Cellular Senescence Archives - The NOMIS Foundation

It is widely believed that cellular senescence plays a critical role in both aging and cancer, and that senescence is a fundamental, permanent growth arrest that somatic cells cannot avoid. Here we show that Myc plays an important role in self-renewal of esophageal epithelial cells, contributing to their resistance to cellular senescence. Myc is homogeneously expressed in basal cells of the esophageal epithelium and Myc positively regulates their self-renewal by maintaining their undifferentiated state. Indeed, Myc knockout induced a loss of the undifferentiated state of esophageal epithelial cells resulting in cellular senescence while forced MYC expression promoted oncogenic cell proliferation. A superoxide scavenger counteracted Myc knockout-induced senescence, therefore suggesting that a mitochondrial superoxide takes part in inducing senescence. Taken together, these analyses reveal extremely low levels of cellular senescence and senescence-associated phenotypes in the esophageal epithelium, as well as a critical role for Myc in self-renewal of basal cells in this organ. This provides new avenues for studying and understanding the links between stemness and resistance to cellular senescence.

The development of clinical interventions that significantly improve human healthspan requires robust markers of biological age as well as thoughtful therapeutic targets. To promote these goals, we performed a systematic review and analysis of human aging and proteomics studies. The systematic review includes 36 different proteomics analyses, each of which identified proteins that significantly changed with age. We discovered 1,128 proteins that had been reported by at least two or more analyses and 32 proteins that had been reported by five or more analyses. Each of these 32 proteins has known connections relevant to aging and age-related disease. GDF15, for example, extends both lifespan and healthspan when overexpressed in mice and is additionally required for the anti-diabetic drug metformin to exert beneficial effects on body weight and energy balance. Bioinformatic enrichment analyses of our 1,128 commonly identified proteins heavily implicated processes relevant to inflammation, the extracellular matrix, and gene regulation. We additionally propose a novel proteomic aging clock comprised of proteins that were reported to change with age in plasma in three or more different studies. Using a large patient cohort comprised of 3,301 subjects (aged 18–76 years), we demonstrate that this clock is able to accurately predict human age.

Publications in Cellular Senescence by NOMIS researchers

Myc Supports Self-Renewal of Basal Cells in the Esophageal Epithelium

Systematic review and analysis of human proteomics aging studies unveils a novel proteomic aging clock and identifies key processes that change with age