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Chaperone biomarkers of lifespan and penetrance track the dosages of many other proteins

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Many traits vary among isogenic individuals in homogeneous environments. In microbes, plants and animals, variation in the protein chaperone system affects many such traits. In the animal model C. elegans,… Click to show full abstract

Many traits vary among isogenic individuals in homogeneous environments. In microbes, plants and animals, variation in the protein chaperone system affects many such traits. In the animal model C. elegans, the expression level of hsp-16.2 chaperone biomarkers correlates with or predicts the penetrance of mutations and lifespan after heat shock. But the physiological mechanisms causing cells to express different amounts of the biomarker were unknown. Here, we used an in vivo microscopy approach to dissect different contributions to cell-to-cell variation in hsp-16.2 expression in the intestines of young adult animals, which generate the most lifespan predicting signal. While we detected both cell autonomous intrinsic noise and signaling noise, we found both contributions were relatively unimportant. The major contributor to cell-to-cell variation in biomarker expression was general differences in protein dosage. The hsp-16.2 biomarker reveals states of high or low effective dosage for many genes. In C. elegans the chaperone hsp-16.2 predicts the penetrance of mutations and lifespan after heat shock, but it is not known why cells express different amounts of hsp-16.2. Here the authors show hsp-16.2 tracks differences in global gene expression capacity, rather than differences in signaling or intrinsic noise in adult intestine cells.

Keywords: chaperone biomarkers; penetrance; biomarkers lifespan; penetrance track; cell; lifespan penetrance

Journal Title: Nature Communications
Year Published: 2019

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