Trehalose, Calorie Restriction, and Longevity in Yeast

You might recall that a few years ago, researchers extended life in nematode worms by feeding them trehalose. Here, scientists link normal abundances of trehalose in yeast cells with the longevity induced by calorie restriction: "Our recent investigation of how a lifespan-extending caloric restriction (CR) diet alters the metabolic history of chronologically aging yeast suggested that their longevity is programmed by the level of metabolic capacity - including trehalose biosynthesis and degradation - that yeast cells developed prior to entry into quiescence. To investigate whether trehalose homeostasis in chronologically aging yeast may play a role in longevity extension by CR, in this study we examined how single-gene-deletion mutations affecting trehalose biosynthesis and degradation impact (1) the age-related dynamics of changes in trehalose concentration; (2) yeast chronological lifespan under CR conditions; (3) the chronology of oxidative protein damage, intracellular ROS level and protein aggregation; and (4) the timeline of thermal inactivation of a protein in heat-shocked yeast cells and its subsequent reactivation in yeast returned to low temperature. Our data imply that CR extends yeast chronological lifespan in part by altering a pattern of age-related changes in trehalose concentration. We outline a model for molecular mechanisms underlying the essential role of trehalose in defining yeast longevity by modulating protein folding, misfolding, unfolding, refolding, oxidative damage, solubility, and aggregation throughout lifespan." Trehelose stimulates autophagy in higher animals, the all-important set of mechanisms that recycle damaged cell components, so one would expect it to be beneficial there as well.



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