Unravelling the complexities of colon aging
A cellular and spatial atlas of the mouse colon has provided insight into how the cells and tissues of the intestine are affected by ageing. The international research study, recently published in the scientific journal Nature Biotechnology, may contribute to increased knowledge about diseases and conditions in older people.
Aging is a universal process that profoundly influences the structure and function of our organs. Yet, many of the molecular mechanisms behind these changes remain elusive. In the current study, which was led by Sanja Vicković at IGP, the researchers profiled nearly 1,500 mouse gut tissues from different anatomical regions and different age groups to chart how tissues and cells change across the lifespan.
“Our study resulted in one of the most comprehensive datasets to date on colon aging, providing a multi-dimensional view of how aging impacts tissue structure and molecular circuitry. We could for instance detect cellular changes in the colonic tract that are consistent with the elevated incidence of premalignant states of colorectal cancer in the elderly,” says Sanja Vicković.
A major innovation from the study is the development of the novel computational framework cSplotch. This combines histological and gene expression data to estimate cell type abundance across tissues and to infer how gene expression varies with factors like age, region, sex, and tissue structure.
“cSplotch allowed us to identify subtle but important patterns associated with age, tissue region, and sex. This way we could map cellular and molecular gradients along the adult colonic tract and identify multicellular programmes specifically linked to aging in the large intestine,” says Vicković.
Understanding how aging reshapes the colon at a cellular and molecular level has critical implications. Not only for basic biology, but also for diseases like colorectal cancer and inflammatory bowel disease, which become more prevalent with age. In addition, better knowledge of the molecular mechanism behind common geriatric conditions such as constipation and malnutrition could pave the way for interventions aimed to support the quality of life.