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New Surface Marker Could Advance Precision Therapies for Type 2 Diabetes

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BUFFALO, NY — July 23, 2026 — A new #research paper was #published in Volume 18 of Aging on July 8, 2026, titled “TM4SF1 is a surface marker of senescent pancreatic β-cells.”

The study was led by first author Ana Beathriz Leite Lorente from Joslin Diabetes Center and Harvard Medical School, and São Paulo State University (UNESP), Brazil, and corresponding author Cristina Aguayo-Mazzucato from Joslin Diabetes Center and Harvard Medical School.

Type 2 diabetes is characterized by insulin resistance and the progressive loss of pancreatic β-cell function. With aging and metabolic stress, senescent β-cells accumulate within the pancreas, producing less insulin while releasing inflammatory signals that contribute to disease progression. Although eliminating these dysfunctional cells has emerged as a promising therapeutic strategy, a major challenge has been identifying markers that distinguish senescent β-cells from healthy cells with sufficient precision. This study identifies transmembrane 4 L six family member 1 (TM4SF1) as a highly selective surface marker of senescent β-cells, providing a promising candidate for the future development of more selective therapies for type 2 diabetes.

In this study, the researchers searched for cell-surface proteins that specifically identify senescent β-cells. Using RNA sequencing, flow cytometry, immunofluorescence, and analyses of both mouse and human pancreatic tissue, they compared TM4SF1 with the previously established senescence marker urokinase-type plasminogen activator receptor (uPAR/PLAUR). Their findings showed that TM4SF1 is expressed predominantly in senescent β-cells while exhibiting much lower expression in non-senescent β-cells and other tissues, making it a more β-cell-specific surface marker than uPAR.

Full press release - https://www.aging-us.com/news-room/new-surface-marker-could-advance-precision-therapies-for-type-2-diabetes

DOI - https://doi.org/10.18632/aging.206398

Corresponding author - Cristina Aguayo-Mazzucato - Cristina.aguayo-mazzucato@joslin.harvard.edu

Abstract video - https://www.youtube.com/watch?v=tNbFKdleTJo

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Keywords - aging, senescent β-cell, type 2 diabetes, transmembrane 4 l six family member 1, urokinase-type plasminogen activator receptor

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