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Proteostasis is essential for cellular health, with its disruption contributing to aging, neurodegeneration, and metabolic disorders. While the upstream proteotoxic stress-sensing and protein-folding mechanisms in the ER and cytosol are well studied, the transcriptional regulation of proteostasis remains incompletely understood, particularly concerning the temporal epigenome dynamics, chromatin landscapes, and co-regulatory networks underlying dynamic proteostasis control. Traditionally,...

The DNA damage response (DDR) pathway has emerged as the central signaling network that preserves genome stability by using sensors to monitor the genome for aberrant structures and establishing signaling centers that promote organismal homeostasis. This review revisits the formative years of DDR research, focusing on the genetic dissection of the pathway in Saccharomyces cerevisiae and its evolution into a broadly conserved eukaryotic signaling system. Early studies of ribonucleotide reductase...

The extraordinary lifespan variation in domestic dogs provides a natural experiment for testing how intrinsic rates of biological aging shape lifespan. Using 1640 methylomes from 894 dogs, we developed an epigenetic clock that predicted mortality and demonstrated that epigenetic aging is fastest early in life. At orthologs of human age-associated genes, dogs exhibited concordant age effects on promoter methylation, highlighting conserved remodeling of immune pathways. We found that larger and...

Time-restricted feeding (TRF) restricts food intake to daily windows, yet its efficacy against vascular aging and underlying mechanisms remain unclear. Here, we demonstrate that TRF attenuates angiotension II -induced accelerated vascular aging by reshaping gut microbiota, stabilizing microbial diversity, and elevating the Firmicutes/Bacteroidetes ratio. TRF preserved intestinal barrier integrity, upregulated tight junction proteins (Occludin, ZO-1, MUC2), reduced serum lipopolysaccharide, and...

Just seven strength-training sessions helped obese mice shrink visceral fat cells and reactivate molecular pathways involved in burning stored fat, despite no change in overall body weight. The findings suggest some benefits of resistance exercise may begin long before weight loss becomes visible, though the results still need to be confirmed in humans.

Science, Ahead of Print.

Science, Ahead of Print.