Monitoring changes in the cellular content of biomolecules during ageing with FTIR spectroscopy

Abstract

Dietary regimens have proven to promote longevity in several eukaryotic model organisms including the budding yeast Saccharomyces cerevisiae. These interventions are effective strategies for preventing ageing and diseases and many of them are linked to amino acid and protein levels. The aim of this work was to better understand how the age-related TOR1 and SCH9 genes and the presence of amino acids affect cell metabolomes and to establish their impact on the ageing process. Cellular metabolic profiles were determined by FTIR spectroscopy. We demonstrated that metabolic signatures of cells deficient in SCH9, the major TORC1 effector, were very different to those of wild type and TOR1 deficient cells. In cells lacking Sch9 we also observed changes in other processes related to ageing such as endoplasmic reticulum stress and autophagy. We identified several anti-ageing biomarkers being the most relevant the intracellular content of pyruvate, glucose, ribose/deoxyribose associated compounds, and the presence of special protein conformational structures. The very sensitive FTIR technique allowed us to highlight important changes that occur along ageing in the metabolomes of the cells deficient in the key nutrient-sensitive Tor1-Sch9 pathway, even though slight differences on chronological lifespan were detected in our conditions.