Increased cell senescence in human metabolic disorders
Rosa Spinelli, … , Annika Nerstedt, Ulf Smith
Rosa Spinelli, … , Annika Nerstedt, Ulf Smith
Published June 15, 2023
Citation Information: J Clin Invest. 2023;133(12):e169922. https://doi.org/10.1172/JCI169922.
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Increased cell senescence in human metabolic disorders

Abstract

Cell senescence (CS) is at the nexus between aging and associated chronic disorders, and aging increases the burden of CS in all major metabolic tissues. However, CS is also increased in adult obesity, type 2 diabetes (T2D), and nonalcoholic fatty liver disease independent of aging. Senescent tissues are characterized by dysfunctional cells and increased inflammation, and both progenitor cells and mature, fully differentiated and nonproliferating cells are afflicted. Recent studies have shown that hyperinsulinemia and associated insulin resistance (IR) promote CS in both human adipose and liver cells. Similarly, increased CS promotes cellular IR, showing their interdependence. Furthermore, the increased adipose CS in T2D is independent of age, BMI, and degree of hyperinsulinemia, suggesting premature aging. These results suggest that senomorphic/senolytic therapy may become important for treating these common metabolic disorders.

Authors

Rosa Spinelli, Ritesh Kumar Baboota, Silvia Gogg, Francesco Beguinot, Matthias Blüher, Annika Nerstedt, Ulf Smith

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Figure 1

Linking aging to chronic diseases.

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Linking aging to chronic diseases. The hallmarks of aging, including cel...
The hallmarks of aging, including cell senescence, are functionally intertwined and drive the pathophysiology of many chronic disorders, affecting tissues directly involved in disease development. Indeed, senescent cells promote or exacerbate human age-related conditions by inducing chronic inflammation and tissue dysfunction via their SASP. SASP factors are responsible for a number of negative effects, including stem cell dysfunction, immune cell recruitment, fibrogenic myofibroblast induction, and extracellular matrix secretion. The left side of the figure displays the most common cell types and mechanisms that cause tissue damage, all of which contribute to the age-related chronic diseases depicted to the right. The right side of the figure depicts some of the most common chronic diseases associated with aging. CVD, cardiovascular disease.