Ageing transcriptomes of selected mutants on different carbon sources

Here we show that an unrestricted galactose diet in early life minimises pathology during replicative ageing in budding yeast, irrespective of diet later in life. Lifespan and average mother cell division rate are comparable between glucose and galactose diets, but markers of senescence and the progressive dysregulation of gene expression observed on glucose are minimal on galactose, showing these to be facets of ageing pathology rather than intrinsic parts of the replicative ageing process. Respiration on galactose is critical for minimising ageing pathology, and forced respiration during ageing on glucose by over-expression of Hap4 also has the same effect though only in a fraction of cells. This fraction maintains Hap4 activity to advanced age with low senescence and a youthful gene expression profile, whereas other cells in the same population that lose Hap4 activity undergo dramatic dysregulation of gene expression and accumulate aneuploid fragments of chromosome XII aneuploidy (ChrXIIr), which are tightly associated with ageing pathology.本研究证实，生命早期采用不限量半乳糖膳食，可减轻出芽酵母（budding yeast）复制性衰老过程中的病理损伤，且不受后期膳食结构的影响。葡萄糖膳食与半乳糖膳食组的酵母寿命及母细胞平均分裂速率相当，但在半乳糖膳食条件下，衰老标志物以及葡萄糖膳食中观察到的基因表达进行性失调现象均显著减弱，这表明上述现象属于衰老病理的表现形式，而非复制性衰老过程的固有组成部分。以半乳糖为碳源时的呼吸作用对减轻衰老病理至关重要；而通过过表达Hap4在葡萄糖膳食的衰老过程中强制诱导呼吸作用，同样可达到相同效果，不过仅在部分细胞中生效。该部分细胞可维持Hap4活性至衰老晚期，表现出低衰老水平与年轻态的基因表达谱；而同群体中其他丧失Hap4活性的细胞则会出现严重的基因表达失调，并积累第十二号染色体非整倍体片段（ChrXIIr），该片段与衰老病理密切相关。