Diabetes compromises DNA damage repair and telomere maintenance in adipose tissue stromal cells leading to cellular senescence.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Diabetes mellitus (DM) is characterized by chronic metabolic stress that promotes oxidative damage, genomic instability, and premature cellular aging, with adipose tissue senescence being a pivotal contributor to metabolic dysfunction. Yet the impact on DNA damage repair (DDR) and telomere maintenance in adipose tissue remains poorly defined. This study investigated DDR capacity, telomere integrity, and the senescence-associated secretory phenotype (SASP) in adipose tissue and adipose-derived stromal cells (ADSCs) under diabetic conditions. Using an obese diabetic (ob/ob) mouse model, we confirmed whole-blood telomere shortening, significant adipose tissue hypertrophy, metabolic dysregulation, and elevated DNA damage, evidenced by increased γH2AX-positive staining. In vitro, ADSCs exposed to a diabetic microenvironment (AGEs and TNFα) exhibited increased reactive oxygen species and DNA damage without a corresponding activation of DDR pathways, as indicated by unchanged PARP1 levels and broad downregulation of key DNA repair genes, including sensors (ATM, ABL1, RAD17) and effectors across MMR, NER, HR, and NHEJ pathways. This impaired genomic surveillance was accompanied by premature cellular senescence and significant repression of genes involved in telomere protection (shelterin complex), telomerase activity, and telomere maintenance, together with marked telomere shortening f

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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