Type 2 diabetes is condition produced by excess weight in the vast majority of patients, and losing weight can reverse the progression of the condition even in later stages. Separately, researchers have demonstrated that excess visceral fat tissue promotes a greater burden of cellular senescence in older individuals. Senescent cells contribute to the chronic inflammation of aging, disruptive to tissue structure and function. Here, researchers note that type 2 diabetes patients exhibit a greater burden of cellular senescence, as determined by a range of measures - not all that surprising. Interestingly, other investigations have suggested that senescent cells in the pancreas drive dysfunction in both type 1 diabetes and type 2 diabetes, an important common mechanism in conditions with very different root causes.
Although animal studies have linked cellular senescence to the pathogenesis and complications of type 2 diabetes mellitus (T2DM), there is a paucity of corroborating data in humans. Thus, we measured a previously validated marker for senescent cell burden in humans, T-cell expression of p16 mRNA, along with additional biomarkers, to compare the senescence phenotypes of postmenopausal control (lean, N = 37) and T2DM (N = 27) participants. To control for effects of obesity alone, we included a third group of obese but non-diabetic women (N = 29) who were matched for body mass index to the T2DM participants. In addition, given the increase in fracture risk in T2DM despite preserved or even increased bone mineral density, we related these senescence biomarkers in the T2DM participants to skeletal microarchitectural parameters.
Relative to the lean participants, T-cell p16 and p21Cip1 expression was increased in the T2DM, but not the obese, non-diabetic participants. Expression of p16 and p21Cip1 was positively associated with HbA1c and an index of skin advanced glycation end-products. T2DM was also associated with an increase in a number of SASP factors. Among participants with T2DM, women in the highest tertile for T-cell expression of p16 had significantly reduced tibial cortical area and thickness as compared to those in the lower two tertiles. Overall, our studies link cellular senescence to metabolic and skeletal alterations in T2DM and point to the need for further studies evaluating the role of cellular senescence in mediating skeletal fragility, as well as potentially other complications in T2DM.
Link: https://doi.org/10.1111/acel.70120
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