Immunofluorescence imaging of platelet-derived progress issue α (PDGFRα) expression in exocrine areas of histological pancreatic sections. Credit score: G. Soultoukis/DIfE
As age will increase, the pancreas modifications, which will increase the chance of metabolic illnesses reminiscent of sort 2 diabetes, digestive problems, and in addition most cancers. Researchers on the German Institute of Human Diet Potsdam-Rehbruecke (DIfE) have now been in a position to present in an animal mannequin that stellate cells, in interplay with blood vessels, play a key position in age-related modifications within the pancreas. They printed their ends in the journal Redox Biology.
The pancreas is a yellowish organ, roughly 80 to 120 grams in weight, 15 centimeters lengthy, 5 centimeters extensive, and a couple of–3 centimeters thick, positioned behind the abdomen. It consists of roughly 95% of exocrine tissue, which produces digestive enzymes, and 5% of endocrine tissue, which releases the hormones insulin and glucagon to control blood sugar ranges.
Along with these useful cells, two different cell varieties play an essential position: First, stellate cells form the construction of the organ by way of the formation of the extracellular matrix. Second, endothelial cells type the blood vessels and are due to this fact important for the blood provide of the pancreas.
With growing age, modifications resulting in fats deposits (steatosis) or the pathological proliferation of connective tissue (fibrosis) can result in cell modifications within the pancreas that impair perform. Particularly, the formation of fats and connective tissue by stellate cells has been insufficiently investigated in relation to getting old up to now. Furthermore, little was beforehand identified in regards to the position of blood vessels, which signify a type of hub between the pancreas and the remainder of the physique.
Growing old analysis on the mobile stage
To research the age-related modifications in stellate cells and blood vessels of the pancreas, DIfE researchers, in collaboration with researchers from the German Middle for Diabetes Analysis (DZD) and the European Molecular Biology Laboratory (EMBL), studied younger and previous mice. They remoted particular person pancreatic cells and analyzed their gene expression.
This single-cell transcriptomic evaluation allowed them to establish completely different cell varieties and examine their particular features. For the exact localization of stellate cells within the pancreas and their altered distribution in previous age, the researchers used immunofluorescence investigations.
The analysis workforce led by Dr. Marina Leer and Dr. George A. Soultoukis from the Division of Adipocyte Growth and Diet recognized completely different subgroups of stellate cells that type various quantities of fats or connective tissue.
With growing age, the distribution of the recognized stellate cell subgroups shifted towards a stronger tendency to fibrosis. This was accompanied by the activation of particular fibrosis-promoting signaling pathways (Remodeling progress issue beta, TGFbeta and Platelet-derived progress issue, PDGF), which altered the composition of the extracellular matrix of the pancreas.
One other essential discovering was that the stellate cells of the getting old mice interacted extra strongly with the blood vessels. This cell communication triggered older stellate cells to launch extra pro-inflammatory substances, damaging blood vessels and worsening fibrosis.
Implications for the prevention and therapy of age-related pancreatic illnesses
“Our results suggest that pancreatic stellate cells change their identity with age and transform into fibrotic cells. These fibrotic cells contribute to the formation of scar tissue, which can impair the production of hormones and digestive enzymes,” explains Soultoukis.
His colleague Leer provides, “Fibrosis and inflammation can alter the microenvironment in the pancreas and promote the development of cancer cells.” The research outcomes present new approaches for the event of methods for the prevention and therapy of age-related illnesses of the pancreas, reminiscent of sort 2 diabetes. For example, understanding the mobile mechanisms underlying fibrosis could assist to develop new medicine that decelerate or reverse tissue harm.
The researchers now plan to analyze the temporal elements that affect the age-related transformation of stellate cells. In future research, in addition they need to look at life-style elements reminiscent of food regimen and bodily exercise in additional element, which might modulate this course of.
Extra info:
George A. Soultoukis et al, Pancreatic stellate cells have adipogenic and fibrogenic potentials however solely present elevated pro-fibrogenic propensity upon getting old, Redox Biology (2025). DOI: 10.1016/j.redox.2025.103791
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Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke
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