Protein catabolites as blood-based biomarkers of aging physiology: Findings from the Dog Aging Project.

Our understanding of age-related physiology and metabolism has grown through the study of systems biology, including transcriptomics, single-cell analysis, proteomics and metabolomics. Studies in lab organisms in controlled environments, while powerful and complex, fall short of capturing the breadth of genetic and environmental variation in nature. Thus, there is now a major effort in geroscience to identify aging biomarkers and to develop aging interventions that might be applied across the diversity of humans and other free-living species.

DNA methylation of transposons pattern aging differences across a diverse cohort of dogs from the Dog Aging Project.

Unlabelled: Within a species, larger individuals often have shorter lives and higher rates of age-related disease. Despite this well-known link, we still know little about underlying age-related epigenetic differences, which could help us better understand inter-individual variation in aging and the etiology, onset, and progression of age-associated disease. Dogs exhibit this negative correlation between size, health, and longevity and thus represent an excellent system in which to test the underlying mechanisms.

Multiomics of -Dependent Replicative Lifespan Extension Models Reveals Gcn4 as a Regulator of Protein Turnover in Yeast.

We have shown that multiple tRNA synthetase inhibitors can increase lifespan in both the nematode and the budding yeast by acting through the conserved transcription factor Gcn4 (yeast)/ATF-4 (worms). To further understand the biology downstream from this conserved transcription factor in the yeast model system, we looked at two different yeast models known to have upregulated Gcn4 and -dependent increased replicative lifespan. These two models were yeast and yeast treated with the tRNA synthetase inhibitor borrelidin.

Easy Worm Lifespan Plotting and Statistics with WLSplot.

WLSplot is an R package used to easily analyze lifespan survival data, and display results graphically as a survival curve with useful labels and statistical information auto-generated from the data and added to the graph, within a single function. It is designed primarily with lifespan data in mind initially but can easily be used for other types of survival data. The WLSplot GitHub repository provides a blank template spreadsheet to be used for collecting lifespan data, instructions on how to install and run WLSplot, and examples covering RNAi, Genotype, or Drug lifespan experimental set-ups.

Induction of proteasomal activity in mammalian cells by lifespan-extending tRNA synthetase inhibitors.

We have recently shown that multiple tRNA synthetase inhibitors can greatly increase lifespan in multiple models by acting through the conserved transcription factor ATF4. Here, we show that these compounds, and several others of the same class, can greatly upregulate mammalian ATF4 in cells in vitro, in a dose dependent manner. Further, RNASeq analysis of these cells pointed toward changes in protein turnover.