Language

English

Publication Date

8-1-2025

Journal

Aging Cell

DOI

10.1111/acel.70120

PMID

40448295

PMCID

PMC12341793

PubMedCentral® Posted Date

5-30-2025

PubMedCentral® Full Text Version

Post-print

Abstract

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 p21 Cip1 expression was increased in the T2DM, but not the obese, non‐diabetic participants. Expression of p16 and p21 Cip1 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.

Keywords

Humans, Diabetes Mellitus, Type 2, Cellular Senescence, Female, Biomarkers, Middle Aged, Aged, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinase Inhibitor p21, Obesity, aging, diabetes, obesity, osteoporosis, senescence

Published Open-Access

yes

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