors that protect the cell from proteotoxicity disappear into aggregates, leading to further aggregation.

Cherry Tang (Zhong Lab, Berkeley): The Clearance of Ubiquitinated Protein Aggregates Via Autophagy. Autophagic protein degradation has been implicated in control of lifespan: autophagy slows cell and tissue aging. Tang has identified a protein that participates in degradation of ubiquitinated proteins and co-localizes with autophagosomes; when the protein is knocked down, protein aggregates become more toxic.

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