The common non-steroidal anti-inflammatory drug ibuprofen has been associated with a reduced risk of some age-related pathologies. However, a general pro-longevity role for ibuprofen and its mechanistic basis remains unclear. Here we show that ibuprofen increased the lifespan of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster, indicative of conserved eukaryotic longevity effects. Studies in yeast indicate that ibuprofen destabilizes the Tat2p permease and inhibits tryptophan uptake. Loss of Tat2p increased replicative lifespan (RLS), but ibuprofen did not increase RLS when Tat2p was stabilized or in an already long-lived strain background impaired for aromatic amino acid uptake. Concomitant with lifespan extension, ibuprofen moderately reduced cell size at birth, leading to a delay in the G1 phase of the cell cycle. Similar changes in cell cycle progression were evident in a large dataset of replicatively long-lived yeast deletion strains. These results point to fundamental cell cycle signatures linked with longevity, implicate aromatic amino acid import in aging and identify a largely safe drug that extends lifespan across different kingdoms of life.

SummarySgf73, a core component of SAGA, is the yeast orthologue of ataxin‐7, which undergoes CAG–polyglutamine repeat expansion leading to the human neurodegenerative disease spinocerebellar ataxia type 7 (SCA7). Deletion of SGF73 dramatically extends replicative lifespan (RLS) in yeast. To further define the basis for Sgf73‐mediated RLS extension, we performed ChIP‐Seq, identified 388 unique genomic regions occupied by Sgf73, and noted enrichment in promoters of ribosomal protein (RP)‐encoding genes. Of 388 Sgf73 binding sites, 33 correspond to 5′ regions of genes implicated in RLS extension, including 20 genes encoding RPs. Furthermore, half of Sgf73‐occupied, RLS‐linked RP genes displayed significantly reduced expression in sgf73Δ mutants, and double null strains lacking SGF73 and a Sgf73‐regulated, RLS‐linked RP gene exhibited no further increase in replicative lifespan. We also found that sgf73Δ mutants display altered acetylation of Ifh1, an important regulator of RP gene transcription. These findings implicate altered ribosomal protein expression in sgf73Δ yeast RLS and highlight altered acetylation as a pathway of relevance for SCA7 neurodegeneration.

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Review: Optimized FRET pairs and quantification approaches to detect the activation of Aurora kinase A at mitosis.In this manuscript, Bertolin et al. improve on their original Aurora Kinase A biosensor to produce a second generation that would help follow AURKA activation in regions where it is extremely low in concentration and undetectable with the original AURKA biosensor. The authors develop two independent strategies to improve on their previous work. First, they develop a single-color AURKA biosensor for multiplex FRET and second, a method to observe and quantify FRET efficiency in areas with very low AURKA abundance. The authors show that dark acceptors ShadowG and ShadowY allow for single-color FRET/FLIM measurements while first generation tandem GFP isn't suitable due to low concentration of AURKA. They also show the inability of the original construct to measure FRET by 2c-FCCS and thus develop a novel method by replacing the donor-acceptor pair with a mTurquoise2 and novel superYFP. The experiments allowed the authors to develop guidelines when making new FRET biosensors such as characterizing the nature of the protein and making sure the conformational changes of the protein fall within the Forster's radius of the donor-acceptor pair.The improvements to AURKA biosensors represent a novel way for studying the function of this kinase. While fluorescence anisotropy has been used in the past to study FRET in different kinases such as PKA, ERK, and cAMP, it has not been known to work with AURKA due to the nature of the protein and it's function. Also, given the fact that levels of AURKA is regulated throughout the cell cycle, the ability to detect it at low levels will help understand it's function in diverse contexts.

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