Mapping the Core Senescence Phenotype of Human Colon Fibroblasts

02-29-2024

“[...] despite the impact of aging on colon health and colon cancer, an atlas of the SASP produced by colon fibroblasts has not been established.”

Listen to an audio version of this press release

BUFFALO, NY- February 29, 2024 – A new research paper was published on the cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 4, entitled, “Mapping the core senescence phenotype of primary human colon fibroblasts.

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, researchers 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.

In this new study, to generate a SASP atlas of human colon fibroblasts, researchers Namita Ganesh Hattangady, Kelly Carter, Brett Maroni-Rana, Ting Wang, Jessica Lee Ayers, Ming Yu, and William M. Grady from Fred Hutchinson Cancer Center and the University of Washington School of Medicine induced senescence in primary human colon fibroblasts using various in vitro methods and assessed the resulting transcriptome.

“[...] we utilized various relevant stressors to induce senescence in primary cultures of colon fibroblasts and perform RNA sequencing (RNASeq) to define an atlas of stressor-specific senescent profiles and a core senescent profile that is commonly regulated by all senescence inducers.”

Using RNA Sequencing and further validation by quantitative RT-PCR and Luminex assays, the team define and validate a ‘core senescent profile’ that might play a significant role in shaping the colon microenvironment. They 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.

“Further studies will be needed to address the limitations of our study and to translate our understanding of the SASP and disease into clinical care.”

Read the full study: DOI: https://doi.org/10.18632/aging.205577 

Corresponding Authors: William M. Grady, Ming Yu - wgrady@fredhutch.org, myu@fredhutch.org 

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

Click here to sign up for free Altmetric alerts about this article.

About Aging-US:

Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer’s diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases.

Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed CentralWeb of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

Please visit our website at www.Aging-US.com and connect with us:

For media inquiries, please contact media@impactjournals.com.