In this installment of the Longevity & Aging Series, Dr. Ming Yu and Namita Hattangady from the Fred Hutchinson Cancer Center in Seattle, join host Dr. Evgeniy Galimov to discuss a research paper they co-authored that was published as the cover for Volume 16, Issue 4 of Aging (Aging-US), entitled, “Mapping the core senescence phenotype of primary human colon fibroblasts.”

DOI - https://doi.org/10.18632/aging.205577

Corresponding authors - William M. Grady - [email protected], and Ming Yu - [email protected]

Video interview - https://www.youtube.com/watch?v=eqSa7My_a7w

Interview transcription - https://www.aging-us.com/interviews/longevity-aging-series-s2-e2-dr-ming-yu-and-namita-hattangady

Abstract

Advanced age is the largest risk factor for many diseases and several types of cancer, including colorectal cancer (CRC). Senescent cells are known to accumulate with age in various tissues, where they can modulate the surrounding tissue microenvironment through their senescence associated secretory phenotype (SASP). Recently, we showed that there is an increased number of senescent cells in the colons of CRC patients and demonstrated that senescent fibroblasts and their SASP create microniches in the colon that are conducive to CRC onset and progression. However, the composition of the SASP is heterogenous and cell-specific, and the precise senescence profile of colon fibroblasts has not been well-defined. To generate a SASP atlas of human colon fibroblasts, we induced senescence in primary human colon fibroblasts using various in vitro methods and assessed the resulting transcriptome. Using RNASequencing and further validation by quantitative RT-PCR and Luminex assays, we define and validate a ‘core senescent profile’ that might play a significant role in shaping the colon microenvironment. We also performed KEGG analysis and GO analyses to identify key pathways and biological processes that are differentially regulated in colon fibroblast senescence. These studies provide insights into potential driver proteins involved in senescence-associated diseases, like CRC, which may lead to therapies to improve overall health in the elderly and to prevent CRC.

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Keywords - aging, senescence, senescence associated secretory phenotype, SASP, colorectal cancer, cancer

About Aging-US

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

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