Showing papers by "Carles Cantó published in 2013"
TL;DR: The data suggest that augmenting mitochondrial stress signaling through the modulation of NAD(+) levels may be a target to improve mitochondrial function and prevent or treat age-associated decline.
935 citations
TL;DR: The current understanding of the SIRT-PARP interplay is reviewed in regard to the biochemical nature of the interaction, mutual posttranslational modifications and direct transcriptional effects and the physiological or pathophysiological consequences of the interactions.
210 citations
TL;DR: Here, it is described how to perform the analysis of the acetylation status of key SIRT1 and SIRT3 targets in rodent tissues and cultured cells.
Abstract: Evaluating the precise catalytic activity of sirtuin proteins in vivo is a challenging endeavor. Enzymological methods, including those employed in commercially available kits, require the isolation of immunopurified protein from cells or tissues, which can perturb regulatory protein-protein interactions as well as remove the enzyme from the reaction-altering effects of intracellular NAD(+), nicotinamide, and O-acetyl-ADP ribose concentrations. As such, the measurement of the steady state acetylation status of select sirtuin substrates in vivo remains an important tool for evaluating changes in sirtuin activity. Here, we describe how to perform the analysis of the acetylation status of key SIRT1 and SIRT3 targets in rodent tissues and cultured cells.
4 citations
TL;DR: In this article, SRT1720, a synthetic compound that was identified for its ability to activate Sirt1 in vitro, extends both mean and maximum lifespan of adult mice fed a high-fat diet.
Abstract: Sirt1 is an NAD+-dependent deacetylase that extends lifespan in lower organisms and improves metabolism and delays the onset of age-related diseases in mammals. Here we show that SRT1720, a synthetic compound that was identified for its ability to activate Sirt1 in vitro, extends both mean and maximum lifespan of adult mice fed a high-fat diet. This lifespan extension is accompanied by health benefits including reduced liver steatosis, increased insulin sensitivity, enhanced locomotor activity and normalization of gene expression profiles and markers of inflammation and apoptosis, all in the absence of any observable toxicity. Using a conditional SIRT1 knockout mouse and specific gene knockdowns we show SRT1720 affects mitochondrial respiration in a Sirt1- and PGC-1α-dependent manner. These findings indicate that SRT1720 has long-term benefits and demonstrate for the first time the feasibility of designing novel molecules that are safe and effective in promoting longevity and preventing multiple age-related diseases in mammals.
1 citations